WorldWideScience

Sample records for human disorders including

  1. A Preliminary Classification of Human Functional Sexual Disorders

    Science.gov (United States)

    Sharpe, Lawrence; And Others

    1976-01-01

    A preliminary classification is presented for functional human sexual disorders. This system is based on objective behavior and reports of distress. Five categories of sexual disorders are proposed, including the behavioral, psychological and informational components of sexual functioning in the individual and the couple. (Author)

  2. Glutamate synapses in human cognitive disorders.

    Science.gov (United States)

    Volk, Lenora; Chiu, Shu-Ling; Sharma, Kamal; Huganir, Richard L

    2015-07-08

    Accumulating data, including those from large genetic association studies, indicate that alterations in glutamatergic synapse structure and function represent a common underlying pathology in many symptomatically distinct cognitive disorders. In this review, we discuss evidence from human genetic studies and data from animal models supporting a role for aberrant glutamatergic synapse function in the etiology of intellectual disability (ID), autism spectrum disorder (ASD), and schizophrenia (SCZ), neurodevelopmental disorders that comprise a significant proportion of human cognitive disease and exact a substantial financial and social burden. The varied manifestations of impaired perceptual processing, executive function, social interaction, communication, and/or intellectual ability in ID, ASD, and SCZ appear to emerge from altered neural microstructure, function, and/or wiring rather than gross changes in neuron number or morphology. Here, we review evidence that these disorders may share a common underlying neuropathy: altered excitatory synapse function. We focus on the most promising candidate genes affecting glutamatergic synapse function, highlighting the likely disease-relevant functional consequences of each. We first present a brief overview of glutamatergic synapses and then explore the genetic and phenotypic evidence for altered glutamate signaling in ID, ASD, and SCZ.

  3. Non-human Primate Models for Brain Disorders - Towards Genetic Manipulations via Innovative Technology.

    Science.gov (United States)

    Qiu, Zilong; Li, Xiao

    2017-04-01

    Modeling brain disorders has always been one of the key tasks in neurobiological studies. A wide range of organisms including worms, fruit flies, zebrafish, and rodents have been used for modeling brain disorders. However, whether complicated neurological and psychiatric symptoms can be faithfully mimicked in animals is still debatable. In this review, we discuss key findings using non-human primates to address the neural mechanisms underlying stress and anxiety behaviors, as well as technical advances for establishing genetically-engineered non-human primate models of autism spectrum disorders and other disorders. Considering the close evolutionary connections and similarity of brain structures between non-human primates and humans, together with the rapid progress in genome-editing technology, non-human primates will be indispensable for pathophysiological studies and exploring potential therapeutic methods for treating brain disorders.

  4. Shining evolutionary light on human sleep and sleep disorders.

    Science.gov (United States)

    Nunn, Charles L; Samson, David R; Krystal, Andrew D

    2016-01-01

    Sleep is essential to cognitive function and health in humans, yet the ultimate reasons for sleep-i.e. 'why' sleep evolved-remain mysterious. We integrate findings from human sleep studies, the ethnographic record, and the ecology and evolution of mammalian sleep to better understand sleep along the human lineage and in the modern world. Compared to other primates, sleep in great apes has undergone substantial evolutionary change, with all great apes building a sleeping platform or 'nest'. Further evolutionary change characterizes human sleep, with humans having the shortest sleep duration, yet the highest proportion of rapid eye movement sleep among primates. These changes likely reflect that our ancestors experienced fitness benefits from being active for a greater portion of the 24-h cycle than other primates, potentially related to advantages arising from learning, socializing and defending against predators and hostile conspecifics. Perspectives from evolutionary medicine have implications for understanding sleep disorders; we consider these perspectives in the context of insomnia, narcolepsy, seasonal affective disorder, circadian rhythm disorders and sleep apnea. We also identify how human sleep today differs from sleep through most of human evolution, and the implications of these changes for global health and health disparities. More generally, our review highlights the importance of phylogenetic comparisons in understanding human health, including well-known links between sleep, cognitive performance and health in humans. © The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

  5. [Basic disorders in human communication].

    Science.gov (United States)

    Peñaloza-López, Y; Gutiérrez-Silva, J; Andrade-Illañez, E N; Fierro-Evans, M A; Hernández-López, X

    1989-01-01

    This paper specifies the areas and disorders that concern human communication medicine. The frequency of the diverse disorders is analyzed in relation to age and sex, and the distribution in group ages of several disabling diseases is also discussed.

  6. Evolutionary Conservation in Genes Underlying Human Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Lisa Michelle Ogawa

    2014-05-01

    Full Text Available Many psychiatric diseases observed in humans have tenuous or absent analogs in other species. Most notable among these are schizophrenia and autism. One hypothesis has posited that these diseases have arisen as a consequence of human brain evolution, for example, that the same processes that led to advances in cognition, language, and executive function also resulted in novel diseases in humans when dysfunctional. Here, the molecular evolution of genes associated with these and other psychiatric disorders are compared among species. Genes associated with psychiatric disorders are drawn from the literature and orthologous sequences are collected from eleven primate species (human, chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, baboon, marmoset, squirrel monkey, and galago and thirty one non-primate mammalian species. Evolutionary parameters, including dN/dS, are calculated for each gene and compared between disease classes and among species, focusing on humans and primates compared to other mammals and on large-brained taxa (cetaceans, rhinoceros, walrus, bear, and elephant compared to their small-brained sister species. Evidence of differential selection in primates supports the hypothesis that schizophrenia and autism are a cost of higher brain function. Through this work a better understanding of the molecular evolution of the human brain, the pathophysiology of disease, and the genetic basis of human psychiatric disease is gained.

  7. A new mouse model for mania shares genetic correlates with human bipolar disorder.

    Directory of Open Access Journals (Sweden)

    Michael C Saul

    Full Text Available Bipolar disorder (BPD is a debilitating heritable psychiatric disorder. Contemporary rodent models for the manic pole of BPD have primarily utilized either single locus transgenics or treatment with psychostimulants. Our lab recently characterized a mouse strain termed Madison (MSN that naturally displays a manic phenotype, exhibiting elevated locomotor activity, increased sexual behavior, and higher forced swimming relative to control strains. Lithium chloride and olanzapine treatments attenuate this phenotype. In this study, we replicated our locomotor activity experiment, showing that MSN mice display generationally-stable mania relative to their outbred ancestral strain, hsd:ICR (ICR. We then performed a gene expression microarray experiment to compare hippocampus of MSN and ICR mice. We found dysregulation of multiple transcripts whose human orthologs are associated with BPD and other psychiatric disorders including schizophrenia and ADHD, including: Epor, Smarca4, Cmklr1, Cat, Tac1, Npsr1, Fhit, and P2rx7. RT-qPCR confirmed dysregulation for all of seven transcripts tested. Using a novel genome enrichment algorithm, we found enrichment in genome regions homologous to human loci implicated in BPD in replicated linkage studies including homologs of human cytobands 1p36, 3p14, 3q29, 6p21-22, 12q24, 16q24, and 17q25. Using a functional network analysis, we found dysregulation of a gene system related to chromatin packaging, a result convergent with recent human findings on BPD. Our findings suggest that MSN mice represent a polygenic model for the manic pole of BPD showing much of the genetic systems complexity of the corresponding human disorder. Further, the high degree of convergence between our findings and the human literature on BPD brings up novel questions about evolution by analogy in mammalian genomes.

  8. Human GRIN2B variants in neurodevelopmental disorders

    Directory of Open Access Journals (Sweden)

    Chun Hu

    2016-10-01

    Full Text Available The development of whole exome/genome sequencing technologies has given rise to an unprecedented volume of data linking patient genomic variability to brain disorder phenotypes. A surprising number of variants have been found in the N-methyl-d-aspartate receptor (NMDAR gene family, with the GRIN2B gene encoding the GluN2B subunit being implicated in many cases of neurodevelopmental disorders, which are psychiatric conditions originating in childhood and include language, motor, and learning disorders, autism spectrum disorder (ASD, attention deficit hyperactivity disorder (ADHD, developmental delay, epilepsy, and schizophrenia. The GRIN2B gene plays a crucial role in normal neuronal development and is important for learning and memory. Mutations in human GRIN2B were distributed throughout the entire gene in a number of patients with various neuropsychiatric and developmental disorders. Studies that provide functional analysis of variants are still lacking, however current analysis of de novo variants that segregate with disease cases such as intellectual disability, developmental delay, ASD or epileptic encephalopathies reveal altered NMDAR function. Here, we summarize the current reports of disease-associated variants in GRIN2B from patients with multiple neurodevelopmental disorders, and discuss implications, highlighting the importance of functional analysis and precision medicine therapies.

  9. Large animals as potential models of human mental and behavioral disorders.

    Science.gov (United States)

    Danek, Michał; Danek, Janusz; Araszkiewicz, Aleksander

    2017-12-30

    Many animal models in different species have been developed for mental and behavioral disorders. This review presents large animals (dog, ovine, swine, horse) as potential models of this disorders. The article was based on the researches that were published in the peer-reviewed journals. Aliterature research was carried out using the PubMed database. The above issues were discussed in the several problem groups in accordance with the WHO International Statistical Classification of Diseases and Related Health Problems 10thRevision (ICD-10), in particular regarding: organic, including symptomatic, disorders; mental disorders (Alzheimer's disease and Huntington's disease, pernicious anemia and hepatic encephalopathy, epilepsy, Parkinson's disease, Creutzfeldt-Jakob disease); behavioral disorders due to psychoactive substance use (alcoholic intoxication, abuse of morphine); schizophrenia and other schizotypal disorders (puerperal psychosis); mood (affective) disorders (depressive episode); neurotic, stress-related and somatoform disorders (posttraumatic stress disorder, obsessive-compulsive disorder); behavioral syndromes associated with physiological disturbances and physical factors (anxiety disorders, anorexia nervosa, narcolepsy); mental retardation (Cohen syndrome, Down syndrome, Hunter syndrome); behavioral and emotional disorders (attention deficit hyperactivity disorder). This data indicates many large animal disorders which can be models to examine the above human mental and behavioral disorders.

  10. DisFace: A Database of Human Facial Disorders

    Directory of Open Access Journals (Sweden)

    Paramjit Kaur

    2017-10-01

    Full Text Available Face is an integral part of human body by which an individual communicates in the society. Its importance can be highlighted by the fact that a person deprived of face cannot sustain in the living world. In the past few decades, human face has gained attention of several researchers, whether it is related to facial anthropometry, facial disorder, face transplantation or face reconstruction. Several researches have also shown the correlation between neuropsychiatry disorders and human face and also that how face recognition abilities are correlated with these disorders. Currently, several databases exist which contain the facial images of several individuals captured from different sources. The advantage of these databases is that the images in these databases can be used for testing and training purpose. However, in current date no such database exists which would provide not only facial images of individuals; but also the literature concerning the human face, list of several genes controlling human face, list of facial disorders and various tools which work on facial images. Thus, the current research aims at developing a database of human facial disorders using bioinformatics approach. The database will contain information about facial diseases, medications, symptoms, findings, etc. The information will be extracted from several other databases like OMIM, PubChem, Radiopedia, Medline Plus, FDA, etc. and links to them will also be provided. Initially, the diseases specific for human face have been obtained from already created published corpora of literature using text mining approach. Becas tool was used to obtain the specific task.  A dataset will be created and stored in the form of database. It will be a database containing cross-referenced index of human facial diseases, medications, symptoms, signs, etc. Thus, a database on human face with complete existing information about human facial disorders will be developed. The novelty of the

  11. The effect of childhood conduct disorder on human capital.

    Science.gov (United States)

    Webbink, Dinand; Vujić, Sunčica; Koning, Pierre; Martin, Nicholas G

    2012-08-01

    This paper estimates the longer-term effects of childhood conduct disorder on human capital accumulation and violent and criminal behavior later in life using data of Australian twins. We measure conduct disorder with a rich set of indicators based on diagnostic criteria from psychiatry. Using ordinary least squares and twin fixed effects estimation approaches, we find that early-age (pre-18) conduct disorder problems significantly affect both human capital accumulation and violent and criminal behavior over the life course. In addition, we find that conduct disorder is more deleterious if these behaviors occur earlier in life. Copyright © 2011 John Wiley & Sons, Ltd.

  12. Should an obsessive-compulsive spectrum grouping of disorders be included in DSM-V?

    Science.gov (United States)

    Phillips, Katharine A; Stein, Dan J; Rauch, Scott L; Hollander, Eric; Fallon, Brian A; Barsky, Arthur; Fineberg, Naomi; Mataix-Cols, David; Ferrão, Ygor Arzeno; Saxena, Sanjaya; Wilhelm, Sabine; Kelly, Megan M; Clark, Lee Anna; Pinto, Anthony; Bienvenu, O Joseph; Farrow, Joanne; Leckman, James

    2010-06-01

    The obsessive-compulsive (OC) spectrum has been discussed in the literature for two decades. Proponents of this concept propose that certain disorders characterized by repetitive thoughts and/or behaviors are related to obsessive-compulsive disorder (OCD), and suggest that such disorders be grouped together in the same category (i.e. grouping, or "chapter") in DSM. This article addresses this topic and presents options and preliminary recommendations to be considered for DSM-V. The article builds upon and extends prior reviews of this topic that were prepared for and discussed at a DSM-V Research Planning Conference on Obsessive-Compulsive Spectrum Disorders held in 2006. Our preliminary recommendation is that an OC-spectrum grouping of disorders be included in DSM-V. Furthermore, we preliminarily recommend that consideration be given to including this group of disorders within a larger supraordinate category of "Anxiety and Obsessive-Compulsive Spectrum Disorders." These preliminary recommendations must be evaluated in light of recommendations for, and constraints upon, the overall structure of DSM-V. (c) 2010 Wiley-Liss, Inc.

  13. Sleep Disorders in Childhood Neurogenetic Disorders

    Directory of Open Access Journals (Sweden)

    Laura Beth Mann Dosier

    2017-09-01

    Full Text Available Genetic advances in the past three decades have transformed our understanding and treatment of many human diseases including neurogenetic disorders. Most neurogenetic disorders can be classified as “rare disease,” but collectively neurogenetic disorders are not rare and are commonly encountered in general pediatric practice. The authors decided to select eight relatively well-known neurogenetic disorders including Down syndrome, Angelman syndrome, Prader–Willi syndrome, Smith–Magenis syndrome, congenital central hypoventilation syndrome, achondroplasia, mucopolysaccharidoses, and Duchenne muscular dystrophy. Each disorder is presented in the following format: overview, clinical characteristics, developmental aspects, associated sleep disorders, management and research/future directions.

  14. Modeling human neurological disorders with induced pluripotent stem cells.

    Science.gov (United States)

    Imaizumi, Yoichi; Okano, Hideyuki

    2014-05-01

    Human induced pluripotent stem (iPS) cells obtained by reprogramming technology are a source of great hope, not only in terms of applications in regenerative medicine, such as cell transplantation therapy, but also for modeling human diseases and new drug development. In particular, the production of iPS cells from the somatic cells of patients with intractable diseases and their subsequent differentiation into cells at affected sites (e.g., neurons, cardiomyocytes, hepatocytes, and myocytes) has permitted the in vitro construction of disease models that contain patient-specific genetic information. For example, disease-specific iPS cells have been established from patients with neuropsychiatric disorders, including schizophrenia and autism, as well as from those with neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. A multi-omics analysis of neural cells originating from patient-derived iPS cells may thus enable investigators to elucidate the pathogenic mechanisms of neurological diseases that have heretofore been unknown. In addition, large-scale screening of chemical libraries with disease-specific iPS cells is currently underway and is expected to lead to new drug discovery. Accordingly, this review outlines the progress made via the use of patient-derived iPS cells toward the modeling of neurological disorders, the testing of existing drugs, and the discovery of new drugs. The production of human induced pluripotent stem (iPS) cells from the patients' somatic cells and their subsequent differentiation into specific cells have permitted the in vitro construction of disease models that contain patient-specific genetic information. Furthermore, innovations of gene-editing technologies on iPS cells are enabling new approaches for illuminating the pathogenic mechanisms of human diseases. In this review article, we outlined the current status of neurological diseases-specific iPS cell research and described recently obtained

  15. Association of endogenous retroviruses and long terminal repeats with human disorders

    Directory of Open Access Journals (Sweden)

    Iyoko eKatoh

    2013-09-01

    Full Text Available Since the human genome sequences became available in 2001, our knowledge about the human transposable elements which comprise ~40% of the total nucleotides has been expanding. Non- LTR (long terminal repeat retrotransposons are actively transposing in the present-day human genome, and have been found to cause ~100 identified clinical cases of varied disorders. In contrast, almost all of the human endogenous retroviruses (HERVs originating from ancient infectious retroviruses lost their infectivity and transposing activity at various times before the human-chimpanzee speciation (~6 million years ago, and no known HERV is presently infectious. Insertion of HERVs and mammalian apparent LTR retrotransposons (MaLRs into the chromosomal DNA influenced a number of host genes in various modes during human evolution. Apart from the aspect of genome evolution, HERVs and solitary LTRs being suppressed in normal biological processes can potentially act as extra transcriptional apparatuses of cellular genes by re-activation in individuals. There has been a reasonable prediction that aberrant LTR activation could trigger malignant disorders and autoimmune responses if epigenetic changes including DNA hypomethylation occur in somatic cells. Evidence supporting this hypothesis has begun to emerge only recently: a MaLR family LTR activation in the pathogenesis of Hodgkin’s lymphoma and a HERV-E antigen expression in an anti-renal cell carcinoma immune response. This mini review addresses the impacts of the remnant-form LTR retrotransposons on human pathogenesis.

  16. A Descriptive Study on the Neonatal Morbidity Profile of Autism Spectrum Disorders, Including a Comparison with Other Neurodevelopmental Disorders

    Science.gov (United States)

    Atladóttir, H. Ó.; Schendel, D. E.; Parner, E. T.; Henriksen, T. B.

    2015-01-01

    The aim of this study was to describe the profile of specific neonatal morbidities in children later diagnosed with autism spectrum disorder (ASD), and to compare this profile with the profile of children with hyperkinetic disorder, cerebral palsy, epilepsy or intellectual disability. This is a Danish population based cohort study, including all…

  17. Burden and health-related quality of life of eating disorders, including Avoidant/Restrictive Food Intake Disorder (ARFID), in the Australian population.

    Science.gov (United States)

    Hay, Phillipa; Mitchison, Deborah; Collado, Abraham Ernesto Lopez; González-Chica, David Alejandro; Stocks, Nigel; Touyz, Stephen

    2017-01-01

    Little is known about the epidemiology and health related quality of life (HRQoL) of the new DSM-5 diagnoses, Binge Eating Disorder (BED) and Avoidant/Restrictive Food Intake Disorder (ARFID) in the Australian population. We aimed to investigate the prevalance and burden of these disorders. We conducted two sequential population-based surveys including individuals aged over 15 years who were interviewed in 2014 ( n  = 2732) and 2015 ( n =3005). Demographic information and diagnostic features of DSM-5 eating disorders were asked including the occurrence of regular (at least weekly over the past 3 months) objective binge eating with levels of distress, extreme dietary restriction/fasting for weight/shape control, purging behaviors, overvaluation of shape and/or weight, and the presence of an avoidant/restrictive food intake without overvaluation of shape and/or weight. In 2014 functional impact or role performance was measured with the 'days out of role' question and in 2015, Health Related Quality of Life (HRQoL) was assessed with the Short Form -12 item questionnaire (SF-12v1). The 2014 and 2015 3-month prevalence of eating disorders were: anorexia nervosa-broad 0.4% (95% CI 0.2-0.7) and 0.5% (0.3-0.9); bulimia nervosa 1.1% (0.7-1.5) and 1.2% (0.9-1.7); ARFID 0.3% (0.1-0.5) and 0.3% (0.2-0.6). The 2015 3-month prevalence rates were: BED-broad 1.5% (1.1-2.0); Other Specified Feeding or Eating Disorder (OSFED) 3.2 (2.6-3.9); and Unspecified Feeding or Eating Disorder (UFED) 10.4% (0.9-11.5). Most people with OSFED had atypical anorexia nervosa and majority with UFED were characterised by having recurrent binge eating without marked distress. Eating disorders were represented throughout sociodemographic groups and those with bulimia nervosa and BED-broad had mean weight (BMI, kg/m 2 ) in the obese range. Mental HRQoL was poor in all eating disorder groups but particularly poor for those with BED-broad and ARFID. Individuals with bulimia nervosa, BED

  18. Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders.

    Science.gov (United States)

    Lazzeri, Elena; Ronconi, Elisa; Angelotti, Maria Lucia; Peired, Anna; Mazzinghi, Benedetta; Becherucci, Francesca; Conti, Sara; Sansavini, Giulia; Sisti, Alessandro; Ravaglia, Fiammetta; Lombardi, Duccio; Provenzano, Aldesia; Manonelles, Anna; Cruzado, Josep M; Giglio, Sabrina; Roperto, Rosa Maria; Materassi, Marco; Lasagni, Laura; Romagnani, Paola

    2015-08-01

    The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from (1) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and (2) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders. Copyright © 2015 by the American Society of Nephrology.

  19. Comparing ESC and iPSC?Based Models for Human Genetic Disorders

    OpenAIRE

    Halevy, Tomer; Urbach, Achia

    2014-01-01

    Traditionally, human disorders were studied using animal models or somatic cells taken from patients. Such studies enabled the analysis of the molecular mechanisms of numerous disorders, and led to the discovery of new treatments. Yet, these systems are limited or even irrelevant in modeling multiple genetic diseases. The isolation of human embryonic stem cells (ESCs) from diseased blastocysts, the derivation of induced pluripotent stem cells (iPSCs) from patients’ somatic cells, and the ne...

  20. [Consensus statement on the clinical management of human immunodeficiency virus-associated neurocognitive disorders].

    Science.gov (United States)

    Podzamczer Palter, Daniel; Muñoz-Moreno, José A; Alcolea Rodríguez, Daniel; Alonso Villaverde, Carlos; Antela López, Antonio; Blanch Andreu, Jordi; Casado Osorio, José Luis; Galindo Puerto, M José; Garolera i Freixa, Maite; Locutura Rupérez, Jaime; Lleó Bisa, Albert; Prats París, Anna; Pérez-Valero, Ignacio; Portilla Sogorb, Joaquín; Rovira Cañellas, Alex; Téllez Molina, M Jesús; Tiraboschi, Juan Manuel; Vergara Moragues, Esperanza; Arribas López, José Ramón; Goenaga Sánchez, Miguel Ángel; de León-Naranjo, Fernando Lozano; Martínez Chamorro, Esteban; Polo Rodríguez, Rosa; Muñoz-Moreno, José A; Podzamczer, Daniel

    2014-01-01

    To develop a consensus document containing clinical recommendations for the management of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND). We assembled a panel of experts appointed by GeSIDA and the Secretariat of the National AIDS Plan (PNS), including internal medicine physicians with expertise in the field of HIV, neuropsychologists, neurologists and neuroradiologists. Scientific information was reviewed to October 2012 in publications and conference papers. In support of the recommendations using two levels of evidence: the strength of the recommendation in the opinion of the experts (A, B, C) and the level of empirical evidence (I, II, III), two levels based on the criteria of the Infectious Disease Society of America, already used in previous documents GeSIDA/SPNS. Multiple recommendations for the clinical management of these disorders are provided, including two graphics algorithms, considering both the diagnostic and possible therapeutic strategies. Neurocognitive disorders associated with HIV infection is currently highly prevalent, are associated with a decreased quality of life and daily activities, and given the possibility of occurrence of an increase in the coming years, there is a need to adequately manage these disorders, from a diagnostic as well as therapeutic point of view, and always from a multidisciplinary perspective. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  1. Burden and health-related quality of life of eating disorders, including Avoidant/Restrictive Food Intake Disorder (ARFID), in the Australian population

    OpenAIRE

    Hay, Phillipa; Mitchison, Deborah; Collado, Abraham Ernesto Lopez; Gonz?lez-Chica, David Alejandro; Stocks, Nigel; Touyz, Stephen

    2017-01-01

    Background Little is known about the epidemiology and health related quality of life (HRQoL) of the new DSM-5 diagnoses, Binge Eating Disorder (BED) and Avoidant/Restrictive Food Intake Disorder (ARFID) in the Australian population. We aimed to investigate the prevalance and burden of these disorders. Methods We conducted two sequential population-based surveys including individuals aged over 15?years who were interviewed in 2014 (n?=?2732) and 2015 (n =3005). Demographic information and diag...

  2. Pathophysiological Significance of Dermatan Sulfate Proteoglycans Revealed by Human Genetic Disorders

    Directory of Open Access Journals (Sweden)

    Shuji Mizumoto

    2017-03-01

    Full Text Available The indispensable roles of dermatan sulfate-proteoglycans (DS-PGs have been demonstrated in various biological events including construction of the extracellular matrix and cell signaling through interactions with collagen and transforming growth factor-β, respectively. Defects in the core proteins of DS-PGs such as decorin and biglycan cause congenital stromal dystrophy of the cornea, spondyloepimetaphyseal dysplasia, and Meester-Loeys syndrome. Furthermore, mutations in human genes encoding the glycosyltransferases, epimerases, and sulfotransferases responsible for the biosynthesis of DS chains cause connective tissue disorders including Ehlers-Danlos syndrome and spondyloepimetaphyseal dysplasia with joint laxity characterized by skin hyperextensibility, joint hypermobility, and tissue fragility, and by severe skeletal disorders such as kyphoscoliosis, short trunk, dislocation, and joint laxity. Glycobiological approaches revealed that mutations in DS-biosynthetic enzymes cause reductions in enzymatic activities and in the amount of synthesized DS and also disrupt the formation of collagen bundles. This review focused on the growing number of glycobiological studies on recently reported genetic diseases caused by defects in the biosynthesis of DS and DS-PGs.

  3. Human Genetic Disorders and Knockout Mice Deficient in Glycosaminoglycan

    Directory of Open Access Journals (Sweden)

    Shuji Mizumoto

    2014-01-01

    Full Text Available Glycosaminoglycans (GAGs are constructed through the stepwise addition of respective monosaccharides by various glycosyltransferases and maturated by epimerases and sulfotransferases. The structural diversity of GAG polysaccharides, including their sulfation patterns and sequential arrangements, is essential for a wide range of biological activities such as cell signaling, cell proliferation, tissue morphogenesis, and interactions with various growth factors. Studies using knockout mice of enzymes responsible for the biosynthesis of the GAG side chains of proteoglycans have revealed their physiological functions. Furthermore, mutations in the human genes encoding glycosyltransferases, sulfotransferases, and related enzymes responsible for the biosynthesis of GAGs cause a number of genetic disorders including chondrodysplasia, spondyloepiphyseal dysplasia, and Ehlers-Danlos syndromes. This review focused on the increasing number of glycobiological studies on knockout mice and genetic diseases caused by disturbances in the biosynthetic enzymes for GAGs.

  4. Transplantation of Human Chorion-Derived Cholinergic Progenitor Cells: a Novel Treatment for Neurological Disorders.

    Science.gov (United States)

    Mohammadi, Alireza; Maleki-Jamshid, Ali; Sanooghi, Davood; Milan, Peiman Brouki; Rahmani, Arash; Sefat, Farshid; Shahpasand, Koorosh; Soleimani, Mansoureh; Bakhtiari, Mehrdad; Belali, Rafie; Faghihi, Faezeh; Joghataei, Mohammad Taghi; Perry, George; Mozafari, Masoud

    2018-03-16

    A neurological disorder is any disorder or abnormality in the nervous system. Among different neurological disorders, Alzheimer's disease (AD) is recognized as the sixth leading cause of death globally. Considerable research has been conducted to find pioneer treatments for this devastating disorder among which cell therapy has attracted remarkable attentions over the last decade. Up to now, targeted differentiation into specific desirable cell types has remained a major obstacle to clinical application of cell therapy. Also, potential risks including uncontrolled growth of stem cells could be disastrous. In our novel protocol, we used basal forebrain cholinergic progenitor cells (BFCN) derived from human chorion-derived mesenchymal stem cells (hC-MSCs) which made it possible to obtain high-quality population of cholinergic neurons and in vivo in much shorter time period than previous established methods. Remarkably, the transplanted progenitors fully differentiated to cholinergic neurons which in turn integrated in higher cortical networks of host brains, resulting in significant improvement in cognitive assessments. This method may have profound implications in cell therapies for any other neurodegenerative disorders. Graphical Abstract ᅟ.

  5. Contrasting Features of Urea Cycle Disorders in Human Patients and Knockout Mouse Models

    OpenAIRE

    Deignan, Joshua L.; Cederbaum, Stephen D.; Grody, Wayne W.

    2007-01-01

    The urea cycle exists for the removal of excess nitrogen from the body. Six separate enzymes comprise the urea cycle, and a deficiency in any one of them causes a urea cycle disorder (UCD) in humans. Arginase is the only urea cycle enzyme with an alternate isoform, though no known human disorder currently exists due to a deficiency in the second isoform. While all of the UCDs usually present with hyperammonemia in the first few days to months of life, most disorders are distinguished by a cha...

  6. Contrasting features of urea cycle disorders in human patients and knockout mouse models.

    Science.gov (United States)

    Deignan, Joshua L; Cederbaum, Stephen D; Grody, Wayne W

    2008-01-01

    The urea cycle exists for the removal of excess nitrogen from the body. Six separate enzymes comprise the urea cycle, and a deficiency in any one of them causes a urea cycle disorder (UCD) in humans. Arginase is the only urea cycle enzyme with an alternate isoform, though no known human disorder currently exists due to a deficiency in the second isoform. While all of the UCDs usually present with hyperammonemia in the first few days to months of life, most disorders are distinguished by a characteristic profile of plasma amino acid alterations that can be utilized for diagnosis. While enzyme assay is possible, an analysis of the underlying mutation is preferable for an accurate diagnosis. Mouse models for each of the urea cycle disorders exist (with the exception of NAGS deficiency), and for almost all of them, their clinical and biochemical phenotypes rather closely resemble the phenotypes seen in human patients. Consequently, all of the current mouse models are highly useful for future research into novel pharmacological and dietary treatments and gene therapy protocols for the management of urea cycle disorders.

  7. Role of Vitamin D in human Diseases and Disorders – An Overview

    Directory of Open Access Journals (Sweden)

    Priyanshee Gohil

    2014-06-01

    Full Text Available Vitamin D is a fat soluble vitamin and generated in human skin by ultraviolet (UV light. Today, vitamin D is considered to be a steroidal hormone and plays a central role in bone mineralization and calcium homeostasis. The active form of the vitamin D is 1, 25-dihydroxyvitamin D [1, 25-dihydroxycholecalciferol (DHCC] which mediatesproliferation, differentiation and various functions at the cellular level through Vitamin D receptors (VDR.Therefore, compromised vitamin D status is likely to be involved in progression or pathogenesis of various disorders. This assumption is consistent with findings from epidemiological studies that a compromised vitamin D status in humans increases the risk of autoimmune diseases, such as inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus (SLE, multiple sclerosis and type I diabetes mellitus. However, diseases like cancer, cardiovascular disorders and bone disorders are yet not focused. Thus the role of vitamin D in pathogenesis of various diseases is complex and controversial. This review briefly summarizes the role of vitamin D in development and progression of different human disorders.

  8. Axon guidance pathways served as common targets for human speech/language evolution and related disorders.

    Science.gov (United States)

    Lei, Huimeng; Yan, Zhangming; Sun, Xiaohong; Zhang, Yue; Wang, Jianhong; Ma, Caihong; Xu, Qunyuan; Wang, Rui; Jarvis, Erich D; Sun, Zhirong

    2017-11-01

    Human and several nonhuman species share the rare ability of modifying acoustic and/or syntactic features of sounds produced, i.e. vocal learning, which is the important neurobiological and behavioral substrate of human speech/language. This convergent trait was suggested to be associated with significant genomic convergence and best manifested at the ROBO-SLIT axon guidance pathway. Here we verified the significance of such genomic convergence and assessed its functional relevance to human speech/language using human genetic variation data. In normal human populations, we found the affected amino acid sites were well fixed and accompanied with significantly more associated protein-coding SNPs in the same genes than the rest genes. Diseased individuals with speech/language disorders have significant more low frequency protein coding SNPs but they preferentially occurred outside the affected genes. Such patients' SNPs were enriched in several functional categories including two axon guidance pathways (mediated by netrin and semaphorin) that interact with ROBO-SLITs. Four of the six patients have homozygous missense SNPs on PRAME gene family, one youngest gene family in human lineage, which possibly acts upon retinoic acid receptor signaling, similarly as FOXP2, to modulate axon guidance. Taken together, we suggest the axon guidance pathways (e.g. ROBO-SLIT, PRAME gene family) served as common targets for human speech/language evolution and related disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Mitochondrial dysfunction in human skeletal muscle biopsies of lipid storage disorder.

    Science.gov (United States)

    Debashree, Bandopadhyay; Kumar, Manish; Keshava Prasad, Thottethodi Subrahmanya; Natarajan, Archana; Christopher, Rita; Nalini, Atchayaram; Bindu, Parayil Sankaran; Gayathri, Narayanappa; Srinivas Bharath, Muchukunte Mukunda

    2018-02-09

    Mitochondria regulate the balance between lipid metabolism and storage in the skeletal muscle. Altered lipid transport, metabolism and storage influence the bioenergetics, redox status and insulin signalling, contributing to cardiac and neurological diseases. Lipid storage disorders (LSDs) are neurological disorders which entail intramuscular lipid accumulation and impaired mitochondrial bioenergetics in the skeletal muscle causing progressive myopathy with muscle weakness. However, the mitochondrial changes including molecular events associated with impaired lipid storage have not been completely understood in the human skeletal muscle. We carried out morphological and biochemical analysis of mitochondrial function in muscle biopsies of human subjects with LSDs (n = 7), compared to controls (n = 10). Routine histology, enzyme histochemistry and ultrastructural analysis indicated altered muscle cell morphology and mitochondrial structure. Protein profiling of the muscle mitochondria from LSD samples (n = 5) (vs. control, n = 5) by high-throughput mass spectrometric analysis revealed that impaired metabolic processes could contribute to mitochondrial dysfunction and ensuing myopathy in LSDs. We propose that impaired fatty acid and respiratory metabolism along with increased membrane permeability, elevated lipolysis and altered cristae entail mitochondrial dysfunction in LSDs. Some of these mechanisms were unique to LSD apart from others that were common to dystrophic and inflammatory muscle pathologies. Many differentially regulated mitochondrial proteins in LSD are linked with other human diseases, indicating that mitochondrial protection via targeted drugs could be a treatment modality in LSD and related metabolic diseases. © 2018 International Society for Neurochemistry.

  10. Acupuncture for neurological disorders in the Cochrane reviews:Characteristics of included reviews and studies

    Institute of Scientific and Technical Information of China (English)

    Deren Wang; Weimin Yang; Ming Liu

    2011-01-01

    OBJECTIVE: To summarize Cochrane reviews of acupuncture for neurological disorders, and characteristics of included reviews and studies.DATA SOURCES: A computer-based online search of the Cochrane Library (Issue 7 of 12, July 2010) was performed with the key word "acupuncture" and systematic evaluations for acupuncture for neurological disorders were screened.STUDY SELECTION: Systematic reviews on acupuncture in the treatment of neurological disorders were included, and the characteristics of these reviews were analyzed based on methods recommended by the Cochrane collaboration.MAIN OUTCOME MEASURES: Basic characteristics, methodological quality, main reasons for excluding trials, results and conclusions of Cochrane reviews were assessed.RESULTS: A total of 18 Cochrane systematic reviews were included, including 13 completed reviews and five research protocols. The 13 completed reviews involved 111 randomized controlled trials, including 43 trials (38.7%) conducted in China, 47 trials (42.3%) using sham-acupuncture or placebo as control, 15 trials (13.5%) with relatively high quality, 91 trials (81.9%) reporting data on follow-up. Primary outcomes used in the Cochrane reviews were reported by 65 trials (58.6%), and adverse events were reported in 11 trials (9.9%). Two hundred and eighty three trials were excluded. Two reviews on headache suggested that acupuncture is a valuable non-drug treatment for patients with chronic or recurrent headache, and has better curative effects on migraine compared with preventative drug treatment. CONCLUSION: Of the Cochrane reviews on acupuncture in the treatment of neurological disorders, two reviews evaluating the efficacy of acupuncture in treating headaches drew positive conculsions, while other reviews did not obtain positive conclusions due to a small sample size or low methodological quality. The methodological quality of acupuncture trials needs further improvement.

  11. Face scanning in autism spectrum disorder (ASD and attention deficit/hyperactivity disorder (ADHD: human versus dog face scanning

    Directory of Open Access Journals (Sweden)

    Mauro eMuszkat

    2015-10-01

    Full Text Available This study used eye-tracking to explore attention allocation to human and dog faces in children and adolescents with autism spectrum disorder (ASD, attention deficit/hyperactivity disorder (ADHD, and typical development (TD. Significant differences were found among the three groups. TD participants looked longer at the eyes than ASD and ADHD ones, irrespective of the faces presented. In spite of this difference, groups were similar in that they looked more to the eyes than to the mouth areas of interest. The ADHD group gazed longer at the mouth region than the other groups. Furthermore, groups were also similar in that they looked more to the dog than to the human faces. The eye tracking technology proved to be useful for behavioral investigation in different neurodevelopmental disorders.

  12. Does D-cycloserine enhance exposure therapy for anxiety disorders in humans? A meta-analysis.

    Directory of Open Access Journals (Sweden)

    Helga Rodrigues

    Full Text Available The treatment of anxiety is on the edge of a new era of combinations of pharmacologic and psychosocial interventions. A new wave of translational research has focused on the use of pharmacological agents as psychotherapy adjuvants using neurobiological insights into the mechanism of the action of certain psychological treatments such as exposure therapy. Recently, d-cycloserine (DCS an antibiotic used to treat tuberculosis has been applied to enhance exposure-based treatment for anxiety and has proved to be a promising, but as yet unproven intervention. The present study aimed to evaluate the efficacy of DCS in the enhancement of exposure therapy in anxiety disorders. A systematic review/meta-analysis was conducted. Electronic searches were conducted in the databases ISI-Web of Science, Pubmed and PsycINFO. We included only randomized, double-blind, placebo-controlled trials with humans, focusing on the role of DCS in enhancing the action of exposure therapy for anxiety disorders. We identified 328 references, 13 studies were included in our final sample: 4 on obsessive-compulsive disorder, 2 on panic disorder, 2 on social anxiety disorder, 2 on posttraumatic stress disorder, one on acrophobia, and 2 on snake phobia. The results of the present meta-analysis show that DCS enhances exposure therapy in the treatment of anxiety disorders (Cohen d =  -0.34; CI: -0.54 to -0.14, facilitating the specific process of extinction of fear. DCS seems to be effective when administered at a time close to the exposure therapy, at low doses and a limited number of times. DCS emerges as a potential new therapeutic approach for patients with refractory anxiety disorders that are unresponsive to the conventional treatments available. When administered correctly, DCS is a promising strategy for augmentation of CBT and could reduce health care costs, drop-out rates and bring faster relief to patients.

  13. Current Applications of Chromatographic Methods in the Study of Human Body Fluids for Diagnosing Disorders.

    Science.gov (United States)

    Jóźwik, Jagoda; Kałużna-Czaplińska, Joanna

    2016-01-01

    Currently, analysis of various human body fluids is one of the most essential and promising approaches to enable the discovery of biomarkers or pathophysiological mechanisms for disorders and diseases. Analysis of these fluids is challenging due to their complex composition and unique characteristics. Development of new analytical methods in this field has made it possible to analyze body fluids with higher selectivity, sensitivity, and precision. The composition and concentration of analytes in body fluids are most often determined by chromatography-based techniques. There is no doubt that proper use of knowledge that comes from a better understanding of the role of body fluids requires the cooperation of scientists of diverse specializations, including analytical chemists, biologists, and physicians. This article summarizes current knowledge about the application of different chromatographic methods in analyses of a wide range of compounds in human body fluids in order to diagnose certain diseases and disorders.

  14. DMPD: Nod1 and Nod2 in innate immunity and human inflammatory disorders. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18031249 Nod1 and Nod2 in innate immunity and human inflammatory disorders. Le Bour...w Nod1 and Nod2 in innate immunity and human inflammatory disorders. PubmedID 18031249 Title Nod1 and Nod2 in innate immunity and hum...an inflammatory disorders. Authors Le Bourhis L, Benko S

  15. Endocrine and metabolic disorders associated with human immune deficiency virus infection.

    Science.gov (United States)

    Unachukwu, C N; Uchenna, D I; Young, E E

    2009-01-01

    Many reports have described endocrine and metabolic disorders in the human immunodeficiency virus (HIV) infection. This article reviewed various reports in the literature in order to increase the awareness and thus the need for early intervention when necessary. Data were obtained from MEDLINE, Google search and otherjournals on 'HIV, Endocrinopathies/Metabolic Disorders' from 1985 till 2007. Studies related to HIV associated endocrinopathies and metabolic disorders in the last two decades were reviewed. Information on epidemiology, pathogenesis, diagnosis and treatment of the target organ endocrinopathies and metabolic disorders in HIV/AIDS were extracted from relevant literature. Endocrine and metabolic disturbances occur in the course of HIV infection. Pathogenesis includes direct infection of endocrine glands by HIV or opportunistic organisms, infiltration by neoplasms and side effects of drugs. Adrenal insufficiency is the commonest HIV endocrinopathy with cytomegalovirus adrenalitis occurring in 40-88% of cases. Thyroid dysfunction may occur as euthyroid sick syndrome or sub-clinical hypothyroidism. Hypogonadotrophic dysfunction accounts for 75% of HIV-associated hypogonadism, with prolonged amenorrhoea being three times more likely in the women. Pancreatic dysfunction may result in hypoglycaemia or diabetes mellitus (DM). Highly active antiretroviral therapy (HAART) especially protease inhibitors has been noted to result in insulin resistance and lipodystrophy. Virtually every endocrine organ is involved in the course of HIV infection. Detailed endocrinological and metabolic evaluation and appropriate treatment is necessary in the optimal management of patients with HIV infection in our environment.

  16. Perpetration of gross human rights violations in South Africa: association with psychiatric disorders.

    Science.gov (United States)

    Stein, Dan J; Williams, Stacey L; Jackson, Pamela B; Seedat, Soraya; Myer, Landon; Herman, Allen; Williams, David R

    2009-05-01

    A nationally representative study of psychiatric disorders in South Africa provided an opportunity to study the association between perpetration of human rights violations (HRVs) during apartheid and psychiatric disorder. Prior work has suggested an association between perpetration and post-traumatic stress disorder (PTSD), but this remains controversial. Subjects reported on their perpetration of human rights violations, purposeful injury, accidental injury and domestic violence. Lifetime and 12-month prevalence of DSM-IV (Diagnostic and Statistical Manual, 4th edition) disorders were assessed with Version 3.0 of the World Health Organization Composite International Diagnostic Interview (CIDI 3.0). Socio-demographic characteristics of these groups were calculated. Odds ratios for the association between the major categories of psychiatric disorders and perpetration were assessed. HRV perpetrators were more likely to be male, black and more educated, while perpetrators of domestic violence (DV) were more likely to be female, older, married, less educated and with lower income. HRV perpetration was associated with lifetime and 12-month anxiety and substance use disorders, particularly PTSD. Purposeful and DV perpetration were associated with lifetime and 12-month history of all categories of disorders, whereas accidental perpetration was associated most strongly with mood disorders. Socio-demographic profiles of perpetrators of HRV and DV in South Africa differ. While the causal relationship between perpetration and psychiatric disorders deserves further study, it is possible that some HRV and DV perpetrators were themselves once victims. The association between accidental perpetration and mood disorder also deserves further attention.

  17. Klotho: a humeral mediator in CSF and plasma that influences longevity and susceptibility to multiple complex disorders, including depression.

    Science.gov (United States)

    Pavlatou, M G; Remaley, A T; Gold, P W

    2016-08-30

    Klotho is a hormone secreted into human cerebrospinal fluid (CSF), plasma and urine that promotes longevity and influences the onset of several premature senescent phenotypes in mice and humans, including atherosclerosis, cardiovascular disease, stroke and osteoporosis. Preliminary studies also suggest that Klotho possesses tumor suppressor properties. Klotho's roles in these phenomena were first suggested by studies demonstrating that a defect in the Klotho gene in mice results in a significant decrease in lifespan. The Klotho-deficient mouse dies prematurely at 8-9 weeks of age. At 4-5 weeks of age, a syndrome resembling human ageing emerges consisting of atherosclerosis, osteoporosis, cognitive disturbances and alterations of hippocampal architecture. Several deficits in Klotho-deficient mice are likely to contribute to these phenomena. These include an inability to defend against oxidative stress in the central nervous system and periphery, decreased capacity to generate nitric oxide to sustain normal endothelial reactivity, defective Klotho-related mediation of glycosylation and ion channel regulation, increased insulin/insulin-like growth factor signaling and a disturbed calcium and phosphate homeostasis accompanied by altered vitamin D levels and ectopic calcification. Identifying the mechanisms by which Klotho influences multiple important pathways is an emerging field in human biology that will contribute significantly to understanding basic physiologic processes and targets for the treatment of complex diseases. Because many of the phenomena seen in Klotho-deficient mice occur in depressive illness, major depression and bipolar disorder represent illnesses potentially associated with Klotho dysregulation. Klotho's presence in CSF, blood and urine should facilitate its study in clinical populations.

  18. Human Mendelian pain disorders: a key to discovery and validation of novel analgesics.

    Science.gov (United States)

    Goldberg, Y P; Pimstone, S N; Namdari, R; Price, N; Cohen, C; Sherrington, R P; Hayden, M R

    2012-10-01

    We have utilized a novel application of human genetics, illuminating the important role that rare genetic disorders can play in the development of novel drugs that may be of relevance for the treatment of both rare and common diseases. By studying a very rare Mendelian disorder of absent pain perception, congenital indifference to pain, we have defined Nav1.7 (endocded by SCN9A) as a critical and novel target for analgesic development. Strong human validation has emerged with SCN9A gain-of-function mutations causing inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder, both Mendelian disorder of spontaneous or easily evoked pain. Furthermore, variations in the Nav1.7 channel also modulate pain perception in healthy subjects as well as in painful conditions such as osteoarthritis and Parkinson disease. On the basis of this, we have developed a novel compound (XEN402) that exhibits potent, voltage-dependent block of Nav1.7. In a small pilot study, we showed that XEN402 blocks Nav1.7 mediated pain associated with IEM thereby demonstrating the use of rare genetic disorders with mutant target channels as a novel approach to rapid proof-of-concept. Our approach underscores the critical role that human genetics can play by illuminating novel and critical pathways pertinent for drug discovery. © 2012 John Wiley & Sons A/S.

  19. The pathological consequences of impaired genome integrity in humans; disorders of the DNA replication machinery.

    Science.gov (United States)

    O'Driscoll, Mark

    2017-01-01

    Accurate and efficient replication of the human genome occurs in the context of an array of constitutional barriers, including regional topological constraints imposed by chromatin architecture and processes such as transcription, catenation of the helical polymer and spontaneously generated DNA lesions, including base modifications and strand breaks. DNA replication is fundamentally important for tissue development and homeostasis; differentiation programmes are intimately linked with stem cell division. Unsurprisingly, impairments of the DNA replication machinery can have catastrophic consequences for genome stability and cell division. Functional impacts on DNA replication and genome stability have long been known to play roles in malignant transformation through a variety of complex mechanisms, and significant further insights have been gained from studying model organisms in this context. Congenital hypomorphic defects in components of the DNA replication machinery have been and continue to be identified in humans. These disorders present with a wide range of clinical features. Indeed, in some instances, different mutations in the same gene underlie different clinical presentations. Understanding the origin and molecular basis of these features opens a window onto the range of developmental impacts of suboptimal DNA replication and genome instability in humans. Here, I will briefly overview the basic steps involved in DNA replication and the key concepts that have emerged from this area of research, before switching emphasis to the pathological consequences of defects within the DNA replication network; the human disorders. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  20. Loss-of-function of neuroplasticity-related genes confers risk for human neurodevelopmental disorders.

    Science.gov (United States)

    Smith, Milo R; Glicksberg, Benjamin S; Li, Li; Chen, Rong; Morishita, Hirofumi; Dudley, Joel T

    2018-01-01

    High and increasing prevalence of neurodevelopmental disorders place enormous personal and economic burdens on society. Given the growing realization that the roots of neurodevelopmental disorders often lie in early childhood, there is an urgent need to identify childhood risk factors. Neurodevelopment is marked by periods of heightened experience-dependent neuroplasticity wherein neural circuitry is optimized by the environment. If these critical periods are disrupted, development of normal brain function can be permanently altered, leading to neurodevelopmental disorders. Here, we aim to systematically identify human variants in neuroplasticity-related genes that confer risk for neurodevelopmental disorders. Historically, this knowledge has been limited by a lack of techniques to identify genes related to neurodevelopmental plasticity in a high-throughput manner and a lack of methods to systematically identify mutations in these genes that confer risk for neurodevelopmental disorders. Using an integrative genomics approach, we determined loss-of-function (LOF) variants in putative plasticity genes, identified from transcriptional profiles of brain from mice with elevated plasticity, that were associated with neurodevelopmental disorders. From five shared differentially expressed genes found in two mouse models of juvenile-like elevated plasticity (juvenile wild-type or adult Lynx1-/- relative to adult wild-type) that were also genotyped in the Mount Sinai BioMe Biobank we identified multiple associations between LOF genes and increased risk for neurodevelopmental disorders across 10,510 patients linked to the Mount Sinai Electronic Medical Records (EMR), including epilepsy and schizophrenia. This work demonstrates a novel approach to identify neurodevelopmental risk genes and points toward a promising avenue to discover new drug targets to address the unmet therapeutic needs of neurodevelopmental disease.

  1. Human iPSC-derived neurons and lymphoblastoid cells for personalized medicine research in neuropsychiatric disorders.

    Science.gov (United States)

    Gurwitz, David

    2016-09-01

    The development and clinical implementation of personalized medicine crucially depends on the availability of high-quality human biosamples; animal models, although capable of modeling complex human diseases, cannot reflect the large variation in the human genome, epigenome, transcriptome, proteome, and metabolome. Although the biosamples available from public biobanks that store human tissues and cells may represent the large human diversity for most diseases, these samples are not always sufficient for developing biomarkers for patient-tailored therapies for neuropsychiatric disorders. Postmortem human tissues are available from many biobanks; nevertheless, collections of neuronal human cells from large patient cohorts representing the human diversity remain scarce. Two tools are gaining popularity for personalized medicine research on neuropsychiatric disorders: human induced pluripotent stem cell-derived neurons and human lymphoblastoid cell lines. This review examines and contrasts the advantages and limitations of each tool for personalized medicine research.

  2. Convergent integration of animal model and human studies of bipolar disorder (manic-depressive illness).

    Science.gov (United States)

    Le-Niculescu, Helen; Patel, Sagar D; Niculescu, Alexander B

    2010-10-01

    Animal models and human studies of bipolar disorder and other psychiatric disorders are becoming increasingly integrated, prompted by recent successes. Particularly for genomics, the convergence and integration of data across species, experimental modalities and technical platforms is providing a fit-to-disease way of extracting reproducible and biologically important signal, in sharp contrast to the fit-to-cohort effect, disappointing findings to date, and limited reproducibility of human genetic analyses alone. Such work in psychiatry can provide an example of how to address other genetically complex disorders, and in turn will benefit by incorporating concepts from other areas, such as cancer biology and diabetes. Copyright © 2010. Published by Elsevier Ltd.

  3. The human right to communicate and our need to listen: Learning from people with a history of childhood communication disorder.

    Science.gov (United States)

    McCormack, Jane; Baker, Elise; Crowe, Kathryn

    2018-02-01

    In 2013, the Australian Government Senate formed a committee for inquiry and report into the prevalence of speech, language, and communication disorders and speech pathology services in Australia. Submissions were sought from individuals and organisations. In this paper, submissions made by individuals with a history of childhood communication disorder were examined to explore their life experiences and the impact on their lives when the right to communicate could not be enacted. There were 305 submissions to the Australian Government Senate Committee Inquiry, of which 288 were publically accessible. In this study, the submissions (n = 17) from children or adults with a history of communication disorder (including speech, language and stuttering), who provided personal accounts of their experiences, were analysed using an interpretative phenomenological approach. Four themes emerged relating to: personal identity, life with communication disorder, the importance of help, and how life would be different without a communication disorder. This paper gives voice to children and adults with communication disorder. In listening to these voices, the impact of communication disorder on the right to communicate and on other human rights can be heard, and the need for a response is clear. However, the challenge is to determine how the voices of these individuals, and others like them, can be enabled to exert real influence on practice and policy so communication disorder will no longer be a barrier to attainment of their human rights.

  4. Comparing ESC and iPSC—Based Models for Human Genetic Disorders

    Directory of Open Access Journals (Sweden)

    Tomer Halevy

    2014-10-01

    Full Text Available Traditionally, human disorders were studied using animal models or somatic cells taken from patients. Such studies enabled the analysis of the molecular mechanisms of numerous disorders, and led to the discovery of new treatments. Yet, these systems are limited or even irrelevant in modeling multiple genetic diseases. The isolation of human embryonic stem cells (ESCs from diseased blastocysts, the derivation of induced pluripotent stem cells (iPSCs from patients’ somatic cells, and the new technologies for genome editing of pluripotent stem cells have opened a new window of opportunities in the field of disease modeling, and enabled studying diseases that couldn’t be modeled in the past. Importantly, despite the high similarity between ESCs and iPSCs, there are several fundamental differences between these cells, which have important implications regarding disease modeling. In this review we compare ESC-based models to iPSC-based models, and highlight the advantages and disadvantages of each system. We further suggest a roadmap for how to choose the optimal strategy to model each specific disorder.

  5. Comparing ESC and iPSC-Based Models for Human Genetic Disorders.

    Science.gov (United States)

    Halevy, Tomer; Urbach, Achia

    2014-10-24

    Traditionally, human disorders were studied using animal models or somatic cells taken from patients. Such studies enabled the analysis of the molecular mechanisms of numerous disorders, and led to the discovery of new treatments. Yet, these systems are limited or even irrelevant in modeling multiple genetic diseases. The isolation of human embryonic stem cells (ESCs) from diseased blastocysts, the derivation of induced pluripotent stem cells (iPSCs) from patients' somatic cells, and the new technologies for genome editing of pluripotent stem cells have opened a new window of opportunities in the field of disease modeling, and enabled studying diseases that couldn't be modeled in the past. Importantly, despite the high similarity between ESCs and iPSCs, there are several fundamental differences between these cells, which have important implications regarding disease modeling. In this review we compare ESC-based models to iPSC-based models, and highlight the advantages and disadvantages of each system. We further suggest a roadmap for how to choose the optimal strategy to model each specific disorder.

  6. Data on overlapping brain disorders and emerging drug targets in human Dopamine Receptors Interaction Network

    Directory of Open Access Journals (Sweden)

    Avijit Podder

    2017-06-01

    Full Text Available Intercommunication of Dopamine Receptors (DRs with their associate protein partners is crucial to maintain regular brain function in human. Majority of the brain disorders arise due to malfunctioning of such communication process. Hence, contributions of genetic factors, as well as phenotypic indications for various neurological and psychiatric disorders are often attributed as sharing in nature. In our earlier research article entitled “Human Dopamine Receptors Interaction Network (DRIN: a systems biology perspective on topology, stability and functionality of the network” (Podder et al., 2014 [1], we had depicted a holistic interaction map of human Dopamine Receptors. Given emphasis on the topological parameters, we had characterized the functionality along with the vulnerable properties of the network. In support of this, we hereby provide an additional data highlighting the genetic overlapping of various brain disorders in the network. The data indicates the sharing nature of disease genes for various neurological and psychiatric disorders in dopamine receptors connecting protein-protein interactions network. The data also indicates toward an alternative approach to prioritize proteins for overlapping brain disorders as valuable drug targets in the network.

  7. PHD fingers in human diseases: Disorders arising from misinterpreting epigenetic marks

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Lindsey A. [Rockefeller University, Laboratory of Chromatin Biology and Epigenetics, 1230 York Avenue, Box 78, New York, NY 10065 (United States); Allis, C. David [Rockefeller University, Laboratory of Chromatin Biology and Epigenetics, 1230 York Avenue, Box 78, New York, NY 10065 (United States)], E-mail: alliscd@rockefeller.edu; Wang, Gang G. [Rockefeller University, Laboratory of Chromatin Biology and Epigenetics, 1230 York Avenue, Box 78, New York, NY 10065 (United States)], E-mail: gwang@rockefeller.edu

    2008-12-01

    Histone covalent modifications regulate many, if not all, DNA-templated processes, including gene expression and DNA damage response. The biological consequences of histone modifications are mediated partially by evolutionarily conserved 'reader/effector' modules that bind to histone marks in a modification- and context-specific fashion and subsequently enact chromatin changes or recruit other proteins to do so. Recently, the Plant Homeodomain (PHD) finger has emerged as a class of specialized 'reader' modules that, in some instances, recognize the methylation status of histone lysine residues, such as histone H3 lysine 4 (H3K4). While mutations in catalytic enzymes that mediate the addition or removal of histone modifications (i.e., 'writers' and 'erasers') are already known to be involved in various human diseases, mutations in the modification-specific 'reader' proteins are only beginning to be recognized as contributing to human diseases. For instance, point mutations, deletions or chromosomal translocations that target PHD fingers encoded by many genes (such as recombination activating gene 2 (RAG2), Inhibitor of Growth (ING), nuclear receptor-binding SET domain-containing 1 (NSD1) and Alpha Thalassaemia and Mental Retardation Syndrome, X-linked (ATRX)) have been associated with a wide range of human pathologies including immunological disorders, cancers, and neurological diseases. In this review, we will discuss the structural features of PHD fingers as well as the diseases for which direct mutation or dysregulation of the PHD finger has been reported. We propose that misinterpretation of the epigenetic marks may serve as a general mechanism for human diseases of this category. Determining the regulatory roles of histone covalent modifications in the context of human disease will allow for a more thorough understanding of normal and pathological development, and may provide innovative therapeutic strategies

  8. PHD fingers in human diseases: Disorders arising from misinterpreting epigenetic marks

    International Nuclear Information System (INIS)

    Baker, Lindsey A.; Allis, C. David; Wang, Gang G.

    2008-01-01

    Histone covalent modifications regulate many, if not all, DNA-templated processes, including gene expression and DNA damage response. The biological consequences of histone modifications are mediated partially by evolutionarily conserved 'reader/effector' modules that bind to histone marks in a modification- and context-specific fashion and subsequently enact chromatin changes or recruit other proteins to do so. Recently, the Plant Homeodomain (PHD) finger has emerged as a class of specialized 'reader' modules that, in some instances, recognize the methylation status of histone lysine residues, such as histone H3 lysine 4 (H3K4). While mutations in catalytic enzymes that mediate the addition or removal of histone modifications (i.e., 'writers' and 'erasers') are already known to be involved in various human diseases, mutations in the modification-specific 'reader' proteins are only beginning to be recognized as contributing to human diseases. For instance, point mutations, deletions or chromosomal translocations that target PHD fingers encoded by many genes (such as recombination activating gene 2 (RAG2), Inhibitor of Growth (ING), nuclear receptor-binding SET domain-containing 1 (NSD1) and Alpha Thalassaemia and Mental Retardation Syndrome, X-linked (ATRX)) have been associated with a wide range of human pathologies including immunological disorders, cancers, and neurological diseases. In this review, we will discuss the structural features of PHD fingers as well as the diseases for which direct mutation or dysregulation of the PHD finger has been reported. We propose that misinterpretation of the epigenetic marks may serve as a general mechanism for human diseases of this category. Determining the regulatory roles of histone covalent modifications in the context of human disease will allow for a more thorough understanding of normal and pathological development, and may provide innovative therapeutic strategies wherein 'chromatin readers' stand as potential drug

  9. Psychological Factors Including Demographic Features, Mental Illnesses, and Personality Disorders as Predictors in Internet Addiction Disorders

    Directory of Open Access Journals (Sweden)

    Malihe Farahani

    2018-04-01

    Full Text Available Objective: Problematic internet use is an important social problem among adolescents and has become a global health issue. This study identified predictors and patterns of problematic internet use among adult students.Method: In this study, 400 students were recruited using stratified sampling technique. Participants were selected among students from 4 universities in Tehran and Karaj, Iran, during 2016 and 2017. Internet Addiction Test (IAT, Millon Clinical Multiaxial Inventory - Third Edition (MCMI-III, Structured Clinical Interview for DSM (SCID-I, and semi-structured interview were used to diagnose internet addiction. Then, the association between main psychiatric disorders and internet addiction was surveyed. Data were analyzed using SPSS18 software by performing descriptive statistics and multiple logistic regression analysis methods. P- Values less than 0.05 were considered statistically significant.Results: After controlling the demographic variables, it was found that narcissistic personality disorder, obsessive- compulsive personality disorder, anxiety, bipolar disorders, depression, and phobia could increase the odds ratio (OR of internet addiction by 2.1, 1.1, 2.6, 1.1, 2.2 and 2.5-folds, respectively (p-value<0.05, however, other psychiatric or personality disorders did not have a significant effect on the equation.Conclusion: The findings of this study revealed that some mental disorders affect internet addiction. Considering the sensitivity and importance of the cyberspace, it is necessary to evaluate mental disorders that correlate with internet addiction.

  10. Curcumin for neuropsychiatric disorders: a review of in vitro, animal and human studies.

    Science.gov (United States)

    Lopresti, Adrian L

    2017-03-01

    Turmeric has been used in traditional medicine for centuries to treat a range of ailments. Its primary active constituent curcumin, can influence an array of biological activities. Many of these, such as its anti-inflammatory, antioxidant, neuroprotective, and monoaminergic effects are dysregulated in several neuropsychiatric disorders. In this systematic review, in vitro, animal, and human studies investigating the potential of curcumin as a treatment for neuropsychiatric disorders such as major depressive disorder, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), bipolar disorder, psychotic disorders, and autism are reviewed, and directions for future research are proposed. It is concluded that curcumin is a promising, natural agent for many of these conditions, however, further research utilising robust, clinical designs are essential. The problem associated with the poor oral bioavailability of standard curcumin also requires consideration. Currently the greatest support for the efficacy of curcumin is for the treatment of major depressive disorder.

  11. Motor-auditory-visual integration: The role of the human mirror neuron system in communication and communication disorders.

    Science.gov (United States)

    Le Bel, Ronald M; Pineda, Jaime A; Sharma, Anu

    2009-01-01

    The mirror neuron system (MNS) is a trimodal system composed of neuronal populations that respond to motor, visual, and auditory stimulation, such as when an action is performed, observed, heard or read about. In humans, the MNS has been identified using neuroimaging techniques (such as fMRI and mu suppression in the EEG). It reflects an integration of motor-auditory-visual information processing related to aspects of language learning including action understanding and recognition. Such integration may also form the basis for language-related constructs such as theory of mind. In this article, we review the MNS system as it relates to the cognitive development of language in typically developing children and in children at-risk for communication disorders, such as children with autism spectrum disorder (ASD) or hearing impairment. Studying MNS development in these children may help illuminate an important role of the MNS in children with communication disorders. Studies with deaf children are especially important because they offer potential insights into how the MNS is reorganized when one modality, such as audition, is deprived during early cognitive development, and this may have long-term consequences on language maturation and theory of mind abilities. Readers will be able to (1) understand the concept of mirror neurons, (2) identify cortical areas associated with the MNS in animal and human studies, (3) discuss the use of mu suppression in the EEG for measuring the MNS in humans, and (4) discuss MNS dysfunction in children with (ASD).

  12. Human pluripotent stem cells in modeling human disorders: the case of fragile X syndrome.

    Science.gov (United States)

    Vershkov, Dan; Benvenisty, Nissim

    2017-01-01

    Human pluripotent stem cells (PSCs) generated from affected blastocysts or from patient-derived somatic cells are an emerging platform for disease modeling and drug discovery. Fragile X syndrome (FXS), the leading cause of inherited intellectual disability, was one of the first disorders modeled in both embryonic stem cells and induced PCSs and can serve as an exemplary case for the utilization of human PSCs in the study of human diseases. Over the past decade, FXS-PSCs have been used to address the fundamental questions regarding the pathophysiology of FXS. In this review we summarize the methodologies for generation of FXS-PSCs, discuss their advantages and disadvantages compared with existing modeling systems and describe their utilization in the study of FXS pathogenesis and in the development of targeted treatment.

  13. Rethinking dependent personality disorder: comparing different human relatedness in cultural contexts.

    Science.gov (United States)

    Chen, YuJu; Nettles, Margaret E; Chen, Shun-Wen

    2009-11-01

    We argue that the Diagnostic and Statistical Manual of Mental Disorders dependent personality disorder is a culturally related concept reflecting deeply rooted values, beliefs, and assumptions of American individualistic convictions about self and interpersonal relationship. This article integrates social psychology concepts into the exploration of psychopathology. Beginning with the construct of individualism and collectivism, we demonstrate the limitations of this commonly used framework. The indigenous Chinese concept of Confucianism and Chinese Relationalism is introduced to highlight that a well-differentiated self is not a universal premise of human beings, healthy existence. In East Asian Confucianism the manifestation of dependence and submission may be considered individuals' proper behavior and required for their social obligation, rather than a direct display of individuals' personality. Thus, the complexity of dependent personality disorder is beyond the neo-Kraepelinian approach assumed by the Diagnostic and Statistical Manual of Mental Disorders system.

  14. The DSM-5 Dimensional Anxiety Scales in a Dutch non-clinical sample: psychometric properties including the adult separation anxiety disorder scale.

    Science.gov (United States)

    Möller, Eline L; Bögels, Susan M

    2016-09-01

    With DSM-5, the American Psychiatric Association encourages complementing categorical diagnoses with dimensional severity ratings. We therefore examined the psychometric properties of the DSM-5 Dimensional Anxiety Scales, a set of brief dimensional scales that are consistent in content and structure and assess DSM-5-based core features of anxiety disorders. Participants (285 males, 255 females) completed the DSM-5 Dimensional Anxiety Scales for social anxiety disorder, generalized anxiety disorder, specific phobia, agoraphobia, and panic disorder that were included in previous studies on the scales, and also for separation anxiety disorder, which is included in the DSM-5 chapter on anxiety disorders. Moreover, they completed the Screen for Child Anxiety Related Emotional Disorders Adult version (SCARED-A). The DSM-5 Dimensional Anxiety Scales demonstrated high internal consistency, and the scales correlated significantly and substantially with corresponding SCARED-A subscales, supporting convergent validity. Separation anxiety appeared present among adults, supporting the DSM-5 recognition of separation anxiety as an anxiety disorder across the life span. To conclude, the DSM-5 Dimensional Anxiety Scales are a valuable tool to screen for specific adult anxiety disorders, including separation anxiety. Research in more diverse and clinical samples with anxiety disorders is needed. © 2016 The Authors International Journal of Methods in Psychiatric Research Published by John Wiley & Sons Ltd. © 2016 The Authors International Journal of Methods in Psychiatric Research Published by John Wiley & Sons Ltd.

  15. Binge eating disorder should be included in DSM-IV: a reply to Fairburn et al.'s "the classification of recurrent overeating: the binge eating disorder proposal".

    Science.gov (United States)

    Spitzer, R L; Stunkard, A; Yanovski, S; Marcus, M D; Wadden, T; Wing, R; Mitchell, J; Hasin, D

    1993-03-01

    Extensive recent research supports a proposal that a new eating disorder, binge eating disorder (BED), be included in DSM-IV. BED criteria define a relatively pure group of individuals who are distressed by recurrent binge eating who do not exhibit the compensatory features of bulimia nervosa. This large number of patients currently can only be diagnosed as eating disorder not otherwise specified (EDNOS). Recognizing this new disorder will help stimulate research and clinical programs for these patients. Fairburn et al.'s critique of BED fails to acknowledge the large body of knowledge that indicates that BED represents a distinct and definable subgroup of eating disordered patients and that the diagnosis provides useful information about psychopathology, prognosis, and outcome (Fairburn, Welch, & Hay [in press]. The classification of recurrent overeating: The "binge eating disorder" proposal. International Journal of Eating Disorders.) Against any reasonable standard for adding a new diagnosis to DSM-IV, BED meets the test.

  16. Transferrin receptors on human reticulocytes: variation in site number in hematologic disorders

    International Nuclear Information System (INIS)

    Shumak, K.H.; Rachkewich, R.A.

    1984-01-01

    Assays of binding of 125iodine-labeled ( 125 I) human transferrin were used to study transferrin receptor sites on reticulocytes from 15 normal subjects and from 66 patients with various hematologic disorders. In normal subjects, few or no transferrin receptors were detected whereas the average number of receptors per reticulocyte varied greatly from patient to patient, ranging from 0 to 67,700 in samples, from 35 patients, on which Scatchard analysis of binding of [ 125 I]-transferrin was done. Marked heterogeneity in the number of reticulocyte transferrin receptors in different hematologic disorders was also found in assays with [ 125 I]-OKT9 (monoclonal antibody to the human transferrin receptor). The number of receptors was not correlated with either the reticulocyte count or the hemoglobin

  17. Dystonia and paroxysmal dyskinesias: under-recognized movement disorders in domestic animals? A comparison with human dystonia/paroxysmal dyskinesias.

    Directory of Open Access Journals (Sweden)

    Angelika eRichter

    2015-11-01

    Full Text Available Dystonia is defined as a neurological syndrome characterized by involuntary sustained or intermittent muscle contractions causing twisting, often repetitive movements and postures. Paroxysmal dyskinesias are episodic movement disorders encompassing dystonia, chorea, athetosis and ballism in conscious individuals. Several decades of research have enhanced the understanding of the etiology of human dystonia and dyskinesias that are associated with dystonia, but the pathophysiology remains largely unknown. The spontaneous occurrence of hereditary dystonia and paroxysmal dyskinesia is well documented in rodents used as animal models in basic dystonia research. Several hyperkinetic movement disorders, described in dogs, horses and cattle, show similarities to these human movement disorders. Although dystonia is regarded as the third most common movement disorder in humans, it is often misdiagnosed because of the heterogeneity of etiology and clinical presentation. Since these conditions are poorly known in veterinary practice, their prevalence may be underestimated in veterinary medicine. In order to attract attention to these movement disorders, i.e. dystonia and paroxysmal dyskinesias associated with dystonia, and to enhance interest in translational research, this review gives a brief overview of the current literature regarding dystonia/paroxysmal dyskinesia in humans, and summarizes similar hereditary movement disorders reported in domestic animals.

  18. Including Pupils with Autistic Spectrum Disorders in the Classroom: The Role of Teaching Assistants

    Science.gov (United States)

    Symes, Wendy; Humphrey, Neil

    2012-01-01

    The aims of the current study were (i) to explore the extent to which pupils with Autistic Spectrum Disorders (ASD) were effectively included in lessons, compared with pupils with dyslexia (DYS) or no Special Educational Needs (CON) and (ii) to understand how the presence of a teaching assistant (TA) influences the inclusion/exclusion process. One…

  19. Socially Impaired Robots: Human Social Disorders and Robots' Socio-Emotional Intelligence

    OpenAIRE

    Vitale, Jonathan; Williams, Mary-Anne; Johnston, Benjamin

    2016-01-01

    Social robots need intelligence in order to safely coexist and interact with humans. Robots without functional abilities in understanding others and unable to empathise might be a societal risk and they may lead to a society of socially impaired robots. In this work we provide a survey of three relevant human social disorders, namely autism, psychopathy and schizophrenia, as a means to gain a better understanding of social robots' future capability requirements. We provide evidence supporting...

  20. Free Software for Disorders of Human Communication

    Directory of Open Access Journals (Sweden)

    William Ricardo Rodríguez Dueñas

    2015-05-01

    Full Text Available Introduction: New technologies are increasingly used by the health sector for its implementation in therapeutic interventions. However, in the case of speech therapists, there are many unknown free software-based tools which could support their daily work. This paper summarizes fourteen free software-based tools that can support interventions in early stimulation, assessment and control of voice and speech, several resources for augmentative and alternative communication and tools that facilitate access to the computer. Materials and methods: The information presented here is the result of a general review of software-based tools designed to treat human communication disorders. Criteria for inclusion and exclusion were established to select tools and these were installed and tested. Results: 22 tools were found and 14 were selected and classified in these categories: Early stimulation and capture attention, acoustic signal processing of voice, speech processing, Augmentative and Alternative Communication and Other; the latter includes tools for access to the computer without the need for advanced computer skills. Discussion: The set of tools discussed in this paper provides free computer-based tools to therapists in order to help their interventions, additionally, promotes the improvement of computer skills so necessary in today’s society of professionals.

  1. Video Analysis of Human Gait and Posture to Determine Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Ivan Lee

    2008-08-01

    Full Text Available This paper investigates the application of digital image processing techniques to the detection of neurological disorder. Visual information extracted from the postures and movements of a human gait cycle can be used by an experienced neurologist to determine the mental health of the person. However, the current visual assessment of diagnosing neurological disorder is based very much on subjective observation, and hence the accuracy of diagnosis heavily relies on experience. Other diagnostic techniques employed involve the use of imaging systems which can only be operated under highly constructed environment. A prototype has been developed in this work that is able to capture the subject's gait on video in a relatively simple setup, and from which to process the selected frames of the gait in a computer. Based on the static visual features such as swing distances and joint angles of human limbs, the system identifies patients with Parkinsonism from the test subjects. To our knowledge, it is the first time swing distances are utilized and identified as an effective means for characterizing human gait. The experimental results have shown a promising potential in medical application to assist the clinicians in diagnosing Parkinsonism.

  2. Animal models of human anxiety disorders: reappraisal from a developmental psychopathology vantage point.

    Science.gov (United States)

    Lampis, Valentina; Maziade, Michel; Battaglia, Marco

    2011-05-01

    We are witnessing a tremendous expansion of strategies and techniques that derive from basic and preclinical science to study the fine genetic, epigenetic, and proteomic regulation of behavior in the laboratory animal. In this endeavor, animal models of psychiatric illness are becoming the almost exclusive domain of basic researchers, with lesser involvement of clinician researchers in their conceptual design, and transfer into practice of new paradigms. From the side of human behavioral research, the growing interest in gene-environment interplay and the fostering of valid endophenotypes are among the few substantial innovations in the effort of linking common mental disorders to cutting-edge clinical research questions. We argue that it is time for cross-fertilization between these camps. In this article, we a) observe that the "translational divide" can-and should-be crossed by having investigators from both the basic and the clinical sides cowork on simpler, valid "endophenotypes" of neurodevelopmental relevance; b) emphasize the importance of unambiguous physiological readouts, more than behavioral equivalents of human symptoms/syndromes, for animal research; c) indicate and discuss how this could be fostered and implemented in a developmental framework of reference for some common anxiety disorders and ultimately lead to better animal models of human mental disorders.

  3. Temporal, Diagnostic, and Tissue-Specific Regulation of NRG3 Isoform Expression in Human Brain Development and Affective Disorders

    Science.gov (United States)

    Paterson, Clare; Wang, Yanhong; Hyde, Thomas M.; Weinberger, Daniel R.; Kleinman, Joel E.; Law, Amanda J.

    2018-01-01

    Objective Genes implicated in schizophrenia are enriched in networks differentially regulated during human CNS development. Neuregulin 3 (NRG3), a brain-enriched neurotrophin, undergoes alternative splicing and is implicated in several neurological disorders with developmental origins. Isoform-specific increases in NRG3 are observed in schizophrenia and associated with rs10748842, a NRG3 risk polymorphism, suggesting NRG3 transcriptional dysregulation as a molecular mechanism of risk. The authors quantitatively mapped the temporal trajectories of NRG3 isoforms (classes I–IV) in the neocortex throughout the human lifespan, examined whether tissue-specific regulation of NRG3 occurs in humans, and determined if abnormalities in NRG3 transcriptomics occur in mood disorders and are genetically determined. Method NRG3 isoform classes I–IV were quantified using quantitative real-time polymerase chain reaction in human postmortem dorsolateral prefrontal cortex from 286 nonpsychiatric control individuals, from gestational week 14 to 85 years old, and individuals diagnosed with either bipolar disorder (N=34) or major depressive disorder (N=69). Tissue-specific mapping was investigated in several human tissues. rs10748842 was genotyped in individuals with mood disorders, and association with NRG3 isoform expression examined. Results NRG3 classes displayed individually specific expression trajectories across human neocortical development and aging; classes I, II, and IV were significantly associated with developmental stage. NRG3 class I was increased in bipolar and major depressive disorder, consistent with observations in schizophrenia. NRG3 class II was increased in bipolar disorder, and class III was increased in major depression. The rs10748842 risk genotype predicted elevated class II and III expression, consistent with previous reports in the brain, with tissue-specific analyses suggesting that classes II and III are brain-specific isoforms of NRG3. Conclusions

  4. S5-4: Formal Modeling of Affordance in Human-Included Systems

    Directory of Open Access Journals (Sweden)

    Namhun Kim

    2012-10-01

    Full Text Available In spite of it being necessary for humans to consider modeling, analysis, and control of human-included systems, it has been considered a challenging problem because of the critical role of humans in complex systems and of humans' capability of executing unanticipated actions–both beneficial and detrimental ones. Thus, to provide systematic approaches to modeling human actions as a part of system behaviors, a formal modeling framework for human-involved systems in which humans play a controlling role based on their perceptual information is presented. The theory of affordance provides definitions of human actions and their associated properties; Finite State Automata (FSA based modeling is capable of mapping nondeterministic humans into computable components in the system representation. In this talk, we investigate the role of perception in human actions in the system operation and examine the representation of perceptual elements in affordance-based modeling formalism. The proposed framework is expected to capture the natural ways in which humans participate in the system as part of its operation. A human-machine cooperative manufacturing system control example and a human agent simulation example will be introduced for the illustrative purposes at the end of the presentation.

  5. Risk factors for mental disorders in women survivors of human trafficking: a historical cohort study

    Science.gov (United States)

    2013-01-01

    Background Previous studies have found high levels of symptoms of depression, anxiety, and post-traumatic stress disorder among women survivors of human trafficking. No previous research has described risk factors for diagnosed mental disorders in this population. Methods A historical cohort study of women survivors of trafficked women aged 18 and over who returned to Moldova and registered for assistance with the International Organisation for Migration (IOM). Women were approached by IOM social workers and, if they gave informed consented to participate in the study, interviewed by the research team. At 2–12 months post-return to Moldova, a psychiatrist assessed DSM-IV mental disorders blind to information about women’s pre-trafficking and post-trafficking experiences using the Structured Clinical Interview for DSM-IV (SCID). A backwards stepwise selection procedure was used to create a multivariable regression model of risk factors for DSM-IV mental disorder measured at an average of 6 months post-return. Results 120/176 (68%) eligible women participated. At an average of 6 months post-return, 54% met criteria for any DSM-IV mental disorder: 35.8% of women had PTSD (alone or co-morbid), 12.5% had depression without PTSD and 5.8% had another anxiety disorder. Multivariable regression analysis found that childhood sexual abuse (Adjusted Odds Ratio [AOR] 4.68, 95% CI 1.04-20.92), increased number of post-trafficking unmet needs (AOR 1.80; 95% CI 1.28-2.52) and post-trafficking social support (AOR 0.64; 95% CI 0.52-0.79) were independent risk factors for mental disorder, and that duration of trafficking showed a borderline association with mental disorder (AOR 1.12, 95% CI 0.98-1.29). Conclusions Assessment for mental disorders should be part of re-integration follow-up care for women survivors of human trafficking. Mental disorders at that time, most commonly PTSD and depression, are likely to be influenced by a range of predisposing, precipitating and

  6. Risk factors for mental disorders in women survivors of human trafficking: a historical cohort study.

    Science.gov (United States)

    Abas, Melanie; Ostrovschi, Nicolae V; Prince, Martin; Gorceag, Viorel I; Trigub, Carolina; Oram, Siân

    2013-08-03

    Previous studies have found high levels of symptoms of depression, anxiety, and post-traumatic stress disorder among women survivors of human trafficking. No previous research has described risk factors for diagnosed mental disorders in this population. A historical cohort study of women survivors of trafficked women aged 18 and over who returned to Moldova and registered for assistance with the International Organisation for Migration (IOM). Women were approached by IOM social workers and, if they gave informed consented to participate in the study, interviewed by the research team. At 2-12 months post-return to Moldova, a psychiatrist assessed DSM-IV mental disorders blind to information about women's pre-trafficking and post-trafficking experiences using the Structured Clinical Interview for DSM-IV (SCID). A backwards stepwise selection procedure was used to create a multivariable regression model of risk factors for DSM-IV mental disorder measured at an average of 6 months post-return. 120/176 (68%) eligible women participated. At an average of 6 months post-return, 54% met criteria for any DSM-IV mental disorder: 35.8% of women had PTSD (alone or co-morbid), 12.5% had depression without PTSD and 5.8% had another anxiety disorder. Multivariable regression analysis found that childhood sexual abuse (Adjusted Odds Ratio [AOR] 4.68, 95% CI 1.04-20.92), increased number of post-trafficking unmet needs (AOR 1.80; 95% CI 1.28-2.52) and post-trafficking social support (AOR 0.64; 95% CI 0.52-0.79) were independent risk factors for mental disorder, and that duration of trafficking showed a borderline association with mental disorder (AOR 1.12, 95% CI 0.98-1.29). Assessment for mental disorders should be part of re-integration follow-up care for women survivors of human trafficking. Mental disorders at that time, most commonly PTSD and depression, are likely to be influenced by a range of predisposing, precipitating and maintaining factors. Care plans for survivors of

  7. Order-disorder transitions govern kinetic cooperativity and allostery of monomeric human glucokinase.

    Directory of Open Access Journals (Sweden)

    Mioara Larion

    Full Text Available Glucokinase (GCK catalyzes the rate-limiting step of glucose catabolism in the pancreas, where it functions as the body's principal glucose sensor. GCK dysfunction leads to several potentially fatal diseases including maturity-onset diabetes of the young type II (MODY-II and persistent hypoglycemic hyperinsulinemia of infancy (PHHI. GCK maintains glucose homeostasis by displaying a sigmoidal kinetic response to increasing blood glucose levels. This positive cooperativity is unique because the enzyme functions exclusively as a monomer and possesses only a single glucose binding site. Despite nearly a half century of research, the mechanistic basis for GCK's homotropic allostery remains unresolved. Here we explain GCK cooperativity in terms of large-scale, glucose-mediated disorder-order transitions using 17 isotopically labeled isoleucine methyl groups and three tryptophan side chains as sensitive nuclear magnetic resonance (NMR probes. We find that the small domain of unliganded GCK is intrinsically disordered and samples a broad conformational ensemble. We also demonstrate that small-molecule diabetes therapeutic agents and hyperinsulinemia-associated GCK mutations share a strikingly similar activation mechanism, characterized by a population shift toward a more narrow, well-ordered ensemble resembling the glucose-bound conformation. Our results support a model in which GCK generates its cooperative kinetic response at low glucose concentrations by using a millisecond disorder-order cycle of the small domain as a "time-delay loop," which is bypassed at high glucose concentrations, providing a unique mechanism to allosterically regulate the activity of human GCK under physiological conditions.

  8. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder

    Directory of Open Access Journals (Sweden)

    Ubadah Sabbagh

    2016-01-01

    Full Text Available The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES. A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study.

  9. Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder.

    Science.gov (United States)

    Sabbagh, Ubadah; Mullegama, Saman; Wyckoff, Gerald J

    2016-01-01

    The purpose of this study was to find genes linked with eating disorders and associated with both metabolic and neural systems. Our operating hypothesis was that there are genetic factors underlying some eating disorders resting in both those pathways. Specifically, we are interested in disorders that may rest in both sleep and metabolic function, generally called Night Eating Syndrome (NES). A meta-analysis of the Gene Expression Omnibus targeting the mammalian nervous system, sleep, and obesity studies was performed, yielding numerous genes of interest. Through a text-based analysis of the results, a number of potential candidate genes were identified. VGF, in particular, appeared to be relevant both to obesity and, broadly, to brain or neural development. VGF is a highly connected protein that interacts with numerous targets via proteolytically digested peptides. We examined VGF from an evolutionary perspective to determine whether other available evidence supported a role for the gene in human disease. We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. Our data suggest that there is enough evidence to warrant eGWAS and GWAS analysis of these genes in NES patients in a case-control study.

  10. From Pavlov to PTSD: the extinction of conditioned fear in rodents, humans, and anxiety disorders.

    Science.gov (United States)

    VanElzakker, Michael B; Dahlgren, M Kathryn; Davis, F Caroline; Dubois, Stacey; Shin, Lisa M

    2014-09-01

    Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a neutral cue to predict a biologically relevant event: after repeated predictive pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell, which caused them to salivate. Like sustenance, danger is biologically relevant, and neutral cues can take on great salience when they predict a threat to survival. In anxiety disorders such as posttraumatic stress disorder (PTSD), this type of conditioned fear fails to extinguish, and reminders of traumatic events can cause pathological conditioned fear responses for decades after danger has passed. In this review, we use fear conditioning and extinction studies to draw a direct line from Pavlov to PTSD and other anxiety disorders. We explain how rodent studies have informed neuroimaging studies of healthy humans and humans with PTSD. We describe several genes that have been linked to both PTSD and fear conditioning and extinction and explain how abnormalities in fear conditioning or extinction may reflect a general biomarker of anxiety disorders. Finally, we explore drug and neuromodulation treatments that may enhance therapeutic extinction in anxiety disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. [Hypersexual disorder will not be included in the DSM V : a contextual analysis].

    Science.gov (United States)

    Toussaint, I; Pitchot, W

    2013-01-01

    Hypersexuality disorder has not been added to the list of psychiatric disorders for the Diagnostic and Statistical Manual of Mental Disorders (DSM) V, to be published in May 2013. The evolution of the concept of hypersexuality disorder and its series of different models call into question the controversial context within which its inclusion is considered for the DSM V. A brief contextual analysis makes clear that the creation of this concept follows moral norms and psychosocial values. The construction of hypersexuality disorder in terms of a diagnostic entity rests on the clash of social forces at play in the development process. This article lays the foundation to contemplate the manner in which entities for psychiatric disorders are constructed.

  12. Puberty as a Critical Risk Period for Eating Disorders: A Review of Human and Animal Studies

    Science.gov (United States)

    Klump, Kelly L.

    2013-01-01

    Puberty is one of the most frequently discussed risk periods for the development of eating disorders. Prevailing theories propose environmentally mediated sources of risk arising from the psychosocial effects (e.g., increased body dissatisfaction, decreased self-esteem) of pubertal development in girls. However, recent research highlights the potential role of ovarian hormones in phenotypic and genetic risk for eating disorders during puberty. The goal of this paper is to review data from human and animal studies in support of puberty as a critical risk period for eating disorders and evaluate the evidence for hormonal contributions. Data are consistent in suggesting that both pubertal status and pubertal timing significantly impact risk for most eating disorders in girls, such that advanced pubertal development and early pubertal timing are associated with increased rates of eating disorders and their symptoms in both cross-sectional and longitudinal research. Findings in boys have been much less consistent and suggest a smaller role for puberty in risk for eating disorders in boys. Twin and animal studies indicate that at least part of the female-specific risk is due to genetic factors associated with estrogen activation at puberty. In conclusion, data thus far support a role for puberty in risk for eating disorders and highlight the need for additional human and animal studies of hormonal and genetic risk for eating disorders during puberty. PMID:23998681

  13. Maternal obesity and neurodevelopmental and psychiatric disorders in offspring

    Science.gov (United States)

    Edlow, Andrea G.

    2017-01-01

    There is a growing body of evidence from both human epidemiologic and animal studies that prenatal and lactational exposure to maternal obesity and high-fat diet are associated with neurodevelopmental and psychiatric disorders in offspring. These disorders include cognitive impairment, autism spectrum disorders, attention deficit hyperactivity disorder, cerebral palsy, anxiety and depression, schizophrenia, and eating disorders. This review synthesizes human and animal data linking maternal obesity and high-fat diet consumption to abnormal fetal brain development and neurodevelopmental and psychiatric morbidity in offspring. In addition, it highlights key mechanisms by which maternal obesity and maternal diet might impact fetal and offspring neurodevelopment, including neuroinflammation; increased oxidative stress, dysregulated insulin, glucose, and leptin signaling; dysregulated serotonergic and dopaminergic signaling; and perturbations in synaptic plasticity. Finally, the review summarizes available evidence regarding investigational therapeutic approaches to mitigate the harmful effects of maternal obesity on fetal and offspring neurodevelopment. PMID:27684946

  14. Towards Developmental Models of Psychiatric Disorders in Zebrafish

    Directory of Open Access Journals (Sweden)

    William Howard James Norton

    2013-04-01

    Full Text Available Psychiatric disorders are a diverse set of diseases that affect all aspects of mental function including social interaction, thinking, feeling and mood. Although psychiatric disorders place a large economic burden on society, the drugs available to treat them are often palliative with variable efficacy and intolerable side-effects. The development of novel drugs has been hindered by a lack of knowledge about the etiology of these diseases. It is thus necessary to further investigate psychiatric disorders using a combination of human molecular genetics, gene-by-environment studies, in vitro pharmacological and biochemistry experiments, animal models and investigation of the non-biological basis of these diseases, such as environmental effects.Many psychiatric disorders, including autism spectrum disorder, attention-deficit/hyperactivity disorder, mental retardation and schizophrenia can be triggered by alterations to neural development. The zebrafish is a popular model for developmental biology that is increasingly used to study human disease. Recent work has extended this approach to examine psychiatric disorders as well. However, since psychiatric disorders affect complex mental functions that might be human specific, it is not possible to fully model them in fish. In this review, I will propose that the suitability of zebrafish for developmental studies, and the genetic tools available to manipulate them, provide a powerful model to study the roles of genes that are linked to psychiatric disorders during neural development. The relative speed and ease of conducting experiments in zebrafish can be used to address two areas of future research: the contribution of environmental factors to disease onset, and screening for novel therapeutic compounds.

  15. Introduction to Neurogenic Communication Disorders. Fifth Edition.

    Science.gov (United States)

    Brookshire, Robert H.

    This book provides an overview of the causes and symptoms, and the typical courses, treatments, and outcomes of neurogenic communication disorders. Chapter 1 reviews the human nervous system and neurologic causes of adult communication disorders. Chapter 2 discusses the neurologic assessment and arriving at a diagnosis, including the neurologist's…

  16. Emotion Recognition in Animated Compared to Human Stimuli in Adolescents with Autism Spectrum Disorder

    Science.gov (United States)

    Brosnan, Mark; Johnson, Hilary; Grawmeyer, Beate; Chapman, Emma; Benton, Laura

    2015-01-01

    There is equivocal evidence as to whether there is a deficit in recognising emotional expressions in Autism spectrum disorder (ASD). This study compared emotion recognition in ASD in three types of emotion expression media (still image, dynamic image, auditory) across human stimuli (e.g. photo of a human face) and animated stimuli (e.g. cartoon…

  17. Puberty as a critical risk period for eating disorders: a review of human and animal studies.

    Science.gov (United States)

    Klump, Kelly L

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". Puberty is one of the most frequently discussed risk periods for the development of eating disorders. Prevailing theories propose environmentally mediated sources of risk arising from the psychosocial effects (e.g., increased body dissatisfaction, decreased self-esteem) of pubertal development in girls. However, recent research highlights the potential role of ovarian hormones in phenotypic and genetic risk for eating disorders during puberty. The goal of this paper is to review data from human and animal studies in support of puberty as a critical risk period for eating disorders and evaluate the evidence for hormonal contributions. Data are consistent in suggesting that both pubertal status and pubertal timing significantly impact risk for most eating disorders in girls, such that advanced pubertal development and early pubertal timing are associated with increased rates of eating disorders and their symptoms in both cross-sectional and longitudinal research. Findings in boys have been much less consistent and suggest a smaller role for puberty in risk for eating disorders in boys. Twin and animal studies indicate that at least part of the female-specific risk is due to genetic factors associated with estrogen activation at puberty. In conclusion, data thus far support a role for puberty in risk for eating disorders and highlight the need for additional human and animal studies of hormonal and genetic risk for eating disorders during puberty. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Pituitary adenylate cyclase activating polypeptide in stress-related disorders: data convergence from animal and human studies.

    Science.gov (United States)

    Hammack, Sayamwong E; May, Victor

    2015-08-01

    The maladaptive expression and function of several stress-associated hormones have been implicated in pathological stress and anxiety-related disorders. Among these, recent evidence has suggested that pituitary adenylate cyclase activating polypeptide (PACAP) has critical roles in central neurocircuits mediating stress-related emotional behaviors. We describe the PACAPergic systems, the data implicating PACAP in stress biology, and how altered PACAP expression and signaling may result in psychopathologies. We include our work implicating PACAP signaling within the bed nucleus of the stria terminalis in mediating the consequences of stressor exposure and relatedly, describe more recent studies suggesting that PACAP in the central nucleus of the amygdala may impact the emotional aspects of chronic pain states. In aggregate, these results are consistent with data suggesting that PACAP dysregulation is associated with posttraumatic stress disorder in humans. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Pharmacotherapy in the Management of Voiding and Storage Disorders, Including Enuresis and Encopresis

    Science.gov (United States)

    Reiner, William G.

    2008-01-01

    Enuresis and encopresis are disorders of the bladder and rectum, and this article helps in understanding the neurobiology of lower urinary tract and anorectal function to help in the treatment of these disorders. Treatment for children with these disorders emphasizes either a psychological or pharmacological approach.

  20. Should borderline personality disorder be included in the fourth edition of the Chinese classification of mental disorders?

    Institute of Scientific and Technical Information of China (English)

    ZHONG Jie; LEUNG Freedom

    2007-01-01

    @@ Borderline personality disorder (BPD) is a serious Bpersonality disorder characterized by a pervasive pattern of disturbances in mood regulation, impulse control, self-image and interpersonal relationships.1 In the United States, the prevalence of BPD has been estimated at 1%-2% of the general population, 10% of psychiatric outpatients, and 20% of inpatients.2,3 According to the 4th text revision of diagnostic and statistical manual of mental disorders (DSM-Ⅳ-TR),1 about 75% of BPD patients are women. The BPD diagnosis has been associated with heightened risk (8.5% to 10.0% among BPD patients) for completed suicide, a rate almost 50times higher than in the general population.4

  1. Should DSM-V include dimensional diagnostic criteria for alcohol use disorders?

    Science.gov (United States)

    Helzer, John E; Bucholz, Kathleen K; Bierut, Laura Jean; Regier, Darrel A; Schuckit, Marc A; Guth, Sarah E

    2006-02-01

    This program calls attention to the upcoming timetable for the revision of the Diagnostic and Statistical Manual (DSM)-IV and the publication of DSM-V. It is vitally important for Research Society of Alcoholism members to be aware of the current discussions of the important scientific questions related to the next DSM revision and to use the opportunity for input. The title of the symposium highlights 1 key question, i.e., whether the DSM definitions should remain strictly categorical as in the past or whether a dimensional component should be included in this revision. Two substantive and 1 conceptual paper are included in this portion of the symposium. The fourth and final presentation detailing the revision timetable and the opportunities for input is by Dr. Darrel Regier. Dr. Regier is the director of American Psychiatric Institute for Research and Education the research and education branch of the American Psychiatric Association and the organization within the APA that will oversee the DSM revision. The discussion is by Marc Schuckit, who was chair of the Substance Use disorders (SUD) Committee for DSM-IV and cochair of the international group of experts reviewing the SUD definitions for DSM-V.

  2. Examination on Impact of Air Ions toward Human Social Disorder Behavior

    International Nuclear Information System (INIS)

    Ganesha-Tri-Chandrasa

    2000-01-01

    Air ions are something that people can not see and feel. However, they exist surrounding human life. Imbalance inhalation of air ions can affect central nervous system, and physically it will affect human activities and create social disorder behavior. Some investigations have proved the relation above and devices for anticipating ionization have been innovated and available on the market. Furthermore, it has been found that individual resistance against ionization is different between genders. Therefore it is important to study character and to anticipate effects of ions and ionization, in order to build more comfortable environment. (author)

  3. From Pavlov to PTSD: The extinction of conditioned fear in rodents, humans, and in anxiety disorders

    Science.gov (United States)

    VanElzakker, Michael B.; Dahlgren, M. Kathryn; Davis, F. Caroline; Dubois, Stacey; Shin, Lisa M.

    2014-01-01

    Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a neutral cue to predict a biologically relevant event: after repeated predictive pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell, which caused them to salivate. Like sustenance, danger is biologically relevant, and neutral cues can take on great salience when they predict a threat to survival. In anxiety disorders such as posttraumatic stress disorder (PTSD), this type of conditioned fear fails to extinguish, and reminders of traumatic events can cause pathological conditioned fear responses for decades after danger has passed. In this review, we use fear conditioning and extinction studies to draw a direct line from Pavlov to PTSD and other anxiety disorders. We explain how rodent studies have informed neuroimaging studies of healthy humans and humans with PTSD. We describe several genes that have been linked to both PTSD and fear conditioning and extinction and explain how abnormalities in fear conditioning or extinction may reflect a general biomarker of anxiety disorders. Finally, we explore drug and neuromodulation treatments that may enhance therapeutic extinction in anxiety disorders. PMID:24321650

  4. The human figure drawing as related to attention-deficit hyperactivity disorder (ADHD).

    Science.gov (United States)

    Perets-Dubrovsky, Sharon; Kaveh, Michelle; Deutsh-Castel, Tsofia; Cohen, Ayala; Tirosh, Emanuel

    2010-06-01

    To assess the reliability and validity of the human figure drawing test among children with attention-deficit hyperactivity disorder (ADHD) and/or learning disability, boys (n = 136) between the ages of 8 and 10 years, with either or both ADHD and learning disability, were included. Two drawings were used: person and house, tree and person. The drawings were analyzed using the Koppitz emotional and developmental scales. Conners teacher and parent rating scales and the Matching Familiar Figure Test were administered. High intertest reliability for the emotional scale and a significant negative correlation between the 2 scales were found. The reported anxiety and learning were significantly correlated with the cognitive score. A combination of cognitive and emotional items resulted in 67% correct classification of ADHD and learning disability. This test can be used as part of the assessment of ADHD/learning disability.

  5. STATISTICAL INSIGHT INTO THE BINDING REGIONS IN DISORDERED HUMAN PROTEOME

    Directory of Open Access Journals (Sweden)

    Uttam Pal

    2016-03-01

    Full Text Available The human proteome contains a significant number of intrinsically disordered proteins (IDPs. They show unusual structural features that enable them to participate in diverse cellular functions and play significant roles in cell signaling and reorganization processes. In addition, the actions of IDPs, their functional cooperativity, conformational alterations and folding often accompany binding to a target macromolecule. Applying bioinformatics approaches and with the aid of statistical methodologies, we investigated the statistical parameters of binding regions (BRs found in disordered human proteome. In this report, we detailed the bioinformatics analysis of binding regions found in the IDPs. Statistical models for the occurrence of BRs, their length distribution and percent occupancy in the parent proteins are shown. The frequency of BRs followed a Poisson distribution pattern with increasing expectancy with the degree of disorderedness. The length of the individual BRs also followed Poisson distribution with a mean of 6 residues, whereas, percentage of residues in BR showed a normal distribution pattern. We also explored the physicochemical properties such as the grand average of hydropathy (GRAVY and the theoretical isoelectric points (pIs. The theoretical pIs of the BRs followed a bimodal distribution as in the parent proteins. However, the mean acidic/basic pIs were significantly lower/higher than that of the proteins, respectively. We further showed that the amino acid composition of BRs was enriched in hydrophobic residues such as Ala, Val, Ile, Leu and Phe compared to the average sequence content of the proteins. Sequences in a BR showed conformational adaptability mostly towards flexible coil structure and followed by helix, however, the ordered secondary structural conformation was significantly lower in BRs than the proteins. Combining and comparing these statistical information of BRs with other methods may be useful for high

  6. Crystal structure of human CRMP-4: correction of intensities for lattice-translocation disorder

    Energy Technology Data Exchange (ETDEWEB)

    Ponnusamy, Rajesh [Universidade Nova de Lisboa, Avenida da República, EAN, 2781-901 Oeiras (Portugal); Lebedev, Andrey A. [Research Complex at Harwell, STFC Rutherford Appleton Laboratory, Didcot OX11 0FA (United Kingdom); Pahlow, Steffen [University of Hamburg, Ohnhorststrasse 18, 22609 Hamburg (Germany); Lohkamp, Bernhard, E-mail: bernhard.lohkamp@ki.se [Karolinska Institutet, Tomtebodavägen 6, 4tr, 17177 Stockholm (Sweden); Universidade Nova de Lisboa, Avenida da República, EAN, 2781-901 Oeiras (Portugal)

    2014-06-01

    Crystals of human CRMP-4 showed severe lattice-translocation disorder. Intensities were demodulated using the so-called lattice-alignment method and a new more general method with simplified parameterization, and the structure is presented. Collapsin response mediator proteins (CRMPs) are cytosolic phosphoproteins that are mainly involved in neuronal cell development. In humans, the CRMP family comprises five members. Here, crystal structures of human CRMP-4 in a truncated and a full-length version are presented. The latter was determined from two types of crystals, which were either twinned or partially disordered. The crystal disorder was coupled with translational NCS in ordered domains and manifested itself with a rather sophisticated modulation of intensities. The data were demodulated using either the two-lattice treatment of lattice-translocation effects or a novel method in which demodulation was achieved by independent scaling of several groups of intensities. This iterative protocol does not rely on any particular parameterization of the modulation coefficients, but uses the current refined structure as a reference. The best results in terms of R factors and map correlation coefficients were obtained using this new method. The determined structures of CRMP-4 are similar to those of other CRMPs. Structural comparison allowed the confirmation of known residues, as well as the identification of new residues, that are important for the homo- and hetero-oligomerization of these proteins, which are critical to nerve-cell development. The structures provide further insight into the effects of medically relevant mutations of the DPYSL-3 gene encoding CRMP-4 and the putative enzymatic activities of CRMPs.

  7. Crystal structure of human CRMP-4: correction of intensities for lattice-translocation disorder

    International Nuclear Information System (INIS)

    Ponnusamy, Rajesh; Lebedev, Andrey A.; Pahlow, Steffen; Lohkamp, Bernhard

    2014-01-01

    Crystals of human CRMP-4 showed severe lattice-translocation disorder. Intensities were demodulated using the so-called lattice-alignment method and a new more general method with simplified parameterization, and the structure is presented. Collapsin response mediator proteins (CRMPs) are cytosolic phosphoproteins that are mainly involved in neuronal cell development. In humans, the CRMP family comprises five members. Here, crystal structures of human CRMP-4 in a truncated and a full-length version are presented. The latter was determined from two types of crystals, which were either twinned or partially disordered. The crystal disorder was coupled with translational NCS in ordered domains and manifested itself with a rather sophisticated modulation of intensities. The data were demodulated using either the two-lattice treatment of lattice-translocation effects or a novel method in which demodulation was achieved by independent scaling of several groups of intensities. This iterative protocol does not rely on any particular parameterization of the modulation coefficients, but uses the current refined structure as a reference. The best results in terms of R factors and map correlation coefficients were obtained using this new method. The determined structures of CRMP-4 are similar to those of other CRMPs. Structural comparison allowed the confirmation of known residues, as well as the identification of new residues, that are important for the homo- and hetero-oligomerization of these proteins, which are critical to nerve-cell development. The structures provide further insight into the effects of medically relevant mutations of the DPYSL-3 gene encoding CRMP-4 and the putative enzymatic activities of CRMPs

  8. Non-Human Primates Harbor Diverse Mammalian and Avian Astroviruses Including Those Associated with Human Infections.

    Directory of Open Access Journals (Sweden)

    Erik A Karlsson

    Full Text Available Astroviruses (AstVs are positive sense, single-stranded RNA viruses transmitted to a wide range of hosts via the fecal-oral route. The number of AstV-infected animal hosts has rapidly expanded in recent years with many more likely to be discovered because of the advances in viral surveillance and next generation sequencing. Yet no study to date has identified human AstV genotypes in animals, although diverse AstV genotypes similar to animal-origin viruses have been found in children with diarrhea and in one instance of encephalitis. Here we provide important new evidence that non-human primates (NHP can harbor a wide variety of mammalian and avian AstV genotypes, including those only associated with human infection. Serological analyses confirmed that >25% of the NHP tested had antibodies to human AstVs. Further, we identified a recombinant AstV with parental relationships to known human AstVs. Phylogenetic analysis suggests AstVs in NHP are on average evolutionarily much closer to AstVs from other animals than are AstVs from bats, a frequently proposed reservoir. Our studies not only demonstrate that human astroviruses can be detected in NHP but also suggest that NHP are unique in their ability to support diverse AstV genotypes, further challenging the paradigm that astrovirus infection is species-specific.

  9. Circuit- and Diagnosis-Specific DNA Methylation Changes at γ-Aminobutyric Acid-Related Genes in Postmortem Human Hippocampus in Schizophrenia and Bipolar Disorder.

    Science.gov (United States)

    Ruzicka, W Brad; Subburaju, Sivan; Benes, Francine M

    2015-06-01

    Dysfunction related to γ-aminobutyric acid (GABA)-ergic neurotransmission in the pathophysiology of major psychosis has been well established by the work of multiple groups across several decades, including the widely replicated downregulation of GAD1. Prior gene expression and network analyses within the human hippocampus implicate a broader network of genes, termed the GAD1 regulatory network, in regulation of GAD1 expression. Several genes within this GAD1 regulatory network show diagnosis- and sector-specific expression changes within the circuitry of the hippocampus, influencing abnormal GAD1 expression in schizophrenia and bipolar disorder. To investigate the hypothesis that aberrant DNA methylation contributes to circuit- and diagnosis-specific abnormal expression of GAD1 regulatory network genes in psychotic illness. This epigenetic association study targeting GAD1 regulatory network genes was conducted between July 1, 2012, and June 30, 2014. Postmortem human hippocampus tissue samples were obtained from 8 patients with schizophrenia, 8 patients with bipolar disorder, and 8 healthy control participants matched for age, sex, postmortem interval, and other potential confounds from the Harvard Brain Tissue Resource Center, McLean Hospital, Belmont, Massachusetts. We extracted DNA from laser-microdissected stratum oriens tissue of cornu ammonis 2/3 (CA2/3) and CA1 postmortem human hippocampus, bisulfite modified it, and assessed it with the Infinium HumanMethylation450 BeadChip (Illumina, Inc). The subset of CpG loci associated with GAD1 regulatory network genes was analyzed in R version 3.1.0 software (R Foundation) using the minfi package. Findings were validated using bisulfite pyrosequencing. Methylation levels at 1308 GAD1 regulatory network-associated CpG loci were assessed both as individual sites to identify differentially methylated positions and by sharing information among colocalized probes to identify differentially methylated regions. A total of

  10. Experiences of Students with Specific Learning Disorder (Including ADHD) in Online College Degree Programs: A Phenomenological Study

    Science.gov (United States)

    Bunch, Seleta LeAnn

    2016-01-01

    Enrollment in online degree programs is rapidly expanding due to the convenience and affordability offered to students and improvements in technology. The purpose of this hermeneutical phenomenological study was to understand the shared experiences of students with documented specific learning disorders (including Attention-Deficit/Hyperactivity…

  11. Mental Disorders

    Science.gov (United States)

    Mental disorders include a wide range of problems, including Anxiety disorders, including panic disorder, obsessive-compulsive disorder, ... disorders, including schizophrenia There are many causes of mental disorders. Your genes and family history may play ...

  12. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

    Directory of Open Access Journals (Sweden)

    Wouter Boomsma

    2016-02-01

    Full Text Available The ubiquitin-proteasome system targets misfolded proteins for degradation. Since the accumulation of such proteins is potentially harmful for the cell, their prompt removal is important. E3 ubiquitin-protein ligases mediate substrate ubiquitination by bringing together the substrate with an E2 ubiquitin-conjugating enzyme, which transfers ubiquitin to the substrate. For misfolded proteins, substrate recognition is generally delegated to molecular chaperones that subsequently interact with specific E3 ligases. An important exception is San1, a yeast E3 ligase. San1 harbors extensive regions of intrinsic disorder, which provide both conformational flexibility and sites for direct recognition of misfolded targets of vastly different conformations. So far, no mammalian ortholog of San1 is known, nor is it clear whether other E3 ligases utilize disordered regions for substrate recognition. Here, we conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology of their ordered regions, and did not capture the unique disorder patterns that encode the functional mechanism of San1. However, by searching specifically for key features of the San1 sequence, such as long regions of intrinsic disorder embedded with short stretches predicted to be suitable for substrate interaction, we identified several E3 ligases with these characteristics. Our initial analysis revealed that another remarkable trait of San1 is shared with several candidate E3 ligases: long stretches of complete lysine suppression, which in San1 limits auto-ubiquitination. We encode these characteristic features into a San1 similarity-score, and present a set of proteins that are plausible candidates as San1 counterparts in humans. In conclusion, our work

  13. Pumpkin Seed Oil Extracted From Cucurbita maxima Improves Urinary Disorder in Human Overactive Bladder.

    Science.gov (United States)

    Nishimura, Mie; Ohkawara, Tatsuya; Sato, Hiroji; Takeda, Hiroshi; Nishihira, Jun

    2014-01-01

    The pumpkin seed oil obtained from Cucurbita pepo has been shown to be useful for the treatment of nocturia in patients with urinal disorders in several western countries. In this study, we evaluated the effect of the pumpkin seed oil from Cucurbita maxima on urinary dysfunction in human overactive bladder (OAB). Forty-five subjects were enrolled in this study. An extract of pumpkin seed oil from C. maxima (10 g of oil/day) was orally administrated for 12 weeks. After 6 and 12 weeks, urinary function was evaluated using Overactive Bladder Symptom Score (OABSS). Pumpkin seed oil from C. maxima significantly reduced the degree of OABSS in the subjects. The results from our study suggest that pumpkin seed oil extracts from C. maxima as well as from C. pepo are effective for urinary disorders such as OAB in humans.

  14. Pumpkin Seed Oil Extracted From Cucurbita maxima Improves Urinary Disorder in Human Overactive Bladder

    Science.gov (United States)

    Nishimura, Mie; Ohkawara, Tatsuya; Sato, Hiroji; Takeda, Hiroshi; Nishihira, Jun

    2014-01-01

    The pumpkin seed oil obtained from Cucurbita pepo has been shown to be useful for the treatment of nocturia in patients with urinal disorders in several western countries. In this study, we evaluated the effect of the pumpkin seed oil from Cucurbita maxima on urinary dysfunction in human overactive bladder (OAB). Forty-five subjects were enrolled in this study. An extract of pumpkin seed oil from C. maxima (10 g of oil/day) was orally administrated for 12 weeks. After 6 and 12 weeks, urinary function was evaluated using Overactive Bladder Symptom Score (OABSS). Pumpkin seed oil from C. maxima significantly reduced the degree of OABSS in the subjects. The results from our study suggest that pumpkin seed oil extracts from C. maxima as well as from C. pepo are effective for urinary disorders such as OAB in humans. PMID:24872936

  15. Stem Cell Technology for (Epi)genetic Brain Disorders.

    Science.gov (United States)

    Riemens, Renzo J M; Soares, Edilene S; Esteller, Manel; Delgado-Morales, Raul

    2017-01-01

    Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems. This, together with our incomplete knowledge of the multifactorial causes in the majority of these disorders, as well as a thorough understanding of associated (epi)genetic alterations, has been impeding progress in gaining more mechanistic insights from translational studies. Over the last years, however, stem cell technology has been offering an alternative approach to study and treat human brain disorders. Owing to this technology, we are now able to obtain a theoretically inexhaustible source of human neural cells and precursors in vitro that offer a platform for disease modeling and the establishment of therapeutic interventions. In addition to the potential to increase our general understanding of how (epi)genetic alterations contribute to the pathology of brain disorders, stem cells and derivatives allow for high-throughput drugs and toxicity testing, and provide a cell source for transplant therapies in regenerative medicine. In the current chapter, we will demonstrate the validity of human stem cell-based models and address the utility of other stem cell-based applications for several human brain disorders with multifactorial and (epi)genetic bases, including Parkinson's disease (PD), Alzheimer's disease (AD), fragile X syndrome (FXS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Rett syndrome (RTT).

  16. Overlap of food addiction and substance use disorders definitions: analysis of animal and human studies.

    Science.gov (United States)

    Hone-Blanchet, Antoine; Fecteau, Shirley

    2014-10-01

    Food has both homeostatic and hedonic components, which makes it a potent natural reward. Food related reward could therefore promote an escalation of intake and trigger symptoms associated to withdrawal, suggesting a behavioral parallel with substance abuse. Animal and human theoretical models of food reward and addiction have emerged, raising further interrogations on the validity of a bond between Substance Use Disorders, as clinically categorized in the DSM 5, and food reward. These models propose that highly palatable food items, rich in sugar and/or fat, are overly stimulating to the brain's reward pathways. Moreover, studies have also investigated the possibility of causal link between food reward and the contemporary obesity epidemic, with obesity being potentiated and maintained due to this overwhelming food reward. Although natural rewards are a hot topic in the definition and categorization of Substance Use Disorders, proofs of concept and definite evidence are still inconclusive. This review focuses on available results from experimental studies in animal and human models exploring the concept of food addiction, in an effort to determine if it depicts a specific phenotype and if there is truly a neurobiological similarity between food addiction and Substance Use Disorders. It describes results from sugar, fat and sweet-fat bingeing in rodent models, and behavioral and neurobiological assessments in different human populations. Although pieces of behavioral and neurobiological evidence supporting a food addiction phenotype in animals and humans are interesting, it seems premature to conclude on its validity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. 21 CFR 878.4630 - Ultraviolet lamp for dermatologic disorders.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ultraviolet lamp for dermatologic disorders. 878.4630 Section 878.4630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... disorders is a device (including a fixture) intended to provide ultraviolet radiation of the body to...

  18. Psilocybin for treating substance use disorders?

    NARCIS (Netherlands)

    Veen, B.T. de; Schellekens, A.F.A.; Verheij, M.M.M.; Homberg, J.R.

    2017-01-01

    INTRODUCTION: Evidence based treatment for Substance use disorders (SUD) includes psychotherapy and pharmacotherapy. However, these are only partially effective. Hallucinogens, such as psilocybin, may represent potential new treatment options for SUD. This review provides a summary of (human)

  19. Construct validity and parent-child agreement of the six new or modified disorders included in the Spanish version of the Kiddie Schedule for Affective Disorders and Schizophrenia present and Lifetime Version DSM-5 (K-SADS-PL-5).

    Science.gov (United States)

    de la Peña, Francisco R; Rosetti, Marcos F; Rodríguez-Delgado, Andrés; Villavicencio, Lino R; Palacio, Juan D; Montiel, Cecilia; Mayer, Pablo A; Félix, Fernando J; Larraguibel, Marcela; Viola, Laura; Ortiz, Silvia; Fernández, Sofía; Jaímes, Aurora; Feria, Miriam; Sosa, Liz; Palacios-Cruz, Lino; Ulloa, Rosa E

    2018-06-01

    Changes to the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) incorporate the inclusion or modification of six disorders: Autism Spectrum Disorder, Social Anxiety Disorder, Intermittent Explosive Disorder, Disruptive Mood Dysregulation Disorder, Avoidant/Restrictive Food Intake Disorder and Binge Eating Disorder. The objectives of this study were to assess the construct validity and parent-child agreement of these six disorders in the Spanish language Schedule for Affective Disorders and Schizophrenia for School Age Children Present and Lifetime Version (K-SADS-PL-5) in a clinical population of children and adolescents from Latin America. The Spanish version of the K-SADS-PL was modified to integrate changes made to the DSM-5. Clinicians received training in the K-SADS-PL-5 and 90% agreement between raters was obtained. A total of 80 patients were recruited in four different countries in Latin America. All items from each of the six disorders were included in a factor analysis. Parent-child agreement was calculated for every item of the six disorders, including the effect of sex and age. The factor analysis revealed 6 factors separately grouping the items defining each of the new or modified disorders, with Eigenvalues greater than 2. Very good parent-child agreements (r>0.8) were found for the large majority of the items (93%), even when considering the sex or age of the patient. This independent grouping of disorders suggests that the manner in which the disorders were included into the K-SADS-PL-5 reflects robustly the DSM-5 constructs and displayed a significant inter-informant reliability. These findings support the use of K-SADS-PL-5 as a clinical and research tool to evaluate these new or modified diagnoses. Copyright © 2018. Published by Elsevier Ltd.

  20. Pumpkin Seed Oil Extracted From Cucurbita maxima Improves Urinary Disorder in Human Overactive Bladder

    Directory of Open Access Journals (Sweden)

    Mie Nishimura

    2014-01-01

    Full Text Available The pumpkin seed oil obtained from Cucurbita pepo has been shown to be useful for the treatment of nocturia in patients with urinal disorders in several western countries. In this study, we evaluated the effect of the pumpkin seed oil from Cucurbita maxima on urinary dysfunction in human overactive bladder (OAB. Forty-five subjects were enrolled in this study. An extract of pumpkin seed oil from C. maxima (10 g of oil/day was orally administrated for 12 weeks. After 6 and 12 weeks, urinary function was evaluated using Overactive Bladder Symptom Score (OABSS. Pumpkin seed oil from C. maxima significantly reduced the degree of OABSS in the subjects. The results from our study suggest that pumpkin seed oil extracts from C. maxima as well as from C. pepo are effective for urinary disorders such as OAB in humans.

  1. Diseases and disorders of muscle.

    Science.gov (United States)

    Pearson, A M; Young, R B

    1993-01-01

    Muscle may suffer from a number of diseases or disorders, some being fatal to humans and animals. Their management or treatment depends on correct diagnosis. Although no single method may be used to identify all diseases, recognition depends on the following diagnostic procedures: (1) history and clinical examination, (2) blood biochemistry, (3) electromyography, (4) muscle biopsy, (5) nuclear magnetic resonance, (6) measurement of muscle cross-sectional area, (7) tests of muscle function, (8) provocation tests, and (9) studies on protein turnover. One or all of these procedures may prove helpful in diagnosis, but even then identification of the disorder may not be possible. Nevertheless, each of these procedures can provide useful information. Among the most common diseases in muscle are the muscular dystrophies, in which the newly identified muscle protein dystrophin is either absent or present at less than normal amounts in both Duchenne and Becker's muscular dystrophy. Although the identification of dystrophin represents a major breakthrough, treatment has not progressed to the experimental stage. Other major diseases of muscle include the inflammatory myopathies and neuropathies. Atrophy and hypertrophy of muscle and the relationship of aging, exercise, and fatigue all add to our understanding of the behavior of normal and abnormal muscle. Some other interesting related diseases and disorders of muscle include myasthenia gravis, muscular dysgenesis, and myclonus. Disorders of energy metabolism include those caused by abnormal glycolysis (Von Gierke's, Pompe's, Cori-Forbes, Andersen's, McArdle's, Hers', and Tauri's diseases) and by the acquired diseases of glycolysis (disorders of mitochondrial oxidation). Still other diseases associated with abnormal energy metabolism include lipid-related disorders (carnitine and carnitine palmitoyl-transferase deficiencies) and myotonic syndromes (myotonia congenita, paramyotonia congenita, hypokalemic and hyperkalemic

  2. Human Sexual Desire Disorder: Do We Have a Problem?

    Science.gov (United States)

    McNab, Warren L.; Henry, Jean

    2006-01-01

    Hypoactive Sexual Desire Disorder (HSDD), loss of sexual desire for sexual activity, is one of the most common sexual dysfunctions of men and women in the United States. This article presents an overview of this specific sexual dysfunction including incidence, possible causes, treatment options, and the role of the health educator in addressing…

  3. X-ray diffraction evidence for myelin disorder in brain from humans with Alzheimer's disease.

    Science.gov (United States)

    Chia, L S; Thompson, J E; Moscarello, M A

    1984-09-05

    Wide-angle X-ray diffraction studies revealed that the lipid phase transition temperature of myelin from brain tissue of humans with Alzheimer's disease was about 12 degrees C lower than that of normal age-matched controls, indicating differences in the physical organization of the myelin lipid bilayer. Elevated levels of malondialdehyde and conjugated diene were found in brain tissue from humans with Alzheimer's disease, indicating an increased amount of lipid peroxidation over the controls. An increase in myelin disorder and in lipid peroxidation can both be correlated with aging in human brain, but the changes in myelin from humans with Alzheimer's disease are more pronounced than in normal aging. These changes might represent severe or accelerated aging.

  4. Zebrafish homologs of genes within 16p11.2, a genomic region associated with brain disorders, are active during brain development, and include two deletion dosage sensor genes

    Directory of Open Access Journals (Sweden)

    Alicia Blaker-Lee

    2012-11-01

    Deletion or duplication of one copy of the human 16p11.2 interval is tightly associated with impaired brain function, including autism spectrum disorders (ASDs, intellectual disability disorder (IDD and other phenotypes, indicating the importance of gene dosage in this copy number variant region (CNV. The core of this CNV includes 25 genes; however, the number of genes that contribute to these phenotypes is not known. Furthermore, genes whose functional levels change with deletion or duplication (termed ‘dosage sensors’, which can associate the CNV with pathologies, have not been identified in this region. Using the zebrafish as a tool, a set of 16p11.2 homologs was identified, primarily on chromosomes 3 and 12. Use of 11 phenotypic assays, spanning the first 5 days of development, demonstrated that this set of genes is highly active, such that 21 out of the 22 homologs tested showed loss-of-function phenotypes. Most genes in this region were required for nervous system development – impacting brain morphology, eye development, axonal density or organization, and motor response. In general, human genes were able to substitute for the fish homolog, demonstrating orthology and suggesting conserved molecular pathways. In a screen for 16p11.2 genes whose function is sensitive to hemizygosity, the aldolase a (aldoaa and kinesin family member 22 (kif22 genes were identified as giving clear phenotypes when RNA levels were reduced by ∼50%, suggesting that these genes are deletion dosage sensors. This study leads to two major findings. The first is that the 16p11.2 region comprises a highly active set of genes, which could present a large genetic target and might explain why multiple brain function, and other, phenotypes are associated with this interval. The second major finding is that there are (at least two genes with deletion dosage sensor properties among the 16p11.2 set, and these could link this CNV to brain disorders such as ASD and IDD.

  5. Emerging Treatments in Eating Disorders.

    Science.gov (United States)

    Lutter, Michael

    2017-07-01

    Eating disorders (EDs), including anorexia nervosa, bulimia nervosa, and binge-eating disorder, constitute a class of common and deadly psychiatric disorders. While numerous studies in humans highlight the important role of neurobiological alterations in the development of ED-related behaviors, the precise neural substrate that mediates this risk is unknown. Historically, pharmacological interventions have played a limited role in the treatment of eating disorders, typically providing symptomatic relief of comorbid psychiatric issues, like depression and anxiety, in support of the standard nutritional and psychological treatments. To date there are no Food and Drug Administration-approved medications or procedures for anorexia nervosa, and only one Food and Drug Administration-approved medication each for bulimia nervosa (fluoxetine) and binge-eating disorder (lisdexamfetamine). While there is little primary interest in drug development for eating disorders, postmarket monitoring of medications and procedures approved for other indications has identified several novel treatment options for patients with eating disorders. In this review, I utilize searches of the PubMed and ClinicalTrials.gov databases to highlight emerging treatments in eating disorders.

  6. Circuit- and Diagnosis-Specific DNA Methylation Changes at γ-Aminobutyric Acid–Related Genes in Postmortem Human Hippocampus in Schizophrenia and Bipolar Disorder

    Science.gov (United States)

    Ruzicka, W. Brad; Subburaju, Sivan; Benes, Francine M.

    2017-01-01

    IMPORTANCE Dysfunction related to γ-aminobutyric acid (GABA)–ergic neurotransmission in the pathophysiology of major psychosis has been well established by the work of multiple groups across several decades, including the widely replicated downregulation of GAD1. Prior gene expression and network analyses within the human hippocampus implicate a broader network of genes, termed the GAD1 regulatory network, in regulation of GAD1 expression. Several genes within this GAD1 regulatory network show diagnosis- and sector-specific expression changes within the circuitry of the hippocampus, influencing abnormal GAD1 expression in schizophrenia and bipolar disorder. OBJECTIVE To investigate the hypothesis that aberrant DNA methylation contributes to circuit- and diagnosis-specific abnormal expression of GAD1 regulatory network genes in psychotic illness. DESIGN, SETTING, AND PARTICIPANTS This epigenetic association study targeting GAD1 regulatory network genes was conducted between July 1, 2012, and June 30, 2014. Postmortem human hippocampus tissue samples were obtained from 8patients with schizophrenia, 8 patients with bipolar disorder, and 8 healthy control participants matched for age, sex, postmortem interval, and other potential confounds from the Harvard Brain Tissue Resource Center, McLean Hospital, Belmont,Massachusetts. We extracted DNA from laser-microdissected stratum oriens tissue of cornu ammonis 2/3 (CA2/3) and CA1 postmortem human hippocampus, bisulfite modified it, and assessed it with the Infinium HumanMethylation450 BeadChip (Illumina, Inc). The subset of CpG loci associated with GAD1 regulatory network genes was analyzed in R version 3.1.0 software (R Foundation) using the minfi package. Findings were validated using bisulfite pyrosequencing. MAIN OUTCOMES AND MEASURES Methylation levels at 1308 GAD1 regulatory network–associated CpG loci were assessed both as individual sites to identify differentially methylated positions and by sharing

  7. A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder

    Directory of Open Access Journals (Sweden)

    David G Ashbrook

    2015-07-01

    Full Text Available Bipolar disorder (BD is a significant neuropsychiatric disorder with a lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS have been carried out. While many variants of small effect associated with BD have been identified few have yet been confirmed, partly because of the low power of GWAS due to multiple comparisons being made. Complementary mapping studies using murine models have identified genetic variants for behavioral traits linked to BD, often with high power, but these identified regions often contain too many genes for clear identification of candidate genes. In the current study we have aligned human BD GWAS results and mouse linkage studies to help define and evaluate candidate genes linked to BD, seeking to use the power of the mouse mapping with the precision of GWAS. We use quantitative trait mapping for open field test and elevated zero maze data in the largest mammalian model system, the BXD recombinant inbred mouse population, to identify genomic regions associated with these BD-like phenotypes. We then investigate these regions in whole genome data from the Psychiatric Genomics Consortium’s bipolar disorder GWAS to identify candidate genes associated with BD. Finally we establish the biological relevance and pathways of these genes in a comprehensive systems genetics analysis.We identify four genes associated with both mouse anxiety and human BD. While TNR is a novel candidate for BD, we can confirm previously suggested associations with CMYA5, MCTP1 and RXRG. A cross-species, systems genetics analysis shows that MCTP1, RXRG and TNR coexpress with genes linked to psychiatric disorders and identify the striatum as a potential site of action. CMYA5, MCTP1, RXRG and TNR are associated with mouse anxiety and human BD. We hypothesize that MCTP1, RXRG and TNR influence intercellular signaling in the striatum.

  8. The Role of Serotonin Transporter in Human Lung Development and in Neonatal Lung Disorders

    Directory of Open Access Journals (Sweden)

    E. C. C. Castro

    2017-01-01

    Full Text Available Introduction. Failure of the vascular pulmonary remodeling at birth often manifests as pulmonary hypertension (PHT and is associated with a variety of neonatal lung disorders including a uniformly fatal developmental disorder known as alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV. Serum serotonin regulation has been linked to pulmonary vascular function and disease, and serotonin transporter (SERT is thought to be one of the key regulators in these processes. We sought to find evidence of a role that SERT plays in the neonatal respiratory adaptation process and in the pathomechanism of ACD/MPV. Methods. We used histology and immunohistochemistry to determine the timetable of SERT protein expression in normal human fetal and postnatal lungs and in cases of newborn and childhood PHT of varied etiology. In addition, we tested for a SERT gene promoter defect in ACD/MPV patients. Results. We found that SERT protein expression begins at 30 weeks of gestation, increases to term, and stays high postnatally. ACD/MPV patients had diminished SERT expression without SERT promoter alteration. Conclusion. We concluded that SERT/serotonin pathway is crucial in the process of pulmonary vascular remodeling/adaptation at birth and plays a key role in the pathobiology of ACD/MPV.

  9. Impressions of Humanness for Android Robot May Represent an Endophenotype for Autism Spectrum Disorders

    Science.gov (United States)

    Kumazaki, Hirokazu; Warren, Zachary; Swanson, Amy; Yoshikawa, Yuichiro; Matsumoto, Yoshio; Ishiguro, Hiroshi; Sarkar, Nilanjan; Minabe, Yoshio; Kikuchi, Mitsuru

    2018-01-01

    Identification of meaningful endophenotypes may be critical to unraveling the etiology and pathophysiology of autism spectrum disorders (ASD). We investigated whether impressions of "humanness" for android robot might represent a candidate characteristic of an ASD endophenotype. We used a female type of android robot with an appearance…

  10. The serotonergic anatomy of the developing human medulla oblongata: implications for pediatric disorders of homeostasis.

    Science.gov (United States)

    Kinney, Hannah C; Broadbelt, Kevin G; Haynes, Robin L; Rognum, Ingvar J; Paterson, David S

    2011-07-01

    The caudal serotonergic (5-HT) system is a critical component of a medullary "homeostatic network" that regulates protective responses to metabolic stressors such as hypoxia, hypercapnia, and hyperthermia. We define anatomically the caudal 5-HT system in the human medulla as 5-HT neuronal cell bodies located in the raphé (raphé obscurus, raphé magnus, and raphé pallidus), extra-raphé (gigantocellularis, paragigantocellularis lateralis, intermediate reticular zone, lateral reticular nucleus, and nucleus subtrigeminalis), and ventral surface (arcuate nucleus). These 5-HT neurons are adjacent to all of the respiratory- and autonomic-related nuclei in the medulla where they are positioned to modulate directly the responses of these effector nuclei. In the following review, we highlight the topography and development of the caudal 5-HT system in the human fetus and infant, and its inter-relationships with nicotinic, GABAergic, and cytokine receptors. We also summarize pediatric disorders in early life which we term "developmental serotonopathies" of the caudal (as well as rostral) 5-HT domain and which are associated with homeostatic imbalances. The delineation of the development and organization of the human caudal 5-HT system provides the critical foundation for the neuropathologic elucidation of its disorders directly in the human brain. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Canine disorder mirrors human disease: exonic deletion in HES7 causes autosomal recessive spondylocostal dysostosis in miniature Schnauzer dogs.

    Directory of Open Access Journals (Sweden)

    Cali E Willet

    Full Text Available Spondylocostal dysostosis is a congenital disorder of the axial skeleton documented in human families from diverse racial backgrounds. The condition is characterised by truncal shortening, extensive hemivertebrae and rib anomalies including malalignment, fusion and reduction in number. Mutations in the Notch signalling pathway genes DLL3, MESP2, LFNG, HES7 and TBX6 have been associated with this defect. In this study, spondylocostal dysostosis in an outbred family of miniature schnauzer dogs is described. Computed tomography demonstrated that the condition mirrors the skeletal defects observed in human cases, but unlike most human cases, the affected dogs were stillborn or died shortly after birth. Through gene mapping and whole genome sequencing, we identified a single-base deletion in the coding region of HES7. The frameshift mutation causes loss of functional domains essential for the oscillatory transcriptional autorepression of HES7 during somitogenesis. A restriction fragment length polymorphism test was applied within the immediate family and supported a highly penetrant autosomal recessive mode of inheritance. The mutation was not observed in wider testing of 117 randomly sampled adult miniature schnauzer and six adult standard schnauzer dogs; providing a significance of association of Praw = 4.759e-36 (genome-wide significant. Despite this apparently low frequency in the Australian population, the allele may be globally distributed based on its presence in two unrelated sires from geographically distant locations. While isolated hemivertebrae have been observed in a small number of other dog breeds, this is the first clinical and genetic diagnosis of spontaneously occurring spondylocostal dysostosis in a non-human mammal and offers an excellent model in which to study this devastating human disorder. The genetic test can be utilized by dog breeders to select away from the disease and avoid unnecessary neonatal losses.

  12. Canine disorder mirrors human disease: exonic deletion in HES7 causes autosomal recessive spondylocostal dysostosis in miniature Schnauzer dogs.

    Science.gov (United States)

    Willet, Cali E; Makara, Mariano; Reppas, George; Tsoukalas, George; Malik, Richard; Haase, Bianca; Wade, Claire M

    2015-01-01

    Spondylocostal dysostosis is a congenital disorder of the axial skeleton documented in human families from diverse racial backgrounds. The condition is characterised by truncal shortening, extensive hemivertebrae and rib anomalies including malalignment, fusion and reduction in number. Mutations in the Notch signalling pathway genes DLL3, MESP2, LFNG, HES7 and TBX6 have been associated with this defect. In this study, spondylocostal dysostosis in an outbred family of miniature schnauzer dogs is described. Computed tomography demonstrated that the condition mirrors the skeletal defects observed in human cases, but unlike most human cases, the affected dogs were stillborn or died shortly after birth. Through gene mapping and whole genome sequencing, we identified a single-base deletion in the coding region of HES7. The frameshift mutation causes loss of functional domains essential for the oscillatory transcriptional autorepression of HES7 during somitogenesis. A restriction fragment length polymorphism test was applied within the immediate family and supported a highly penetrant autosomal recessive mode of inheritance. The mutation was not observed in wider testing of 117 randomly sampled adult miniature schnauzer and six adult standard schnauzer dogs; providing a significance of association of Praw = 4.759e-36 (genome-wide significant). Despite this apparently low frequency in the Australian population, the allele may be globally distributed based on its presence in two unrelated sires from geographically distant locations. While isolated hemivertebrae have been observed in a small number of other dog breeds, this is the first clinical and genetic diagnosis of spontaneously occurring spondylocostal dysostosis in a non-human mammal and offers an excellent model in which to study this devastating human disorder. The genetic test can be utilized by dog breeders to select away from the disease and avoid unnecessary neonatal losses.

  13. Entrainment of the circadian clock in humans: mechanism and implications for sleep disorders.

    Directory of Open Access Journals (Sweden)

    David Metcalfe

    2007-01-01

    Full Text Available Humans exhibit behaviour and physiology controlled by a circadian clock. The circadian period is genetically determined and administered by a series of interlocked autoregulatory feedback loops largely in the suprachiasmatic nuclei of the hypothalamus. The phase of the clock is, however, synchronised by a number of external environmental cues such as light. A failure or change in any one of the requisite clock components may result in the onset of a long-term sleep disorder. This review discusses the mechanism regulating circadian physiology in humans and explores how disturbances of this mechanism may result in sleep pathologies.

  14. Genetics of bipolar disorder

    Directory of Open Access Journals (Sweden)

    Kerner B

    2014-02-01

    Full Text Available Berit Kerner Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA Abstract: Bipolar disorder is a common, complex genetic disorder, but the mode of transmission remains to be discovered. Many researchers assume that common genomic variants carry some risk for manifesting the disease. The research community has celebrated the first genome-wide significant associations between common single nucleotide polymorphisms (SNPs and bipolar disorder. Currently, attempts are under way to translate these findings into clinical practice, genetic counseling, and predictive testing. However, some experts remain cautious. After all, common variants explain only a very small percentage of the genetic risk, and functional consequences of the discovered SNPs are inconclusive. Furthermore, the associated SNPs are not disease specific, and the majority of individuals with a “risk” allele are healthy. On the other hand, population-based genome-wide studies in psychiatric disorders have rediscovered rare structural variants and mutations in genes, which were previously known to cause genetic syndromes and monogenic Mendelian disorders. In many Mendelian syndromes, psychiatric symptoms are prevalent. Although these conditions do not fit the classic description of any specific psychiatric disorder, they often show nonspecific psychiatric symptoms that cross diagnostic boundaries, including intellectual disability, behavioral abnormalities, mood disorders, anxiety disorders, attention deficit, impulse control deficit, and psychosis. Although testing for chromosomal disorders and monogenic Mendelian disorders is well established, testing for common variants is still controversial. The standard concept of genetic testing includes at least three broad criteria that need to be fulfilled before new genetic tests should be introduced: analytical validity, clinical validity, and clinical utility. These criteria are

  15. Biomedical and Clinical Promises of Human Pluripotent Stem Cells for Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Nopporn Jongkamonwiwat

    2013-01-01

    Full Text Available Neurological disorders are characterized by the chronic and progressive loss of neuronal structures and functions. There is a variability of the onsets and causes of clinical manifestations. Cell therapy has brought a new concept to overcome brain diseases, but the advancement of this therapy is limited by the demands of specialized neurons. Human pluripotent stem cells (hPSCs have been promised as a renewable resource for generating human neurons for both laboratory and clinical purposes. By the modulations of appropriate signalling pathways, desired neuron subtypes can be obtained, and induced pluripotent stem cells (iPSCs provide genetically matched neurons for treating patients. These hPSC-derived neurons can also be used for disease modeling and drug screening. Since the most urgent problem today in transplantation is the lack of suitable donor organs and tissues, the derivation of neural progenitor cells from hPSCs has opened a new avenue for regenerative medicine. In this review, we summarize the recent reports that show how to generate neural derivatives from hPSCs, and discuss the current evidence of using these cells in animal studies. We also highlight the possibilities and concerns of translating these hPSC-derived neurons for biomedical and clinical uses in order to fight against neurological disorders.

  16. Genetic disorders of thyroid metabolism and brain development

    Science.gov (United States)

    Kurian, Manju A; Jungbluth, Heinz

    2014-01-01

    Normal thyroid metabolism is essential for human development, including the formation and functioning of the central and peripheral nervous system. Disorders of thyroid metabolism are increasingly recognized within the spectrum of paediatric neurological disorders. Both hypothyroid and hyperthyroid disease states (resulting from genetic and acquired aetiologies) can lead to characteristic neurological syndromes, with cognitive delay, extrapyramidal movement disorders, neuropsychiatric symptoms, and neuromuscular manifestations. In this review, the neurological manifestations of genetic disorders of thyroid metabolism are outlined, with particular focus on Allan-Herndon-Dudley syndrome and benign hereditary chorea. We report in detail the clinical features, major neurological and neuropsychiatric manifestations, molecular genetic findings, disease mechanisms, and therapeutic strategies for these emerging genetic ‘brain-thyroid’ disorders. PMID:24665922

  17. [Personality disorders, psychopathy and serial killers].

    Science.gov (United States)

    Morana, Hilda C P; Stone, Michael H; Abdalla-Filho, Elias

    2006-10-01

    To illustrate the basic characteristics of several specific personality disorders, focusing mainly in antisocial personality disorder. The differences between antisocial personality disorder and psychopathy are highlighted. Serial killers and its psychopathic aspects are also discussed. A bibliographic review was completed in order to outline convergences and divergences among different authors about this controversial issue, especially those concerning the possibility of treatment. While anti-social personality disorder is a medical diagnosis, the term "psychopathy" (which belongs to the sphere of forensic psychiatry) may be understood as a "legal diagnosis". It is not still possible to identify an effective treatment for serial killers. Personality disorders, especially of the antisocial type, still represent a formidable challenge to forensic psychiatry today. Questions as yet unanswered include the best and most humane place for patients with this condition and the nature of a standardised treatment recommendation.

  18. Deletions in 16p13 including GRIN2A in patients with intellectual disability, various dysmorphic features, and seizure disorders of the rolandic region.

    NARCIS (Netherlands)

    Reutlinger, C.; Helbig, I.; Gawelczyk, B.; Subero, J.I.; Tonnies, H.; Muhle, H.; Finsterwalder, K.; Vermeer, S.; Pfundt, R.; Sperner, J.; Stefanova, I.; Gillessen-Kaesbach, G.; Spiczak, S. von; Baalen, A. van; Boor, R.; Siebert, R.; Stephani, U.; Caliebe, A.

    2010-01-01

    Seizure disorders of the rolandic region comprise a spectrum of different epilepsy syndromes ranging from benign rolandic epilepsy to more severe seizure disorders including atypical benign partial epilepsy/pseudo-Lennox syndrome,electrical status epilepticus during sleep, and Landau-Kleffner

  19. The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder.

    Science.gov (United States)

    Malki, Karim; Keers, Robert; Tosto, Maria Grazia; Lourdusamy, Anbarasu; Carboni, Lucia; Domenici, Enrico; Uher, Rudolf; McGuffin, Peter; Schalkwyk, Leonard C

    2014-05-07

    Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either 'reactive' or 'endogenous' subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of 'reactive' or 'endogenous' subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of 'reactive' and 'endogenous' depression. We then translated these findings to clinical samples using a human post-mortem mRNA study. Affymetrix mouse whole-genome oligonucleotide arrays were used to measure gene expression from hippocampal tissues of 144 mice from the Genome-based Therapeutic Drugs for Depression (GENDEP) project. The study used four inbred mouse strains and two depressogenic 'stress' protocols (maternal separation and Unpredictable Chronic Mild Stress) to model 'reactive' depression. Stress-related mRNA differences in mouse were compared with a parallel mRNA study using Flinders Sensitive and Resistant rat lines as a model of 'endogenous' depression. Convergent genes differentially expressed across the animal studies were used to inform candidate gene selection in a human mRNA post-mortem case control study from the Stanley Brain Consortium. In the mouse 'reactive' model, the expression of 350 genes changed in response to early stresses and 370 in response to late stresses. A minimal genetic overlap (less than 8.8%) was detected in response to both stress protocols, but 30% of these genes (21) were also differentially regulated in the 'endogenous' rat study. This overlap is significantly greater than expected by chance. The VAMP-2 gene, differentially expressed across the rodent studies, was also significantly altered in the human study after correcting for multiple testing. Our results suggest that 'endogenous' and 'reactive' subtypes of depression are associated with largely

  20. BIOLOGY OF HUMAN MALARIA PLASMODIA INCLUDING PLASMODIUM KNOWLESI

    Directory of Open Access Journals (Sweden)

    Spinello Antinori

    2012-03-01

    Full Text Available Malaria is a vector-borne infection caused by unicellular parasite of the genus Plasmodium. Plasmodia are obligate intracellular parasites that in humans after a clinically silent replication phase in the liver are able to infect and replicate within the erythrocytes. Four species (P.falciparum, P.malariae, P.ovale and P.vivax are traditionally recognized as responsible of natural infection in human beings but the recent upsurge of P.knowlesi malaria in South-East Asia has led clinicians to consider it as the fifth human malaria parasite. Recent studies in wild-living apes in Africa have revealed that P.falciparum, the most deadly form of human malaria, is not only human-host restricted as previously believed and its phylogenetic lineage is much more complex with new species identified in gorilla, bonobo and chimpanzee. Although less impressive, new data on biology of P.malariae, P.ovale and P.vivax are also emerging and will be briefly discussed in this review.

  1. RNA-Seq of human neurons derived from iPS cells reveals candidate long non-coding RNAs involved in neurogenesis and neuropsychiatric disorders.

    Directory of Open Access Journals (Sweden)

    Mingyan Lin

    Full Text Available Genome-wide expression analysis using next generation sequencing (RNA-Seq provides an opportunity for in-depth molecular profiling of fundamental biological processes, such as cellular differentiation and malignant transformation. Differentiating human neurons derived from induced pluripotent stem cells (iPSCs provide an ideal system for RNA-Seq since defective neurogenesis caused by abnormalities in transcription factors, DNA methylation, and chromatin modifiers lie at the heart of some neuropsychiatric disorders. As a preliminary step towards applying next generation sequencing using neurons derived from patient-specific iPSCs, we have carried out an RNA-Seq analysis on control human neurons. Dramatic changes in the expression of coding genes, long non-coding RNAs (lncRNAs, pseudogenes, and splice isoforms were seen during the transition from pluripotent stem cells to early differentiating neurons. A number of genes that undergo radical changes in expression during this transition include candidates for schizophrenia (SZ, bipolar disorder (BD and autism spectrum disorders (ASD that function as transcription factors and chromatin modifiers, such as POU3F2 and ZNF804A, and genes coding for cell adhesion proteins implicated in these conditions including NRXN1 and NLGN1. In addition, a number of novel lncRNAs were found to undergo dramatic changes in expression, one of which is HOTAIRM1, a regulator of several HOXA genes during myelopoiesis. The increase we observed in differentiating neurons suggests a role in neurogenesis as well. Finally, several lncRNAs that map near SNPs associated with SZ in genome wide association studies also increase during neuronal differentiation, suggesting that these novel transcripts may be abnormally regulated in a subgroup of patients.

  2. Muscle layer histopathology and manometry pattern of primary esophageal motility disorders including achalasia.

    Science.gov (United States)

    Nakajima, N; Sato, H; Takahashi, K; Hasegawa, G; Mizuno, K; Hashimoto, S; Sato, Y; Terai, S

    2017-03-01

    Histopathology of muscularis externa in primary esophageal motility disorders has been characterized previously. We aimed to correlate the results of high-resolution manometry with those of histopathology. During peroral endoscopic myotomy, peroral esophageal muscle biopsy was performed in patients with primary esophageal motility disorders. Immunohistochemical staining for c-kit was performed to assess the interstitial cells of Cajal (ICCs). Hematoxylin Eosin and Azan-Mallory staining were used to detect muscle atrophy, inflammation, and fibrosis, respectively. Slides from 30 patients with the following motility disorders were analyzed: achalasia (type I: 14, type II: 5, type III: 3), one diffuse esophageal spasm (DES), two outflow obstruction (OO), four jackhammer esophagus (JE), and one nutcracker esophagus (NE). ICCs were preserved in high numbers in type III achalasia (n=9.4±1.2 cells/high power field [HPF]), compared to types I (n=3.7±0.3 cells/HPF) and II (n=3.5±1.0 cells/HPF). Moreover, severe fibrosis was only observed in type I achalasia and not in other types of achalasia, OO, or DES. Four of five patients with JE and NE had severe inflammation with eosinophilic infiltration of the esophageal muscle layer (73.8±50.3 eosinophils/HPF) with no epithelial eosinophils. One patient with JE showed a visceral myopathy pattern. Compared to types I and II, type III achalasia showed preserved ICCs, with variable data regarding DES and OO. In disorders considered as primary esophageal motility disorders, a disease category exists, which shows eosinophilic infiltration in the esophageal muscle layer with no eosinophils in the epithelium. © 2016 John Wiley & Sons Ltd.

  3. The Effects of Including a Callous-Unemotional Specifier for the Diagnosis of Conduct Disorder

    Science.gov (United States)

    Kahn, Rachel E.; Frick, Paul J.; Youngstrom, Eric; Findling, Robert L.; Youngstrom, Jennifer Kogos

    2012-01-01

    Background: "With Significant Callous-Unemotional Traits" has been proposed as a specifier for conduct disorder (CD) in the upcoming revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). The impact of this specifier on children diagnosed with CD should be considered. Methods: A multi-site cross-sectional design with…

  4. Dysregulated Translational Control: From Brain Disorders to Psychoactive Drugs

    Directory of Open Access Journals (Sweden)

    Emanuela eSantini

    2011-11-01

    Full Text Available In the last decade, a plethora of studies utilizing pharmacological, biochemical, and genetic approaches have shown that precise translational control is required for long-lasting synaptic plasticity and the formation of long-term memory. Moreover, more recent studies indicate that alterations in translational control are a common pathophysiological feature of human neurological disorders, including developmental disorders, neuropsychiatric disorders, and neurodegenerative diseases. Finally, translational control mechanisms are susceptible to modification by psychoactive drugs. Taken together, these findings point to a central role for translational control in the regulation of synaptic function and behavior.

  5. Quadrivalent human papillomavirus vaccination in girls and the risk of autoimmune disorders: the Ontario Grade 8 HPV Vaccine Cohort Study

    Science.gov (United States)

    Liu, Erin Y.; Smith, Leah M.; Ellis, Anne K.; Whitaker, Heather; Law, Barbara; Kwong, Jeffrey C.; Farrington, Paddy

    2018-01-01

    BACKGROUND: Despite demonstrated effectiveness in real-world settings, concerns persist regarding the safety of the quadrivalent human papillomavirus (HPV4) vaccine. We sought to assess the risk of autoimmune disorders following HPV4 vaccination among grade 8 girls eligible for Ontario’s school-based HPV vaccination program. METHODS: We undertook a population-based retrospective cohort study using Ontario’s administrative health and vaccination databases from 2007 to 2013. The self-controlled case series method was used to compare the rate of a composite end point of autoimmune disorders diagnosed during days 7–60 post-vaccination (“exposed” follow-up) to that at any other time (“unexposed”). The analysis was repeated to assess the effect of a history of immune-mediated diseases and time since vaccination. We also conducted an exploratory analysis of individual autoimmune disorders. Rate ratios and 95% confidence intervals (CIs) were estimated using conditional Poisson regression, adjusted for age, seasonality, concomitant vaccinations and infections. RESULTS: The study cohort consisted of 290 939 girls aged 12–17 years who were eligible for vaccination between 2007 and 2013. There was no significant risk for developing an autoimmune disorder following HPV4 vaccination (n = 681; rate ratio 1.12, 95% CI 0.85–1.47), and the association was unchanged by a history of immune-mediated disorders and time since vaccination. Exploratory analyses of individual autoimmune disorders found no significant risks, including for Bell palsy (n = 65; rate ratio 1.73, 95% CI 0.77–3.89), optic neuritis (n = 67; rate ratio 1.57, 95% CI 0.74–3.33) and Graves disease (n = 47; rate ratio 1.55, 95% CI 0.92–2.63). INTERPRETATION: We did not observe an increased risk of autoimmune disorders following HPV4 vaccination among teenaged girls. These findings should reassure parents and health care providers. PMID:29807937

  6. Epigenome-Wide Association Study of Tic Disorders.

    Science.gov (United States)

    Zilhão, Nuno R; Padmanabhuni, Shanmukha S; Pagliaroli, Luca; Barta, Csaba; Smit, Dirk J A; Cath, Danielle; Nivard, Michel G; Baselmans, Bart M L; van Dongen, Jenny; Paschou, Peristera; Boomsma, Dorret I

    2015-12-01

    Tic disorders are moderately heritable common psychiatric disorders that can be highly troubling, both in childhood and in adulthood. In this study, we report results obtained in the first epigenome-wide association study (EWAS) of tic disorders. The subjects are participants in surveys at the Netherlands Twin Register (NTR) and the NTR biobank project. Tic disorders were measured with a self-report version of the Yale Global Tic Severity Scale Abbreviated version (YGTSS-ABBR), included in the 8th wave NTR data collection (2008). DNA methylation data consisted of 411,169 autosomal methylation sites assessed by the Illumina Infinium HumanMethylation450 BeadChip Kit (HM450k array). Phenotype and DNA methylation data were available in 1,678 subjects (mean age = 41.5). No probes reached genome-wide significance (p tic disorders. The top significantly enriched gene ontology (GO) terms among higher ranking methylation sites included anatomical structure morphogenesis (GO:0009653, p = 4.6 × 10-(15)) developmental process (GO:0032502, p = 2.96 × 10(-12)), and cellular developmental process (GO:0048869, p = 1.96 × 10(-12)). Overall, these results provide a first insight into the epigenetic mechanisms of tic disorders. This first study assesses the role of DNA methylation in tic disorders, and it lays the foundations for future work aiming to unravel the biological mechanisms underlying the architecture of this disorder.

  7. Disordered eating practices in gastrointestinal disorders.

    Science.gov (United States)

    Satherley, R; Howard, R; Higgs, S

    2015-01-01

    To systematically review evidence concerning disordered eating practices in dietary-controlled gastrointestinal conditions. Three key questions were examined: a) are disordered eating practices a feature of GI disorders?; b) what abnormal eating practices are present in those with GI disorders?; and c) what factors are associated with the presence of disordered eating in those with GI disorders? By exploring these questions, we aim to develop a conceptual model of disordered eating development in GI disease. Five key databases, Web of Science with Conference Proceedings (1900-2014) and MEDLINE (1950-2014), PubMed, PsycINFO (1967-2014) and Google Scholar, were searched for papers relating to disordered eating practices in those with GI disorders. All papers were quality assessed before being included in the review. Nine papers were included in the review. The majority of papers reported that the prevalence of disordered eating behaviours is greater in populations with GI disorders than in populations of healthy controls. Disordered eating patterns in dietary-controlled GI disorders may be associated with both anxiety and GI symptoms. Evidence concerning the correlates of disordered eating was limited. The presence of disordered eating behaviours is greater in populations with GI disorders than in populations of healthy controls, but the direction of the relationship is not clear. Implications for further research are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Prenatal irradiation and developmental disorders of the brain

    International Nuclear Information System (INIS)

    Kameyama, Yoshiro

    1987-01-01

    The radiation sensitivity of the brain of a growing fetus is higher than that of other organs and tissues. Of the various organs in the human body, the brain has the most complicated structure. The major features of developmental disorders of the brain, which are produced rather easily by external causes, are: (a) the sensitive period for developmental disorders is long, (b) undifferentiated nerve cells are sensitive to external causes and (c) such disorders leads to irreversible functional failures after birth. The malformation of the brain and its relations with the sensitivity are briefly described. Experiments with prenatal animals have shown that major developmental disorders of brain tissue include death of undifferentiated cells, lack of constituent neurons and disturbance in structure of the cortex, and that typical developmental abnormalities include dysgenetic hydrocephaly, microcephalia, etc. Teratological features of histogenetic disorders of the brain are then briefly outlined. Various experimental results on these and other disorders caused by radiations are presented and discussed. Data on fetuses exposed to radiations at Hiroshima and Nagasaki are also given and discussed. The last section of the report deals with risk evaluation. (Nogami, K.)

  9. The neurobiological basis of binge-eating disorder.

    Science.gov (United States)

    Kessler, Robert M; Hutson, Peter H; Herman, Barry K; Potenza, Marc N

    2016-04-01

    Relatively little is known about the neuropathophysiology of binge-eating disorder (BED). Here, the evidence from neuroimaging, neurocognitive, genetics, and animal studies are reviewed to synthesize our current understanding of the pathophysiology of BED. Binge-eating disorder may be conceptualized as an impulsive/compulsive disorder, with altered reward sensitivity and food-related attentional biases. Neuroimaging studies suggest there are corticostriatal circuitry alterations in BED similar to those observed in substance abuse, including altered function of prefrontal, insular, and orbitofrontal cortices and the striatum. Human genetics and animal studies suggest that there are changes in neurotransmitter networks, including dopaminergic and opioidergic systems, associated with binge-eating behaviors. Overall, the current evidence suggests that BED may be related to maladaptation of the corticostriatal circuitry regulating motivation and impulse control similar to that found in other impulsive/compulsive disorders. Further studies are needed to understand the genetics of BED and how neurotransmitter activity and neurocircuitry function are altered in BED and how pharmacotherapies may influence these systems to reduce BED symptoms. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. GAD2 Alternative Transcripts in the Human Prefrontal Cortex, and in Schizophrenia and Affective Disorders.

    Directory of Open Access Journals (Sweden)

    Kasey N Davis

    Full Text Available Genetic variation and early adverse environmental events work together to increase risk for schizophrenia. γ-aminobutyric acid (GABA, the major inhibitory neurotransmitter in adult mammalian brain, plays a major role in normal brain development, and has been strongly implicated in the pathobiology of schizophrenia. GABA synthesis is controlled by two glutamic acid decarboxylase (GAD genes, GAD1 and GAD2, both of which produce a number of alternative transcripts. Genetic variants in the GAD1 gene are associated with increased risk for schizophrenia, and reduced expression of its major transcript in the human dorsolateral prefrontal cortex (DLPFC. No consistent changes in GAD2 expression have been found in brains from patients with schizophrenia. In this work, with the use of RNA sequencing and PCR technologies, we confirmed and tracked the expression of an alternative truncated transcript of GAD2 (ENST00000428517 in human control DLPFC homogenates across lifespan besides the well-known full length transcript of GAD2. In addition, using quantitative RT-PCR, expression of GAD2 full length and truncated transcripts were measured in the DLPFC of patients with schizophrenia, bipolar disorder and major depression. The expression of GAD2 full length transcript is decreased in the DLPFC of schizophrenia and bipolar disorder patients, while GAD2 truncated transcript is increased in bipolar disorder patients but decreased in schizophrenia patients. Moreover, the patients with schizophrenia with completed suicide or positive nicotine exposure showed significantly higher expression of GAD2 full length transcript. Alternative transcripts of GAD2 may be important in the growth and development of GABA-synthesizing neurons as well as abnormal GABA signaling in the DLPFC of patients with schizophrenia and affective disorders.

  11. Introducing directly induced microglia-like (iMG cells from fresh human monocytes: A novel translational research tool for psychiatric disorders.

    Directory of Open Access Journals (Sweden)

    Masahiro eOhgidani

    2015-05-01

    Full Text Available Microglia, glial cells with immunological functions, have been implicated in various neurological diseases and psychiatric disorders in rodent studies, and human postmortem and PET studies. However, the deeper molecular implications of living human microglia have not been clarified.Here, we introduce a novel translational research approach focusing on human microglia. We have recently developed a new technique for creating induced microglia-like (iMG cells from human peripheral blood. Two cytokines, GM-CSF and IL-34, converted human monocytes into the iMG cells within 14 days, which show various microglial characterizations; expressing markers, forming a ramified morphology, and phagocytic activity with various cytokine releases. We have already confirmed the applicability of this technique by analyzing iMG cells from a patient of Nasu-Hakola disease (Ohgidani et al., Sci Rep 2014. We herein show possible applications of the iMG cells in translational research.We believe that this iMG technique will open the door to explore various unknown dynamic aspects of human microglia in psychiatric disorders. This also opens new routes for psychopharmacological approach such as drug efficacy screening and personalized medicine.

  12. Mapping pathological phenotypes in a mouse model of CDKL5 disorder.

    Directory of Open Access Journals (Sweden)

    Elena Amendola

    Full Text Available Mutations in cyclin-dependent kinase-like 5 (CDKL5 cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG responses to convulsant treatment, decreased visual evoked responses (VEPs, and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder.

  13. Mapping pathological phenotypes in a mouse model of CDKL5 disorder.

    Science.gov (United States)

    Amendola, Elena; Zhan, Yang; Mattucci, Camilla; Castroflorio, Enrico; Calcagno, Eleonora; Fuchs, Claudia; Lonetti, Giuseppina; Silingardi, Davide; Vyssotski, Alexei L; Farley, Dominika; Ciani, Elisabetta; Pizzorusso, Tommaso; Giustetto, Maurizio; Gross, Cornelius T

    2014-01-01

    Mutations in cyclin-dependent kinase-like 5 (CDKL5) cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG) responses to convulsant treatment, decreased visual evoked responses (VEPs), and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder.

  14. The continuum between Bipolar Disorder and Borderline Personality Disorder.

    Science.gov (United States)

    Elisei, Sandro; Anastasi, Serena; Verdolini, Norma

    2012-09-01

    Several studies have been carried out regarding the possible overlap between Bipolar Disorder and borderline personality disorder. Up to now, it is not possible to provide a definitive picture. In fact, there is currently significant debate about the relationship between Borderline Personality Disorder and Bipolar Disorder. MEDLINE searches were performed to identify the latest studies of these disorders, considering psychodynamic aspects. Bipolar disorder and borderline personality disorder share common clinical features, namely affective instability and impulsivity which however differ in quality. Consequently, to better understand these aspects, it is necessary to trace the stages of childhood psychological development. It has been claimed that Bipolar Disorder Type II can be divided into two subtypes: one stable and functional between episodes and one unstable between episodes which is related to Borderline Personality Disorder. However, better diagnostic theories, psychiatrist's empathy and patience remain the essential tool to understand and to face human suffering.

  15. Tremor cells in the human thalamus: differences among neurological disorders.

    Science.gov (United States)

    Brodkey, Jason A; Tasker, Ronald R; Hamani, Clement; McAndrews, Mary Pat; Dostrovsky, Jonathan O; Lozano, Andres M

    2004-07-01

    Thalamic neurons firing at frequencies synchronous with tremor are thought to play a critical role in the generation and maintenance of tremor. The authors studied the incidence and locations of neurons with tremor-related activity (TRA) in the thalamus of patients with varied pathological conditions-including Parkinson disease (PD), essential tremor (ET), multiple sclerosis (MS), and cerebellar disorders--to determine whether known differences in the effectiveness of thalamic stereotactic procedures for these tremors could be correlated to differences in the incidence or locations of TRA cells. Seventy-five operations were performed in 61 patients during which 686 TRA cells were recorded from 440 microelectrode trajectories in the thalamus. The locations of the TRA cells in relation to electrophysiologically defined thalamic nuclei and the commissural coordinates were compared among patient groups. The authors found that TRA cells are present in patients with each of these disorders and that these cells populate several nuclei in the ventral lateral tier of the thalamus. There were no large differences in the locations of TRA cells among the different diagnostic classes, although there was a difference in the incidence of TRA cells in patients with PD, who had greater than 3.8 times more cells per thalamic trajectory than patients with ET and approximately five times more cells than patients with MS or cerebellar disorders. There was an increased incidence of TRA in the thalamus of patients with PD. The location of thalamic TRA cells in patients with basal ganglia and other tremor disorders was similar.

  16. Developmental trauma disorder: pros and cons of including formal criteria in the psychiatric diagnostic systems

    Directory of Open Access Journals (Sweden)

    Schmid Marc

    2013-01-01

    Full Text Available Abstract Background This article reviews the current debate on developmental trauma disorder (DTD with respect to formalizing its diagnostic criteria. Victims of abuse, neglect, and maltreatment in childhood often develop a wide range of age-dependent psychopathologies with various mental comorbidities. The supporters of a formal DTD diagnosis argue that post-traumatic stress disorder (PTSD does not cover all consequences of severe and complex traumatization in childhood. Discussion Traumatized individuals are difficult to treat, but clinical experience has shown that they tend to benefit from specific trauma therapy. A main argument against inclusion of formal DTD criteria into existing diagnostic systems is that emphasis on the etiology of the disorder might force current diagnostic systems to deviate from their purely descriptive nature. Furthermore, comorbidities and biological aspects of the disorder may be underdiagnosed using the DTD criteria. Summary Here, we discuss arguments for and against the proposal of DTD criteria and address implications and consequences for the clinical practice.

  17. Genetic factors associated with small for gestational age birth and the use of human growth hormone in treating the disorder

    Directory of Open Access Journals (Sweden)

    Saenger Paul

    2012-05-01

    Full Text Available Abstract The term small for gestational age (SGA refers to infants whose birth weights and/or lengths are at least two standard deviation (SD units less than the mean for gestational age. This condition affects approximately 3%–10% of newborns. Causes for SGA birth include environmental factors, placental factors such as abnormal uteroplacental blood flow, and inherited genetic mutations. In the past two decades, an enhanced understanding of genetics has identified several potential causes for SGA. These include mutations that affect the growth hormone (GH/insulin-like growth factor (IGF-1 axis, including mutations in the IGF-1 gene and acid-labile subunit (ALS deficiency. In addition, select polymorphisms observed in patients with SGA include those involved in genes associated with obesity, type 2 diabetes, hypertension, ischemic heart disease and deletion of exon 3 growth hormone receptor (d3-GHR polymorphism. Uniparental disomy (UPD and imprinting effects may also underlie some of the phenotypes observed in SGA individuals. The variety of genetic mutations associated with SGA births helps explain the diversity of phenotype characteristics, such as impaired motor or mental development, present in individuals with this disorder. Predicting the effectiveness of recombinant human GH (hGH therapy for each type of mutation remains challenging. Factors affecting response to hGH therapy include the dose and method of hGH administration as well as the age of initiation of hGH therapy. This article reviews the results of these studies and summarizes the success of hGH therapy in treating this difficult and genetically heterogenous disorder.

  18. A rat model of post-traumatic stress disorder reproduces the hippocampal deficits seen in the human syndrome

    OpenAIRE

    Goswami, Sonal; Samuel, Sherin; Sierra, Olga R.; Cascardi, Michele; Paré, Denis

    2012-01-01

    Despite recent progress, the causes and pathophysiology of post-traumatic stress disorder (PTSD) remain poorly understood, partly because of ethical limitations inherent to human studies. One approach to circumvent this obstacle is to study PTSD in a valid animal model of the human syndrome. In one such model, extreme and long-lasting behavioral manifestations of anxiety develop in a subset of Lewis rats after exposure to an intense predatory threat that mimics the type of life-and-death situ...

  19. Annual Research Review: Hoarding Disorder-- Potential Benefits and Pitfalls of a New Mental Disorder

    Science.gov (United States)

    Mataix-Cols, David; Pertusa, Alberto

    2012-01-01

    Background: The inclusion of a new mental disorder in the nomenclature is not a trivial matter. Many have highlighted the risks of an ever-increasing number of mental disorders and of overpathologizing human behaviour. Given the proposed inclusion of a new hoarding disorder (HD) in DSM-5 (Diagnostic and Statistical Manual of Mental Disorders,…

  20. A new web-based data mining tool for the identification of candidate genes for human genetic disorders

    NARCIS (Netherlands)

    Driel, van M.A.; Cuelenaere, K.; Kemmeren, P.P.C.W.; Leunissen, J.A.M.; Brunner, H.G.

    2003-01-01

    To identify the gene underlying a human genetic disorder can be difficult and time-consuming. Typically, positional data delimit a chromosomal region that contains between 20 and 200 genes. The choice then lies between sequencing large numbers of genes, or setting priorities by combining positional

  1. From an animal model to human patients: An example of a translational study on obsessive compulsive disorder (OCD).

    Science.gov (United States)

    Eilam, David

    2017-05-01

    The application of similar analyses enables a direct projection from translational research in animals to human studies. Following is an example of how the methodology of a specific animal model of obsessive-compulsive disorder (OCD) was applied to study human patients. Specifically, the quinpirole rat model for OCD was based on analyzing the trajectories of travel among different locales, and scoring the set of acts performed at each locale. Applying this analytic approach in human patients unveiled various aspects of OCD, such as the repetition and addition of acts, incompleteness, and the link between behavior and specific locations. It is also illustrated how the same analytical approach could be applicable to studying other mental disorders. Finally, it is suggested that the development of OCD could be explained by the four-phase sequence of Repetition, Addition, Condensation, and Elimination, as outlined in the study of ontogeny and phylogeny and applied to normal development of behavior. In OCD, this sequence is curtailed, resulting in the abundant repetition and addition of acts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Immunologic Endocrine Disorders

    Science.gov (United States)

    Michels, Aaron W.; Eisenbarth, George S.

    2010-01-01

    Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA (human leukocyte antigen)-like molecules determining tissue specific targeting that with the loss of tolerance leads to organ specific autoimmunity. Disorders such as type 1A diabetes, Grave's disease, Hashimoto's thyroiditis, Addison's disease, and many others result from autoimmune mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. While therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies. PMID:20176260

  3. Abnormal Uterine Bleeding including coagulopathies and other menstrual disorders.

    Science.gov (United States)

    Deligeoroglou, Efthimios; Karountzos, Vasileios

    2018-04-01

    Abnormal Uterine Bleeding (AUB) is a frequent cause of visits to the emergency department and a major reason for concern among adolescents and their families. The most common cause of AUB, in otherwise healthy adolescents, is ovulatory dysfunction, although 5-36% of adolescents who present with heavy menstrual bleeding, have an underlying bleeding disorder (BD). The most common form of BDs is von Willebrand Disease, reflecting 13% of adolescents with AUB. Management of AUB depends on the underlying etiology, the bleeding severity, as well as the need for hospitalization. Treatment of adolescents with an underlying coagulopathy depends on the severity of the BD, while therapeutic interventions are summarized in supportive measures, hormonal treatments (e.g. Combined Oral Contraceptives), non-hormonal treatments (e.g. tranexamic acid and desmopressin), surgical options (e.g. dilatation & curettage) and treatment options in specific conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. The Endocannabinoid System, Aggression, and the Violence of Synthetic Cannabinoid Use, Borderline Personality Disorder, Antisocial Personality Disorder, and Other Psychiatric Disorders.

    Science.gov (United States)

    Kolla, Nathan J; Mishra, Achal

    2018-01-01

    Endogenous and exogenous cannabinoids bind to central cannabinoid receptors to control a multitude of behavioral functions, including aggression. The first main objective of this review is to dissect components of the endocannabinoid system, including cannabinoid 1 and cannabinoid 2 receptors; the endogenous cannabinoids anandamide and 2-arachidonoylglycerol; and the indirect cannabinoid modulators fatty acid amide hydrolase and monoacylglycerol lipase; that have shown abnormalities in basic research studies investigating mechanisms of aggression. While most human research has concluded that the active ingredient of marijuana, Δ9-tetrahydrocannabinol, tends to dampen rather than provoke aggression in acute doses, recent evidence supports a relationship between the ingestion of synthetic cannabinoids and emergence of violent or aggressive behavior. Thus, another objective is to evaluate the emerging clinical data. This paper also discusses the relationship between prenatal and perinatal exposure to cannabis as well as use of cannabis in adolescence on aggressive outcomes. A final objective of the paper is to discuss endocannabinoid abnormalities in psychotic and affective disorders, as well as clinically aggressive populations, such as borderline personality disorder and antisocial personality disorder. With regard to the former condition, decreased anandamide metabolites have been reported in the cerebrospinal fluid, while some preliminary evidence suggests that fatty acid amide hydrolase genetic polymorphisms are linked to antisocial personality disorder and impulsive-antisocial psychopathic traits. To summarize, this paper will draw upon basic and clinical research to explain how the endocannabinoid system may contribute to the genesis of aggressive behavior.

  5. The Endocannabinoid System, Aggression, and the Violence of Synthetic Cannabinoid Use, Borderline Personality Disorder, Antisocial Personality Disorder, and Other Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Nathan J. Kolla

    2018-03-01

    Full Text Available Endogenous and exogenous cannabinoids bind to central cannabinoid receptors to control a multitude of behavioral functions, including aggression. The first main objective of this review is to dissect components of the endocannabinoid system, including cannabinoid 1 and cannabinoid 2 receptors; the endogenous cannabinoids anandamide and 2-arachidonoylglycerol; and the indirect cannabinoid modulators fatty acid amide hydrolase and monoacylglycerol lipase; that have shown abnormalities in basic research studies investigating mechanisms of aggression. While most human research has concluded that the active ingredient of marijuana, Δ9-tetrahydrocannabinol, tends to dampen rather than provoke aggression in acute doses, recent evidence supports a relationship between the ingestion of synthetic cannabinoids and emergence of violent or aggressive behavior. Thus, another objective is to evaluate the emerging clinical data. This paper also discusses the relationship between prenatal and perinatal exposure to cannabis as well as use of cannabis in adolescence on aggressive outcomes. A final objective of the paper is to discuss endocannabinoid abnormalities in psychotic and affective disorders, as well as clinically aggressive populations, such as borderline personality disorder and antisocial personality disorder. With regard to the former condition, decreased anandamide metabolites have been reported in the cerebrospinal fluid, while some preliminary evidence suggests that fatty acid amide hydrolase genetic polymorphisms are linked to antisocial personality disorder and impulsive-antisocial psychopathic traits. To summarize, this paper will draw upon basic and clinical research to explain how the endocannabinoid system may contribute to the genesis of aggressive behavior.

  6. A neuroscientific account of how vestibular disorders impair bodily self-consciousness

    Directory of Open Access Journals (Sweden)

    Christophe eLopez

    2013-12-01

    Full Text Available The consequences of vestibular disorders on balance, oculomotor control and self-motion perception have been extensively described in humans and animals. More recently, vestibular disorders have been related to cognitive deficits in spatial navigation and memory tasks. Less frequently, abnormal bodily perceptions have been described in patients with vestibular disorders. Altered forms of bodily self-consciousness include distorted body image and body schema, disembodied self-location (out-of-body experience, altered sense of agency, as well as more complex experiences of dissociation and detachment from the self (depersonalization. In this article, I suggest that vestibular disorders create sensory conflict or mismatch in multisensory brain regions, producing perceptual incoherence and abnormal body and self perceptions. This hypothesis is based on recent functional mapping of the human vestibular cortex, showing vestibular projections to the primary and secondary somatosensory cortex and in several multisensory areas found to be crucial for bodily self-consciousness.

  7. Of mice and monkeys: using non-human primate models to bridge mouse- and human-based investigations of autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Watson Karli K

    2012-07-01

    Full Text Available Abstract The autism spectrum disorders (ASDs arise from a diverse array of genetic and environmental origins that disrupt the typical developmental trajectory of neural connectivity and synaptogenesis. ASDs are marked by dysfunctional social behavior and cognition, among other deficits. Greater understanding of the biological substrates of typical social behavior in animal models will further our understanding of the etiology of ASDs. Despite the precision and tractability of molecular genetics models of ASDs in rodents, these organisms lack the complexity of human social behavior, thus limiting their impact on understanding ASDs to basic mechanisms. Non-human primates (NHPs provide an attractive, complementary model for ASDs, due in part to the complexity and dynamics of social structures, reliance on vision for social signaling, and deep homology in brain circuitry mediating social behavior and reward. This knowledge is based on a rich literature, compiled over 50 years of observing primate behavior in the wild, which, in the case of rhesus macaques, is complemented by a large body of research characterizing neuronal activity during cognitive behavior. Several recent developments in this field are directly relevant to ASDs, including how the brain represents the perceptual features of social stimuli, how social information influences attention processes in the brain, and how the value of social interaction is computed. Because the symptoms of ASDs may represent extreme manifestations of traits that vary in intensity within the general population, we will additionally discuss ways in which nonhuman primates also show variation in social behavior and reward sensitivity. In cases where variation in species-typical behavior is analogous to similar variations in human behavior, we believe that study of the neural circuitry underlying this variation will provide important insights into the systems-level mechanisms contributing to ASD pathology.

  8. Trichotillomania (hair pulling disorder), skin picking disorder, and stereotypic movement disorder: toward DSM-V.

    Science.gov (United States)

    Stein, Dan J; Grant, Jon E; Franklin, Martin E; Keuthen, Nancy; Lochner, Christine; Singer, Harvey S; Woods, Douglas W

    2010-06-01

    In DSM-IV-TR, trichotillomania (TTM) is classified as an impulse control disorder (not classified elsewhere), skin picking lacks its own diagnostic category (but might be diagnosed as an impulse control disorder not otherwise specified), and stereotypic movement disorder is classified as a disorder usually first diagnosed in infancy, childhood, or adolescence. ICD-10 classifies TTM as a habit and impulse disorder, and includes stereotyped movement disorders in a section on other behavioral and emotional disorders with onset usually occurring in childhood and adolescence. This article provides a focused review of nosological issues relevant to DSM-V, given recent empirical findings. This review presents a number of options and preliminary recommendations to be considered for DSM-V: (1) Although TTM fits optimally into a category of body-focused repetitive behavioral disorders, in a nosology comprised of relatively few major categories it fits best within a category of motoric obsessive-compulsive spectrum disorders, (2) available evidence does not support continuing to include (current) diagnostic criteria B and C for TTM in DSM-V, (3) the text for TTM should be updated to describe subtypes and forms of hair pulling, (4) there are persuasive reasons for referring to TTM as "hair pulling disorder (trichotillomania)," (5) diagnostic criteria for skin picking disorder should be included in DSM-V or in DSM-Vs Appendix of Criteria Sets Provided for Further Study, and (6) the diagnostic criteria for stereotypic movement disorder should be clarified and simplified, bringing them in line with those for hair pulling and skin picking disorder. (c) 2010 Wiley-Liss, Inc.

  9. The genus Malassezia and human disease

    Directory of Open Access Journals (Sweden)

    Inamadar A

    2003-07-01

    Full Text Available Sabouraud's Pityrosporum is now recognized as Malassezia. With taxonomic revision of the genus, newer species have been included. The role of this member of the normal human skin flora in different cutaneous and systemic disorders is becoming clearer. The immunological responses it induces in the human body are conflicting and their relevance to clinical features is yet to be explored.

  10. Comorbid personality disorders in subjects with panic disorder: which personality disorders increase clinical severity?

    OpenAIRE

    Mustafa Ozkan; Abdurrahman Altindag

    2003-01-01

    Personality disorders are common in subjects with panic disorder. Personality disorders have shown to affect the course of panic disorder. The purpose of this study was to examine which personality disorders effect clinical severity in subjects with panic disorder. This study included 122 adults (71 female, 41 male), who met DSM-IV criteria for panic disorder (with or without agoraphobia). Clinical assessment was conducted by using the Structured Clinical Interview for DSM-IV Axis I Disorders...

  11. Psilocybin for treating substance use disorders?

    OpenAIRE

    Veen, B.T. de; Schellekens, A.F.A.; Verheij, M.M.M.; Homberg, J.R.

    2017-01-01

    INTRODUCTION: Evidence based treatment for Substance use disorders (SUD) includes psychotherapy and pharmacotherapy. However, these are only partially effective. Hallucinogens, such as psilocybin, may represent potential new treatment options for SUD. This review provides a summary of (human) studies on the putative therapeutic effects of psilocybin, and discusses the receptor systems, brain regions and cognitive and emotional processes mediating psilocybin's effects. Psilocybin's chemical st...

  12. Skeletal Muscle Na+ Channel Disorders

    Directory of Open Access Journals (Sweden)

    Dina eSimkin

    2011-10-01

    Full Text Available Five inherited human disorders affecting skeletal muscle contraction have been traced to mutations in the gene encoding the voltage-gated sodium channel Nav1.4. The main symptoms of these disorders are myotonia or periodic paralysis caused by changes in skeletal muscle fiber excitability. Symptoms of these disorders vary from mild or latent disease to incapacitating or even death in severe cases. As new human sodium channel mutations corresponding to disease states become discovered, the importance of understanding the role of the sodium channel in skeletal muscle function and disease state grows.

  13. Extracellular RNAs: development as biomarkers of human disease

    Directory of Open Access Journals (Sweden)

    Joseph F. Quinn

    2015-08-01

    Full Text Available Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.

  14. Comparing the results of DAADD and ABC of children included in autism spectrum disorders.

    Science.gov (United States)

    Barbosa, Milene Rossi Pereira; Fernandes, Fernanda Dreux Miranda

    2014-01-01

    To verify if there are characteristic behaviors of the different diagnosis included in the autism spectrum according to the Differential Assessment of Autism and Other Developmental Disorders (DAADD) and to the Autism Behavior Checklist (ABC). Participants were 45 individuals and their respective speech-language therapists. All therapists are graduate students working with the children for at least 1 year. This time was considered sufficient to the therapists to have the information required by the DAADD questionnaire. It is comprised by 3 protocols specifically designed to children with 2 to 4 years, 4 to 6 years and 6 to 8 years, the same criteria used to separate the research groups, G1, G2 and G3, respectively. Data referring to the ABC were retrieved from the subject's files at the Laboratório de Investigação Fonoaudiológica nos Distúrbios do Espectro do Autismo (Research Laboratory on Language Disorders in the Autism Spectrum) of the School of Medicine, Universidade de São Paulo, where it is routinely applied during the annual assessment. Answers to the different areas of DAADD are similar to the different areas of ABC. These data show data the diagnosis by DAADD is easier in older children. Although there is no significant difference, the large occurrence of Rett's syndrome diagnosis according to the DAADD was associated to higher risk for autism according to the ABC in G1. With increasing age this tendency decreases and either in G2 and G3 Autism is the most frequent diagnosis. Although the results of both questionnaires tend to agree more with increasing age, the DAADD is more sensitive in the different ages while the ABC if more specific only to older children.

  15. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders.

    Science.gov (United States)

    Hamosh, Ada; Scott, Alan F; Amberger, Joanna S; Bocchini, Carol A; McKusick, Victor A

    2005-01-01

    Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support human genetics research and education and the practice of clinical genetics. Started by Dr Victor A. McKusick as the definitive reference Mendelian Inheritance in Man, OMIM (http://www.ncbi.nlm.nih.gov/omim/) is now distributed electronically by the National Center for Biotechnology Information, where it is integrated with the Entrez suite of databases. Derived from the biomedical literature, OMIM is written and edited at Johns Hopkins University with input from scientists and physicians around the world. Each OMIM entry has a full-text summary of a genetically determined phenotype and/or gene and has numerous links to other genetic databases such as DNA and protein sequence, PubMed references, general and locus-specific mutation databases, HUGO nomenclature, MapViewer, GeneTests, patient support groups and many others. OMIM is an easy and straightforward portal to the burgeoning information in human genetics.

  16. Disordering of human telomeric G-quadruplex with novel antiproliferative anthrathiophenedione.

    Directory of Open Access Journals (Sweden)

    Dmitry Kaluzhny

    Full Text Available Linear heteroareneanthracenediones have been shown to interfere with DNA functions, thereby causing death of human tumor cells and their drug resistant counterparts. Here we report the interaction of our novel antiproliferative agent 4,11-bis[(2-{[acetimido]amino}ethylamino]anthra[2,3-b]thiophene-5,10-dione with telomeric DNA structures studied by isothermal titration calorimetry, circular dichroism and UV absorption spectroscopy. New compound demonstrated a high affinity (K(ass∼10⁶ M⁻¹ for human telomeric antiparallel quadruplex d(TTAGGG₄ and duplex d(TTAGGG₄∶d(CCCTAA₄. Importantly, a ∼100-fold higher affinity was determined for the ligand binding to an unordered oligonucleotide d(TTAGGG TTAGAG TTAGGG TTAGGG unable to form quadruplex structures. Moreover, in the presence of Na+ the compound caused dramatic conformational perturbation of the telomeric G-quadruplex, namely, almost complete disordering of G-quartets. Disorganization of a portion of G-quartets in the presence of K+ was also detected. Molecular dynamics simulations were performed to illustrate how the binding of one molecule of the ligand might disrupt the G-quartet adjacent to the diagonal loop of telomeric G-quadruplex. Our results provide evidence for a non-trivial mode of alteration of G-quadruplex structure by tentative antiproliferative drugs.

  17. [Non-autistic pervasive developmental disorders: Rett syndrome, disintegrative disorder and pervasive developmental disorder not otherwise specified

    NARCIS (Netherlands)

    Mercadante, M.T.; Gaag, R.J. van der; Schwartzman, J.S.

    2006-01-01

    The category "Pervasive Developmental Disorders" includes autistic disorder, Asperger's syndrome, Rett's syndrome, childhood disintegrative disorder, and a residual category, named pervasive developmental disorder not otherwise specified. In this review, Rett's syndrome and childhood disintegrative

  18. Postmodern Stress Disorder (PMSD): A Possible New Disorder.

    Science.gov (United States)

    Eiser, Arnold R

    2015-11-01

    The murder of cardiovascular surgeon, Michael Davidson, MD, suggests the existence of a new disorder, postmodern stress disorder. This disorder is characterized by repetitive exposure to digital images of violence in a variety of electronic media, including films, television, video games, music videos, and other online sources. This disorder appears to be a variant of posttraumatic stress disorder, and shares with it excessive stimulation of the amygdala and loss of the normal inhibitory inputs from the orbitofrontal cingulate cortical gyrus. In postmodern stress disorder, repetitive digital microtraumas appear to have an effect similar to that of macrotraumas of warfare or civilian assaults. Other elements of the disorder include the development of fixed ideas of bullying or public shaming, access to weapons, and loss of impulse control. This syndrome could explain a number of previously inexplicable murders/suicides. Violence against health care professionals is a profound concern for the medical profession, as are assaults on nonclinicians. The recommendation is made to change forensic procedures to include obtaining historic information concerning the use of digital media during investigations of violent crimes and murders so that the disorder may be further characterized. Gaining an understanding of this disorder will require a multidisciplinary approach to this life-threatening public health problem. Research should also focus on the development and evaluation of possible antidotes to postmodern toxicities. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Binge Eating Disorder

    Directory of Open Access Journals (Sweden)

    Senol Turan

    2015-12-01

    Full Text Available Binge Eating Disorder, characterized by frequent and persistent overeating episodes that are accompanied by feeling of loss of control over eating without regular compensatory behaviors and was identified in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition as a new eating disorder category. Binge Eating Disorder is the most common eating disorder among adults. Binge Eating Disorder is associated with significant morbidity, including medical complications related to obesity, eating disorder psychopathology, psychiatric comorbidity; reduced quality of life, and impaired social functioning. Current treatments of Binge Eating Disorder include pharmacotherapy, psychotherapy and bariatric surgery. In this review, the definition, epidemiology, etiology, clinical features, and also mainly treatment of Binge Eating Disorder are discussed.

  20. Autism and Related Disorders

    Science.gov (United States)

    McPartland, James; Volkmar, Fred R.

    2012-01-01

    The Pervasive Developmental Disorders are a group of neurodevelopmental disorders that include Autistic Disorder, Asperger’s Disorder, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS), Childhood Disintegrative Disorder (CDD), and Rett’s Disorder. All feature childhood onset with a constellation of symptoms spanning social interaction and communication and including atypical behavior patterns. The first three disorders (Autistic Disorder, Asperger’s Disorder, and PDD-NOS) are currently referred to as Autism Spectrum Disorders, reflecting divergent phenotypic and etiologic characteristics compared to Rett’s Disorder and CDD. This chapter reviews relevant research and clinical information relevant to appropriate medical diagnosis and treatment. PMID:22608634

  1. Psilocybin for treating substance use disorders?

    Science.gov (United States)

    de Veen, Bas T H; Schellekens, Arnt F A; Verheij, Michel M M; Homberg, Judith R

    2017-02-01

    Evidence based treatment for Substance use disorders (SUD) includes psychotherapy and pharmacotherapy. However, these are only partially effective. Hallucinogens, such as psilocybin, may represent potential new treatment options for SUD. This review provides a summary of (human) studies on the putative therapeutic effects of psilocybin, and discusses the receptor systems, brain regions and cognitive and emotional processes mediating psilocybin's effects. Psilocybin's chemical structure is similar to that of serotonin. Dysregulations in the serotonin system are associated with alterations in stress hormones, such as cortisol, and mood disorders. After psilocybin administration cortisol levels spike and activate the executive control network, with subsequent increased control over emotional processes, and relief of negative thinking and persistent negative emotions. Preliminary data of ongoing alcohol and smoking addiction studies in humans shows promising effects of psilocybin administration on substance use. Importantly, psilocybin has a low risk of toxicity and dependence and can be used safely under controlled clinical conditions. Areas covered: This paper is a narrative review based on the search terms: psilocybin, substance use disorder, addiction, depression, serotonin. Literature on potential efficacy and mechanisms of action of psilocybin in SUD is discussed. Expert commentary: Recent positive findings with psilocybin need confirmation in well-designed placebo controlled randomized trials employing a large sample size.

  2. Genetic Aspects of Autism Spectrum Disorders: Insights from Animal Models

    Directory of Open Access Journals (Sweden)

    Swati eBanerjee

    2014-02-01

    Full Text Available Autism spectrum disorders (ASD are a complex neurodevelopmental disorder that display a triad of core behavioral deficits including restricted interests, often accompanied by repetitive behavior, deficits in language and communication, and an inability to engage in reciprocal social interactions. ASD is among the most heritable disorders but is not a simple disorder with a singular pathology and has a rather complex etiology. It is interesting to note that perturbations in synaptic growth, development and stability underlie a variety of neuropsychiatric disorders, including ASD, schizophrenia, epilepsy and intellectual disability. Biological characterization of an increasing repertoire of synaptic mutants in various model organisms indicates synaptic dysfunction as causal in the pathophysiology of ASD. Our understanding of the genes and genetic pathways that contribute towards the formation, stabilization and maintenance of functional synapses coupled with an in-depth phenotypic analysis of the cellular and behavioral characteristics is therefore essential to unraveling the pathogenesis of these disorders. In this review, we discuss the genetic aspects of ASD emphasizing on the well conserved set of genes and genetic pathways implicated in this disorder, many of which contribute to synapse assembly and maintenance across species. We also review how fundamental research using animal models is providing key insights into the various facets of human ASD.

  3. Influence of interface-included disorder on classical quantum conductivity of CdTe:In epitaxial layers

    International Nuclear Information System (INIS)

    Lusakowski, J.; Karpierz, K.; Grynberg, M.; Karczewski, G.; Wojtowicz, T.; Contreras, S.; Callen, O.

    1997-01-01

    An influence of disorder originated from the substrate/layer interface on electrical properties of CdTe:In layers was investigated by means of the Hall effect and magnetoresistance measurements at low temperatures. An estimation of a scattering rate due to interface induced disorder is given. Characteristic features of a magnetic field dependence of magnetoresistance are explained by an influence of quantum interference of scattered electron waves both in the hopping and the free electron conductivity regimes. (author)

  4. Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans

    Science.gov (United States)

    Lile, Joshua A.; Stoops, William W.; Rush, Craig R.; Negus, S. Stevens; Glaser, Paul E. A.; Hatton, Kevin W.; Hays, Lon R.

    2016-01-01

    Background A medication for treating cocaine use disorder has yet to be approved. Laboratory-based evaluation of candidate medications in animals and humans is a valuable means to demonstrate safety, tolerability and initial efficacy of potential medications. However, animal-to-human translation has been hampered by a lack of coordination. Therefore, we designed homologous cocaine self-administration studies in rhesus monkeys (see companion article) and human subjects in an attempt to develop linked, functionally equivalent procedures for research on candidate medications for cocaine use disorder. Methods Eight (N=8) subjects with cocaine use disorder completed 12 experimental sessions in which they responded to receive money ($0.01, $1.00 and $3.00) or intravenous cocaine (0, 3, 10 and 30 mg/70 kg) under independent, concurrent progressive-ratio schedules. Prior to the completion of 9 choice trials, subjects sampled the cocaine dose available during that session and were informed of the monetary alternative value. Results The allocation of behavior varied systematically as a function of cocaine dose and money value. Moreover, a similar pattern of cocaine choice was demonstrated in rhesus monkeys and humans across different cocaine doses and magnitudes of the species-specific alternative reinforcers. The subjective and cardiovascular responses to IV cocaine were an orderly function of dose, although heart rate and blood pressure remained within safe limits. Conclusions These coordinated studies successfully established drug vs. non-drug choice procedures in humans and rhesus monkeys that yielded similar cocaine choice behavior across species. This translational research platform will be used in future research to enhance the efficiency of developing interventions to reduce cocaine use. PMID:27269368

  5. Human movement stochastic variability leads to diagnostic biomarkers In Autism Spectrum Disorders (ASD)

    Science.gov (United States)

    Wu, Di; Torres, Elizabeth B.; Jose, Jorge V.

    2015-03-01

    ASD is a spectrum of neurodevelopmental disorders. The high heterogeneity of the symptoms associated with the disorder impedes efficient diagnoses based on human observations. Recent advances with high-resolution MEM wearable sensors enable accurate movement measurements that may escape the naked eye. It calls for objective metrics to extract physiological relevant information from the rapidly accumulating data. In this talk we'll discuss the statistical analysis of movement data continuously collected with high-resolution sensors at 240Hz. We calculated statistical properties of speed fluctuations within the millisecond time range that closely correlate with the subjects' cognitive abilities. We computed the periodicity and synchronicity of the speed fluctuations' from their power spectrum and ensemble averaged two-point cross-correlation function. We built a two-parameter phase space from the temporal statistical analyses of the nearest neighbor fluctuations that provided a quantitative biomarker for ASD and adult normal subjects and further classified ASD severity. We also found age related developmental statistical signatures and potential ASD parental links in our movement dynamical studies. Our results may have direct clinical applications.

  6. High-Frequency EEG Variations in Children with Autism Spectrum Disorder during Human Faces Visualization

    Directory of Open Access Journals (Sweden)

    Celina A. Reis Paula

    2017-01-01

    Full Text Available Autism spectrum disorder (ASD is a neuropsychiatric disorder characterized by the impairment in the social reciprocity, interaction/language, and behavior, with stereotypes and signs of sensory function deficits. Electroencephalography (EEG is a well-established and noninvasive tool for neurophysiological characterization and monitoring of the brain electrical activity, able to identify abnormalities related to frequency range, connectivity, and lateralization of brain functions. This research aims to evidence quantitative differences in the frequency spectrum pattern between EEG signals of children with and without ASD during visualization of human faces in three different expressions: neutral, happy, and angry. Quantitative clinical evaluations, neuropsychological evaluation, and EEG of children with and without ASD were analyzed paired by age and gender. The results showed stronger activation in higher frequencies (above 30 Hz in frontal, central, parietal, and occipital regions in the ASD group. This pattern of activation may correlate with developmental characteristics in the children with ASD.

  7. Chronobiology and Mood Disorders

    Directory of Open Access Journals (Sweden)

    Yavuz Selvi

    2011-09-01

    Full Text Available Living organizms show cyclic rhythmicity in a variety of physiological, hormonal, behavioral, and psychological processes. Sleep-wake cycles, body temperature, hormone levels, mood and cognition display a circadian rhythm in humans. Delays, advances or desynchronizations of circadian rhythm are known to be strongly associated with mental illness especially mood disorders such as bipolar disorder, major depression and seasonal affective disorder. Furthermore, some of the mood stabilizers, sleep deprivation and light treatment are employed to treat mood disorders by shifting circadian rhythm. This paper reviews the relationship between mood disorders and circadian rhythm, and describes treatment options by altering circadian rhythm.

  8. Histaminergic system in brain disorders: lessons from the translational approach and future perspectives.

    Science.gov (United States)

    Baronio, Diego; Gonchoroski, Taylor; Castro, Kamila; Zanatta, Geancarlo; Gottfried, Carmem; Riesgo, Rudimar

    2014-01-01

    Histamine and its receptors were first described as part of immune and gastrointestinal systems, but their presence in the central nervous system and importance in behavior are gaining more attention. The histaminergic system modulates different processes including wakefulness, feeding, and learning and memory consolidation. Histamine receptors (H1R, H2R, H3R, and H4R) belong to the rhodopsin-like family of G protein-coupled receptors, present constitutive activity, and are subjected to inverse agonist action. The involvement of the histaminergic system in brain disorders, such as Alzheimer's disease, schizophrenia, sleep disorders, drug dependence, and Parkinson's disease, is largely studied. Data obtained from preclinical studies point antagonists of histamine receptors as promising alternatives to treat brain disorders. Thus, clinical trials are currently ongoing to assess the effects of these drugs on humans. This review summarizes the role of histaminergic system in brain disorders, as well as the effects of different histamine antagonists on animal models and humans.

  9. Generalised anxiety disorder

    OpenAIRE

    Gale, Christopher K; Millichamp, Jane

    2011-01-01

    Generalised anxiety disorder is characterised by persistent, excessive and difficult-to-control worry, which may be accompanied by several psychic and somatic symptoms, including suicidality. Generalized anxiety disorder is the most common psychiatric disorder in the primary care, although it is often underrecognised and undertreated. Generalized anxiety disorder is typically a chronic condition with low short- and medium-term remission rates. Clinical presentations often include depression, ...

  10. Cannabis Use Disorders and Altered Brain Morphology : Where is the evidence?

    NARCIS (Netherlands)

    Lorenzetti, V; Batalla, A.; Cousijn, J.

    2016-01-01

    Cannabis use disorders (CUDs) affect 13.1 million individuals worldwide. Brain morphology specific to CUDs may mediate the adverse behavioral outcomes of CUDs. We reviewed findings from 20 human neuroimaging studies on grey and white matter morphology in cannabis users that specifically included CUD

  11. Translating cognition from animals to humans.

    Science.gov (United States)

    Keeler, J F; Robbins, T W

    2011-06-15

    Many clinical disorders, whether neurological (e.g. Alzheimer's disease) or neuropsychiatric (e.g. schizophrenia and depression), exhibit cognitive symptoms that require pharmacological treatment. Cognition is multi-faceted and includes processes of perception, attention, working memory, long-term memory, executive function, language and social cognition. This article reviews how it is feasible to model many aspects of human cognition with the use of appropriate animal models and associated techniques, including the use of computer controlled tests (e.g. touch-screens), for optimising translation of experimental research to the clinic. When investigating clinical disorders, test batteries should aim to profile cognitive function in order to determine which aspects are impaired and which are preserved. In this review we have paid particular attention to the validation of translational methods; this may be done through the application of common theoretical principles, by comparing the effects of psychological manipulations and, wherever feasible, with the demonstration of homologous neural circuitry or equivalent pharmacological actions in the animal and human paradigms. Of particular importance is the use of 'back-translation' to ensure that the animal model has validity, for example, in predicting the effects of therapeutic drugs already found in human studies. It is made clear that the choice of appropriate behavioral tests is an important element of animal models of neuropsychiatric or neurological disorder; however, of course it is also important to select appropriate manipulations, whether genetic, neurodevelopmental, neurotoxic, or pharmacological, for simulating the neural substrates relevant to the disorders that lead to predictable behavioral and cognitive impairments, for optimising the testing of candidate compounds. 2011 Elsevier Inc. All rights reserved.

  12. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder

    Science.gov (United States)

    Dalby, Matthew J.; Gadegaard, Nikolaj; Tare, Rahul; Andar, Abhay; Riehle, Mathis O.; Herzyk, Pawel; Wilkinson, Chris D. W.; Oreffo, Richard O. C.

    2007-12-01

    A key tenet of bone tissue engineering is the development of scaffold materials that can stimulate stem cell differentiation in the absence of chemical treatment to become osteoblasts without compromising material properties. At present, conventional implant materials fail owing to encapsulation by soft tissue, rather than direct bone bonding. Here, we demonstrate the use of nanoscale disorder to stimulate human mesenchymal stem cells (MSCs) to produce bone mineral in vitro, in the absence of osteogenic supplements. This approach has similar efficiency to that of cells cultured with osteogenic media. In addition, the current studies show that topographically treated MSCs have a distinct differentiation profile compared with those treated with osteogenic media, which has implications for cell therapies.

  13. Transcranial magnetic stimulation provides means to assess cortical plasticity and excitability in humans with fragile X syndrome and autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Lindsay M Oberman

    2010-06-01

    Full Text Available Fragile X Syndrome (FXS is the most common heritable cause of intellectual disability. In vitro electrophysiologic data from mouse models of FXS suggest that loss of Fragile X Mental Retardation Protein (FMRP affects intracortical excitability and synaptic plasticity. Specifically, the cortex appears hyperexcitable, and use-dependent long-term potentiation (LTP and long-term depression (LTD of synaptic strength are abnormal. Though animal models provide important information, FXS and other neurodevelopmental disorders are human diseases and as such translational research to evaluate cortical excitability and plasticity must be applied in the human. Transcranial magnetic stimulation (TMS paradigms have recently been developed to noninvasively investigate cortical excitability using paired-pulse stimulation, as well as LTP- and LTD-like synaptic plasticity in response to theta burst stimulation (TBS in vivo in the human. TBS applied on consecutive days can be used to measure metaplasticity (the ability of the synapse to undergo a second plastic change following a recent induction of plasticity. The current study investigated intracortical inhibition, plasticity and metaplasticity in full mutation females with FXS, participants with autism spectrum disorders (ASD, and neurotypical controls. Results suggest that intracortical inhibition is normal in participants with FXS, while plasticity and metaplasticity appear abnormal. ASD participants showed abnormalities in plasticity and metaplasticity, as well as heterogeneity in intracortical inhibition. Our findings highlight the utility of noninvasive neurophysiological measures to translate insights from animal models to humans with neurodevelopmental disorders, and thus provide direct confirmation of cortical dysfunction in patients with FXS and ASD.

  14. Schizoaffective Disorder

    Science.gov (United States)

    ... variations in brain chemistry and structure. Risk factors Factors that increase the risk of developing schizoaffective disorder include: Having a close blood relative who has schizoaffective disorder, schizophrenia or bipolar disorder Stressful events that trigger symptoms ...

  15. Pumpkin Seed Oil Extracted From Cucurbita maxima Improves Urinary Disorder in Human Overactive Bladder

    OpenAIRE

    Nishimura, Mie; Ohkawara, Tatsuya; Sato, Hiroji; Takeda, Hiroshi; Nishihira, Jun

    2014-01-01

    The pumpkin seed oil obtained from Cucurbita pepo has been shown to be useful for the treatment of nocturia in patients with urinal disorders in several western countries. In this study, we evaluated the effect of the pumpkin seed oil from Cucurbita maxima on urinary dysfunction in human overactive bladder (OAB). Forty-five subjects were enrolled in this study. An extract of pumpkin seed oil from C. maxima (10 g of oil/day) was orally administrated for 12 weeks. After 6 and 12 weeks, urinary ...

  16. Ancient evolutionary origins of epigenetic regulation associated with posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Levent eSipahi

    2014-05-01

    Full Text Available Epigenetic marks, including DNA methylation, are modifiable molecular factors that may underlie mental disorders, especially responses to trauma, including the development of and resilience to posttraumatic stress disorder (PTSD. Previous work has identified differential DNA methylation at CpG dinucleotide sites genomewide between trauma exposed individuals with and without PTSD, suggesting a role for epigenetic potential – the capacity to epigenetically regulate behavior and physiology in response to lived experiences. The human species is characterized by an increased period of adaptive plasticity during brain development. The evolutionary history of epigenetic potential in relation to adaptive plasticity is currently unknown. Using phylogenetic methods and functional annotation analyses, we trace the evolution of over 7,000 CpG dinucleotides, including 203 associated with PTSD, during the descent of humans in during mammalian evolution and characterize the biological significance of this evolution. We demonstrate that few (7% PTSD-associated CpG sites are unique to humans, while the vast majority of sites have deep evolutionary origins: 73% and 93% were unambiguously present in the last common ancestor of humans/orangutans and humans/chimpanzees, respectively. Genes proximal to evolved PTSD-associated CpG sites revealed significant enrichment for immune function during recent human evolution and regulation of gene expression during more ancient periods of human evolution. Additionally, 765 putative transcription factor binding sites (TFBS were identified that overlap with PTSD-associated CpG sites. Elucidation of the evolutionary history of PTSD-associated CpG sites may provide insights into the function and origin of epigenetic potential in trauma responses, generally, and PTSD, specifically. The human capacity to respond to trauma with stable physiologic and behavioral changes may be due to epigenetic potentials that are shared among many

  17. Dissociative disorders in DSM-5.

    Science.gov (United States)

    Spiegel, David; Lewis-Fernández, Roberto; Lanius, Ruth; Vermetten, Eric; Simeon, Daphne; Friedman, Matthew

    2013-01-01

    The rationale, research literature, and proposed changes to the dissociative disorders and conversion disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) are presented. Dissociative identity disorder will include reference to possession as well as identity fragmentation, to make the disorder more applicable to culturally diverse situations. Dissociative amnesia will include dissociative fugue as a subtype, since fugue is a rare disorder that always involves amnesia but does not always include confused wandering or loss of personality identity. Depersonalization disorder will include derealization as well, since the two often co-occur. A dissociative subtype of posttraumatic stress disorder (PTSD), defined by the presence of depersonalization or derealization in addition to other PTSD symptoms, is being recommended, based upon new epidemiological and neuroimaging evidence linking it to an early life history of adversity and a combination of frontal activation and limbic inhibition. Conversion disorder (functional neurological symptom disorder) will likely remain with the somatic symptom disorders, despite considerable dissociative comorbidity.

  18. Mortality from Musculoskeletal Disorders Including Rheumatoid Arthritis in Southern Sweden: A Multiple-cause-of-death Analysis, 1998-2014.

    Science.gov (United States)

    Kiadaliri, Aliasghar A; Turkiewicz, Aleksandra; Englund, Martin

    2017-05-01

    To assess mortality related to musculoskeletal (MSK) disorders and rheumatoid arthritis (RA), specifically, among adults (aged ≥ 20 yrs) in southern Sweden using the multiple-cause-of-death approach. All death certificates (DC; n = 201,488) from 1998 to 2014 for adults in the region of Skåne were analyzed when mortality from MSK disorders and RA was listed as the underlying and nonunderlying cause of death (UCD/NUCD). Trends in age-standardized mortality rates (ASMR) were evaluated using joinpoint regression, and associated causes were identified by age- and sex-adjusted observed/expected ratios. MSK (RA) was mentioned on 2.8% (0.8%) of all DC and selected as UCD in 0.6% (0.2%), with higher values among women. Proportion of MSK disorder deaths from all deaths increased from 2.7% in 1998 to 3.1% in 2014, and declined from 0.9% to 0.5% for RA. The mean age at death was higher in DC with mention of MSK/RA than in DC without. The mean ASMR for MSK (RA) was 15.5 (4.3) per 100,000 person-years and declined by 1.1% (3.8%) per year during 1998-2014. When MSK/RA were UCD, pneumonia and heart failure were the main NUCD. When MSK/RA were NUCD, the leading UCD were ischemic heart disease and neoplasms. The greatest observed/expected ratios were seen for infectious diseases (including sepsis) and blood diseases. We observed significant reduction in MSK and RA mortality rates and increase in the mean age at death. Further analyses are required to investigate determinants of these improvements in MSK/RA survival and their potential effect on the Swedish healthcare systems.

  19. Identification of the BRD1 interaction network and its impact on mental disorder risk

    DEFF Research Database (Denmark)

    Fryland, Tue; Christensen, Jane H; Pallesen, Jonatan

    2016-01-01

    and regulates expression of numerous genes, many of which are involved with brain development and susceptibility to mental disorders. Our findings indicate that BRD1 acts as a regulatory hub in a comprehensive schizophrenia risk network which plays a role in many brain regions throughout life, implicating e......Background: The bromodomain containing 1 (BRD1) gene has been implicated with transcriptional regulation, brain development, and susceptibility to schizophrenia and bipolar disorder. To advance the understanding of BRD1 and its role in mental disorders, we characterized the protein and chromatin...... functional molecular data were integrated with human genomic and transcriptomic data using available GWAS, exome-sequencing datasets as well as spatiotemporal transcriptomic datasets from the human brain. Results: We present several novel protein interactions of BRD1, including isoform-specific interactions...

  20. Variations of the candidate SEZ6L2 gene on Chromosome 16p11.2 in patients with autism spectrum disorders and in human populations.

    Directory of Open Access Journals (Sweden)

    Marina Konyukh

    Full Text Available BACKGROUND: Autism spectrum disorders (ASD are a group of severe childhood neurodevelopmental disorders with still unknown etiology. One of the most frequently reported associations is the presence of recurrent de novo or inherited microdeletions and microduplications on chromosome 16p11.2. The analysis of rare variations of 8 candidate genes among the 27 genes located in this region suggested SEZ6L2 as a compelling candidate. METHODOLOGY/PRINCIPAL FINDINGS: We further explored the role of SEZ6L2 variations by screening its coding part in a group of 452 individuals, including 170 patients with ASD and 282 individuals from different ethnic backgrounds of the Human Genome Diversity Panel (HGDP, complementing the previously reported screening. We detected 7 previously unidentified non-synonymous variations of SEZ6L2 in ASD patients. We also identified 6 non-synonymous variations present only in HGDP. When we merged our results with the previously published, no enrichment of non-synonymous variation in SEZ6L2 was observed in the ASD group compared with controls. CONCLUSIONS/SIGNIFICANCE: Our results provide an extensive ascertainment of the genetic variability of SEZ6L2 in human populations and do not support a major role for SEZ6L2 sequence variations in the susceptibility to ASD.

  1. Basal ganglia, movement disorders and deep brain stimulation: advances made through non-human primate research.

    Science.gov (United States)

    Wichmann, Thomas; Bergman, Hagai; DeLong, Mahlon R

    2018-03-01

    Studies in non-human primates (NHPs) have led to major advances in our understanding of the function of the basal ganglia and of the pathophysiologic mechanisms of hypokinetic movement disorders such as Parkinson's disease and hyperkinetic disorders such as chorea and dystonia. Since the brains of NHPs are anatomically very close to those of humans, disease states and the effects of medical and surgical approaches, such as deep brain stimulation (DBS), can be more faithfully modeled in NHPs than in other species. According to the current model of the basal ganglia circuitry, which was strongly influenced by studies in NHPs, the basal ganglia are viewed as components of segregated networks that emanate from specific cortical areas, traverse the basal ganglia, and ventral thalamus, and return to the frontal cortex. Based on the presumed functional domains of the different cortical areas involved, these networks are designated as 'motor', 'oculomotor', 'associative' and 'limbic' circuits. The functions of these networks are strongly modulated by the release of dopamine in the striatum. Striatal dopamine release alters the activity of striatal projection neurons which, in turn, influences the (inhibitory) basal ganglia output. In parkinsonism, the loss of striatal dopamine results in the emergence of oscillatory burst patterns of firing of basal ganglia output neurons, increased synchrony of the discharge of neighboring basal ganglia neurons, and an overall increase in basal ganglia output. The relevance of these findings is supported by the demonstration, in NHP models of parkinsonism, of the antiparkinsonian effects of inactivation of the motor circuit at the level of the subthalamic nucleus, one of the major components of the basal ganglia. This finding also contributed strongly to the revival of the use of surgical interventions to treat patients with Parkinson's disease. While ablative procedures were first used for this purpose, they have now been largely

  2. Annual Research Review: The neurobehavioral development of multiple memory systems: implications for childhood and adolescent psychiatric disorders

    Science.gov (United States)

    Goodman, Jarid; Marsh, Rachel; Peterson, Bradley S.; Packard, Mark G.

    2014-01-01

    Extensive evidence indicates that mammalian memory is organized into multiple brains systems, including a “cognitive” memory system that depends upon the hippocampus and a stimulus-response “habit” memory system that depends upon the dorsolateral striatum. Dorsal striatal-dependent habit memory may in part influence the development and expression of some human psychopathologies, particularly those characterized by strong habit-like behavioral features. The present review considers this hypothesis as it pertains to psychopathologies that typically emerge during childhood and adolescence. These disorders include Tourette syndrome, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, eating disorders, and autism spectrum disorders. Human and nonhuman animal research shows that the typical development of memory systems comprises the early maturation of striatal-dependent habit memory and the relatively late maturation of hippocampal-dependent cognitive memory. We speculate that the differing rates of development of these memory systems may in part contribute to the early emergence of habit-like symptoms in childhood and adolescence. In addition, abnormalities in hippocampal and striatal brain regions have been observed consistently in youth with these disorders, suggesting that the aberrant development of memory systems may also contribute to the emergence of habit-like symptoms as core pathological features of these illnesses. Considering these disorders within the context of multiple memory systems may help elucidate the pathogenesis of habit-like symptoms in childhood and adolescence, and lead to novel treatments that lessen the habit-like behavioral features of these disorders. PMID:24286520

  3. Neuroimaging of neurotic disorders

    International Nuclear Information System (INIS)

    Okubo, Yoshiro; Yahata, Noriaki

    2006-01-01

    Neuroimaging has been involved in recent biological approaches with evidence for neurotic disorders in place of diagnostic criteria on Freud theory hitherto. This review describes the present states of brain imaging in those disorders. Emotion has such three bases for environmental stimuli as recognition/evaluation of causable factors, manifestation, and its control, each of which occurs in various different regions connected by neuro-net work in the brain. The disorders are regarded as abnormality of the circuit that can be imaged. Documented and discussed are the actual regions imaged by MRI and PET in panic disorder, social phobia, phobias to specified things, posttraumatic stress disorder and obsessive-compulsive disorder. The approach is thought important for elucidating not only the pathogenesis of the disorders but also the human emotional functions and mechanism of the mind, which may lead to a better treatment of the disorders in future. (T.I)

  4. Chronic complex dissociative disorders and borderline personality disorder: disorders of emotion dysregulation?

    Science.gov (United States)

    Brand, Bethany L; Lanius, Ruth A

    2014-01-01

    Emotion dysregulation is a core feature of chronic complex dissociative disorders (DD), as it is for borderline personality disorder (BPD). Chronic complex DD include dissociative identity disorder (DID) and the most common form of dissociative disorder not otherwise specified (DDNOS, type 1), now known as Other Specified Dissociative Disorders (OSDD, type 1). BPD is a common comorbid disorder with DD, although preliminary research indicates the disorders have some distinguishing features as well as considerable overlap. This article focuses on the epidemiology, clinical presentation, psychological profile, treatment, and neurobiology of chronic complex DD with emphasis placed on the role of emotion dysregulation in each of these areas. Trauma experts conceptualize borderline symptoms as often being trauma based, as are chronic complex DD. We review the preliminary research that compares DD to BPD in the hopes that this will stimulate additional comparative research.

  5. Comparing the experience of voices in borderline personality disorder with the experience of voices in a psychotic disorder: A systematic review.

    Science.gov (United States)

    Merrett, Zalie; Rossell, Susan L; Castle, David J

    2016-07-01

    In clinical settings, there is substantial evidence both clinically and empirically to suggest that approximately 50% of individuals with borderline personality disorder experience auditory verbal hallucinations. However, there is limited research investigating the phenomenology of these voices. The aim of this study was to review and compare our current understanding of auditory verbal hallucinations in borderline personality disorder with auditory verbal hallucinations in patients with a psychotic disorder, to critically analyse existing studies investigating auditory verbal hallucinations in borderline personality disorder and to identify gaps in current knowledge, which will help direct future research. The literature was searched using the electronic database Scopus, PubMed and MEDLINE. Relevant studies were included if they were written in English, were empirical studies specifically addressing auditory verbal hallucinations and borderline personality disorder, were peer reviewed, used only adult humans and sample comprising borderline personality disorder as the primary diagnosis, and included a comparison group with a primary psychotic disorder such as schizophrenia. Our search strategy revealed a total of 16 articles investigating the phenomenology of auditory verbal hallucinations in borderline personality disorder. Some studies provided evidence to suggest that the voice experiences in borderline personality disorder are similar to those experienced by people with schizophrenia, for example, occur inside the head, and often involved persecutory voices. Other studies revealed some differences between schizophrenia and borderline personality disorder voice experiences, with the borderline personality disorder voices sounding more derogatory and self-critical in nature and the voice-hearers' response to the voices were more emotionally resistive. Furthermore, in one study, the schizophrenia group's voices resulted in more disruption in daily functioning

  6. Common anorectal disorders.

    Science.gov (United States)

    Foxx-Orenstein, Amy E; Umar, Sarah B; Crowell, Michael D

    2014-05-01

    Anorectal disorders result in many visits to healthcare specialists. These disorders include benign conditions such as hemorrhoids to more serious conditions such as malignancy; thus, it is important for the clinician to be familiar with these disorders as well as know how to conduct an appropriate history and physical examination. This article reviews the most common anorectal disorders, including hemorrhoids, anal fissures, fecal incontinence, proctalgia fugax, excessive perineal descent, and pruritus ani, and provides guidelines on comprehensive evaluation and management.

  7. The Social Studies Should Include More Discussion of International Human Rights.

    Science.gov (United States)

    Torney, Judith V.

    1980-01-01

    Students need more exposure to the concept of human rights. They need to know The Universal Declaration of Human Rights and the subsequent covenants. Also, they need to know that substantial agreement exists in the international community about what constitutes human rights. (Author/KC)

  8. Difference or Disorder? Cultural Issues in Understanding Neurodevelopmental Disorders

    Science.gov (United States)

    Norbury, Courtenay Frazier; Sparks, Alison

    2013-01-01

    Developmental disorders, such as autism spectrum disorder and specific language impairment, are biologically based disorders that currently rely on behaviorally defined criteria for diagnosis and treatment. Specific behaviors that are included in diagnostic frameworks and the point at which individual differences in behavior constitute abnormality…

  9. Aspects of animal models for major neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Lefter Radu

    2014-01-01

    Full Text Available We will review the main animal models for the major neuropsychiatric disorders, focusing on schizophrenia, Alzheimer’s disease, Parkinson’s disease, depression, anxiety and autism. Although these mental disorders are specifically human pathologies and therefore impossible to perfectly replicate in animals, the use of experimental animals is based on the physiological and anatomical similarities between humans and animals such as the rat, and mouse, and on the fact that 99% of human and murine genomes are shared. Pathological conditions in animals can be assessed by manipulating the metabolism of neurotransmitters, through various behavioral tests, and by determining biochemical parameters that can serve as important markers of disorders.

  10. Detecting and Measuring Back Disorders in Nonverbal Individuals: The Example of Domestic Horses

    Directory of Open Access Journals (Sweden)

    Clémence Lesimple

    2016-08-01

    Full Text Available Back disorders are amongst the major health-related disorders associated to working conditions in our society. Horses share with humans the exposure to potential physically harmful working conditions leading to back disorders. However, despite their high prevalence, these problems are often unacknowledged in the horse industry, mostly because their diagnosis remains difficult, particularly in field conditions. In the present review, we review the current scientific knowledge on back vertebral, muscular and musculoskeletal disorders. We will first present the existing knowledge about their prevalence and the tools available for diagnosis. Then, the different potential sources of back pain, including anatomical implications, the effect of emotionality and working conditions will be discussed. We finally present the existing behavioral, postural and physiological indicators of back pain that could help an early detection of back disorders.

  11. Brain connectivity and psychiatric comorbidity in adolescents with Internet gaming disorder.

    Science.gov (United States)

    Han, Doug Hyun; Kim, Sun Mi; Bae, Sujin; Renshaw, Perry F; Anderson, Jeffrey S

    2017-05-01

    Prolonged Internet video game play may have multiple and complex effects on human cognition and brain development in both negative and positive ways. There is not currently a consensus on the principle effects of video game play neither on brain development nor on the relationship to psychiatric comorbidity. In this study, 78 adolescents with Internet gaming disorder (IGD) and 73 comparison subjects without IGD, including subgroups with no other psychiatric comorbid disease, with major depressive disorder and with attention deficit hyperactivity disorder (ADHD), were included in a 3 T resting state functional magnetic resonance imaging analysis. The severity of Internet gaming disorder, depression, anxiety and ADHD symptoms were assessed with the Young Internet Addiction Scale, the Beck Depression Inventory, the Beck Anxiety Inventory and the Korean ADHD rating scales, respectively. Patients with IGD showed an increased functional correlation between seven pairs of regions, all satisfying q game play and suggest a risk or predisposition in game players for over-connectivity of the default mode and executive control networks that may relate to psychiatric comorbidity. © 2015 Society for the Study of Addiction.

  12. Functional neuroimaging of sleep disorders

    International Nuclear Information System (INIS)

    Qiu Chun; Zhao Jun; Guan Yihui

    2013-01-01

    Sleep disorders may affect the health and normal life of human badly. However, the pathophysiology underlying adult sleep disorders is still unclear. Functional neuroimaging can be used to investigate whether sleep disorders are associated with specific changes in brain structure or regional activity. This paper reviews functional brain imaging findings in major intrinsic sleep disorders (i.e., idiopathic insomnia, narcolepsy, and obstructive sleep apnea) and in abnormal motor behavior during sleep (i.e., periodic limb movement disorder and REM sleep behavior disorder). Metabolic/functional investigations (positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging) are mainly reviewed, as well as neuroanatomical assessments (voxel-based morphometry, magnetic resonance spectroscopy). Meanwhile, here are some brief introduction of different kinds of sleep disorders. (authors)

  13. REM sleep behavior disorder and other sleep disturbances in Disney animated films.

    Science.gov (United States)

    Iranzo, Alex; Schenck, Carlos H; Fonte, Jorge

    2007-08-01

    During a viewing of Disney's animated film Cinderella (1950), one author (AI) noticed a dog having nightmares with dream-enactment that strongly resembled RBD. This prompted a study in which all Disney classic full-length animated films and shorts were analyzed for other examples of RBD. Three additional dogs were found with presumed RBD in the classic films Lady and the Tramp (1955) and The Fox and the Hound (1981), and in the short Pluto's Judgment Day (1935). These dogs were elderly males who would pant, whine, snuffle, howl, laugh, paddle, kick, and propel themselves while dreaming that they were chasing someone or running away. In Lady and the Tramp the dog was also losing both his sense of smell and his memory, two associated features of human RBD. These four films were released before RBD was first formally described in humans and dogs. In addition, systematic viewing of the Disney films identified a broad range of sleep disorders, including nightmares, sleepwalking, sleep related seizures, disruptive snoring, excessive daytime sleepiness, insomnia and circadian rhythm sleep disorder. These sleep disorders were inserted as comic elements. The inclusion of a broad range of accurately depicted sleep disorders in these films indicates that the Disney screenwriters were astute observers of sleep and its disorders.

  14. Genetic Variation in Cardiomyopathy and Cardiovascular Disorders.

    Science.gov (United States)

    McNally, Elizabeth M; Puckelwartz, Megan J

    2015-01-01

    With the wider deployment of massively-parallel, next-generation sequencing, it is now possible to survey human genome data for research and clinical purposes. The reduced cost of producing short-read sequencing has now shifted the burden to data analysis. Analysis of genome sequencing remains challenged by the complexity of the human genome, including redundancy and the repetitive nature of genome elements and the large amount of variation in individual genomes. Public databases of human genome sequences greatly facilitate interpretation of common and rare genetic variation, although linking database sequence information to detailed clinical information is limited by privacy and practical issues. Genetic variation is a rich source of knowledge for cardiovascular disease because many, if not all, cardiovascular disorders are highly heritable. The role of rare genetic variation in predicting risk and complications of cardiovascular diseases has been well established for hypertrophic and dilated cardiomyopathy, where the number of genes that are linked to these disorders is growing. Bolstered by family data, where genetic variants segregate with disease, rare variation can be linked to specific genetic variation that offers profound diagnostic information. Understanding genetic variation in cardiomyopathy is likely to help stratify forms of heart failure and guide therapy. Ultimately, genetic variation may be amenable to gene correction and gene editing strategies.

  15. The molecular genetics of the telomere biology disorders.

    Science.gov (United States)

    Bertuch, Alison A

    2016-08-02

    The importance of telomere function for human health is exemplified by a collection of Mendelian disorders referred to as the telomere biology disorders (TBDs), telomeropathies, or syndromes of telomere shortening. Collectively, the TBDs cover a spectrum of conditions from multisystem disease presenting in infancy to isolated disease presentations in adulthood, most notably idiopathic pulmonary fibrosis. Eleven genes have been found mutated in the TBDs to date, each of which is linked to some aspect of telomere maintenance. This review summarizes the molecular defects that result from mutations in these genes, highlighting recent advances, including the addition of PARN to the TBD gene family and the discovery of heterozygous mutations in RTEL1 as a cause of familial pulmonary fibrosis.

  16. Munchausen Syndrome and the Wide Spectrum of Factitious Disorders.

    Science.gov (United States)

    Tatu, Laurent; Aybek, Selma; Bogousslavsky, Julien

    2018-01-01

    Since its initial description in 1851, Munchausen syndrome has been widely used interchangeably with factitious disorder. Nevertheless, this syndrome is only one form of factitious disorder that is both severe and chronic. The syndrome was named after Karl Friedrich Hieronymus, Baron von Münchhausen (1720-1797), a German nobleman who became famous as a narrator of false and exaggerated exploits. His name was progressively corrupted to Munchausen. Factitious disorders and Munchausen syndrome remain a great diagnosis challenge for physicians. All medical specialities are concerned by these disorders. The diagnosis process involves a first step to exclude an unusual presentation of a common medical condition. The second step consists of excluding somatoform disorders and malingering. Unfortunately, the boundaries between factitious disorder, somatization, and malingering are often unclear. In 1977, the term "Munchausen's syndrome by proxy" was coined to define a situation where a person produces false symptoms in another one, especially a child. This term was extended to similar interactions between human and pets. Because varied conditions have been included in the definition of this syndrome, there is ongoing debate about alternative names. © 2018 S. Karger AG, Basel.

  17. Global warming and neurodegenerative disorders: speculations on their linkage.

    Science.gov (United States)

    Habibi, Laleh; Perry, George; Mahmoudi, Morteza

    2014-01-01

    Climate change is having considerable impact on biological systems. Eras of ice ages and warming shaped the contemporary earth and origin of creatures including humans. Warming forces stress conditions on cells. Therefore, cells evolved elaborate defense mechanisms, such as creation of heat shock proteins, to combat heat stress. Global warming is becoming a crisis and this process would yield an undefined increasing rate of neurodegenerative disorders in future decades. Since heat stress is known to have a degenerative effects on neurons and, conversely, cold conditions have protective effect on these cells, we hypothesize that persistent heat stress forced by global warming might play a crucial role in increasing neurodegenerative disorders.

  18. Copy-number variants in neurodevelopmental disorders: promises and challenges.

    LENUS (Irish Health Repository)

    Merikangas, Alison K

    2012-02-01

    Copy-number variation (CNV) is the most prevalent type of structural variation in the human genome. There is emerging evidence that copy-number variants (CNVs) provide a new vista on understanding susceptibility to neuropsychiatric disorders. Some challenges in the interpretation of current CNV studies include the use of overlapping samples, differing phenotypic definitions, an absence of population norms for CNVs and a lack of consensus in methods for CNV detection and analysis. Here, we review current CNV association study methods and results in autism spectrum disorders (ASD) and schizophrenia, and provide suggestions for design approaches to future studies that might maximize the translation of this work to etiological understanding.

  19. Heme orientational disorder in human adult hemoglobin reconstituted with a ring fluorinated heme and its functional consequences

    International Nuclear Information System (INIS)

    Nagao, Satoshi; Hirai, Yueki; Kawano, Shin; Imai, Kiyohiro; Suzuki, Akihiro; Yamamoto, Yasuhiko

    2007-01-01

    A ring fluorinated heme, 13,17-bis(2-carboxylatoethyl)-3,8-diethyl-2-fluoro-7,12, 18-trimethyl-porphyrin-atoiron(III), has been incorporated into human adult hemoglobin (Hb A). The heme orientational disorder in the individual subunits of the protein has been readily characterized using 19 F NMR and the O 2 binding properties of the protein have been evaluated through the oxygen equilibrium analysis. The equilibrated orientations of hemes in α- and β- subunits of the reconstituted protein were found to be almost completely opposite to each other, and hence were largely different from those of the native and the previously reported reconstituted proteins [T. Jue, G.N. La Mar, Heme orientational heterogeneity in deuterohemin-reconstituted horse and human hemoglobin characterized by proton nuclear magnetic resonance spectroscopy, Biochem. Biophys. Res. Commun. 119 (1984) 640-645]. Despite the large difference in the degree of the heme orientational disorder in the subunits of the proteins, the O 2 affinity and the cooperativity of the protein reconstituted with 2-MF were similar to those of the proteins reconstituted with a series of hemes chemically modified at the heme 3- and 8-positions [K. Kawabe, K. Imaizumi, Z. Yoshida, K. Imai, I. Tyuma, Studies on reconstituted myoglobins and hemoglobins II. Role of the heme side chains in the oxygenation of hemoglobin, J. Biochem. 92 (1982) 1713-1722], whose O 2 affinity and cooperativity were higher and lower, respectively, relative to those of native protein. These results indicated that the heme orientational disorder could exert little effect, if any, on the O 2 affinity properties of Hb A. This finding provides new insights into structure-function relationship of Hb A

  20. Generalised anxiety disorder

    Directory of Open Access Journals (Sweden)

    Bojana Avguštin Avčin

    2013-10-01

    Full Text Available Generalised anxiety disorder is characterised by persistent, excessive and difficult-to-control worry, which may be accompanied by several psychic and somatic symptoms, including suicidality. Generalized anxiety disorder is the most common psychiatric disorder in the primary care, although it is often underrecognised and undertreated. Generalized anxiety disorder is typically a chronic condition with low short- and medium-term remission rates. Clinical presentations often include depression, somatic illness, pain, fatigue and problems sleeping. The evaluation of prognosis is complicated by frequent comorbidity with other anxiety disorders and depression, which worsen the long-term outcome and accompanying burden of disability. The two main treatments for generalised anxiety disorder are medications and psychotherapy. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors represent first-line psychopharmacologic treatment for generalised anxiety disorder. The most extensively studied psychotherapy for anxiety is cognitive behavioural therapy which has demonstrated efficacy throughout controlled studies.

  1. Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism

    Science.gov (United States)

    2017-01-01

    The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD) hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates), persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment. PMID:28567415

  2. Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism

    Directory of Open Access Journals (Sweden)

    Nguyen Quoc Vuong Tran

    2017-01-01

    Full Text Available The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD and attention deficit hyperactivity disorder (ADHD, calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates, persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment.

  3. Revertant mosaicism in a human skin fragility disorder results from slipped mispairing and mitotic recombination

    NARCIS (Netherlands)

    Kiritsi, Dimitra; He, Yinghong; Pasmooij, Anna M. G.; Onder, Meltem; Happle, Rudolf; Jonkman, Marcel F.; Bruckner-Tuderman, Leena; Has, Cristina

    Spontaneous gene repair, also called revertant mosaicism, has been documented in several genetic disorders involving organs that undergo self-regeneration, including the skin. Genetic reversion may occur through different mechanisms, and in a single individual, the mutation can be repaired in

  4. Neural markers of errors as endophenotypes in neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Dara S Manoach

    2013-07-01

    Full Text Available Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a promising approach.

  5. Neural markers of errors as endophenotypes in neuropsychiatric disorders.

    Science.gov (United States)

    Manoach, Dara S; Agam, Yigal

    2013-01-01

    Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach.

  6. Pigmented skin disorders: Evaluation and treatment

    NARCIS (Netherlands)

    Kroon, M.W.

    2015-01-01

    Pigmentary disorders are disturbances of human skin color. Minor changes in the cellular physiology of the skin can dramatically affect pigment production in positive or negative manner. In this these, associated diseases, therapeutical options and disease parameters for the pigmentation disorder

  7. What is a mental disorder? A perspective from cognitive-affective science.

    Science.gov (United States)

    Stein, Dan J

    2013-12-01

    Defining disease and disorder remains a key conceptual question in philosophy of medicine and psychiatry, and is currently a very practical matter for psychiatric nosology, given the new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the upcoming International Classification of Diseases, 11th Revision. There have been advances in the cognitive-affective science of human categorization, and it is timely to consider implications for our understanding of the category of psychiatric disorder. The category of mental disorder has graded boundaries, and conditions within this category can be conceptualized using MEDICAL or MORAL metaphors. One key set of constructs used in MEDICAL metaphors relates to the notion of dysfunction, and it may, in turn, be useful to conceptualize such dysfunction in evolutionary terms. For typical disorders, it is relatively easy to agree that dysfunction is present. However, for atypical disorders, there may be considerable debate about the presence and extent of dysfunction. Rational arguments can be brought to bear to help decide whether particular entities should be included in our nosologies, and, if so, what their boundaries should be. However, it is appropriate that there should be ongoing debate on diagnostic validity, clinical utility, and other relevant facts and values, for cases that are difficult to decide. The perspective here can be illustrated using many nosological debates within the anxiety disorders and the obsessive-compulsive and related disorders, including the question of delineating normal from abnormal anxiety, of deciding whether anxiety is psychiatric or medical, and the debate about the optimal meta-structure for anxiety disorders.

  8. Insertional translocation leading to a 4q13 duplication including the EPHA5 gene in two siblings with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Matoso, Eunice; Melo, Joana B; Ferreira, Susana I; Jardim, Ana; Castelo, Teresa M; Weise, Anja; Carreira, Isabel M

    2013-08-01

    An insertional translocation (IT) can result in pure segmental aneusomy for the inserted genomic segment allowing to define a more accurate clinical phenotype. Here, we report on two siblings sharing an unbalanced IT inherited from the mother with a history of learning difficulty. An 8-year-old girl with developmental delay, speech disability, and attention-deficit hyperactivity disorder (ADHD), showed by GTG banding analysis a subtle interstitial alteration in 21q21. Oligonucleotide array comparative genomic hybridization (array-CGH) analysis showed a 4q13.1-q13.3 duplication spanning 8.6 Mb. Fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) clones confirmed the rearrangement, a der(21)ins(21;4)(q21;q13.1q13.3). The duplication described involves 50 RefSeq genes including the EPHA5 gene that encodes for the EphA5 receptor involved in embryonic development of the brain and also in synaptic remodeling and plasticity thought to underlie learning and memory. The same rearrangement was observed in a younger brother with behavioral problems and also exhibiting ADHD. ADHD is among the most heritable of neuropsychiatric disorders. There are few reports of patients with duplications involving the proximal region of 4q and a mild phenotype. To the best of our knowledge this is the first report of a duplication restricted to band 4q13. This abnormality could be easily missed in children who have nonspecific cognitive impairment. The presence of this behavioral disorder in the two siblings reinforces the hypothesis that the region involved could include genes involved in ADHD. Copyright © 2013 Wiley Periodicals, Inc.

  9. Genetic disorders as collective phenomena

    International Nuclear Information System (INIS)

    Chela-Flores, J.

    1987-05-01

    Genetic disorders due to human chromosome aberrations in number are discussed from the point of view of Molecular Genetics. The etiology of trisomy is discussed in the light of the collective variables recently introduced and an age-dependent metabolic disorder is suggested as a possible etiological factor. (author). 11 refs

  10. Cost-effectiveness of collaborative care including PST and an antidepressant treatment algorithm for the treatment of major depressive disorder in primary care; a randomised clinical trial

    Directory of Open Access Journals (Sweden)

    Beekman Aartjan TF

    2007-03-01

    Full Text Available Abstract Background Depressive disorder is currently one of the most burdensome disorders worldwide. Evidence-based treatments for depressive disorder are already available, but these are used insufficiently, and with less positive results than possible. Earlier research in the USA has shown good results in the treatment of depressive disorder based on a collaborative care approach with Problem Solving Treatment and an antidepressant treatment algorithm, and research in the UK has also shown good results with Problem Solving Treatment. These treatment strategies may also work very well in the Netherlands too, even though health care systems differ between countries. Methods/design This study is a two-armed randomised clinical trial, with randomization on patient-level. The aim of the trial is to evaluate the treatment of depressive disorder in primary care in the Netherlands by means of an adapted collaborative care framework, including contracting and adherence-improving strategies, combined with Problem Solving Treatment and antidepressant medication according to a treatment algorithm. Forty general practices will be randomised to either the intervention group or the control group. Included will be patients who are diagnosed with moderate to severe depression, based on DSM-IV criteria, and stratified according to comorbid chronic physical illness. Patients in the intervention group will receive treatment based on the collaborative care approach, and patients in the control group will receive care as usual. Baseline measurements and follow up measures (3, 6, 9 and 12 months are assessed using questionnaires and an interview. The primary outcome measure is severity of depressive symptoms, according to the PHQ9. Secondary outcome measures are remission as measured with the PHQ9 and the IDS-SR, and cost-effectiveness measured with the TiC-P, the EQ-5D and the SF-36. Discussion In this study, an American model to enhance care for patients with a

  11. The quartet theory: Implications for autism spectrum disorder. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

    Science.gov (United States)

    Pehrs, Corinna; Samson, Andrea C.; Gross, James J.

    2015-06-01

    Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits as well as restricted and repetitive behaviors [1]. Specific deficits include failure to initiate reciprocal social interactions, verbal and non-verbal communication difficulties, decreased sensitivity to social and emotional cues, and limited perspective-taking abilities. Social withdrawal, avoidance or indifference to affection or physical contact, lack of eye contact, and decreased joint attention and facial responsiveness are also common [2]. In addition to these core features, there is a growing body of literature that describes problematic patterns of emotional reactivity (increased negative and decreased positive emotions) and emotion regulation (increased use of maladaptive and decreased use of adaptive emotion regulation strategies) [3-5]. The present comment seeks to link difficulties in socio-emotional domains to the Quartet Theory of Human Emotions by mapping characteristic ASD social deficits and emotion dysregulation onto two of the affect systems described in this theory: the hippocampal and orbitofrontal-centered systems.

  12. A decision support system prototype including human factors based on the TOGA meta-theory approach

    International Nuclear Information System (INIS)

    Cappelli, M.; Memmi, F.; Gadomski, A. M.; Sepielli, M.

    2012-01-01

    The human contribution to the risk of operation of complex technological systems is often not negligible and sometimes tends to become significant, as shown by many reports on incidents and accidents occurred in the past inside Nuclear Power Plants (NPPs). An error of a human operator of a NPP can derive by both omission and commission. For instance, complex commission errors can also lead to significant catastrophic technological accidents, as for the case of the Three Mile Island accident. Typically, the problem is analyzed by focusing on the single event chain that has provoked the incident or accident. What is needed is a general framework able to include as many parameters as possible, i.e. both technological and human factors. Such a general model could allow to envisage an omission or commission error before it can happen or, alternatively, suggest preferred actions to do in order to take countermeasures to neutralize the effect of the error before it becomes critical. In this paper, a preliminary Decision Support System (DSS) based on the so-called (-) TOGA meta-theory approach is presented. The application of such a theory to the management of nuclear power plants has been presented in the previous ICAPP 2011. Here, a human factor simulator prototype is proposed in order to include the effect of human errors in the decision path. The DSS has been developed using a TRIGA research reactor as reference plant, and implemented using the LabVIEW programming environment and the Finite State Machine (FSM) model The proposed DSS shows how to apply the Universal Reasoning Paradigm (URP) and the Universal Management Paradigm (UMP) to a real plant context. The DSS receives inputs from instrumentation data and gives as output a suggested decision. It is obtained as the result of an internal elaborating process based on a performance function. The latter, describes the degree of satisfaction and efficiency, which are dependent on the level of responsibility related to

  13. Are mice pigmentary genes throwing light on humans?

    Directory of Open Access Journals (Sweden)

    Bose S

    1993-01-01

    Full Text Available In this article the rapid advances made in the molecular genetics of inherited disorders of hypo and hyperpigmentation during the past three years are reviewed. The main focus is on studies in mice as compared to homologues in humans. The main hypomelanotic diseases included are, piebaldism (white spotting due to mutations of c-KIT, PDGF and MGF genes; vitiligo (microphathalmia mice mutations of c-Kit and c-fms genes; Waardenburg syndrome (splotch locus mutations of mice PAX-3 or human Hup-2 genes; albinism (mutations of tyrosinase genes, Menkes disease (Mottled mouse, premature graying (mutations in light/brown locus/gp75/ TRP-1; Griscelli disease (mutations in TRP-1 and steel; Prader-willi and Angelman syndromes, tyrosinase-positive oculocutaneous albinism and hypomelanosis of lto (mutations of pink-eyed dilution gene/mapping to human chromosomes 15 q 11.2 - q12; and human platelet storage pool deficiency diseases due to defects in pallidin, an erythrocyte membrane protein (pallid mouse / mapping to 4.2 pallidin gene. The genetic characterization of hypermelanosis includes, neurofibromatosis 1 (Café-au-lait spots and McCune-Albright Syndrome. Rapid evolving knowledge about pigmentary genes will increase further the knowledge about these hypo and hyperpigmentary disorders.

  14. Development of a versatile enrichment analysis tool reveals associations between the maternal brain and mental health disorders, including autism

    Science.gov (United States)

    2013-01-01

    Background A recent study of lateral septum (LS) suggested a large number of autism-related genes with altered expression in the postpartum state. However, formally testing the findings for enrichment of autism-associated genes proved to be problematic with existing software. Many gene-disease association databases have been curated which are not currently incorporated in popular, full-featured enrichment tools, and the use of custom gene lists in these programs can be difficult to perform and interpret. As a simple alternative, we have developed the Modular Single-set Enrichment Test (MSET), a minimal tool that enables one to easily evaluate expression data for enrichment of any conceivable gene list of interest. Results The MSET approach was validated by testing several publicly available expression data sets for expected enrichment in areas of autism, attention deficit hyperactivity disorder (ADHD), and arthritis. Using nine independent, unique autism gene lists extracted from association databases and two recent publications, a striking consensus of enrichment was detected within gene expression changes in LS of postpartum mice. A network of 160 autism-related genes was identified, representing developmental processes such as synaptic plasticity, neuronal morphogenesis, and differentiation. Additionally, maternal LS displayed enrichment for genes associated with bipolar disorder, schizophrenia, ADHD, and depression. Conclusions The transition to motherhood includes the most fundamental social bonding event in mammals and features naturally occurring changes in sociability. Some individuals with autism, schizophrenia, or other mental health disorders exhibit impaired social traits. Genes involved in these deficits may also contribute to elevated sociability in the maternal brain. To date, this is the first study to show a significant, quantitative link between the maternal brain and mental health disorders using large scale gene expression data. Thus, the

  15. Models of disordered media: some new results, including some new connections between composite-media, fluid-state, and random-flight theories

    International Nuclear Information System (INIS)

    Stell, G.

    1983-01-01

    Some new theoretical results on the microstructure of models of two-phase disordered media are given, as well as the new quantitative bounds on the thermal conductivity that follows for one such model (randomly centered spherical inclusions). A second set of results is then given for random flights, including random flights with hit expectancy prescribed in a unit hall around the flight origin. Finally, some interesting correspondences are demonstrated, via the Ornstein-Zernike equation, between random-flight results, liquid-state results and percolation-theory results. 27 references, 6 figures, 4 tables

  16. The promises of stem cells: stem cell therapy for movement disorders.

    Science.gov (United States)

    Mochizuki, Hideki; Choong, Chi-Jing; Yasuda, Toru

    2014-01-01

    Despite the multitude of intensive research, the exact pathophysiological mechanisms underlying movement disorders including Parkinson's disease, multiple system atrophy and Huntington's disease remain more or less elusive. Treatments to halt these disease progressions are currently unavailable. With the recent induced pluripotent stem cells breakthrough and accomplishment, stem cell research, as the vast majority of scientists agree, holds great promise for relieving and treating debilitating movement disorders. As stem cells are the precursors of all cells in the human body, an understanding of the molecular mechanisms that govern how they develop and work would provide us many fundamental insights into human biology of health and disease. Moreover, stem-cell-derived neurons may be a renewable source of replacement cells for damaged neurons in movement disorders. While stem cells show potential for regenerative medicine, their use as tools for research and drug testing is thought to have more immediate impact. The use of stem-cell-based drug screening technology could be a big boost in drug discovery for these movement disorders. Particular attention should also be given to the involvement of neural stem cells in adult neurogenesis so as to encourage its development as a therapeutic option. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Carboxylesterases in lipid metabolism: from mouse to human

    Directory of Open Access Journals (Sweden)

    Jihong Lian

    2017-07-01

    Full Text Available ABSTRACT Mammalian carboxylesterases hydrolyze a wide range of xenobiotic and endogenous compounds, including lipid esters. Physiological functions of carboxylesterases in lipid metabolism and energy homeostasis in vivo have been demonstrated by genetic manipulations and chemical inhibition in mice, and in vitro through (overexpression, knockdown of expression, and chemical inhibition in a variety of cells. Recent research advances have revealed the relevance of carboxylesterases to metabolic diseases such as obesity and fatty liver disease, suggesting these enzymes might be potential targets for treatment of metabolic disorders. In order to translate pre-clinical studies in cellular and mouse models to humans, differences and similarities of carboxylesterases between mice and human need to be elucidated. This review presents and discusses the research progress in structure and function of mouse and human carboxylesterases, and the role of these enzymes in lipid metabolism and metabolic disorders.

  18. The neurogenetics of atypical parkinsonian disorders.

    Science.gov (United States)

    Fogel, Brent L; Clark, Mary C; Geschwind, Daniel H

    2014-04-01

    Although classic Parkinson disease is the disorder most commonly associated with the clinical feature of parkinsonism, there is in fact a broader spectrum of disease represented by a collection of phenotypically similar neurodegenerative conditions that mimic many of its core features. These atypical parkinsonian disorders most commonly include progressive supranuclear palsy and corticobasal degeneration, disorders both associated with frontotemporal dementia, as well as multiple system atrophy and dementia with Lewy bodies. Although the clinical distinction of these disorders still remains a challenge to physicians, recent advances in genetics are poised to tease apart the differences. Insights into the molecular etiologies underlying these conditions will improve diagnosis, yield a better understanding of the underlying disease pathology, and ultimately lend stimulation to the development of potential treatments. At the same time, the wide range of phenotypes observed from mutations in a single gene warrants broad testing facilitated by advances in DNA sequencing. These expanding genomic approaches, ranging from the use of next-generation sequencing to identify causative or risk-associated gene variations to the study of epigenetic modification linking human genetics to environmental factors, are poised to lead the field into a new age of discovery. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  19. Eating disorders among women of childbearing age

    Directory of Open Access Journals (Sweden)

    Agnieszka Maria Bień

    2017-02-01

    Full Text Available Introduction. Nutrition is one of the fundamental human needs, which allows for the proper functioning of the body. Nowadays, people are increasingly turning attention to the type and quantity of food intake, in order to preserve health and slim. Rigorous adherence to the principles of nutrition only healthy meals can lead to disorder orthorexia nervosa, which can lead to many complications (such as weight loss, vitamin deficiencies and mineral, hormonal disorders, psychological problems. The aim of the study was to investigate the prevalence of eating disorders such orthorexia nervosa in women of childbearing age and to check whether there is a relationship between the occurrence of eating disorders and a global orientation of life of respondents. Material and method. The study included 280 women aged between 18 and 35 years old who voluntarily joined the study. The study used the questionnaire technique, consisting of the author's questionnaire and standardized research tools (ORTO-15 Questionnaire, the SCOFF Eating Disorders Questionnaire and the Sense of Coherence Scale SOC-29. Results. After conducting these studies found an association between the occurrence of eating disorders such as orthorexia nervosa to religion, and between type of eating disorder anorexia and bulimia and marital status, and body mass index (BMI. It was also shown that the lower the overall level of sense of coherence and its components is more common in individuals at risk of developing anorexia or bulimia. Conclusion. There is a relationship between the occurrence of eating disorders such as orthorexia nervosa to religion. There is a relationship between the occurrence of eating disorders such as anorexia and bulimia marital status and body mass index of women.

  20. Human Environmental Disease Network

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Audouze, Karine

    2017-01-01

    During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied...... by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information...... and their disease relationships from the reported TDDB database. The resulting human EDN takes into consideration the level of evidence of the toxicant-disease relationships allowing including some degrees of significance in the disease-disease associations. Such network can be used to identify uncharacterized...

  1. [Gender dysphoria in pervasive developmental disorders].

    Science.gov (United States)

    Tateno, Masaru; Ikeda, Hiroshi; Saito, Toshikazu

    2011-01-01

    Pervasive developmental disorders (PDD) are characterized by two essential symptoms: impairment in social interaction, and restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. PDD include autistic disorder, Asperger's disorder, and PDD-Not Otherwise Specified (PDD-NOS). These three disorders are sometimes termed autism spectrum disorders. A recent epidemiological survey demonstrated that the rate of PDD may be almost 1% and that many PDD cases might not be diagnosed properly in childhood. Erik Erikson described eight stages of psychosocial development through which a normally developing human should pass from infancy to adulthood. In the theory, an adolescent shows 'Identity vs. Role Confusion'. It has been reported that individuals with PDD often have identity crises which sometimes include gender dysphoria. This phenomenon might be related to the so-called identity diffusion in youth. When they reach their young youth, it has been said that subjects with PDD realize their uniqueness and differences compared to others, and, as a result, they may develop confusion of identity which could be exhibited as gender identity disorder. A recent study demonstrated that, amongst 204 children and adolescents who visited a GID clinic in the Netherlands, 7.8% were diagnosed with autism spectrum disorders after a careful diagnostic procedure by a multi-disciplinary team. Taken together, PDD and GID seem closely related to each other. In this paper, we present four PDD cases with gender dysphoria and related symptoms: 1) a girl with PDD who repeatedly asserted gender identity disorder (GID) symptoms in response to social isolation at school, 2) a junior high school boy with PDD and transvestism, 3) a boy diagnosed with Asperger's disorder who developed a disturbance of sexual orientation, and 4) a boy with Asperger's disorder and comorbid childhood GID. Many of the clinical symptoms related to gender dysphoria might be explained by the

  2. Topiramate in the treatment of substance related disorders: a critical review of the literature

    Science.gov (United States)

    Shinn, Ann K.; Greenfield, Shelly F.

    2013-01-01

    Objective To critically review the literature on topiramate in the treatment of substance related disorders. Data Sources A PubMed search of human studies published in English through January 2009. Study Selection 26 articles were identified and reviewed; these studies examined topiramate in disorders related to alcohol, nicotine, cocaine, methamphetamine, opioids, ecstasy, and benzodiazepines. Data Extraction Study design, sample size, topiramate dose and duration, and study outcomes were reviewed. Data Synthesis There is compelling evidence for the efficacy of topiramate in the treatment of alcohol dependence. Two trials show trends for topiramate’s superiority over oral naltrexone in alcohol dependence, while one trial suggests topiramate is inferior to disulfiram. Despite suggestive animal models, evidence for topiramate in treating alcohol withdrawal in humans is slim. Studies of topiramate in nicotine dependence show mixed results. Human laboratory studies that used acute topiramate dosing show that topiramate actually enhances the pleasurable effects of both nicotine and methamphetamine. Evidence for topiramate in the treatment of cocaine dependence is promising, but limited by small sample size. The data on opioids, benzodiazepines, and ecstasy are sparse. Conclusion Topiramate is efficacious for the treatment of alcohol dependence, but side effects may limit widespread use. While topiramate’s unique pharmacodynamic profile offers a promising theoretical rationale for use across multiple substance related disorders, heterogeneity both across and within these disorders limits topiramate’s broad applicability in treating substance related disorders. Recommendations for future research include exploration of genetic variants for more targeted pharmacotherapies. PMID:20361908

  3. Identification of de novo copy number variants associated with human disorders of sexual development.

    Directory of Open Access Journals (Sweden)

    Mounia Tannour-Louet

    Full Text Available Disorders of sexual development (DSD, ranging in severity from genital abnormalities to complete sex reversal, are among the most common human birth defects with incidence rates reaching almost 3%. Although causative alterations in key genes controlling gonad development have been identified, the majority of DSD cases remain unexplained. To improve the diagnosis, we screened 116 children born with idiopathic DSD using a clinically validated array-based comparative genomic hybridization platform. 8951 controls without urogenital defects were used to compare with our cohort of affected patients. Clinically relevant imbalances were found in 21.5% of the analyzed patients. Most anomalies (74.2% evaded detection by the routinely ordered karyotype and were scattered across the genome in gene-enriched subtelomeric loci. Among these defects, confirmed de novo duplication and deletion events were noted on 1p36.33, 9p24.3 and 19q12-q13.11 for ambiguous genitalia, 10p14 and Xq28 for cryptorchidism and 12p13 and 16p11.2 for hypospadias. These variants were significantly associated with genitourinary defects (P = 6.08×10(-12. The causality of defects observed in 5p15.3, 9p24.3, 22q12.1 and Xq28 was supported by the presence of overlapping chromosomal rearrangements in several unrelated patients. In addition to known gonad determining genes including SRY and DMRT1, novel candidate genes such as FGFR2, KANK1, ADCY2 and ZEB2 were encompassed. The identification of risk germline rearrangements for urogenital birth defects may impact diagnosis and genetic counseling and contribute to the elucidation of the molecular mechanisms underlying the pathogenesis of human sexual development.

  4. Drosophila mutants of the autism candidate gene neurobeachin (rugose) exhibit neuro-developmental disorders, aberrant synaptic properties, altered locomotion, impaired adult social behavior and activity patterns

    OpenAIRE

    Wise, Alexandra; Tenezaca, Luis; Fernandez, Robert W.; Schatoff, Emma; Flores, Julian; Ueda, Atsushi; Zhong, Xiaotian; Wu, Chun-Fang; Simon, Anne F.; Venkatesh, Tadmiri

    2015-01-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder in humans characterized by complex behavioral deficits, including intellectual disability, impaired social interactions and hyperactivity. ASD exhibits a strong genetic component with underlying multi-gene interactions. Candidate gene studies have shown that the neurobeachin gene is disrupted in human patients with idiopathic autism (Castermans et al., 2003). The gene for neurobeachin (NBEA) spans the common fragile site FRA 13A ...

  5. Using the mood disorder questionnaire and bipolar spectrum diagnostic scale to detect bipolar disorder and borderline personality disorder among eating disorder patients

    Science.gov (United States)

    2013-01-01

    Background Screening scales for bipolar disorder including the Mood Disorder Questionnaire (MDQ) and Bipolar Spectrum Diagnostic Scale (BSDS) have been plagued by high false positive rates confounded by presence of borderline personality disorder. This study examined the accuracy of these scales for detecting bipolar disorder among patients referred for eating disorders and explored the possibility of simultaneous assessment of co-morbid borderline personality disorder. Methods Participants were 78 consecutive female patients who were referred for evaluation of an eating disorder. All participants completed the mood and eating disorder sections of the SCID-I/P and the borderline personality disorder section of the SCID-II, in addition to the MDQ and BSDS. Predictive validity of the MDQ and BSDS was evaluated by Receiver Operating Characteristic analysis of the Area Under the Curve (AUC). Results Fifteen (19%) and twelve (15%) patients fulfilled criteria for bipolar II disorder and borderline personality disorder, respectively. The AUCs for bipolar II disorder were 0.78 (MDQ) and 0.78 (BDSD), and the AUCs for borderline personality disorder were 0.75 (MDQ) and 0.79 (BSDS). Conclusions Among patients being evaluated for eating disorders, the MDQ and BSDS show promise as screening questionnaires for both bipolar disorder and borderline personality disorder. PMID:23443034

  6. Intermittent explosive disorder amongst women in conflict affected Timor-Leste: associations with human rights trauma, ongoing violence, poverty, and injustice.

    Science.gov (United States)

    Rees, Susan; Silove, Derrick; Verdial, Teresa; Tam, Natalino; Savio, Elisa; Fonseca, Zulmira; Thorpe, Rosamund; Liddell, Belinda; Zwi, Anthony; Tay, Kuowei; Brooks, Robert; Steel, Zachary

    2013-01-01

    Women in conflict-affected countries are at risk of mental disorders such as posttraumatic stress disorder and depression. No studies have investigated the association between experiences of abuse and injustice and explosive anger amongst women in these settings, and the impact of anger on women's health, family relationships and ability to participate in development. A mixed methods study including an epidemiological survey (n = 1513, 92.6% response) and qualitative interviews (n = 77) was conducted in Timor-Leste. The indices measured included Intermittent Explosive Disorder, posttraumatic stress disorder; severe distress; days out of role (the number of days that the person was unable to undertake normal activities); gender-specific trauma; conflict/violence; poverty; and preoccupations with injustice. Women with Intermittent Explosive Disorder (n = 184, 12.2%) were more disabled than those without the disorder (for >5 days out of role, 40.8% versus 31.5%, X(2) (2) = 12.93 p = 0.0016). Multivariable associations with Intermittent Explosive Disorder, controlling for the presence of PTSD, psychological distress and other predictors in the model, included the sense of being sick (OR 1.73; 95% CI 1.08-2.77); victimization as a result of helping the resistance movement (OR 2.33, 95% CI 1.48-3.68); war-related trauma specific to being a woman (OR 1.95, 95%, CI 1.09-3.50); ongoing family violence and community conflict (OR 1.88, 95% CI 1.27-2.77); extreme poverty (OR 1.23, 95%, CI 1.08-1.39); and distressing preoccupations with injustice (relating to 2/3 historical periods, OR 2.10, 95% CI 1.35-3.28). In the qualitative study, women elaborated on the determinants of anger and its impact on their health, family and community functioning, child-rearing, and capacity to engage in development. Women reflected on the strategies that might help them overcome their anger. Intermittent Explosive Disorder is prevalent and disabling amongst women in conflict-affected Timor

  7. [Eating disorders].

    Science.gov (United States)

    Miyake, Yoshie; Okamoto, Yuri; Jinnin, Ran; Shishida, Kazuhiro; Okamoto, Yasumasa

    2015-02-01

    Eating disorders are characterized by aberrant patterns of eating behavior, including such symptoms as extreme restriction of food intake or binge eating, and severe disturbances in the perception of body shape and weight, as well as a drive for thinness and obsessive fears of becoming fat. Eating disorder is an important cause for physical and psychosocial morbidity in young women. Patients with eating disorders have a deficit in the cognitive process and functional abnormalities in the brain system. Recently, brain-imaging techniques have been used to identify specific brain areas that function abnormally in patients with eating disorders. We have discussed the clinical and cognitive aspects of eating disorders and summarized neuroimaging studies of eating disorders.

  8. Frequency of Different Psychiatric Disorders in Patients With Functional Bowel Disorders: A Short Report

    Directory of Open Access Journals (Sweden)

    Fakhraei

    2015-06-01

    Full Text Available Background Functional gastrointestinal (GI disorders are very common and many patients with such disorders are not satisfied with treatment outcomes. Psychological aspects of functional disorders need special attention that may play an important role in patient management. Objectives In this study, psychology evaluation was performed for a population of patients with functional bowel disorders. Patients and Methods One hundred patients with functional bowel disorders including 50 patients with irritable bowel syndrome (IBS referred to GI clinics were candidates for psychiatry evaluation; of those 60 patients completed the study. Psychiatric disorders were diagnosed using a structured clinical interview based on diagnostic and statistical manual of mental disorders IV (DSM IV. Results Of 60 patients with functional bowel disorders (including 39 IBS, 51 (85% were diagnosed with at least one psychiatry disorder. The most common disorders were dysthymia (25% and obsessive-compulsive disorder (20%. There was no significant difference between IBS patients and other functional bowel disorders regarding the prevalence of psychiatric disorders. Conclusions Psychiatric disorders are very prevalent among patients with functional bowel disorders. Prompt diagnosis and appropriate management of associated psychiatric disorders along with GI targeted treatments may lead to a better outcome in these patients.

  9. Global warming and neurodegenerative disorders: speculations on their linkage

    Science.gov (United States)

    Habibi, Laleh; Perry, George; Mahmoudi, Morteza

    2014-01-01

    Climate change is having considerable impact on biological systems. Eras of ice ages and warming shaped the contemporary earth and origin of creatures including humans. Warming forces stress conditions on cells. Therefore, cells evolved elaborate defense mechanisms, such as creation of heat shock proteins, to combat heat stress. Global warming is becoming a crisis and this process would yield an undefined increasing rate of neurodegenerative disorders in future decades. Since heat stress is known to have a degenerative effects on neurons and, conversely, cold conditions have protective effect on these cells, we hypothesize that persistent heat stress forced by global warming might play a crucial role in increasing neurodegenerative disorders. PMID:25671171

  10. Should Relational Aggression Be Included in DSM-V?

    Science.gov (United States)

    Keenan, Kate; Coyne, Claire; Lahey, Benjamin B.

    2008-01-01

    The study examines whether relational aggression should be included in DSM-V disruptive behavior disorders. The results conclude that some additional information is gathered from assessing relational aggression but not enough to be included in DSM-V.

  11. Gendered mental disorders: masculine and feminine stereotypes about mental disorders and their relation to stigma.

    Science.gov (United States)

    Boysen, Guy; Ebersole, Ashley; Casner, Robert; Coston, Nykhala

    2014-01-01

    Research indicates that stereotypes can intersect. For example, the intersection of stereotypes about gender and mental disorders could result in perceptions of gendered mental disorders. In the current research, Studies 1 and 2 showed that people view specific disorders as being masculine or feminine. The masculine stereotype included antisocial personality disorder, addictions, and paraphilias. The feminine stereotype included eating disorders, histrionic personality disorder, body dysmorphia, and orgasmic disorder. In both studies, the perception of disorders as masculine was positively correlated with stigma. Study 3 showed that the positive correlation between masculinity and stigma also occurred when examining specific symptoms rather than full mental disorders. The findings provide further evidence for the intersection of stereotypes and indicate a novel factor in the understanding of stigma.

  12. Paediatric Anxiety Disorders

    Directory of Open Access Journals (Sweden)

    Beena Johnson

    2017-07-01

    Full Text Available Anxiety disorders are highly prevalent among children and are associated with serious morbidity. Lifetime prevalence of paediatric anxiety disorders is about fifteen percent. Social phobia, generalized anxiety disorder and separation anxiety disorder are included in the triad of paediatric anxiety disorders. Specific phobia, obsessive compulsive disorder and post-traumatic stress disorder are also commonly seen in children. Overprotection by parents, parental death or separation, female sex, low educational status, family history of anxiety disorder, financial stress in family and adverse childhood experiences are risk factors for the development of anxiety disorders. If not diagnosed and managed at the earliest, paediatric anxiety disorders can cause life threatening problems in the future. Hence early and scientific management of anxiety disorders is essential. Cognitive behavioural therapy is the effective evidence based treatment for paediatric anxiety disorders.

  13. Sleep disorders, obesity, and aging: the role of orexin.

    Science.gov (United States)

    Nixon, Joshua P; Mavanji, Vijayakumar; Butterick, Tammy A; Billington, Charles J; Kotz, Catherine M; Teske, Jennifer A

    2015-03-01

    The hypothalamic neuropeptides orexin A and B (hypocretin 1 and 2) are important homeostatic mediators of central control of energy metabolism and maintenance of sleep/wake states. Dysregulation or loss of orexin signaling has been linked to narcolepsy, obesity, and age-related disorders. In this review, we present an overview of our current understanding of orexin function, focusing on sleep disorders, energy balance, and aging, in both rodents and humans. We first discuss animal models used in studies of obesity and sleep, including loss of function using transgenic or viral-mediated approaches, gain of function models using exogenous delivery of orexin receptor agonist, and naturally-occurring models in which orexin responsiveness varies by individual. We next explore rodent models of orexin in aging, presenting evidence that orexin loss contributes to age-related changes in sleep and energy balance. In the next section, we focus on clinical importance of orexin in human obesity, sleep, and aging. We include discussion of orexin loss in narcolepsy and potential importance of orexin in insomnia, correlations between animal and human studies of age-related decline, and evidence for orexin involvement in age-related changes in cognitive performance. Finally, we present a summary of recent studies of orexin in neurodegenerative disease. We conclude that orexin acts as an integrative homeostatic signal influencing numerous brain regions, and that this pivotal role results in potential dysregulation of multiple physiological processes when orexin signaling is disrupted or lost. Published by Elsevier B.V.

  14. Syndromes, Disorders and Maternal Risk Factors Associated With Neural Tube Defects (VI

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2008-09-01

    Full Text Available Neural tube defects (NTDs may be associated with syndromes, disorders, and maternal and fetal risk factors. This article provides a comprehensive review of the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, including maternal fumonisin consumption, periconceptional zinc deficiency, parental occupational exposure and residential proximity to pesticides, lower socioeconomic status, fetal alcohol syndrome, mutations in the VANGL1 gene, human athymic Nude/SCID fetus, and single nucleotide polymorphism in the NOS3 gene. NTDs associated with these syndromes, disorders, and maternal and fetal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.

  15. Ensuring effective prevention of iodine-deficiency disorders

    DEFF Research Database (Denmark)

    Völzke, Henry; Caron, Philippe Jean; Dahl, Lisbeth

    2016-01-01

    BACKGROUND: Programs initiated to prevent iodine deficiency disorders (IDD) may not remain effective due to changes in government policies, commercial factors, and human behavior that may affect the efficacy of IDD prevention programs in unpredictable directions. Monitoring and outcome studies...... by the lack of centralized standardization procedures. In addition, data on outcomes and the cost of achieving them are needed in order to provide evidence of the beneficial effects of IDD prevention in countries with mild iodine deficiency. CONCLUSION: Monitoring studies can be optimized by including...... in mildly iodine-deficient areas and that it should include populations from regions with different environmental, ethnic, and cultural backgrounds....

  16. Treatment of middle ear ventilation disorders: sheep as animal model for stenting the human Eustachian tube--a cadaver study.

    Directory of Open Access Journals (Sweden)

    Felicitas Miller

    Full Text Available Eustachian tube disorders can lead to chronic otitis media with consecutive conductive hearing loss. To improve treatment and to develop new types of implants such as stents, an adequate experimental animal model is required. As the middle ear of sheep is known to be comparable to the human middle ear, the dimensions of the Eustachian tube in two strains of sheep were investigated. The Eustachian tube and middle ear of half heads of heathland and blackface sheep were filled with silicone rubber, blended with barium sulfate to induce X-ray visibility. Images were taken by digital volume tomography. The tubes were segmented, and a three-dimensional model of every Eustachian tube was generated. The lengths, diameters and shapes were determined. Additionally, the feasibility of endoscopic stent implantation and fixation was tested in cadaver experiments. The length of the tube between ostium pharyngeum and the isthmus and the diameters were comparable to published values for the human tube. The tube was easily accessible through the nose, and then stents could be implanted and fixed at the isthmus. The sheep appears to be a promising model for testing new stent treatments for middle ear ventilation disorders.

  17. What characteristics of primary anxiety disorders predict subsequent major depressive disorder?

    Science.gov (United States)

    Bittner, Antje; Goodwin, Renee D; Wittchen, Hans-Ulrich; Beesdo, Katja; Höfler, Michael; Lieb, Roselind

    2004-05-01

    The goal of this study was to examine the associations between specific anxiety disorders and the risk of major depressive disorder and to explore the role of various clinical characteristics of anxiety disorders in these relationships using a prospective, longitudinal design. The data are from a 4-year prospective, longitudinal community study, which included both baseline and follow-up survey data on 2548 adolescents and young adults aged 14 to 24 years at baseline. DSM-IV diagnoses were made using the Munich-Composite International Diagnostic Interview. The presence at baseline of any anxiety disorder (odds ratio [OR] = 2.2 [95% CI = 1.6 to 3.2]) and each of the anxiety disorders (specific phobia, OR = 1.9 [95% CI = 1.3 to 2.8]; social phobia, OR = 2.9 [95% CI = 1.7 to 4.8]; agoraphobia, OR = 3.1 [95% CI = 1.4 to 6.7]; panic disorder, OR = 3.4 [95% CI = 1.2 to 9.0]; generalized anxiety disorder, OR = 4.5 [95% CI = 1.9 to 10.3]) was associated with a significantly (p depressive disorder. These associations remained significant after we adjusted for mental disorders occurring prior to the onset of the anxiety disorder, with the exception of the panic disorder association. The following clinical characteristics of anxiety disorders were associated with a significantly (p depressive disorder: more than 1 anxiety disorder, severe impairment due to the anxiety disorder, and comorbid panic attacks. In the final model, which included all clinical characteristics, severe impairment remained the only clinical characteristic that was an independent predictor of the development of major depressive disorder (OR = 2.2 [95% CI = 1.0 to 4.4]). Our findings suggest that anxiety disorders are risk factors for the first onset of major depressive disorder. Although a number of clinical characteristics of anxiety disorders appear to play a role in the association between anxiety disorders and depression, severe impairment is the strongest predictor of major depressive disorder.

  18. Oat have multifunctional uses including animal feed, human food ...

    African Journals Online (AJOL)

    Akademia Rolnicza

    2014-07-11

    Jul 11, 2014 ... 10 Judyma Street, 71-460 Szczecin, Poland. (Received 1 ... Increasing interest in oat utilization for human consumption has been stimulated by the need for ... Helium was used as a carrier gas at a flow rate of 1.4 cm3/min.

  19. [Nutritional aspects of attention-deficit/hyperactive disorder].

    Science.gov (United States)

    Quintero, J; Rodríguez-Quirós, J; Correas-Lauffer, J; Pérez-Templado, J

    Attention-deficit/hyperactive disorder (ADHD) has received in the past years a lot of attention from the paediatrician's specialties. Even though the studies of its etiopathology have advanced, mainly the ones related with genetics and neuroimaging, the final cause today is still unclear. It has been related to many factors such as diet, like some allergies to additives, toxicity to heavy metals and other toxic substances from the environment, due to low protein diets with a high carbohydrate content, unbalanced minerals, essential fatty acids and phospholipid deficit, amino acid deficits, thyroid disorders, and vitamin B complex disorders and phytochemicals. The way our lifestyle has changed in general and the diet in particular nowadays is being considered as a hypothesis for many disorders and health problems, but what about ADHD? One of the changes that we want to emphasize is related to vegetable fat and oils that dominate human consumption and the reduction income of fatty acids from the omega-3 family, including alpha-linolenic acid, eicosapentaenoic acid and docosapentaenoic acid. The fact is even worse when the amount of omega-6 increases and the ratio between both changes. It is a fact that these kinds of nutrients play an important role in the nervous system development. In this paper the essential fatty acids in neuropsychiatric disorders in general, ADHD in particular, is reviewed.

  20. Narcissistic Personality Disorder and suicidal behavior in mood disorders.

    Science.gov (United States)

    Coleman, Daniel; Lawrence, Ryan; Parekh, Amrita; Galfalvy, Hanga; Blasco-Fontecilla, Hilario; Brent, David A; Mann, J John; Baca-Garcia, Enrique; Oquendo, Maria A

    2017-02-01

    The relationship of Narcissistic Personality Disorder (NPD) to suicidal behavior is understudied. The modest body of existing research suggests that NPD is protective against low-lethality suicide attempts, but is associated with high lethality attempts. Mood-disordered patients (N = 657) received structured interviews including Axis I and II diagnosis and standardized clinical measures. Following chi-square and t-tests, a logistical regression model was constructed to identify predictors of suicide attempt. While there was no bivariate relationship of NPD on suicide attempt, in the logistic regression patients with NPD were 2.4 times less likely to make a suicide attempt (OR = 0.41; 95% CI = 0.19 - 0.88; p disorder, and to have high aggression and hostility scores. Limitations include that the sample consists of only mood-disordered patients, a modest sample size of NPD, and the data are cross-sectional. The multivariate protective effect of NPD on suicide attempt is consistent with most previous research. The lower impulsivity of NPD patients and less severe personality pathology relative to other personality disorders may contribute to this effect. No relationship of NPD to attempt lethality was found, contradicting other research, but perhaps reflecting differences between study samples. Future studies should oversample NPD patients and include suicide death as an outcome. Clinical implications include discussion of individualized suicide risk assessment with NPD patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Genome-wide analysis of protein disorder in Arabidopsis thaliana: implications for plant environmental adaptation.

    Science.gov (United States)

    Pietrosemoli, Natalia; García-Martín, Juan A; Solano, Roberto; Pazos, Florencio

    2013-01-01

    Intrinsically disordered proteins/regions (IDPs/IDRs) are currently recognized as a widespread phenomenon having key cellular functions. Still, many aspects of the function of these proteins need to be unveiled. IDPs conformational flexibility allows them to recognize and interact with multiple partners, and confers them larger interaction surfaces that may increase interaction speed. For this reason, molecular interactions mediated by IDPs/IDRs are particularly abundant in certain types of protein interactions, such as those of signaling and cell cycle control. We present the first large-scale study of IDPs in Arabidopsis thaliana, the most widely used model organism in plant biology, in order to get insight into the biological roles of these proteins in plants. The work includes a comparative analysis with the human proteome to highlight the differential use of disorder in both species. Results show that while human proteins are in general more disordered, certain functional classes, mainly related to environmental response, are significantly more enriched in disorder in Arabidopsis. We propose that because plants cannot escape from environmental conditions as animals do, they use disorder as a simple and fast mechanism, independent of transcriptional control, for introducing versatility in the interaction networks underlying these biological processes so that they can quickly adapt and respond to challenging environmental conditions.

  2. An Emerging Role for Long Non-Coding RNA Dysregulation in Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Elio Scarpini

    2013-10-01

    Full Text Available A novel class of transcripts, long non coding RNAs (lncRNAs, has recently emerged as key players in several biological processes, including dosage compensation, genomic imprinting, chromatin regulation, embryonic development and segmentation, stem cell pluripotency, cell fate determination and potentially many other biological processes, which still are to be elucidated. LncRNAs are pervasively transcribed in the genome and several lines of evidence correlate dysregulation of different lncRNAs to human diseases including neurological disorders. Although their mechanisms of action are yet to be fully elucidated, evidence suggests lncRNA contributions to the pathogenesis of a number of diseases. In this review, the current state of knowledge linking lncRNAs to different neurological disorders is discussed and potential future directions are considered.

  3. An Emerging Role for Long Non-Coding RNA Dysregulation in Neurological Disorders

    Science.gov (United States)

    Fenoglio, Chiara; Ridolfi, Elisa; Galimberti, Daniela; Scarpini, Elio

    2013-01-01

    A novel class of transcripts, long non coding RNAs (lncRNAs), has recently emerged as key players in several biological processes, including dosage compensation, genomic imprinting, chromatin regulation, embryonic development and segmentation, stem cell pluripotency, cell fate determination and potentially many other biological processes, which still are to be elucidated. LncRNAs are pervasively transcribed in the genome and several lines of evidence correlate dysregulation of different lncRNAs to human diseases including neurological disorders. Although their mechanisms of action are yet to be fully elucidated, evidence suggests lncRNA contributions to the pathogenesis of a number of diseases. In this review, the current state of knowledge linking lncRNAs to different neurological disorders is discussed and potential future directions are considered. PMID:24129177

  4. A model for Huanglongbing spread between citrus plants including delay times and human intervention

    Science.gov (United States)

    Vilamiu, Raphael G. d'A.; Ternes, Sonia; Braga, Guilherme A.; Laranjeira, Francisco F.

    2012-09-01

    The objective of this work was to present a compartmental deterministic mathematical model for representing the dynamics of HLB disease in a citrus orchard, including delay in the disease's incubation phase in the plants, and a delay period on the nymphal stage of Diaphorina citri, the most important HLB insect vector in Brazil. Numerical simulations were performed to assess the possible impacts of human detection efficiency of symptomatic plants, as well as the influence of a long incubation period of HLB in the plant.

  5. DSP30 and interleukin-2 as a mitotic stimulant in B-cell disorders including those with a low disease burden.

    Science.gov (United States)

    Dun, Karen A; Riley, Louise A; Diano, Giuseppe; Adams, Leanne B; Chiu, Eleanor; Sharma, Archna

    2018-05-01

    Chromosome abnormalities detected during cytogenetic investigations for B-cell malignancy offer prognostic information that can have wide ranging clinical impacts on patients. These impacts may include monitoring frequency, treatment type, and disease staging level. The use of the synthetic oligonucleotide DSP30 combined with interleukin 2 (IL2) has been described as an effective mitotic stimulant in B-cell disorders, not only in chronic lymphocytic leukemia (CLL) but also in a range of other B-cell malignancies. Here, we describe the comparison of two B-cell mitogens, lipopolysaccharide (LPS), and DSP30 combined with IL2 as mitogens in a range of common B-cell disorders excluding CLL. The results showed that DSP30/IL2 was an effective mitogen in mature B-cell disorders, revealing abnormal cytogenetic results in a range of B-cell malignancies. The abnormality rate increased when compared to the use of LPS to 64% (DSP30/IL2) from 14% (LPS). In a number of cases the disease burden was proportionally very low, less than 10% of white cells. In 37% of these cases, the DSP30 culture revealed abnormal results. Importantly, we also obtained abnormal conventional cytogenetics results in 3 bone marrow cases in which immunophenotyping showed an absence of an abnormal B-cell clone. In these cases, the cytogenetics results correlated with the provisional diagnosis and altered their staging level. The use of DSP30 and IL2 is recommended for use in many B-cell malignancies as an effective mitogen and their use has been shown to enable successful culture of the malignant clone, even at very low levels of disease. © 2018 Wiley Periodicals, Inc.

  6. Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders.

    Science.gov (United States)

    Carter, Anthony M

    2011-04-01

    Deep trophoblast invasion in the placental bed has been considered the hallmark of human pregnancy. It occurs by two routes, interstitial and endovascular, and results in transformation of the walls of the spiral arteries as they traverse the decidua and the inner third of the myometrium. Disturbances in this process are associated with reproductive disorders such preeclampsia. In contrast, trophoblast invasion in Old World monkeys occurs only by the endovascular route and seldom reaches the myometrium. Recently, it was shown that this pattern is maintained in gibbons, but that the human arrangement also occurs in chimpanzee and gorilla. There is an interesting parallel with results from placental immunology regarding the evolution of the major histocompatability complex class I antigen HLA-C and its cognate receptors. HLA-C is not present in Old World monkeys or gibbons. It emerged in the orangutan and became polymorphic in the lineage leading to gorilla, bonobo, chimpanzee, and human. Interaction between HLA-C1 and HLA-C2 on the surface of trophoblast and killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer cells are important regulators of trophoblast invasion. Evolution of this system in great apes may have been one prerequisite for deep trophoblast invasion but seems to have come at a price. The evidence now suggests that certain combinations of maternal genotype for KIRs and fetal genotype for HLA-C imply an increased risk of preeclampsia, fetal growth restriction, and recurrent abortion. The fetal genotype is in part derived from the father providing an explanation for the paternal contribution to reproductive disorders.

  7. Clinical Uses of Melatonin in Neurological Diseases and Mental and Behavioural Disorders.

    Science.gov (United States)

    Sanchez-Barcelo, Emilio J; Rueda, Noemi; Mediavilla, María D; Martinez-Cue, Carmen; Reiter, Russel J

    2017-11-20

    Melatonin is a molecule with numerous properties applicable to the treatment of neurological diseases. Among these properties are the following: potent scavenger of oxygen and nitrogen reactive species, anti-inflammatory features, immuno-enhancing nature, and modulation of circadian rhythmicity. Furthermore, low concentrations of melatonin are usually found in patients with neurological diseases and mental disorders. The positive results obtained in experimental models of diverse pathologies, including diseases of the nervous system (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, epilepsy, headaches, etc.) as well as mental and behavioural disordes (e.g., autism spectrum disorders, attention-deficit hyperactivity disorders, etc.), have served as a basis for the design of clinical trials to study melatonin's possible usefulness in human pathology, although the satisfactory results obtained from the laboratory "bench" are not always applicable to the patient's "bedside". In this article, we review those papers describing the results of the administration of melatonin to humans for various therapeutic purposes in the field of neuropathology. Clinical trials with strong methodologies and appropriate doses of melatonin are necessary to support or reject the usefulness of melatonin in neurological diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. The Comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) in Children and Arabic Speech Sound Disorder

    Science.gov (United States)

    Hariri, Ruaa Osama

    2016-01-01

    Children with Attention-Deficiency/Hyperactive Disorder (ADHD) often have co-existing learning disabilities and developmental weaknesses or delays in some areas including speech (Rief, 2005). Seeing that phonological disorders include articulation errors and other forms of speech disorders, studies pertaining to children with ADHD symptoms who…

  9. Shift, Interrupted: Strategies for Managing Difficult Patients Including Those with Personality Disorders and Somatic Symptoms in the Emergency Department.

    Science.gov (United States)

    Moukaddam, Nidal; AufderHeide, Erin; Flores, Araceli; Tucci, Veronica

    2015-11-01

    Difficult patients are often those who present with a mix of physical and psychiatric symptoms, and seem refractory to usual treatments or reassurance. such patients can include those with personality disorders, those with somatization symptoms; they can come across as entitled, drug-seeking, manipulative, or simply draining to the provider. Such patients are often frequent visitors to Emergency Departments. Other reasons for difficult encounters could be rooted in provider bias or countertransference, rather than sole patient factors. Emergency providers need to have high awareness of these possibilities, and be prepared to manage such situations, otherwise workup can be sub-standard and dangerous medical mistakes can be made. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Functional esophageal disorders

    OpenAIRE

    Clouse, R; Richter, J; Heading, R; Janssens, J; Wilson, J

    1999-01-01

    The functional esophageal disorders include globus, rumination syndrome, and symptoms that typify esophageal diseases (chest pain, heartburn, and dysphagia). Factors responsible for symptom production are poorly understood. The criteria for diagnosis rest not only on compatible symptoms but also on exclusion of structural and metabolic disorders that might mimic the functional disorders. Additionally, a functional diagnosis is precluded by the presence of a pathology-based motor disorder or p...

  11. Tic disorders and Tourette's syndrome

    DEFF Research Database (Denmark)

    Plessen, Kerstin J

    2012-01-01

    Diagnostic categories of tic disorders include both transient and chronic tic disorders and Tourette's disorder. Changes for this group of disorders proposed for the forthcoming DSM-5 system include: (1) The term "stereotyped" will be eliminated in the definition of tics and the new definition...... will be applied consistently across all entities of tic disorders; (2) the diagnosis "Transient Tic Disorder" will change its name to "Provisional Tic Disorder"; (3) introduction of two new categories in individuals whose tics are triggered by illicit drugs or by a medical condition; (4) specification of chronic...... tic disorders into those with motor tics or with vocal tics only; (5) specification of the absence of a period longer than 3 months without tics will disappear for Tourette's Disorder. This overview discusses a number of implications resulting from these diagnostic modifications of the diagnostic...

  12. Meige's Syndrome: Rare Neurological Disorder Presenting as Conversion Disorder.

    Science.gov (United States)

    Debadatta, Mohapatra; Mishra, Ajay K

    2013-07-01

    Meige's syndrome is a rare neurological syndrome characterized by oromandibular dystonia and blepharospasm. Its pathophysiology is not clearly determined. A 35-year-old female presented to psychiatric department with blepharospasm and oromandibular dystonia with clinical provisional diagnosis of psychiatric disorder (Conversion Disorder). After thorough physical examination including detailed neurological exam and psychiatric evaluation no formal medical or psychiatric diagnosis could be made. The other differential diagnoses of extra pyramidal symptom, tardive dyskinesia, conversion disorder, anxiety disorder were ruled out by formal diagnostic criteria. Consequently with suspicion of Meige's syndrome she was referred to the department of Neurology and the diagnosis was confirmed. Hence, Meige's syndrome could be misdiagnosed as a psychiatric disorder such as conversion disorder or anxiety disorder because clinical features of Meige's syndrome are highly variable and affected by psychological factors and also can be inhibited voluntarily to some extent.

  13. Comorbid personality disorders in subjects with panic disorder: which personality disorders increase clinical severity?

    Directory of Open Access Journals (Sweden)

    Mustafa Ozkan

    2003-03-01

    Full Text Available Personality disorders are common in subjects with panic disorder. Personality disorders have shown to affect the course of panic disorder. The purpose of this study was to examine which personality disorders effect clinical severity in subjects with panic disorder. This study included 122 adults (71 female, 41 male, who met DSM-IV criteria for panic disorder (with or without agoraphobia. Clinical assessment was conducted by using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I, the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II and the Panic and Agoraphobia Scale (PAS, Global Assessment Functioning Scale (GAF, Beck Depression Inventory (BDI, and State-Trait Anxiety Inventory (STAI. Patients who had a history of sexual abuse were assessed with Sexual Abuse Severity Scale. Logistic regressions were used to identify predictors of suicide attempts, suicidal ideation, agoraphobia, different panic attack symptoms, sexual abuse, and early onset of disorders. The rates of comorbid Axis I and Axis II psychiatric disorders were 80.3% and 33.9%, consecutively, in patients with panic disorder. Panic disorder patients with comorbid personality disorders had more severe anxiety, depression and agoraphobia symptoms, and had earlier ages of onset, and lower levels of functioning. The rates of suicidal ideation and suicide attempts were 34.8% and 9.8%, consecutively, in subjects with panic disorder. The rate of patients with panic disorder had a history of childhood sexual abuse was 12.5%. The predictor of sexual abuse was more than one comorbid Axis II diagnosis. The predictors of suicide attempt were comorbid paranoid and borderline personality disorders, and the predictor of suicidal ideation was major depressive disorder in subjects with panic disorder. In conclusion, this study documents that comorbid personality disorders increase the clinical severity of panic disorder. Patients with more than one

  14. The overlap between binge eating disorder and substance use disorders

    DEFF Research Database (Denmark)

    Schreiber, Liana R N; Odlaug, Brian Lawrence; Grant, Jon E

    2013-01-01

    BACKGROUND AND AIMS: Binge eating disorder (BED) is a relatively common condition, especially in young adult females, and is characterized by chronic over-consumption of food resulting in embarrassment, distress, and potential health problems. It is formally included as a disorder in DSM-5...... use disorder, binging, obesity, food addiction, comorbidity, dopamine, opioid, serotonin, glutamate, and pharmacological treatment were the keywords used in searching. RESULTS: BED shares similar phenomenology to SUD, including significant urges to engage in binging episodes, resulting in distress...... and impairment. Similar neurobiological pathways are found in both BED and SUD and medications based on similar neurobiology have been examined for both disorders. A subset of individuals with BED may have a "food addiction", but there is no clinical agreement on the meaning of "food addiction". Exploring...

  15. Intermittent Explosive Disorder amongst Women in Conflict Affected Timor-Leste: Associations with Human Rights Trauma, Ongoing Violence, Poverty, and Injustice

    Science.gov (United States)

    Rees, Susan; Silove, Derrick; Verdial, Teresa; Tam, Natalino; Savio, Elisa; Fonseca, Zulmira; Thorpe, Rosamund; Liddell, Belinda; Zwi, Anthony; Tay, Kuowei; Brooks, Robert; Steel, Zachary

    2013-01-01

    Introduction Women in conflict-affected countries are at risk of mental disorders such as posttraumatic stress disorder and depression. No studies have investigated the association between experiences of abuse and injustice and explosive anger amongst women in these settings, and the impact of anger on women's health, family relationships and ability to participate in development. Methods A mixed methods study including an epidemiological survey (n = 1513, 92.6% response) and qualitative interviews (n = 77) was conducted in Timor-Leste. The indices measured included Intermittent Explosive Disorder, posttraumatic stress disorder; severe distress; days out of role (the number of days that the person was unable to undertake normal activities); gender-specific trauma; conflict/violence; poverty; and preoccupations with injustice. Results Women with Intermittent Explosive Disorder (n = 184, 12.2%) were more disabled than those without the disorder (for >5 days out of role, 40.8% versus 31.5%, X2 (2)  = 12.93 p = 0.0016). Multivariable associations with Intermittent Explosive Disorder, controlling for the presence of PTSD, psychological distress and other predictors in the model, included the sense of being sick (OR 1.73; 95% CI 1.08–2.77); victimization as a result of helping the resistance movement (OR 2.33, 95% CI 1.48–3.68); war-related trauma specific to being a woman (OR 1.95, 95%, CI 1.09–3.50); ongoing family violence and community conflict (OR 1.88, 95% CI 1.27–2.77); extreme poverty (OR 1.23, 95%, CI 1.08–1.39); and distressing preoccupations with injustice (relating to 2/3 historical periods, OR 2.10, 95% CI 1.35–3.28). In the qualitative study, women elaborated on the determinants of anger and its impact on their health, family and community functioning, child-rearing, and capacity to engage in development. Women reflected on the strategies that might help them overcome their anger. Conclusions Intermittent Explosive Disorder

  16. Intermittent explosive disorder amongst women in conflict affected Timor-Leste: associations with human rights trauma, ongoing violence, poverty, and injustice.

    Directory of Open Access Journals (Sweden)

    Susan Rees

    Full Text Available INTRODUCTION: Women in conflict-affected countries are at risk of mental disorders such as posttraumatic stress disorder and depression. No studies have investigated the association between experiences of abuse and injustice and explosive anger amongst women in these settings, and the impact of anger on women's health, family relationships and ability to participate in development. METHODS: A mixed methods study including an epidemiological survey (n = 1513, 92.6% response and qualitative interviews (n = 77 was conducted in Timor-Leste. The indices measured included Intermittent Explosive Disorder, posttraumatic stress disorder; severe distress; days out of role (the number of days that the person was unable to undertake normal activities; gender-specific trauma; conflict/violence; poverty; and preoccupations with injustice. RESULTS: Women with Intermittent Explosive Disorder (n = 184, 12.2% were more disabled than those without the disorder (for >5 days out of role, 40.8% versus 31.5%, X(2 (2 = 12.93 p = 0.0016. Multivariable associations with Intermittent Explosive Disorder, controlling for the presence of PTSD, psychological distress and other predictors in the model, included the sense of being sick (OR 1.73; 95% CI 1.08-2.77; victimization as a result of helping the resistance movement (OR 2.33, 95% CI 1.48-3.68; war-related trauma specific to being a woman (OR 1.95, 95%, CI 1.09-3.50; ongoing family violence and community conflict (OR 1.88, 95% CI 1.27-2.77; extreme poverty (OR 1.23, 95%, CI 1.08-1.39; and distressing preoccupations with injustice (relating to 2/3 historical periods, OR 2.10, 95% CI 1.35-3.28. In the qualitative study, women elaborated on the determinants of anger and its impact on their health, family and community functioning, child-rearing, and capacity to engage in development. Women reflected on the strategies that might help them overcome their anger. CONCLUSIONS: Intermittent Explosive Disorder is prevalent and

  17. Is it Important to Talk About Technologies with Eating Disorder Clients? The Health-Care Professional Perspective

    Czech Academy of Sciences Publication Activity Database

    Šmahelová, M.; Čevelíček, M.; Nehybková, E.; Šmahel, D.; Čermák, Ivo

    2017-01-01

    Roč. 32, říjen (2017), s. 1-8 ISSN 1041-0236 Institutional support: RVO:68081740 Keywords : eating disorders * technology * treatment * anorexia nervosa * bulimia nervosa Subject RIV: AN - Psychology OBOR OECD: Psychology (including human - machine relations) Impact factor: 1.487, year: 2016

  18. [Circadian blood pressure variation under several pathophysiological conditions including secondary hypertension].

    Science.gov (United States)

    Imai, Yutaka; Hosaka, Miki; Satoh, Michihiro

    2014-08-01

    Abnormality of circadian blood pressure (BP) variation, i.e. non-dipper, riser, nocturnal hypertension etc, is brought by several pathophysiological conditions especially by secondary hypertension. These pathophysiological conditions are classified into several categories, i.e. disturbance of autonomic nervous system, metabolic disorder, endocrine disorder, disorder of Na and water excretion (e.g. sodium sensitivity), severe target organ damage and ischemia, cardiovascular complications and drug induced hypertension. Each pathophysiological condition which brings disturbance of circadian BP variation is included in several categories, e.g. diabetes mellitus is included in metabolic disorder, autonomic imbalance, sodium sensitivity and endocrine disorder. However, it seems that unified principle of the genesis of disturbance of circadian BP variation in many pathophysiological conditions is autonomic imbalance. Thus, it is concluded that disturbance of circadian BP variation is not purposive biological behavior but the result of autonomic imbalance which looks as if compensatory reaction such as exaggerated Na-water excretion during night in patient with Na-water retention who reveals disturbed circadian BP variation.

  19. Thyroid hormone effect on human mitochondria measured by flow cytometry

    DEFF Research Database (Denmark)

    Kvetny, Jan; Bomholt, Tobias; Pedersen, Palle

    2009-01-01

    BACKGROUND: Mitochondrial function may be impaired in a number of diseases including metabolic syndrome, cardiovascular disease and endocrine disorders. Therefore it is important to be able to measure mitochondrial function in human cells. PURPOSE: The aim of the present study was to evaluate a m...

  20. Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens

    NARCIS (Netherlands)

    Xu, J.; Saunders, C.; Hu, P.; Grant, R.A.; Boekhout, T.; Kuramae, E.E.; Kronstad, J.W.; DeAngelis, Y.M.; Reeder, N.L.; Johnstone, K.R.; Leland, M.; Fieno, A.M.; Begley, W.M.; Sun, Y.; Lacey, M.P.; Chaudhary, T.; Keough, T.; Chu, L.; Sears, R.; Yuan, B.; Dawson Jr., T.L.

    2007-01-01

    Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect >50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably

  1. Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens

    NARCIS (Netherlands)

    Xu, Jun; Saunders, Charles W.; Hu, Ping; Grant, Raymond A.; Boekhout, Teun; Kuramae, Eiko E.; Kronstad, James W.; DeAngelis, Yvonne M.; Reeder, Nancy L.; Johnstone, Kevin R.; Leland, Meredith; Fieno, Angela M.; Begley, William M.; Sun, Yiping; Lacey, Martin P.; Chaudhary, Tanuja; Keough, Thomas; Chu, Lien; Sears, Russell; Yuan, Bo; Dawson, Thomas L.

    2007-01-01

    Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect > 50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably

  2. Stereotyped movement disorder in ICD-11.

    Science.gov (United States)

    Stein, Dan J; Woods, Douglas W

    2014-01-01

    According to current proposals for ICD-11, stereotyped movement disorder will be classified in the grouping of neurodevelopmental disorders, with a qualifier to indicate whether self-injury is present, similar to the classification of stereotypic movement disorder in DSM-5. At the same time, the WHO ICD-11 Working Group on the Classification of Obsessive-Compulsive and Related Disorders has proposed a grouping of body-focused repetitive behavior disorders within the obsessive-compulsive and related disorders (OCRD) cluster to include trichotillomania and skin-picking disorder. DSM-5 has taken a slightly different approach: trichotillomania and excoriation (skin picking) disorder are included in the OCRD grouping, while body-focused repetitive behavior disorder is listed under other specified forms of OCRD. DSM-5 also includes a separate category of nonsuicidal self-injury in the section on "conditions for further study." There are a number of unresolved nosological questions regarding the relationships among stereotyped movement disorder, body-focused repetitive behavior disorders, and nonsuicidal self-injury. In this article, we attempt to provide preliminary answers to some of these questions as they relate to the ICD-11 classification of mental and behavioral disorders.

  3. Age-dependent effects of methylphenidate on the human dopaminergic system in young vs adult patients with attention-deficit/hyperactivity disorder: A randomized clinical trial

    NARCIS (Netherlands)

    Schrantee, A. (Anouk); Tamminga, H.G.H. (Hyke G. H.); C. Bouziane (Cheima); Bottelier, M.A. (Marco A.); E.E. Bron (Esther); H.J.M.M. Mutsaerts (Henri J. M.); A.H. Zwinderman (Ailko); Groote, I.R. (Inge R.); S.A.R.B. Rombouts (Serge); Lindauer, R.J.L. (Ramon J. L.); S. Klein (Stefan); W.J. Niessen (Wiro); B.C. Opmeer (Brent); Boer, F. (Frits); P.J. Lucassen; Andersen, S.L. (Susan L.); H.M. Geurts (Hilde ); L. Reneman (Liesbeth)

    2016-01-01

    textabstractIMPORTANCE Although numerous children receivemethylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly lasting effects of methylphenidate on the human dopaminergic system. OBJECTIVES To determine

  4. Lingual dyskinesia and tics: a novel presentation of copper-metabolism disorder.

    Science.gov (United States)

    Goez, Helly R; Jacob, Francois D; Yager, Jerome Y

    2011-02-01

    Copper is a trace element that is required for cellular respiration, neurotransmitter biosynthesis, pigment formation, antioxidant defense, peptide amidation, and formation of connective tissue. Abnormalities of copper metabolism have been linked with neurologic disorders that affect movement, such as Wilson disease and Menkes disease; however, the diagnosis of non-Wilson, non-Menkes-type copper-metabolism disorders has been more elusive, especially in cases with atypical characteristics. We present here the case of an adolescent with a novel presentation of copper-metabolism disorder who exhibited acute severe hemilingual dyskinesia and prominent tics, with ballismus of the upper limbs, but had normal brain and spinal MRI results and did not show any signs of dysarthria or dysphagia. His serum copper and ceruloplasmin levels were low, but his urinary copper level was elevated after penicillamine challenge. We conclude that copper-metabolism disorders should be included in the differential diagnosis for movement disorders, even in cases with highly unusual presentations, because many of them are treatable. Moreover, a connection between copper-metabolism disorders and tics is presented, to our knowledge, for the first time in humans; further investigation is needed to better establish this connection and understand its underlying pathophysiology.

  5. Psychiatric emergencies (part II): psychiatric disorders coexisting with organic diseases.

    Science.gov (United States)

    Testa, A; Giannuzzi, R; Sollazzo, F; Petrongolo, L; Bernardini, L; Dain, S

    2013-02-01

    In this Part II psychiatric disorders coexisting with organic diseases are discussed. "Comorbidity phenomenon" defines the not univocal interrelation between medical illnesses and psychiatric disorders, each other negatively influencing morbidity and mortality. Most severe psychiatric disorders, such as schizophrenia, bipolar disorder and depression, show increased prevalence of cardiovascular disease, related to poverty, use of psychotropic medication, and higher rate of preventable risk factors such as smoking, addiction, poor diet and lack of exercise. Moreover, psychiatric and organic disorders can develop together in different conditions of toxic substance and prescription drug use or abuse, especially in the emergency setting population. Different combinations with mutual interaction of psychiatric disorders and substance use disorders are defined by the so called "dual diagnosis". The hypotheses that attempt to explain the psychiatric disorders and substance abuse relationship are examined: (1) common risk factors; (2) psychiatric disorders precipitated by substance use; (3) psychiatric disorders precipitating substance use (self-medication hypothesis); and (4) synergistic interaction. Diagnostic and therapeutic difficulty concerning the problem of dual diagnosis, and legal implications, are also discussed. Substance induced psychiatric and organic symptoms can occur both in the intoxication and withdrawal state. Since ancient history, humans selected indigene psychotropic plants for recreational, medicinal, doping or spiritual purpose. After the isolation of active principles or their chemical synthesis, higher blood concentrations reached predispose to substance use, abuse and dependence. Abuse substances have specific molecular targets and very different acute mechanisms of action, mainly involving dopaminergic and serotoninergic systems, but finally converging on the brain's reward pathways, increasing dopamine in nucleus accumbens. The most common

  6. Lost in Translation: Defects in Transfer RNA Modifications and Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Andrea Bednářová

    2017-05-01

    Full Text Available Transfer RNAs (tRNAs are key molecules participating in protein synthesis. To augment their functionality they undergo extensive post-transcriptional modifications and, as such, are subject to regulation at multiple levels including transcription, transcript processing, localization and ribonucleoside base modification. Post-transcriptional enzyme-catalyzed modification of tRNA occurs at a number of base and sugar positions and influences specific anticodon–codon interactions and regulates translation, its efficiency and fidelity. This phenomenon of nucleoside modification is most remarkable and results in a rich structural diversity of tRNA of which over 100 modified nucleosides have been characterized. Most often these hypermodified nucleosides are found in the wobble position of tRNAs, where they play a direct role in codon recognition as well as in maintaining translational efficiency and fidelity, etc. Several recent studies have pointed to a link between defects in tRNA modifications and human diseases including neurological disorders. Therefore, defects in tRNA modifications in humans need intensive characterization at the enzymatic and mechanistic level in order to pave the way to understand how lack of such modifications are associated with neurological disorders with the ultimate goal of gaining insights into therapeutic interventions.

  7. miRNA profiles in plasma from patients with sleep disorders reveal dysregulation of miRNAs in narcolepsy and other central hypersomnias

    DEFF Research Database (Denmark)

    Holm, Anja; Bang-Berthelsen, Claus Heiner; Knudsen, Stine

    2014-01-01

    STUDY OBJECTIVES: MicroRNAs (miRNAs) have been implicated in the pathogenesis of human diseases including neurological disorders. The aim is to address the involvement of miRNAs in the pathophysiology of central hypersomnias including autoimmune narcolepsy with cataplexy and hypocretin deficiency...

  8. Age-Dependent Effects of Methylphenidate on the Human Dopaminergic System in Young vs Adult Patients With Attention-Deficit/Hyperactivity Disorder: A Randomized Clincal Trial

    NARCIS (Netherlands)

    Schrantee, A.; Tamminga, H.G.H.; Bouziane, C.; Bottelier, M.A.; Bron, E.E.; Mutsaerts, H.-J.M.M.; Zwinderman, A.H.; Groote, I.R.; Rombouts, S.A.R.B.; Lindauer, R.J.L.; Klein, S.; Niessen, W.J.; Opmeer, B.C.; Boer, F.; Lucassen, P.J.; Andersen, S.L.; Geurts, H.M.; Reneman, L.

    2016-01-01

    Importance: Although numerous children receive methylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly lasting effects of methylphenidate on the human dopaminergic system. Objectives: To determine whether

  9. Dual Disorders in Adolescent Populations

    NARCIS (Netherlands)

    van West, D.; Vermeiren, R.R.J.M.

    2015-01-01

    Psychiatric comorbidity in adolescents who abuse substances is the rule rather than the exception, and common comorbidities include depression, anxiety disorder, bipolar disorder, conduct disorder, and Attention Deficit Hyperactivity Disorder (ADHD). Among adolescents, the presence of both mental

  10. Thought and language disorders in very early onset schizophrenia, schizoaffective disorder and bipolar disorder

    Directory of Open Access Journals (Sweden)

    Telma Pantano

    Full Text Available Abstract Background Thought and language disorders are main features of adults with schizophrenia and bipolar disorders however studies on such abnormalities are scant in young patients with very early onset psychosis (VEOS. The aim of the present study is to assess the relationship between language and thought disorders in patients with very early onset schizophrenia (SCZ, schizoaffective disorders (SCA and bipolar disorders (BD. Method Forty-one patients (18 SCZ, 16 BD, and 7 SCA with mean age less than 15 years old were assessed through a series of neurocognitive and psycholinguistic tests, including the Thought, Language and Communication Scale (TLC. Results SCZ group performed worse in all tests as well as the TLC, followed by SCA and BD groups respectively. Thought disorders were related to deficits in executive functioning and semantic processing, and the metaphors’ test was the best predictor of TLC functioning. Discussion TD in SCZ, SCA and BD are one of the most important features in patients with VEOS and that the evaluation of metaphor comprehension can be an important instrument in the early detection of this disorder.

  11. Physiochemical basis of human degenerative disease.

    Science.gov (United States)

    Zeliger, Harold I; Lipinski, Boguslaw

    2015-03-01

    The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers.

  12. Physiochemical basis of human degenerative disease

    Directory of Open Access Journals (Sweden)

    Zeliger Harold I.

    2015-03-01

    Full Text Available The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers.

  13. Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans.

    Science.gov (United States)

    Kullmann, Stephanie; Heni, Martin; Hallschmid, Manfred; Fritsche, Andreas; Preissl, Hubert; Häring, Hans-Ulrich

    2016-10-01

    Ever since the brain was identified as an insulin-sensitive organ, evidence has rapidly accumulated that insulin action in the brain produces multiple behavioral and metabolic effects, influencing eating behavior, peripheral metabolism, and cognition. Disturbances in brain insulin action can be observed in obesity and type 2 diabetes (T2D), as well as in aging and dementia. Decreases in insulin sensitivity of central nervous pathways, i.e., brain insulin resistance, may therefore constitute a joint pathological feature of metabolic and cognitive dysfunctions. Modern neuroimaging methods have provided new means of probing brain insulin action, revealing the influence of insulin on both global and regional brain function. In this review, we highlight recent findings on brain insulin action in humans and its impact on metabolism and cognition. Furthermore, we elaborate on the most prominent factors associated with brain insulin resistance, i.e., obesity, T2D, genes, maternal metabolism, normal aging, inflammation, and dementia, and on their roles regarding causes and consequences of brain insulin resistance. We also describe the beneficial effects of enhanced brain insulin signaling on human eating behavior and cognition and discuss potential applications in the treatment of metabolic and cognitive disorders. Copyright © 2016 the American Physiological Society.

  14. Clinical audit of inherited bleeding disorders in a developing country

    Directory of Open Access Journals (Sweden)

    Sajid Raihan

    2010-01-01

    Full Text Available Objective: We did a clinical audit to determine the status of coagulation disorders in a hemophilia care center in Pakistan. Setting: Fatimid foundation blood bank and hematological diseases center, Lahore. Study Design: This is a retrospective descriptive study. Materials and Methods: All patients registered at Lahore center were included. Data was collected using a questionnaire including age, gender, diagnosis, hepatitis and human immune deficiency virus (HIV status, number of episodes of bleeding, most common site of bleeding, severity of disorder and number of transfusions required to treat the episode. Results: During the study period, a total of 923 registered patients were reviewed at Lahore center and of these, 408 patients (44.2% were on regular follow-up. Inherited bleeding disorders identified in these patients included hemophilia A, hemophilia B, vWD, factor VII deficiency, factor V deficiency, factor X deficiency, dysfibrinogenemia, afibrinogenemia, factor XIII deficiency; and platelet function defects. Median age was 17 years with a range of three to 57 years. Median age at diagnosis was one year. There were 329 (80.6% males and 79 (19.3% females. The products used in these patients included factor VIII concentrate, fresh frozen plasma, cryoprecipitate, cryosupernatant and platelets. Testing for transmission of viral infections was also done in these patients and one patient (0.2% was found hepatitis B positive, six patients (1.4% were hepatitis C positive and two patients (0.49% were HIV positive. Conclusion: Hemophilia A, hemophilia B and vWD are the commonly encountered inherited bleeding disorders in our patients followed by other recessively transmitted disorders with a median age of 17 years and male to female ratio of 4: 1. Most of the patients utilized services available at Fatimid foundation with good clinical results. In Pakistan, non-governmental organizations (NGOs are trying their best for providing optimal treatment

  15. Interleukin-1 antagonists in the treatment of autoinflammatory syndromes, including cryopyrin-associated periodic syndrome

    Directory of Open Access Journals (Sweden)

    Pierre Quartier

    2011-01-01

    Full Text Available Pierre QuartierUnité d'Immunologie-Hématologie et Rhumatologie pédiatriques, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, FranceAbstract: Cryopyrin-associated periodic syndrome (CAPS include a group of rare autoinflammatory disorders, the spectrum of which ranges from the mildest form, ie, familial cold autoinflammatory syndrome to more severe phenotypes, ie, Muckle-Wells syndrome, and chronic infantile neurological cutaneous and articular syndrome, also known as neonatal-onset multisystem inflammatory disease. Three interleukin (IL-1 antagonists have been tested in adults and children with CAPS, ie, anakinra, a recombinant homolog of the human IL-1 receptor antagonist; rilonacept, a fusion protein comprising the extracellular domains of IL-1 receptor I and the IL-1 adaptor protein, IL-1RAcP, attached to a human immunoglobulin G molecule; and canakinumab, the anti-IL-1β monoclonal antibody. Following rapid clinical development, rilonacept and canakinumab were approved by both the US Food and Drug Administration and the European Medicines Agency for use in adults and children. This review describes how the study of CAPS has helped us to understand better the way the innate immune system works, the pathogenesis of autoinflammatory syndromes, and the key role of IL-1. It also reviews the effects of IL-1 blockade in CAPS and other disorders, in particular systemic juvenile idiopathic arthritis, adult-onset Still's disease, and gout. Finally, this review covers some issues addressed by very recent and ongoing work regarding treatment indications, from orphan diseases to common disorders, continuous versus intermittent treatment, the pharmacokinetics, pharmacodynamics, and optimal dosages of the different drugs, as well as the need for Phase IV trials, exhaustive registries, and long-term follow-up of several patient cohorts.Keywords: inflammation, interleukin-1, cytokines, treatment

  16. Age-Dependent Effects of Methylphenidate on the Human Dopaminergic System in Young vs Adult Patients With Attention-Deficit/Hyperactivity Disorder: A Randomized Clinical Trial

    NARCIS (Netherlands)

    Schrantee, Anouk; Tamminga, Hyke G. H.; Bouziane, Cheima; Bottelier, Marco A.; Bron, Esther E.; Mutsaerts, Henk-Jan M. M.; Zwinderman, Aeilko H.; Groote, Inge R.; Rombouts, Serge A. R. B.; Lindauer, Ramon J. L.; Klein, Stefan; Niessen, Wiro J.; Opmeer, Brent C.; Boer, Frits; Lucassen, Paul J.; Andersen, Susan L.; Geurts, Hilde M.; Reneman, Liesbeth

    2016-01-01

    Although numerous children receive methylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly lasting effects of methylphenidate on the human dopaminergic system. To determine whether the effects of

  17. Modeling suicide in bipolar disorders.

    Science.gov (United States)

    Malhi, Gin S; Outhred, Tim; Das, Pritha; Morris, Grace; Hamilton, Amber; Mannie, Zola

    2018-02-19

    Suicide is a multicausal human behavior, with devastating and immensely distressing consequences. Its prevalence is estimated to be 20-30 times greater in patients with bipolar disorders than in the general population. The burden of suicide and its high prevalence in bipolar disorders make it imperative that our current understanding be improved to facilitate prediction of suicide and its prevention. In this review, we provide a new perspective on the process of suicide in bipolar disorder, in the form of a novel integrated model that is derived from extant knowledge and recent evidence. A literature search of articles on suicide in bipolar disorder was conducted in recognized databases such as Scopus, PubMed, and PsycINFO using the keywords "suicide", "suicide in bipolar disorders", "suicide process", "suicide risk", "neurobiology of suicide" and "suicide models". Bibliographies of identified articles were further scrutinized for papers and book chapters of relevance. Risk factors for suicide in bipolar disorders are well described, and provide a basis for a framework of epigenetic mechanisms, moderated by neurobiological substrates, neurocognitive functioning, and social inferences within the environment. Relevant models and theories include the diathesis-stress model, the bipolar model of suicide and the ideation-to-action models, the interpersonal theory of suicide, the integrated motivational-volitional model, and the three-step theory. Together, these models provide a basis for the generation of an integrated model that illuminates the suicidal process, from ideation to action. Suicide is complex, and it is evident that a multidimensional and integrated approach is required to reduce its prevalence. The proposed model exposes and provides access to components of the suicide process that are potentially measurable and may serve as novel and specific therapeutic targets for interventions in the context of bipolar disorder. Thus, this model is useful not only

  18. Is it Important to Talk About Technologies with Eating Disorder Clients? The Health-Care Professional Perspective

    Czech Academy of Sciences Publication Activity Database

    Šmahelová, M.; Čevelíček, M.; Nehybková, E.; Šmahel, D.; Čermák, Ivo

    2017-01-01

    Roč. 32, říjen (2017), s. 1-8 ISSN 1041-0236 Institutional support: RVO:68081740 Keywords : eating disorder s * technology * treatment * anorexia nervosa * bulimia nervosa Subject RIV: AN - Psychology OBOR OECD: Psychology (including human - machine relations) Impact factor: 1.487, year: 2016

  19. Genomic Insights into Growth and Its Disorders: An Update

    Science.gov (United States)

    de Bruin, Christiaan; Dauber, Andrew

    2016-01-01

    Purpose of review To provide an update of the most striking new developments in the field of growth genetics over the past 12 months Recent findings A number of large genome-wide association studies have identified new genetic loci and pathways associated to human growth and adult height as well as related traits and comorbidities. New genetic etiologies of primordial dwarfism and several short stature syndromes have been elucidated. Moreover, a breakthrough finding of Xq26 microduplications as a cause of pituitary gigantism was made. Several new developments in imprinted growth-related genes (including the first human mutation in IGF-II) and novel insights into the epigenetic regulation of growth have been reported. Summary Genomic investigations continue to provide new insights into the genetic basis of human growth as well as its disorders. PMID:26702851

  20. Risk of sexual transmitted infection following bipolar disorder: a nationwide population-based cohort study.

    Science.gov (United States)

    Lee, Shyh-Chyang; Hu, Chang-Kuo; Hung, Jeng-Hsiu; Yang, Albert C; Tsai, Shih-Jen; Huang, Min-Wei; Hu, Li-Yu; Shen, Cheng-Che

    2018-04-03

    Bipolar disorder is a severe mental disorder associated with functional and cognitive impairment. Numerous studies have investigated associations between sexually transmitted infections (STIs) and psychiatric illnesses. However, the results of these studies are controversial. We explored the association between bipolar disorder and the subsequent development of STIs, including human immunodeficiency virus infection; primary, secondary, and latent syphilis; genital warts; gonorrhea; chlamydial infection; and trichomoniasis. The bipolar cohort consisted of 1293 patients, and the comparison cohort consisted of 5172 matched control subjects without bipolar disorder. The incidence of subsequent STIs (hazard ratio (HR) = 2.23, 95% confidence interval (CI) 1.68-2.96) was higher among the patients with bipolar disorder than in the comparison cohort. Furthermore, female gender is a risk factor for acquisition of STIs (HR = 2.36, 95% CI 1.73-4.89) among patients with bipolar disorder. For individual STIs, the results indicated that the patients with bipolar disorder exhibited a markedly higher risk for subsequently contracting syphilis, genital warts, and trichomoniasis. Bipolar disorder might increase the risk of subsequent newly diagnosed STIs, including syphilis, genital warts, and trichomoniasis. Clinicians should pay particular attention to STIs in patients with bipolar disorder. Patients with bipolar disorder, especially those with a history of high-risk sexual behaviors, should be routinely screened for STIs. We identified patients who were diagnosed with bipolar disorder in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without bipolar disorder who were matched with the bipolar cohort according to age and gender. The occurrence of subsequent new-onset STIs was evaluated in both cohorts.

  1. Parents' Adoption of Social Communication Intervention Strategies: Families Including Children with Autism Spectrum Disorder Who are Minimally Verbal.

    Science.gov (United States)

    Shire, Stephanie Y; Goods, Kelly; Shih, Wendy; Distefano, Charlotte; Kaiser, Ann; Wright, Courtney; Mathy, Pamela; Landa, Rebecca; Kasari, Connie

    2015-06-01

    Notably absent from the intervention literature are parent training programs targeting school-aged children with autism who have limited communication skills (Tager-Flusberg and Kasari in Autism Res 6:468-478, 2013). Sixty-one children with autism age 5-8 with minimal spontaneous communication received a 6-month social communication intervention including parent training. Parent-child play interactions were coded for parents' strategy implementation and children's time jointly engaged (Adamson et al. in J Autism Dev Disord 39:84-96, 2009). Parents mastered an average of 70% of the strategies. Further analyses indicated some gains in implementation occurred from mere observation of sessions, while the greatest gains occurred in the first month of active coaching and workshops. Children's joint engagement was associated with parents' implementation success across time demonstrating parents' implementation was relevant to children's social engagement.

  2. Neuronal migration and its disorders affecting the CA3 region

    Directory of Open Access Journals (Sweden)

    Richard eBelvindrah

    2014-03-01

    Full Text Available In this review, we focus on CA3 neuronal migration disorders in the rodent. We begin by introducing the main steps of hippocampal development, and we summarize characteristic hippocampal malformations in human. We then describe various mouse mutants showing structural hippocampal defects. Notably, genes identified in human cortical neuronal migration disorders consistently give rise to a CA3 phenotype when mutated in the mouse. We successively describe their molecular, physiological and behavioral phenotypes that together contribute to a better understanding of CA3-dependent functions. We finally discuss potential factors underlying the CA3 vulnerability revealed by these mouse mutants and that may also contribute to other human neurological and psychiatric disorders.

  3. Esophageal motility disorders

    International Nuclear Information System (INIS)

    Hannig, C.; Rummeny, E.; Wuttge-Hannig, A.

    2007-01-01

    For the better understanding of esophageal motility, the muscle texture and the distribution of skeletal and smooth muscle fibers in the esophagus are of crucial importance. Esophageal physiology will be shortly mentioned as far as necessary for a comprehensive understanding of peristaltic disturbances. Besides the pure depiction of morphologic criteria, a complete esophageal study has to include an analysis of the motility. New diagnostic tools with reduced radiation for dynamic imaging (digital fluoroscopy, videofluoroscopy) at 4-30 frames/s are available. Radiomanometry is a combination of a functional pressure measurement and a simultaneous dynamic morphologic analysis. Esophageal motility disorders are subdivided by radiologic and manometric criteria into primary, secondary, and nonclassifiable forms. Primary motility disorders of the esophagus are achalasia, diffuse esophageal spasm, nutcracker esophagus, and the hypertonic lower esophageal sphincter. The secondary motility disorders include pseudoachalasia, reflux-associated motility disorders, functionally caused impactions, Boerhaave's syndrome, Chagas' disease, scleroderma, and presbyesophagus. The nonclassificable motility disorders (NEMD) are a very heterogeneous collective. (orig.) [de

  4. Culture and the anxiety disorders: recommendations for DSM-V.

    Science.gov (United States)

    Lewis-Fernández, Roberto; Hinton, Devon E; Laria, Amaro J; Patterson, Elissa H; Hofmann, Stefan G; Craske, Michelle G; Stein, Dan J; Asnaani, Anu; Liao, Betty

    2010-02-01

    The anxiety disorders specified in the fourth edition, text revision, of The Diagnostic and Statistical Manual (DSM-IV-TR) are identified universally in human societies, and also show substantial cultural particularities in prevalence and symptomatology. Possible explanations for the observed epidemiological variability include lack of measurement equivalence, true differences in prevalence, and limited validity or precision of diagnostic criteria. One central question is whether, through inadvertent "over-specification" of disorders, the post-DSM-III nosology has missed related but somewhat different presentations of the same disorder because they do not exactly fit specified criteria sets. This review canvases the mental health literature for evidence of cross-cultural limitations in DSM-IV-TR anxiety disorder criteria. Searches were conducted of the mental health literature, particularly since 1994, regarding cultural or race/ethnicity-related factors that might limit the universal applicability of the diagnostic criteria for six anxiety disorders. Possible mismatches between the DSM criteria and the local phenomenology of the disorder in specific cultural contexts were found for three anxiety disorders in particular. These involve the unexpectedness and 10-minute crescendo criteria in Panic Disorder; the definition of social anxiety and social reference group in Social Anxiety Disorder; and the priority given to psychological symptoms of worry in Generalized Anxiety Disorder. Limited evidence was found throughout, particularly in terms of neurobiological markers, genetic risk factors, treatment response, and other DSM-V validators that could help clarify the cross-cultural applicability of criteria. On the basis of the available data, options and preliminary recommendations for DSM-V are put forth that should be further evaluated and tested.

  5. Associations among Epstein-Barr virus subtypes, human leukocyte antigen class I alleles, and the development of posttransplantation lymphoproliferative disorder in bone marrow transplant recipients

    NARCIS (Netherlands)

    Görzer, Irene; Puchhammer-Stöckl, Elisabeth; van Esser, Joost W J; Niesters, Hubert G M; Cornelissen, Jan J

    2007-01-01

    The association between Epstein-Barr virus subtype, human leukocyte antigen class I alleles, and the development of posttransplantation lymphoproliferative disorder was examined in a group of 25 bone marrow transplant recipients. A highly statistically significant correlation was observed between

  6. Newer insights into the role of miRNA a tiny genetic tool in psychiatric disorders: focus on post-traumatic stress disorder.

    Science.gov (United States)

    Giridharan, V V; Thandavarayan, R A; Fries, G R; Walss-Bass, C; Barichello, T; Justice, N J; Reddy, M K; Quevedo, J

    2016-11-15

    Post-traumatic stress disorder (PTSD) is a mental disorder occurring in about 2-9% of individuals after their exposure to life-threatening events, such as severe accidents, sexual abuse, combat or a natural catastrophe. Because PTSD patients are exposed to trauma, it is likely that epigenetic modifications have an important role in disease development and prognosis. For the past two decades, abnormal expression of the epigenetic regulators microRNAs (miRs) and miR-mediated gene regulation have been given importance in a variety of human diseases, such as cancer, heart disease and viral infection. Emerging evidence supports a role for miR dysregulation in psychiatric and neurological disorders, including schizophrenia, bipolar disorder, anxiety, major depressive disorder, autism spectrum disorder and Tourette's syndrome. Recently mounting of evidence supports the role of miR both in preclinical and clinical settings of psychiatric disorders. Abnormalities in miR expression can fine-tune the expression of multiple genes within a biological network, suggesting that miR dysregulation may underlie many of the molecular changes observed in PTSD pathogenesis. This provides strong evidence that miR not only has a critical role in PTSD pathogenesis, but can also open up new avenues for the development of diagnostic tools and therapeutic targets for the PTSD phenotype. In this review, we revisit some of the recent evidence associated with miR and PTSD in preclinical and clinical settings. We also discuss the possible clinical applications and future use of miRs in PTSD therapy.

  7. Newer insights into the role of miRNA a tiny genetic tool in psychiatric disorders: focus on post-traumatic stress disorder

    Science.gov (United States)

    Giridharan, V V; Thandavarayan, R A; Fries, G R; Walss-Bass, C; Barichello, T; Justice, N J; Reddy, M K; Quevedo, J

    2016-01-01

    Post-traumatic stress disorder (PTSD) is a mental disorder occurring in about 2–9% of individuals after their exposure to life-threatening events, such as severe accidents, sexual abuse, combat or a natural catastrophe. Because PTSD patients are exposed to trauma, it is likely that epigenetic modifications have an important role in disease development and prognosis. For the past two decades, abnormal expression of the epigenetic regulators microRNAs (miRs) and miR-mediated gene regulation have been given importance in a variety of human diseases, such as cancer, heart disease and viral infection. Emerging evidence supports a role for miR dysregulation in psychiatric and neurological disorders, including schizophrenia, bipolar disorder, anxiety, major depressive disorder, autism spectrum disorder and Tourette's syndrome. Recently mounting of evidence supports the role of miR both in preclinical and clinical settings of psychiatric disorders. Abnormalities in miR expression can fine-tune the expression of multiple genes within a biological network, suggesting that miR dysregulation may underlie many of the molecular changes observed in PTSD pathogenesis. This provides strong evidence that miR not only has a critical role in PTSD pathogenesis, but can also open up new avenues for the development of diagnostic tools and therapeutic targets for the PTSD phenotype. In this review, we revisit some of the recent evidence associated with miR and PTSD in preclinical and clinical settings. We also discuss the possible clinical applications and future use of miRs in PTSD therapy. PMID:27845777

  8. Altered resting-state functional connectivity of the frontal-striatal reward system in social anxiety disorder.

    Science.gov (United States)

    Manning, Joshua; Reynolds, Gretchen; Saygin, Zeynep M; Hofmann, Stefan G; Pollack, Mark; Gabrieli, John D E; Whitfield-Gabrieli, Susan

    2015-01-01

    We investigated differences in the intrinsic functional brain organization (functional connectivity) of the human reward system between healthy control participants and patients with social anxiety disorder. Functional connectivity was measured in the resting-state via functional magnetic resonance imaging (fMRI). 53 patients with social anxiety disorder and 33 healthy control participants underwent a 6-minute resting-state fMRI scan. Functional connectivity of the reward system was analyzed by calculating whole-brain temporal correlations with a bilateral nucleus accumbens seed and a ventromedial prefrontal cortex seed. Patients with social anxiety disorder, relative to the control group, had (1) decreased functional connectivity between the nucleus accumbens seed and other regions associated with reward, including ventromedial prefrontal cortex; (2) decreased functional connectivity between the ventromedial prefrontal cortex seed and lateral prefrontal regions, including the anterior and dorsolateral prefrontal cortices; and (3) increased functional connectivity between both the nucleus accumbens seed and the ventromedial prefrontal cortex seed with more posterior brain regions, including anterior cingulate cortex. Social anxiety disorder appears to be associated with widespread differences in the functional connectivity of the reward system, including markedly decreased functional connectivity between reward regions and between reward regions and lateral prefrontal cortices, and markedly increased functional connectivity between reward regions and posterior brain regions.

  9. Heterogeneous pattern of selective pressure for PRRT2 in human populations, but no association with autism spectrum disorders.

    Directory of Open Access Journals (Sweden)

    Guillaume Huguet

    Full Text Available Inherited and de novo genomic imbalances at chromosome 16p11.2 are associated with autism spectrum disorders (ASD, but the causative genes remain unknown. Among the genes located in this region, PRRT2 codes for a member of the synaptic SNARE complex that allows the release of synaptic vesicles. PRRT2 is a candidate gene for ASD since homozygote mutations are associated with intellectual disability and heterozygote mutations cause benign infantile seizures, paroxysmal dyskinesia, or hemiplegic migraine. Here, we explored the contribution of PRRT2 mutations in ASD by screening its coding part in a large sample of 1578 individuals including 431 individuals with ASD, 186 controls and 961 individuals from the human genome Diversity Panel. We detected 24 nonsynonymous variants, 1 frameshift (A217PfsX8 and 1 in-frame deletion of 6 bp (p.A361_P362del. The frameshift mutation was observed in a control with no history of neurological or psychiatric disorders. The p.A361_P362del was observed in two individuals with autism from sub-Saharan African origin. Overall, the frequency of PRRT2 deleterious variants was not different between individuals with ASD and controls. Remarkably, PRRT2 displays a highly significant excess of nonsynonymous (pN vs synonymous (pS mutations in Asia (pN/pS = 4.85 and Europe (pN/pS = 1.62 compared with Africa (pN/pS = 0.26; Asia vs Africa: P = 0.000087; Europe vs Africa P = 0.00035; Europe vs Asia P = P = 0.084. We also showed that whole genome amplification performed through rolling cycle amplification could artificially introduce the A217PfsX8 mutation indicating that this technology should not be performed prior to PRRT2 mutation screening. In summary, our results do not support a role for PRRT2 coding sequence variants in ASD, but provide an ascertainment of its genetic variability in worldwide populations that should help researchers and clinicians to better investigate the role of PRRT2 in human

  10. Difference or disorder? Cultural issues in understanding neurodevelopmental disorders.

    Science.gov (United States)

    Norbury, Courtenay Frazier; Sparks, Alison

    2013-01-01

    Developmental disorders, such as autism spectrum disorder and specific language impairment, are biologically based disorders that currently rely on behaviorally defined criteria for diagnosis and treatment. Specific behaviors that are included in diagnostic frameworks and the point at which individual differences in behavior constitute abnormality are largely arbitrary decisions. Such decisions are therefore likely to be strongly influenced by cultural values and expectations. This is evident in the dramatically different prevalence rates of autism spectrum disorder across countries and across different ethnic groups within the same country. In this article, we critically evaluate the understanding of developmental disorders from a cultural perspective. We specifically consider the challenges of applying diagnostic methods across cultural contexts, the influence of cultural values and expectations on the identification and treatment of children with suspected disorders, and how cross-cultural studies can help to refine cognitive theories of disorder that have been derived exclusively from Western North American and European investigations. Our review synthesizes clinical, cultural, and theoretical work in this area, highlighting potential universals of disorder and concluding with recommendations for future research and practice.

  11. Following the genes: a framework for animal modeling of psychiatric disorders

    LENUS (Irish Health Repository)

    Mitchell, Kevin

    2011-11-11

    Abstract The number of individual cases of psychiatric disorders that can be ascribed to identified, rare, single mutations is increasing with great rapidity. Such mutations can be recapitulated in mice to generate animal models with direct etiological validity. Defining the underlying pathogenic mechanisms will require an experimental and theoretical framework to make the links from mutation to altered behavior in an animal or psychopathology in a human. Here, we discuss key elements of such a framework, including cell type-based phenotyping, developmental trajectories, linking circuit properties at micro and macro scales and definition of neurobiological phenotypes that are directly translatable to humans.

  12. The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

    Science.gov (United States)

    Smoller, Jordan W

    2016-01-01

    Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors. An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. This review focuses on the genetic basis of three disorder categories—posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and the anxiety disorders—for which environmental stressors and stress responses are understood to be central to pathogenesis. Each of these disorders aggregates in families and is moderately heritable. More recently, molecular genetic approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants. In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene–environment interaction. Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders. Progress in this area will likely require analysis of much larger sample sizes than have been reported to date. The phenotypic complexity and genetic overlap among these disorders present further challenges. The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research. PMID:26321314

  13. Evolutionary Explanations of Eating Disorders

    Directory of Open Access Journals (Sweden)

    Igor Kardum

    2008-12-01

    Full Text Available This article reviews several most important evolutionary mechanisms that underlie eating disorders. The first part clarifies evolutionary foundations of mental disorders and various mechanisms leading to their development. In the second part selective pressures and evolved adaptations causing contemporary epidemic of obesity as well as differences in dietary regimes and life-style between modern humans and their ancestors are described. Concerning eating disorders, a number of current evolutionary explanations of anorexia nervosa are presented together with their main weaknesses. Evolutionary explanations of eating disorders based on the reproductive suppression hypothesis and its variants derived from kin selection theory and the model of parental manipulation were elaborated. The sexual competition hypothesis of eating disorder, adapted to flee famine hypothesis as well as explanation based on the concept of social attention holding power and the need to belonging were also explained. The importance of evolutionary theory in modern conceptualization and research of eating disorders is emphasized.

  14. Post-traumatic stress disorder associated with natural and human-made disasters in the World Mental Health Surveys

    Science.gov (United States)

    Bromet, E. J.; Atwoli, L.; Kawakami, N.; Navarro-Mateu, F.; Piotrowski, P.; King, A. J.; Aguilar-Gaxiola, S.; Alonso, J.; Bunting, B.; Demyttenaere, K.; Florescu, S.; de Girolamo, G.; Gluzman, S.; Haro, J. M.; de Jonge, P.; Karam, E. G.; Lee, S.; Kovess-Masfety, V.; Medina-Mora, M. E.; Mneimneh, Z.; Pennell, B.-E.; Posada-Villa, J.; Salmerón, D.; Takeshima, T.; Kessler, R. C.

    2017-01-01

    Background Research on post-traumatic stress disorder (PTSD) following natural and human-made disasters has been undertaken for more than three decades. Although PTSD prevalence estimates vary widely, most are in the 20–40% range in disaster-focused studies but considerably lower (3–5%) in the few general population epidemiological surveys that evaluated disaster-related PTSD as part of a broader clinical assessment. The World Mental Health (WMH) Surveys provide an opportunity to examine disaster-related PTSD in representative general population surveys across a much wider range of sites than in previous studies. Method Although disaster-related PTSD was evaluated in 18 WMH surveys, only six in high-income countries had enough respondents for a risk factor analysis. Predictors considered were socio-demographics, disaster characteristics, and pre-disaster vulnerability factors (childhood family adversities, prior traumatic experiences, and prior mental disorders). Results Disaster-related PTSD prevalence was 0.0–3.8% among adult (ages 18+) WMH respondents and was significantly related to high education, serious injury or death of someone close, forced displacement from home, and pre-existing vulnerabilities (prior childhood family adversities, other traumas, and mental disorders). Of PTSD cases 44.5% were among the 5% of respondents classified by the model as having highest PTSD risk. Conclusion Disaster-related PTSD is uncommon in high-income WMH countries. Risk factors are consistent with prior research: severity of exposure, history of prior stress exposure, and pre-existing mental disorders. The high concentration of PTSD among respondents with high predicted risk in our model supports the focus of screening assessments that identify disaster survivors most in need of preventive interventions. PMID:27573281

  15. Post-traumatic stress disorder associated with natural and human-made disasters in the World Mental Health Surveys.

    Science.gov (United States)

    Bromet, E J; Atwoli, L; Kawakami, N; Navarro-Mateu, F; Piotrowski, P; King, A J; Aguilar-Gaxiola, S; Alonso, J; Bunting, B; Demyttenaere, K; Florescu, S; de Girolamo, G; Gluzman, S; Haro, J M; de Jonge, P; Karam, E G; Lee, S; Kovess-Masfety, V; Medina-Mora, M E; Mneimneh, Z; Pennell, B-E; Posada-Villa, J; Salmerón, D; Takeshima, T; Kessler, R C

    2017-01-01

    Research on post-traumatic stress disorder (PTSD) following natural and human-made disasters has been undertaken for more than three decades. Although PTSD prevalence estimates vary widely, most are in the 20-40% range in disaster-focused studies but considerably lower (3-5%) in the few general population epidemiological surveys that evaluated disaster-related PTSD as part of a broader clinical assessment. The World Mental Health (WMH) Surveys provide an opportunity to examine disaster-related PTSD in representative general population surveys across a much wider range of sites than in previous studies. Although disaster-related PTSD was evaluated in 18 WMH surveys, only six in high-income countries had enough respondents for a risk factor analysis. Predictors considered were socio-demographics, disaster characteristics, and pre-disaster vulnerability factors (childhood family adversities, prior traumatic experiences, and prior mental disorders). Disaster-related PTSD prevalence was 0.0-3.8% among adult (ages 18+) WMH respondents and was significantly related to high education, serious injury or death of someone close, forced displacement from home, and pre-existing vulnerabilities (prior childhood family adversities, other traumas, and mental disorders). Of PTSD cases 44.5% were among the 5% of respondents classified by the model as having highest PTSD risk. Disaster-related PTSD is uncommon in high-income WMH countries. Risk factors are consistent with prior research: severity of exposure, history of prior stress exposure, and pre-existing mental disorders. The high concentration of PTSD among respondents with high predicted risk in our model supports the focus of screening assessments that identify disaster survivors most in need of preventive interventions.

  16. Skin Picking Disorder

    Directory of Open Access Journals (Sweden)

    Pinar Cetinay Aydin

    2014-08-01

    Full Text Available Skin picking disorder is not a dermatological disorder and it is a table characterized with picking skin excessively and repetitively, leading to damage in skin tissue. Unlike normal picking behaviour, psychogenic skin picking is repetitive and it can lead to severe damage in the skin and even complications which constitute vital danger. While some patients define frequent but short lasting picking attacks, others define rarer attacks which last a few hours. Skin picking disorder, which is not included in the classification systems up to DSM-5 as a separate diagnosis category, is included as an independent diagnosis in Obsessive Compulsive Disorder and Associated Disorders category in DSM-5. In case reports, open label studies and double blind studies selective serotonin reuptake inhibitors are shown to be effective in the treatment of skin picking disorder. Mostly, cognitive-behaviourial techniques are used and have been proven to be useful in psychotherapy. Habit reversal is one of the behaviourial techniques which are frequently applied, give positive results in which well-being state can be maintained. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(4.000: 401-428

  17. Anxiety disorders: Psychiatric comorbidities and psychosocial ...

    African Journals Online (AJOL)

    2018-05-24

    May 24, 2018 ... psychiatric disorders, including other anxiety disorders, mood disorders, substance use disorders ... psychiatric comorbidities present among adults at a tertiary ..... clinical files as well as unclear handwriting and missing.

  18. Diagnosis and treatment of impulse control disorders in patients with movement disorders.

    Science.gov (United States)

    Mestre, Tiago A; Strafella, Antonio P; Thomsen, Teri; Voon, Valerie; Miyasaki, Janis

    2013-05-01

    Impulse control disorders are a psychiatric condition characterized by the failure to resist an impulsive act or behavior that may be harmful to self or others. In movement disorders, impulse control disorders are associated with dopaminergic treatment, notably dopamine agonists (DAs). Impulse control disorders have been studied extensively in Parkinson's disease, but are also recognized in restless leg syndrome and atypical Parkinsonian syndromes. Epidemiological studies suggest younger age, male sex, greater novelty seeking, impulsivity, depression and premorbid impulse control disorders as the most consistent risk factors. Such patients may warrant special monitoring after starting treatment with a DA. Various individual screening tools are available for people without Parkinson's disease. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease has been developed specifically for Parkinson's disease. The best treatment for impulse control disorders is prevention. However, after the development of impulse control disorders, the mainstay intervention is to reduce or discontinue the offending anti-Parkinsonian medication. In refractory cases, other pharmacological interventions are available, including neuroleptics, antiepileptics, amantadine, antiandrogens, lithium and opioid antagonists. Unfortunately, their use is only supported by case reports, small case series or open-label clinical studies. Prospective, controlled studies are warranted. Ongoing investigations include naltrexone and nicotine.

  19. Borderline Personality Disorder is Associated with Lower Confidence in Perception of Emotional Body Movements

    Directory of Open Access Journals (Sweden)

    Morten eKaletsch

    2014-11-01

    Full Text Available Much recent research has shown that personality disorders are associated with an altered emotion perception. Whereas most of this research was conducted with stimuli such as faces, the present study examined possible differences in the perception of emotions expressed via body language and body movements. 30 patients with borderline personality disorder and 30 non-patients observed video scenes of emotional human interactions conveyed by point–light displays, rated the depicted valence, and judged their confidence in this rating. Patients with borderline personality disorder showed no altered emotion perception (i.e., no biased perception in either a negative or a positive direction. They did not perceive and evaluate depicted emotions as being more extreme than healthy controls. However, patients with borderline personality disorder showed less confidence in their perception of depicted emotions, especially when these were difficult to identify. The findings extend insights on altered emotion perception in persons with borderline personality disorder to include the field of body movements.

  20. Topiramate in the treatment of substance-related disorders: a critical review of the literature.

    Science.gov (United States)

    Shinn, Ann K; Greenfield, Shelly F

    2010-05-01

    To critically review the literature on topiramate in the treatment of substance-related disorders. A PubMed search of human studies published in English through January 2009 was conducted using the following search terms: topiramate and substance abuse, topiramate and substance dependence, topiramate and withdrawal, topiramate and alcohol, topiramate and nicotine, topiramate and cocaine, topiramate and opiates, and topiramate and benzodiazepines. 26 articles were identified and reviewed; these studies examined topiramate in disorders related to alcohol, nicotine, cocaine, methamphetamine, opioids, Ecstasy, and benzodiazepines. Study design, sample size, topiramate dose and duration, and study outcomes were reviewed. There is compelling evidence for the efficacy of topiramate in the treatment of alcohol dependence. Two trials show trends for topiramate's superiority over oral naltrexone in alcohol dependence, while 1 trial suggests topiramate is inferior to disulfiram. Despite suggestive animal models, evidence for topiramate in treating alcohol withdrawal in humans is slim. Studies of topiramate in nicotine dependence show mixed results. Human laboratory studies that used acute topiramate dosing show that topiramate actually enhances the pleasurable effects of both nicotine and methamphetamine. Evidence for topiramate in the treatment of cocaine dependence is promising, but limited by small sample size. The data on opioids, benzodiazepines, and Ecstasy are sparse. Topiramate is efficacious for the treatment of alcohol dependence, but side effects may limit widespread use. While topiramate's unique pharmacodynamic profile offers a promising theoretical rationale for use across multiple substance-related disorders, heterogeneity both across and within these disorders limits topiramate's broad applicability in treating substance-related disorders. Recommendations for future research include exploration of genetic variants for more targeted pharmacotherapies.

  1. Musculoskeletal disorders associated with HIV infection and AIDS. Part I: Infectious musculoskeletal conditions

    International Nuclear Information System (INIS)

    Tehranzadeh, Jamshid; Ter-Oganesyan, Ramon R.; Steinbach, Lynne S.

    2004-01-01

    The musculoskeletal system can be affected by a variety of abnormalities in association with human immunodeficiency virus (HIV) infection. Although not as common as complications involving other organ systems, such as the pulmonary and the central nervous systems, HIV-associated musculoskeletal disorders are sometimes the initial presentation of the viral illness. Knowledge of the existence and the characteristic appearance of the conditions affecting bone, joint, and muscle in HIV-infected patients is valuable to radiologists for diagnosis and to clinicians for detection and appropriate treatment. We reviewed recent literature to provide a comprehensive assessment of the HIV-associated musculoskeletal disorders, and present radiologic examples from our own collection. This article is divided into two parts. In the first part we review the infectious musculoskeletal disorders associated with HIV illness and AIDS, including cellulitis, abscesses, pyomyositis, septic bursitis, septic arthritis, osteomyelitis, and bacillary angiomatosis. We also present a comprehensive spectrum of mycobacterial infections, consisting of tuberculous spondylitis and spondylodiskitis, arthritis, osteomyelitis, and tenosynovitis, as well as infections caused by atypical mycobacteria. Part II of this review will concentrate on non-infectious musculoskeletal conditions, including rheumatic disorders and neoplasms. (orig.)

  2. Musculoskeletal disorders associated with HIV infection and AIDS. Part I: Infectious musculoskeletal conditions

    Energy Technology Data Exchange (ETDEWEB)

    Tehranzadeh, Jamshid [Department of Radiological Sciences, University of California, Irvine, Irvine, California (United States); Department of Radiological Sciences, Rt. 140, 101 The City Drive ZC 5005, CA 92868-3298, Orange (United States); Ter-Oganesyan, Ramon R. [College of Medicine, University of California, Irvine, Irvine, California (United States); Steinbach, Lynne S. [Department of Radiological Sciences, University of California, San Francisco, San Francisco, California (United States)

    2004-05-01

    The musculoskeletal system can be affected by a variety of abnormalities in association with human immunodeficiency virus (HIV) infection. Although not as common as complications involving other organ systems, such as the pulmonary and the central nervous systems, HIV-associated musculoskeletal disorders are sometimes the initial presentation of the viral illness. Knowledge of the existence and the characteristic appearance of the conditions affecting bone, joint, and muscle in HIV-infected patients is valuable to radiologists for diagnosis and to clinicians for detection and appropriate treatment. We reviewed recent literature to provide a comprehensive assessment of the HIV-associated musculoskeletal disorders, and present radiologic examples from our own collection. This article is divided into two parts. In the first part we review the infectious musculoskeletal disorders associated with HIV illness and AIDS, including cellulitis, abscesses, pyomyositis, septic bursitis, septic arthritis, osteomyelitis, and bacillary angiomatosis. We also present a comprehensive spectrum of mycobacterial infections, consisting of tuberculous spondylitis and spondylodiskitis, arthritis, osteomyelitis, and tenosynovitis, as well as infections caused by atypical mycobacteria. Part II of this review will concentrate on non-infectious musculoskeletal conditions, including rheumatic disorders and neoplasms. (orig.)

  3. Clinical study of the relation of borderline personality disorder to Briquet's syndrome (hysteria), somatization disorder, antisocial personality disorder, and substance abuse disorders.

    Science.gov (United States)

    Hudziak, J J; Boffeli, T J; Kreisman, J J; Battaglia, M M; Stanger, C; Guze, S B; Kriesman, J J

    1996-12-01

    The criteria for borderline personality disorder seem to select patients with very high rates of Briquet's syndrome (hysteria), somatization disorder, antisocial personality disorder, and substance abuse disorders. This study was undertaken to determine whether systematic assessment of patients with borderline personality disorder would reveal characteristic features of that condition which would distinguish it from these other disorders. Eighty-seven white female patients (75 in St. Louis and 12 in Milan, Italy) who had borderline personality disorder according to both the DSM-III-R criteria and the Revised Diagnostic Interview for Borderlines were further examined with the DSM-III-R Checklist and the Perley-Guze Hysteria Checklist to determine their patterns of psychiatric comorbidity. Every patient had at least one additional DSM diagnosis. Patients in St. Louis and Milan averaged five and four additional diagnoses, respectively. Eighty-four percent of the patients in St. Louis met criteria for either somatization disorder, Briquet's syndrome, antisocial personality disorder, or substance abuse disorders. Patterns of comorbidity for panic (51%), generalized anxiety disorder (55%), and major depression (87%) in St. Louis were consistent with those in other studies. The data indicate that the boundaries for the borderline condition are not specific and identify a high percentage of patients with these other disorders. Furthermore, the comorbidity profiles closely resemble the psychiatric profiles of patients with these disorders. If the borderline syndrome is meant to include all of these disorders, its usefulness as a diagnosis is limited. Until the fundamental features of borderline personality disorder that distinguish it from the others are identified, it is recommended that clinicians carefully assess patients for these other diagnoses. Efforts should be made to change the borderline personality disorder criteria by shifting away from overlap with the

  4. Premenstrual dysphoric disorder in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition: contributions from Asia.

    Science.gov (United States)

    Mehta, N; Mehta, S

    2014-12-01

    Premenstrual dysphoric disorder has been included as a separate diagnostic entity in the chapter of 'Depressive Disorders' of the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). The antecedent, concurrent, and predictive diagnostic validators of premenstrual dysphoric disorder have been reviewed by a sub-workgroup of the DSM-5 Mood Disorders Work Group, which includes a panel of experts on women's mental health. Contributions from the Asian continent have been mainly in the form of prevalence studies. Genetic and neurobiological domains of premenstrual dysphoric disorder largely remain untouched in Asia and offer a potential area for investigation.

  5. An Overview of Practical Applications of Protein Disorder Prediction and Drive for Faster, More Accurate Predictions.

    Science.gov (United States)

    Deng, Xin; Gumm, Jordan; Karki, Suman; Eickholt, Jesse; Cheng, Jianlin

    2015-07-07

    Protein disordered regions are segments of a protein chain that do not adopt a stable structure. Thus far, a variety of protein disorder prediction methods have been developed and have been widely used, not only in traditional bioinformatics domains, including protein structure prediction, protein structure determination and function annotation, but also in many other biomedical fields. The relationship between intrinsically-disordered proteins and some human diseases has played a significant role in disorder prediction in disease identification and epidemiological investigations. Disordered proteins can also serve as potential targets for drug discovery with an emphasis on the disordered-to-ordered transition in the disordered binding regions, and this has led to substantial research in drug discovery or design based on protein disordered region prediction. Furthermore, protein disorder prediction has also been applied to healthcare by predicting the disease risk of mutations in patients and studying the mechanistic basis of diseases. As the applications of disorder prediction increase, so too does the need to make quick and accurate predictions. To fill this need, we also present a new approach to predict protein residue disorder using wide sequence windows that is applicable on the genomic scale.

  6. An Overview of Practical Applications of Protein Disorder Prediction and Drive for Faster, More Accurate Predictions

    Directory of Open Access Journals (Sweden)

    Xin Deng

    2015-07-01

    Full Text Available Protein disordered regions are segments of a protein chain that do not adopt a stable structure. Thus far, a variety of protein disorder prediction methods have been developed and have been widely used, not only in traditional bioinformatics domains, including protein structure prediction, protein structure determination and function annotation, but also in many other biomedical fields. The relationship between intrinsically-disordered proteins and some human diseases has played a significant role in disorder prediction in disease identification and epidemiological investigations. Disordered proteins can also serve as potential targets for drug discovery with an emphasis on the disordered-to-ordered transition in the disordered binding regions, and this has led to substantial research in drug discovery or design based on protein disordered region prediction. Furthermore, protein disorder prediction has also been applied to healthcare by predicting the disease risk of mutations in patients and studying the mechanistic basis of diseases. As the applications of disorder prediction increase, so too does the need to make quick and accurate predictions. To fill this need, we also present a new approach to predict protein residue disorder using wide sequence windows that is applicable on the genomic scale.

  7. Broader prevalence of Wolbachia in insects including potential human disease vectors.

    Science.gov (United States)

    de Oliveira, C D; Gonçalves, D S; Baton, L A; Shimabukuro, P H F; Carvalho, F D; Moreira, L A

    2015-06-01

    Wolbachia are intracellular, maternally transmitted bacteria considered the most abundant endosymbionts found in arthropods. They reproductively manipulate their host in order to increase their chances of being transmitted to the offspring, and currently are being used as a tool to control vector-borne diseases. Studies on distribution of Wolbachia among its arthropod hosts are important both for better understanding why this bacterium is so common, as well as for its potential use as a biological control agent. Here, we studied the incidence of Wolbachia in a broad range of insect species, collected from different regions of Brazil, using three genetic markers (16S rRNA, wsp and ftsZ), which varied in terms of their sensitivity to detect this bacterium. The overall incidence of Wolbachia among species belonging to 58 families and 14 orders was 61.9%. The most common positive insect orders were Coleoptera, Diptera, Hemiptera and Hymenoptera, with Diptera and Hemiptera having the highest numbers of Wolbachia-positive families. They included potential human disease vectors whose infection status has never been reported before. Our study further shows the importance of using quantitative polymerase chain reaction for high-throughput and sensitive Wolbachia screening.

  8. Studies on factors of disorder and regularity in the streeet view. Part 1. ; Studies on disorder and regularity in the central business district. Gairo keikan no ranzatsuter dot seizensei yoin ni kansuru kenkyu. 1. ; Chushin shigaichi ni okeru ranzatsuter dot seizensei ni kansuru kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    Matsunoto, N; Teranishi, N; Senda, M [Nagoya Institute of Technology, Nagoya (Japan). Faculty of Engineering

    1991-11-30

    This study intends to identify the visual confusion in spatial views by the routine human conveption of regularity and disorder, and elucidate physical factors that cause the disorder and regularity in street views. The disorder factors include the additions annexed to the view afterwards, and the regularity factors include those flat objects that decide the pattern of a view. Many factors can be either disorder or reguarity factors according to their sizes, how they look, and how they are affected by surrounding objects. The disorder in a street view is approximately determined of its degree by such distribution patterns as the spread and convergence of the disorder factors. The disorder can be intensified stronger by the spread of the factors widely over an entire area or the existence of objects that give disorderly impressions, rather than by the number of disorder factors. The regularity is affected easily by the disorder factors, it being lowered by intensities of the disorder. The deciding factors for the disorder or regularity are the kinds of objects, how they are laid out and what they are surrounded with. The factors that govern the degrees of the disorder and regularity are how large the area they are distributed in, the number, how they look, and where they are positioned. 24 refs., 9 figs., 6 tabs.

  9. Cross-Disorder Genetic Analysis of Tic Disorders, Obsessive?Compulsive, and Hoarding Symptoms

    OpenAIRE

    Zilh?o, Nuno R.; Smit, Dirk J.; Boomsma, Dorret I.; Cath, Danielle C.

    2016-01-01

    Hoarding, obsessive–compulsive disorder (OCD), and Tourette’s disorder (TD) are psychiatric disorders that share symptom overlap, which might partly be the result of shared genetic variation. Population-based twin studies have found significant genetic correlations between hoarding and OCD symptoms, with genetic correlations varying between 0.1 and 0.45. For tic disorders, studies examining these correlations are lacking. Other lines of research, including clinical samples and GWAS or CNV dat...

  10. Sleep, eating disorder symptoms, and daytime functioning

    Directory of Open Access Journals (Sweden)

    Tromp MD

    2016-01-01

    Full Text Available Marilou DP Tromp,1 Anouk AMT Donners,1 Johan Garssen,1,2 Joris C Verster1,31Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands; 2Nutricia Research, Utrecht, the Netherlands; 3Center for Human Psychopharmacology, Swinburne University, Melbourne, VIC, AustraliaObjective: To investigate the relationship between eating disorders, body mass index (BMI, sleep disorders, and daytime functioning.Design: Survey.Setting: The Netherlands.Participants: N=574 Dutch young adults (18–35 years old.Measurements: Participants completed a survey on eating and sleep habits including the Eating Disorder Screen for Primary care (ESP and SLEEP-50 questionnaire subscales for sleep apnea, insomnia, circadian rhythm disorder (CRD, and daytime functioning. SLEEP-50 outcomes of participants who screened negative (≤2 and positive (>2 on the ESP were compared. In addition, SLEEP-50 scores of groups of participants with different ESP scores (0–4 and different BMI groups (ie, underweight, healthy weight, overweight, and obese were compared using nonparametric statistics.Results: Almost 12% (n=67 of participants screened positive for having an eating disorder. Relative to participants without eating disorders, participants who screened positive for eating disorders reported significantly higher scores on sleep apnea (3.7 versus 2.9, P=0.012, insomnia (7.7 versus 5.5, P<0.0001, CRD (2.9 versus 2.3, P=0.011, and impairment of daytime functioning (8.8 versus 5.8, P=0.0001. ESP scores were associated with insomnia (r=0.117, P=0.005, sleep apnea (r=0.118, P=0.004, sleep quality (r=−0.104, P=0.012, and daytime functioning (r=0.225, P<0.0001, but not with CRD (r=0.066, P=0.112. BMI correlated significantly with ESP scores (r=0.172, P<0.0001 and scores on sleep apnea (r=0.171, P<0.0001. When controlling for BMI, the partial correlation between ESP and sleep apnea remained significant (r=0.10, P=0.015.Conclusion

  11. Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses

    OpenAIRE

    Won, Hyejung; Mah, Won; Kim, Eunjoon

    2013-01-01

    Autism spectrum disorder (ASD) is a group of developmental disabilities characterized by impairments in social interaction and communication and restricted and repetitive interests/behaviors. Advances in human genomics have identified a large number of genetic variations associated with ASD. These associations are being rapidly verified by a growing number of studies using a variety of approaches, including mouse genetics. These studies have also identified key mechanisms underlying the patho...

  12. Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

    Science.gov (United States)

    Barruet, Emilie; Hsiao, Edward C

    2016-01-01

    Musculoskeletal disorders affecting the bones and joints are major health problems among children and adults. Major challenges such as the genetic origins or poor diagnostics of severe skeletal disease hinder our understanding of human skeletal diseases. The recent advent of human induced pluripotent stem cells (human iPS cells) provides an unparalleled opportunity to create human-specific models of human skeletal diseases. iPS cells have the ability to self-renew, allowing us to obtain large amounts of starting material, and have the potential to differentiate into any cell types in the body. In addition, they can carry one or more mutations responsible for the disease of interest or be genetically corrected to create isogenic controls. Our work has focused on modeling rare musculoskeletal disorders including fibrodysplasia ossificans progressive (FOP), a congenital disease of increased heterotopic ossification. In this review, we will discuss our experiences and protocols differentiating human iPS cells toward the osteogenic lineage and their application to model skeletal diseases. A number of critical challenges and exciting new approaches are also discussed, which will allow the skeletal biology field to harness the potential of human iPS cells as a critical model system for understanding diseases of abnormal skeletal formation and bone regeneration.

  13. Molecular cloning of human T-cell lymphotrophic virus type I-like proviral genome from the peripheral lymphocyte DNA of a patient with chronic neurologic disorders

    International Nuclear Information System (INIS)

    Reddy, E.P.; Mettus, R.V.; DeFreitas, E.; Wroblewska, Z.; Cisco, M.; Koprowski, H.

    1988-01-01

    Human T-cell lymphotropic virus type 1 (HTLV-I), the etiologic agent of human T-cell leukemia, has recently been shown to be associated with neurologic disorders such as tropical spastic paraparesis, HTLV-associated myelopathy, and possibly with multiple sclerosis. In this communication, the authors have examined one specific case of neurologic disorder that can be classified as multiple sclerosis or tropical spastic paraparesis. The patient suffering from chronic neurologic disorder was found to contain antibodies to HTLV-I envelope and gag proteins in his serum and cerebrospinal fluid. Lymphocytes from peripheral blood and cerebrospinal fluid of the patient were shown to express viral RNA sequences by in situ hybridization. Southern blot analysis of the patient lymphocyte DNA revealed the presence of HTLV-I-related sequences. Blot-hybridization analysis of the RNA from fresh peripheral lymphocytes stimulated with interleukin 2 revealed the presence of abundant amounts of genomic viral RNA with little or no subgenomic RNA. They have clones the proviral genome from the DNA of the peripheral lymphocytes and determined its restriction map. This analysis shows that this proviral genome is very similar if not identical to that of the prototype HTLV-I genome

  14. Canine models of inherited bleeding disorders in the development of coagulation assays, novel protein replacement and gene therapies.

    Science.gov (United States)

    Nichols, T C; Hough, C; Agersø, H; Ezban, M; Lillicrap, D

    2016-05-01

    Animal models of inherited bleeding disorders are important for understanding disease pathophysiology and are required for preclinical assessment of safety prior to testing of novel therapeutics in human and veterinary medicine. Experiments in these animals represent important translational research aimed at developing safer and better treatments, such as plasma-derived and recombinant protein replacement therapies, gene therapies and immune tolerance protocols for antidrug inhibitory antibodies. Ideally, testing is done in animals with the analogous human disease to provide essential safety information, estimates of the correct starting dose and dose response (pharmacokinetics) and measures of efficacy (pharmacodynamics) that guide the design of human trials. For nearly seven decades, canine models of hemophilia, von Willebrand disease and other inherited bleeding disorders have not only informed our understanding of the natural history and pathophysiology of these disorders but also guided the development of novel therapeutics for use in humans and dogs. This has been especially important for the development of gene therapy, in which unique toxicities such as insertional mutagenesis, germ line gene transfer and viral toxicities must be assessed. There are several issues regarding comparative medicine in these species that have a bearing on these studies, including immune reactions to xenoproteins, varied metabolism or clearance of wild-type and modified proteins, and unique tissue tropism of viral vectors. This review focuses on the results of studies that have been performed in dogs with inherited bleeding disorders that closely mirror the human condition to develop safe and effective protein and gene-based therapies that benefit both species. © 2016 International Society on Thrombosis and Haemostasis.

  15. Type of presentation of dissociative disorder and frequency of co-morbid depressive disorder.

    Science.gov (United States)

    Alvi, Tabassum; Minhas, Fareed Aslam

    2009-02-01

    To determine the frequency distribution of various types of dissociative disorders, along with existing co-morbid depression and its level of severity in patients with dissociative disorder. Observational, cross-sectional study. The Institute of Psychiatry, Rawalpindi General Hospital from October 2004 to March 2005. Fifty consecutive patients were included in the study through non-probable purposive sampling technique. Encounter form included socio-demographic profile and brief psychiatric history. ICD 10 diagnostic criteria for research were administered for determining the presentation of dissociative disorder. Present state examination was applied to make diagnosis of depressive disorder in the studied patients. Descriptive statistics for frequency analysis of sociodemographic variables, type of presentation of dissociative disorder and the frequency of depressive disorder in patients of dissociative disorder. The mean age was 23.6+/-8.67 years with female preponderance (n=40, 80% patients). Most of them were single, unemployed and belonged to urban population. Main stress was primary support group issue. Mixed category of dissociative disorder was highest (n=18, 38%) followed by unspecified and motor symptoms (n=13, 26%) in each group. Depression was present in 42 (84%) patients. Moderate depression was most frequent (n=19, 38%). Mixed dissociative symptoms were found in 38%, while 26% had motor and unspecified category of dissociative symptoms respectively. Depressive disorder was present in 42 (84%) cases of dissociative disorder with 38% having moderate depression.

  16. Diffraction by disordered polycrystalline fibers

    International Nuclear Information System (INIS)

    Stroud, W.J.; Millane, R.P.

    1995-01-01

    X-ray diffraction patterns from some polycrystalline fibers show that the constituent microcrystallites are disordered. The relationship between the crystal structure and the diffracted intensities is then quite complicated and depends on the precise kind and degree of disorder present. The effects of disorder on diffracted intensities must be included in structure determinations using diffraction data from such specimens. Theory and algorithms are developed here that allow the full diffraction pattern to be calculated for a disordered polycrystalline fiber made up of helical molecules. The model accommodates various kinds of disorder and includes the effects of finite crystallite size and cylindrical averaging of the diffracted intensities from a fiber. Simulations using these methods show how different kinds, or components, of disorder produce particular diffraction effects. General properties of disordered arrays of helical molecules and their effects on diffraction patterns are described. Implications for structure determination are discussed. (orig.)

  17. Human body may produce bacteria.

    Science.gov (United States)

    Salerian, Alen J

    2017-06-01

    "Human body may produce bacteria" proposes that human body may produce bacteria and represent an independent source of infections contrary to the current paradigm of infectious disorders proposed by Louis Pasteur in 1880. The following observations are consistent with this hypothesis: A. Bidirectional transformations of both living and nonliving things have been commonly observed in nature. B. Complex multicellular organisms harbor the necessary properties to produce bacteria (water, nitrogen and oxygen). C. Physical laws suggest any previously observed phenomenon or action will occur again (life began on earth; a non living thing). D. Animal muscle cells may generate energy (fermentation). E. Sterilized food products (i.e. boiled eggs), may produce bacteria and fungus under special conditions and without any exposure to foreign living cells. "Human body may produce bacteria" may challenge the current medical paradigm that views human infectious disorders as the exclusive causative byproducts of invading foreign cells. It may also introduce new avenues to treat infectious disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Behavioural medicine and gastrointestinal disorders: the promise of positive psychology.

    Science.gov (United States)

    Keefer, Laurie

    2018-04-12

    Psychosocial risk factors linked to brain-gut dysregulation are prevalent across the spectrum of gastrointestinal disorders and are associated with poor patient outcomes. Robust and reproducible data in the areas of behavioural intervention science and the brain-gut axis have led to major advances in patient care, including the routine use of brain-gut psychotherapies to manage digestive symptoms and optimize coping. The logical next step for the emerging field of psychogastroenterology is to develop a scientific framework that enables the identification of those individual characteristics and coping styles that buffer patients against the negative psychological effects of chronic gastrointestinal disorders. A shift towards a strength-based, positive psychological science of gastrointestinal disorders could facilitate the integration of early, effective psychological care into gastroenterology practice. In this Perspective, I discuss the potential role of three human strengths with relevance to gastrointestinal health - resilience, optimism and self-regulation - and how these three constructs can be cultivated through existing or emerging brain-gut psychotherapies.

  19. The role of social relationships in bipolar disorder: a review.

    Science.gov (United States)

    Greenberg, Sarah; Rosenblum, Katherine L; McInnis, Melvin G; Muzik, Maria

    2014-10-30

    Social relationships and attachment are core developmental elements of human existence and survival that evolve over the lifetime of an individual. The internal and external factors that influence them include the presence of illness in the individual or in their immediate environment. The developmental aspects of attachment and social relationships have become increasingly of interest and relevance in light of early developmental epigenetic modification of gene expression patterns that may influence subsequent behavioral patterns and outcomes. This review examines extant literature on attachment and social relationships in bipolar cohorts. Despite many methodological challenges, the findings indicate that social relationships and capacity for attachment are significantly compromised in individuals with bipolar disorder compared to other mood disorders and normal controls. Though extant research is limited, research clearly points toward the importance of social relationships on the etiology, course, and consequences of bipolar disorder. We highlight a number of key considerations for future research. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Animal Models of Hemophilia and Related Bleeding Disorders

    Science.gov (United States)

    Lozier, Jay N.; Nichols, Timothy C.

    2013-01-01

    Animal models of hemophilia and related diseases are important for development of novel treatments and to understand the pathophysiology of bleeding disorders in humans. Testing in animals with the equivalent human disorder provides informed estimates of doses and measures of efficacy, which aids in design of human trials. Many models of hemophilia A, hemophilia B, and von Willebrand disease have been developed from animals with spontaneous mutations (hemophilia A dogs, rats, sheep; hemophilia B dogs; and von Willebrand disease pigs and dogs), or by targeted gene disruption in mice to create hemophilia A, B, or VWD models. Animal models have been used to generate new insights into the pathophysiology of each bleeding disorder and also to perform pre-clinical assessments of standard protein replacement therapies as well as novel gene transfer technology. Both the differences between species and differences in underlying causative mutations must be considered in choosing the best animal for a specific scientific study PMID:23956467

  1. Sleep Disorders

    DEFF Research Database (Denmark)

    Rahbek Kornum, Birgitte; Mignot, Emmanuel

    2014-01-01

    mediates circadian regulation of sleep. Misalignment with the rhythm of the sun results in circadian disorders and jet lag. The molecular basis of homeostatic sleep regulation is mostly unknown. A network of mutually inhibitory brain nuclei regulates sleep states and sleep-wake transitions. Abnormalities...... in these networks create sleep disorders, including rapid eye movement sleep behavior disorder, sleep walking, and narcolepsy. Physiological changes associated with sleep can be imbalanced, resulting in excess movements such as periodic leg movements during sleep or abnormal breathing in obstructive sleep apneas....... As every organ in the body is affected by sleep directly or indirectly, sleep and sleep-associated disorders are frequent and only now starting to be understood....

  2. Treatment of Binge Eating Disorder

    OpenAIRE

    Crow, Scott

    2014-01-01

    Binge eating disorder is a common eating disorder that recently has received increasing attention. Goals in treating binge eating disorder typically include controlling binge eating and diminishing excess body weight. A variety of treatment approaches have been used, including diet/lifestyle modification, psychotherapy, and pharmacologic treatment. Diet and lifestyle interventions are somewhat effective in diminishing the binge eating behavior and lead to modest weight loss, but the weight ef...

  3. A review of somatoform disorders in DSM-IV and somatic symptom disorders in proposed DSM-V.

    Science.gov (United States)

    Ghanizadeh, Ahmad; Firoozabadi, Ali

    2012-12-01

    Psychiatric care providers should be trained to use current changes in the somatoform disorders criteria. New diagnostic criteria for Somatic Symptom disorders in the proposed DSM-V is discussed and compared with its older counterpart in DSM-IV. A new category called Somatic Syndrome Disorders is suggested. It includes new subcategories such as "Complex Somatic Symptom Disorder" (CSSD) and "Simple Somatic Symptom Disorder" (SSSD). Some of the subcategories of DSM-IV derived disorders are included in CSSD. While there are some changes in diagnostic criteria, there are concerns and limitations about the new classification needed to be more discussed before implementation. Functional somatic disturbance, the counterpart of converion disorder in DSM-IV, can be highly dependet on the developmental level of children. However, the role of developmental level needs to be considered.

  4. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome.

    Science.gov (United States)

    Sharp, Andrew J; Hansen, Sierra; Selzer, Rebecca R; Cheng, Ze; Regan, Regina; Hurst, Jane A; Stewart, Helen; Price, Sue M; Blair, Edward; Hennekam, Raoul C; Fitzpatrick, Carrie A; Segraves, Rick; Richmond, Todd A; Guiver, Cheryl; Albertson, Donna G; Pinkel, Daniel; Eis, Peggy S; Schwartz, Stuart; Knight, Samantha J L; Eichler, Evan E

    2006-09-01

    Genomic disorders are characterized by the presence of flanking segmental duplications that predispose these regions to recurrent rearrangement. Based on the duplication architecture of the genome, we investigated 130 regions that we hypothesized as candidates for previously undescribed genomic disorders. We tested 290 individuals with mental retardation by BAC array comparative genomic hybridization and identified 16 pathogenic rearrangements, including de novo microdeletions of 17q21.31 found in four individuals. Using oligonucleotide arrays, we refined the breakpoints of this microdeletion, defining a 478-kb critical region containing six genes that were deleted in all four individuals. We mapped the breakpoints of this deletion and of four other pathogenic rearrangements in 1q21.1, 15q13, 15q24 and 17q12 to flanking segmental duplications, suggesting that these are also sites of recurrent rearrangement. In common with the 17q21.31 deletion, these breakpoint regions are sites of copy number polymorphism in controls, indicating that these may be inherently unstable genomic regions.

  5. Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells.

    Science.gov (United States)

    Li, Jin; Jørgensen, Silje F; Maggadottir, S Melkorka; Bakay, Marina; Warnatz, Klaus; Glessner, Joseph; Pandey, Rahul; Salzer, Ulrich; Schmidt, Reinhold E; Perez, Elena; Resnick, Elena; Goldacker, Sigune; Buchta, Mary; Witte, Torsten; Padyukov, Leonid; Videm, Vibeke; Folseraas, Trine; Atschekzei, Faranaz; Elder, James T; Nair, Rajan P; Winkelmann, Juliane; Gieger, Christian; Nöthen, Markus M; Büning, Carsten; Brand, Stephan; Sullivan, Kathleen E; Orange, Jordan S; Fevang, Børre; Schreiber, Stefan; Lieb, Wolfgang; Aukrust, Pål; Chapel, Helen; Cunningham-Rundles, Charlotte; Franke, Andre; Karlsen, Tom H; Grimbacher, Bodo; Hakonarson, Hakon; Hammarström, Lennart; Ellinghaus, Eva

    2015-04-20

    Common variable immunodeficiency disorder (CVID) is the most common symptomatic primary immunodeficiency in adults, characterized by B-cell abnormalities and inadequate antibody response. CVID patients have considerable autoimmune comorbidity and we therefore hypothesized that genetic susceptibility to CVID may overlap with autoimmune disorders. Here, in the largest genetic study performed in CVID to date, we compare 778 CVID cases with 10,999 controls across 123,127 single-nucleotide polymorphisms (SNPs) on the Immunochip. We identify the first non-HLA genome-wide significant risk locus at CLEC16A (rs17806056, P=2.0 × 10(-9)) and confirm the previously reported human leukocyte antigen (HLA) associations on chromosome 6p21 (rs1049225, P=4.8 × 10(-16)). Clec16a knockdown (KD) mice showed reduced number of B cells and elevated IgM levels compared with controls, suggesting that CLEC16A may be involved in immune regulatory pathways of relevance to CVID. In conclusion, the CLEC16A associations in CVID represent the first robust evidence of non-HLA associations in this immunodeficiency condition.

  6. Detection of anti-streptococcal, antienolase, and anti-neural antibodies in subjects with early-onset psychiatric disorders.

    Science.gov (United States)

    Nicolini, Humberto; López, Yaumara; Genis-Mendoza, Alma D; Manrique, Viana; Lopez-Canovas, Lilia; Niubo, Esperanza; Hernández, Lázaro; Bobes, María A; Riverón, Ana M; López-Casamichana, Mavil; Flores, Julio; Lanzagorta, Nuria; De la Fuente-Sandoval, Camilo; Santana, Daniel

    2015-01-01

    Infection with group A Streptococcus (StrepA) can cause post-infectious sequelae, including a spectrum of childhood-onset obsessive-compulsive (OCD) and tic disorders with autoimmune origin (PANDAS, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections). Until now, no single immunological test has been designed that unequivocally diagnoses these disorders. In this study, we assessed the detection of serum antibodies against human brain enolase (AE), neural tissue (AN) and Streptococcus (AS) as a laboratory tool for the diagnosis of early-onset psychiatric disorders. Serum antibodies against human brain enolase, total brain proteins, and total proteins from StrepA were detected by ELISA in 37 patients with a presumptive diagnosis of PANDAS and in 12 healthy subjects from Mexico and Cuba. The antibody titers against human brain enolase (AE) and Streptococcal proteins (AS) were higher in patients than in control subjects (t-student, tAE=-2.17, P=0.035; tAS=-2.68, P=0.01, n=12 and 37/group, df=47, significance level 0.05), while the neural antibody titers did not differ between the two groups (P(t)=0.05). The number of subjects (titers> meancontrol + CI95) with simultaneous seropositivity to all three antibodies was higher in the patient group (51.4%) than in the control group (8.3%) group (X2=5.27, P=0.022, df=1, n=49). The simultaneous detection of all three of these antibodies could provide valuable information for the etiologic diagnosis of individuals with early-onset obsessive-compulsive disorders associated with streptococcal infection and, consequently, for prescribing suitable therapy.

  7. The Relationship between Childhood Attention Deficit/Hyperactivity Disorder and Adulthood Borderline Personality Disorder

    Directory of Open Access Journals (Sweden)

    Ali Mashhadi

    2013-02-01

    Full Text Available Background: Attention Deficit Hyperactivity Disorder (ADHD is a risk factor for Borderline Personality Disorder (BPD during adulthood. Studying the relationship between childhood ADHD disorder symptoms and depression and borderline personality disorder symptoms among students was the main aim of this study. Materials and Methods: A total of 291 students, who were studying in Shiraz and Tabriz universities inThe academic year of 2010-2011, were selected from three groups of Humanities, Basic Sciences, and Technical-Engineering Sciences using simple sampling method. They participated in the study through completing Wender Utah Rating Scale (WURS, Borderline Personality Scale (STB and Beck Depression Inventory (BDI-II. Pearsons correlation coefficient and multiple regression analysis were used to analyze the data. Results: The results showed that there is a significant positive relationship between childhood ADHD and borderline Personality Disorder (BPD in adulthood and childhood ADHD is able to predict BPD in adulthood (p<0.01. Similarly, the relationship between symptoms of childhood ADHD and depression was positive and significant (p<0.01. Conclusion: There is a relationship between symptoms of childhood ADHD, BPD and depression in students. It is recommended to pay due attention to the comorbidity disorders such as BPD and depression in the treatment of ADHD disorder.

  8. Critical exploration of co-occurring Attention-Deficit/Hyperactivity Disorder, mood disorder and Substance Use Disorder.

    Science.gov (United States)

    Regnart, Judith; Truter, Ilse; Meyer, Anneke

    2017-06-01

    Co-occurring disorders (CODs) describe a Substance Use Disorder (SUD) accompanied by a comorbid psychiatric disorder. Attention-Deficit/Hyperactivity Disorder (ADHD) and mood disorders are common CODs with high prevalence rates in SUD populations. It is proposed that literature on a tri-condition presentation of ADHD, mood disorder and SUD is limited. Areas covered: A literature search was conducted using a keyword search on EBSCOhost. Initially 2 799 records were identified, however, only two articles included all three conditions occurring concurrently in individuals. CODs constitute a major concern due to their overarching burden on society as a whole. Diagnosis and treatment of such patients is challenging. There is evidence that dysfunction of dopamine in the brain reward circuitry impacts the development or symptomology of all three disorders. Disparity exists regarding whether ADHD or mood disorders are greater modifiers for increased SUD severity. However, it has been reported that poor functional capacity may have a greater influence than comorbidities on SUD development. Expert commentary: Challenges exist which confound the clear distinction of CODs, however, with greater emergence of adult ADHD its screening in SUD populations should become standard practice to establish data on multi-condition presentations with the ultimate goal of improving clinical outcomes.

  9. Genetic approaches to understanding post-traumatic stress disorder

    Science.gov (United States)

    Almli, Lynn M.; Fani, Negar; Smith, Alicia K.; Ressler, Kerry J.

    2015-01-01

    Post-traumatic stress disorder (PTSD) is increasingly recognized as both a disorder of enormous mental health and societal burden, but also as an anxiety disorder that may be particularly understandable from a scientific perspective. Specifically, PTSD can be conceptualized as a disorder of fear and stress dysregulation, and the neural circuitry underlying these pathways in both animals and humans are becoming increasingly well understood. Furthermore, PTSD is the only disorder in psychiatry in which the initiating factor, the trauma exposure, can be identified. Thus, the pathophysiology of the fear and stress response underlying PTSD can be examined and potentially interrupted. Twin studies have shown that the development of PTSD following a trauma is heritable, and that genetic risk factors may account for up to 30–40% of this heritability. A current goal is to understand the gene pathways that are associated with PTSD, and how those genes act on the fear/stress circuitry to mediate risk vs. resilience for PTSD. This review will examine gene pathways that have recently been analysed, primarily through candidate gene studies (including neuroimaging studies of candidate genes), in addition to genome-wide associations and the epigenetic regulation of PTSD. Future and on-going studies are utilizing larger and collaborative cohorts to identify novel gene candidates through genome-wide association and other powerful genomic approaches. Identification of PTSD biological pathways strengthens the hope of progress in the mechanistic understanding of a model psychiatric disorder and allows for the development of targeted treatments and interventions. PMID:24103155

  10. Genetic approaches to understanding post-traumatic stress disorder.

    Science.gov (United States)

    Almli, Lynn M; Fani, Negar; Smith, Alicia K; Ressler, Kerry J

    2014-02-01

    Post-traumatic stress disorder (PTSD) is increasingly recognized as both a disorder of enormous mental health and societal burden, but also as an anxiety disorder that may be particularly understandable from a scientific perspective. Specifically, PTSD can be conceptualized as a disorder of fear and stress dysregulation, and the neural circuitry underlying these pathways in both animals and humans are becoming increasingly well understood. Furthermore, PTSD is the only disorder in psychiatry in which the initiating factor, the trauma exposure, can be identified. Thus, the pathophysiology of the fear and stress response underlying PTSD can be examined and potentially interrupted. Twin studies have shown that the development of PTSD following a trauma is heritable, and that genetic risk factors may account for up to 30-40% of this heritability. A current goal is to understand the gene pathways that are associated with PTSD, and how those genes act on the fear/stress circuitry to mediate risk vs. resilience for PTSD. This review will examine gene pathways that have recently been analysed, primarily through candidate gene studies (including neuroimaging studies of candidate genes), in addition to genome-wide associations and the epigenetic regulation of PTSD. Future and on-going studies are utilizing larger and collaborative cohorts to identify novel gene candidates through genome-wide association and other powerful genomic approaches. Identification of PTSD biological pathways strengthens the hope of progress in the mechanistic understanding of a model psychiatric disorder and allows for the development of targeted treatments and interventions.

  11. TALEN-based generation of a cynomolgus monkey disease model for human microcephaly

    Science.gov (United States)

    Ke, Qiong; Li, Weiqiang; Lai, Xingqiang; Chen, Hong; Huang, Lihua; Kang, Zhuang; Li, Kai; Ren, Jie; Lin, Xiaofeng; Zheng, Haiqing; Huang, Weijun; Ma, Yunhan; Xu, Dongdong; Chen, Zheng; Song, Xinming; Lin, Xinyi; Zhuang, Min; Wang, Tao; Zhuang, Fengfeng; Xi, Jianzhong; Mao, Frank Fuxiang; Xia, Huimin; Lahn, Bruce T; Zhou, Qi; Yang, Shihua; Xiang, Andy Peng

    2016-01-01

    Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size. PMID:27502025

  12. Temperament and parental child-rearing style: unique contributions to clinical anxiety disorders in childhood.

    Science.gov (United States)

    Lindhout, Ingeborg E; Markus, Monica Th; Hoogendijk, Thea H G; Boer, Frits

    2009-07-01

    Both temperament and parental child-rearing style are found to be associated with childhood anxiety disorders in population studies. This study investigates the contribution of not only temperament but also parental child-rearing to clinical childhood anxiety disorders. It also investigates whether the contribution of temperament is moderated by child-rearing style, as is suggested by some studies in the general population. Fifty children were included (25 with anxiety disorders and 25 non-clinical controls). Child-rearing and the child's temperament were assessed by means of parental questionnaire (Child Rearing Practices Report (CRPR) (Block in The Child-Rearing Practices Report. Institute of Human Development. University of California, Berkely, 1965; The Child-Rearing Practices Report (CRPR): a set of Q items for the description of parental socialisation attitudes and values. Unpublished manuscript. Institute of Human Development. University of California, Berkely, 1981), EAS Temperament Survey for Children (Boer and Westenberg in J Pers Assess 62:537-551, 1994; Buss and Plomin in Temperament: early developing personality traits. Lawrence Erlbaum Associates, Inc, Hillsdale, 1984s). Analysis of variance showed that anxiety-disordered children scored significantly higher on the temperamental characteristics emotionality and shyness than non-clinical control children. Hierarchical logistic regression analyses showed that temperament (emotionality and shyness) and child-rearing style (more parental negative affect, and less encouraging independence of the child) both accounted for a unique proportion of the variance of anxiety disorders. Preliminary results suggest that child-rearing style did not moderate the association between children's temperament and childhood anxiety disorders. The limited sample size might have been underpowered to assess this interaction.

  13. Physical biology of human brain development

    Directory of Open Access Journals (Sweden)

    Silvia eBudday

    2015-07-01

    Full Text Available Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view towards surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level towards form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.

  14. Autism spectrum disorder: forensic issues and challenges for mental health professionals and courts.

    Science.gov (United States)

    Freckelton, Ian

    2013-09-01

    Autism spectrum disorder (ASD), as defined in DSM-V, can be relevant in a variety of ways to decision-making by courts and tribunals. This includes the family, disciplinary, discrimination and criminal law contexts. By reviewing decisions made by superior courts in a number of common law jurisdictions, this article identifies a pivotal role for mental health professionals closely familiar with both the disorder and forensic exigencies to educate courts about the inner world of those with ASD. Highlighting areas of criminality that court decisions have dealt with, especially in relation to persons with Asperger's Disorder, as defined by DSM-IV, it calls for further research on the connection between ASD, on the one hand, and conduct, capacities and skills, on the other hand. It urges enhancement of awareness of the forensic repercussions of the disorder so that expert evidence can assist the courts more humanely and informedly to make criminal justice and other decisions. © 2013 John Wiley & Sons Ltd.

  15. Perfluorooctanesulfonate and related fluorochemicals in several organisms including humans from Italy

    Energy Technology Data Exchange (ETDEWEB)

    Corsolini, S. [Siena Univ. (Italy); Kannan, K. [New York State Univ., Albany, NY (United States)

    2004-09-15

    Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant, extremely resistant to environmental degradation and is ubiquitous in the environment. Traditional monitoring studies for persistent chemicals failed to identify this contaminant for a long time because of its unique physicochemical properties and its tendency to bind to proteins instead of accumulating in fatty tissues. PFOS is known to be toxic in laboratory animals (rats, mice, monkeys) at levels close to the range already found in organisms and people. PFOS has been commercially produced by an electrochemical fluorination process for over 40 years. Perfluorooctane sulfonylfluoride (POSF; C{sub 8}F{sub 17}SO{sub 2}F) is used as a building block for further reactions that produce several other sulfonated fluorinated compounds, including perfluorooctane sulfonate (C{sub 8}F{sub 17}SO{sub 3}{sup -}) and other precursor molecules such as n-ethyl or n-methyl perfluorooctanesulfonamidoethanol. POSF-based fluorochemicals have been used in a wide variety of industrial and consumer products, including protective coatings for carpets and apparel, paper coatings, insecticide formulations, and surfactants. These compounds repel water and oil, reduce surface tension, catalyze oligomerization and polymerization, and maintain their properties under extreme conditions. Depending upon the specific functional derivatization or the degree of polymerization, POSF-based chemicals may degrade or metabolize to PFOS, which is known to be the final metabolite of POSF-based fluorochemicals. PFOS is stable, chemically inert, and non-reactive and has the potential to bioaccumulate. It has been found in polar bears from the Arctic, albatross and other fish-eating water birds in the mid-Pacific, and aquatic organisms11 and people world-wide. PFOS and other perfluorinated chemicals such as perfluorooctanesulfonamide (PFOSA), perfluorohexanesulfonate (PFHxS), and perfluorooctanoate (PFOA) have been detected in human blood. In

  16. Amino Acid Metabolism Disorders

    Science.gov (United States)

    ... this process. One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup urine disease. Amino acids are "building blocks" that join together to form ...

  17. What Is Humane Education and Why It Should Be Included in Modern Education

    Science.gov (United States)

    Jacobs, G. M.

    2016-01-01

    Humane education has existed since at least the 18th century (Unti & DeRosa, 2003). This brief chapter begins with a brief definition of humane education and examples of how it can be incorporated in linguistics, cross cultural studies and foreign language education. Next, the chapter discusses why humane education constitutes an important…

  18. Dwarf Eye Disorder

    Science.gov (United States)

    Science Teacher, 2005

    2005-01-01

    Johns Hopkins researchers at the Wilmer Eye Institute have discovered what appears to be the first human gene mutation that causes extreme farsightedness. The researchers report that nanophthalmos, Greek for "dwarf eye," is a rare, potentially blinding disorder caused by an alteration in a gene called MFRP that helps control eye growth and…

  19. A diagnostic and statistical manual of mental disorders history of premenstrual dysphoric disorder.

    Science.gov (United States)

    Zachar, Peter; Kendler, Kenneth S

    2014-04-01

    The proposals to include a menstruation-related mood disorder in the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R), and DSM-IV led to intense public and behind-the-scenes controversy. Although the controversies surrounding the DSM-5 revision were greater in number than the controversies of the earlier revisions, the DSM-5 proposal to include a menstruation-related mood disorder was not among them. Premenstrual dysphoric disorder was made an official disorder in the DSM-5 with no significant protest. To understand the factors that led to this change, we interviewed those psychiatrists and psychologists who were most involved in the DSM-IV revision. On the basis of these interviews, we offer a list of empirical and nonempirical considerations that led to the DSM-IV compromise and explore how key alterations in these considerations led to a different outcome for the DSM-5.

  20. Gambling disorders.

    Science.gov (United States)

    Hodgins, David C; Stea, Jonathan N; Grant, Jon E

    2011-11-26

    Gambling disorders, including pathological gambling and problem gambling, have received increased attention from clinicians and researchers over the past three decades since gambling opportunities have expanded around the world. This Seminar reviews prevalence, causes and associated features, screening and diagnosis, and treatment approaches. Gambling disorders affect 0·2-5·3% of adults worldwide, although measurement and prevalence varies according to the screening instruments and methods used, and availability and accessibility of gambling opportunities. Several distinct treatment approaches have been favourably evaluated, such as cognitive behavioural and brief treatment models and pharmacological interventions. Although promising, family therapy and support from Gamblers Anonymous are less well empirically supported. Gambling disorders are highly comorbid with other mental health and substance use disorders, and a further understanding is needed of both the causes and treatment implications of this disorder. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Following the genes: a framework for animal modeling of psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Sawa Akira

    2011-11-01

    Full Text Available Abstract The number of individual cases of psychiatric disorders that can be ascribed to identified, rare, single mutations is increasing with great rapidity. Such mutations can be recapitulated in mice to generate animal models with direct etiological validity. Defining the underlying pathogenic mechanisms will require an experimental and theoretical framework to make the links from mutation to altered behavior in an animal or psychopathology in a human. Here, we discuss key elements of such a framework, including cell type-based phenotyping, developmental trajectories, linking circuit properties at micro and macro scales and definition of neurobiological phenotypes that are directly translatable to humans.

  2. Multisystem Disease, Including Eosinophilia and Progressive Hyper-Creatine-Kinase-emia over 10 Years, Suggests Mitochondrial Disorder

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2017-04-01

    Full Text Available Background: Eosinophilia has not been reported as a manifestation of a mitochondrial disorder (MID. Here, we report a patient with clinical features suggesting a MID and permanent eosinophilia, multisystem disease, and progressive hyper-creatine-kinase (CK-emia for at least 10 years. Materials and Methods: Methods applied included a clinical exam, blood chemical investigations, electrophysiological investigations, imaging, and invasive cardiological investigations. The patient was repeatedly followed up over several years. He required replacement cardiac surgery. Results: In a 57-year-old male, eosinophilia was first detected at the age of 44 years and has remained almost constantly present until today. In addition to eosinophilia, he developed progressive hyper-CK-emia at the age of 47 years. His history was further positive for hepatopathy, hyperlipidemia, hypothyroidism, renal insufficiency, spontaneous Achilles tendon rupture, double vision, exercise intolerance, muscle aching, mild hypoacusis, sensory neuropathy, seizures, and mitral insufficiency/stenosis requiring valve replacement therapy, oral anticoagulation, and pacemaker implantation. Based on the multisystem nature of his abnormalities and permanent hyper-CK-emia, a MID was suspected. Conclusion: Eosinophilia can be associated with a MID with myopathy, possibly as a reaction to myofiber necrosis. If eosinophilia is associated with progressive hyper-CK-emia and multisystem disease, a MID should be suspected.

  3. Risk of Psychiatric and Neurodevelopmental Disorders Among Siblings of Probands With Autism Spectrum Disorders.

    Science.gov (United States)

    Jokiranta-Olkoniemi, Elina; Cheslack-Postava, Keely; Sucksdorff, Dan; Suominen, Auli; Gyllenberg, David; Chudal, Roshan; Leivonen, Susanna; Gissler, Mika; Brown, Alan S; Sourander, Andre

    2016-06-01

    Previous research has focused on examining the familial clustering of schizophrenia, bipolar disorder, and autism spectrum disorders (ASD). Little is known about the clustering of other psychiatric and neurodevelopmental disorders among siblings of persons with ASD. To examine the risk for psychiatric and neurodevelopmental disorders among full siblings of probands with ASD. The Finnish Prenatal Study of Autism and Autism Spectrum Disorders used a population-based cohort that included children born from January 1, 1987, to December 31, 2005, who received a diagnosis of ASD by December 31, 2007. Each case was individually matched to 4 control participants by sex and date and place of birth. The siblings of the cases and controls were born from January 1, 1977, to December 31, 2005, and received a diagnosis from January 1, 1987, to December 31, 2009. This nested case-control study included 3578 cases with ASD with 6022 full siblings and 11 775 controls with 22 127 siblings from Finnish national registers. Data were analyzed from March 6, 2014, to February 12, 2016. The adjusted risk ratio (RR) for psychiatric and neurodevelopmental disorders among siblings of probands with ASD vs siblings of matched controls. Additional analyses were conducted separately for ASD subgroups, including childhood autism, Asperger syndrome, and pervasive developmental disorders not otherwise specified. Analyses were further stratified by sex and intellectual disability among the probands. Among the 3578 cases with ASD (2841 boys [79.4%]) and 11 775 controls (9345 boys [79.4%]), 1319 cases (36.9%) and 2052 controls (17.4%) had at least 1 sibling diagnosed with any psychiatric or neurodevelopmental disorder (adjusted RR, 2.5; 95% CI, 2.3-2.6). The largest associations were observed for childhood-onset disorders (1061 cases [29.7%] vs 1362 controls [11.6%]; adjusted RR, 3.0; 95% CI, 2.8-3.3), including ASD (374 cases [10.5%] vs 125 controls [1.1%]; adjusted RR, 11.8; 95% CI, 9

  4. Resilience concepts in psychiatry demonstrated with bipolar disorder.

    Science.gov (United States)

    Angeler, David G; Allen, Craig R; Persson, Maj-Liz

    2018-02-09

    The term resilience describes stress-response patterns of subjects across scientific disciplines. In ecology, advances have been made to clearly distinguish resilience definitions based on underlying mechanistic assumptions. Engineering resilience (rebound) is used for describing the ability of subjects to recover from adverse conditions (disturbances), and is the rate of recovery. In contrast, the ecological resilience definition considers a systemic change: when complex systems (including humans) respond to disturbances by reorganizing into a new regime (stable state) where structural and functional aspects have fundamentally changed relative to the prior regime. In this context, resilience is an emergent property of complex systems. We argue that both resilience definitions and uses are appropriate in psychology and psychiatry, but although the differences are subtle, the implications and uses are profoundly different. We borrow from the field of ecology to discuss resilience concepts in the mental health sciences. In psychology and psychiatry, the prevailing view of resilience is adaptation to, coping with, and recovery (engineering resilience) from adverse social and environmental conditions. Ecological resilience may be useful for describing vulnerability, onset, and the irreversibility patterns of mental disorders. We discuss this in the context of bipolar disorder. Rebound, adaptation, and coping are processes that are subsumed within the broader systemic organization of humans, from which ecological resilience emanates. Discerning resilience concepts in psychology and psychiatry has potential for a mechanistically appropriate contextualization of mental disorders at large. This might contribute to a refinement of theory and contextualize clinical practice within the broader systemic functioning of mental illnesses.

  5. Sex steroid-related candidate genes in psychiatric disorders.

    Science.gov (United States)

    Westberg, Lars; Eriksson, Elias

    2008-07-01

    Sex steroids readily pass the blood-brain barrier, and receptors for them are abundant in brain areas important for the regulation of emotions, cognition and behaviour. Animal experiments have revealed both important early effects of these hormones on brain development and their ongoing influence on brain morphology and neurotransmission in the adult organism. The important effects of sex steroids on human behaviour are illustrated by, for example, the effect of reduced levels of these hormones on sexual drive and conditions such as premenstrual dysphoric disorder, perimenopausal dysphoria, postpartum depression, postpartum psychosis, dysphoria induced by oral contraceptives or hormonal replacement therapy and anabolic steroid-induced aggression. The fact that men and women (as groups) differ with respect to the prevalence of several psychiatric disorders, certain aspects of cognitive function and certain personality traits may possibly also reflect an influence of sex steroids on human behaviour. The heritability of most behavioural traits, including personality, cognitive abilities and susceptibility to psychiatric illness, is considerable, but as yet, only few genes of definite importance in this context have been identified. Given the important role of sex steroids for brain function, it is unfortunate that relatively few studies so far have addressed the possible influence of sex steroid-related genes on interindividual differences with respect to personality, cognition and susceptibility to psychiatric disorders. To facilitate further research in this area, this review provides information on several such genes and summarizes what is currently known with respect to their possible influence on brain function.

  6. Smoking, nicotine and psychiatric disorders: evidence for therapeutic role, controversies and implications for future research.

    Science.gov (United States)

    Dursun, S M; Kutcher, S

    1999-02-01

    Researchers interested in investigating the possible therapeutic effects and the mechanisms of action of nicotine in neuropsychiatric disorders face a social-scientific-ethical dilemma. This dilemma comprises three components: (1) the known addictive potential of nicotine makes careful evaluation of the therapeutic potential of this compound socially unattractive; (2) the potential misuse of scientifically determined data by the tobacco 'lobby' creates ethical concerns; and (3) the possible confusion between the differential effects of nicotine in human smokers versus non-smokers creates difficulties in study designs in voluntary human subjects. Therefore, it is imperative that, at the onset of this review, the authors stress that they do not advocate cigarette-smoking as a route of nicotine intake under any circumstances on the basis that controlled dosing of nicotine may be of potential benefit in some neuropsychiatric disorders. In this article, we review the psychopharmacology of nicotine and its effects in a variety of neuropsychiatric disorders including schizophrenia, depression, anxiety and Tourette's syndrome. Possible mechanisms of action of nicotine directly or indirectly via its interaction with other neurotransmitter systems (i.e. serotonin, dopamine and noradrenaline) in relation to its potential role in these disorders are discussed. It is postulated that new drugs may need to be developed that selectively interact with nicotinic receptors without addiction potential.

  7. Psychogenic Balance Disorders: Is It a New Entity of Psychogenic Movement Disorders?

    Directory of Open Access Journals (Sweden)

    Jong Sam Baik

    2012-05-01

    Full Text Available The various reported psychogenic dyskinesias include tremor, dystonia, myoclonus, gait disorder, Parkinsonism, tics, and chorea. It is not easy to diagnose psychogenic movement disorders, especially in patients with underlying organic disease. We describe three patients with balance and/or posture abnormalities that occur when they stand up, start to move, or halt from walking, although their gaits are normal. One had an underlying unilateral frontal lobe lesion. All patients improved dramatically after receiving a placebo-injection or medication. These abnormal features differ from the previously reported features of astasia without abasia and of psychogenic gait disorders, including recumbent gait. We describe and discuss the patients’ unique clinical characteristics.

  8. Chocolate consumption and cardiometabolic disorders: systematic review and meta-analysis.

    Science.gov (United States)

    Buitrago-Lopez, Adriana; Sanderson, Jean; Johnson, Laura; Warnakula, Samantha; Wood, Angela; Di Angelantonio, Emanuele; Franco, Oscar H

    2011-08-26

    To evaluate the association of chocolate consumption with the risk of developing cardiometabolic disorders. Systematic review and meta-analysis of randomised controlled trials and observational studies. Medline, Embase, Cochrane Library, PubMed, CINAHL, IPA, Web of Science, Scopus, Pascal, reference lists of relevant studies to October 2010, and email contact with authors. Randomised trials and cohort, case-control, and cross sectional studies carried out in human adults, in which the association between chocolate consumption and the risk of outcomes related to cardiometabolic disorders were reported. Data were extracted by two independent investigators, and a consensus was reached with the involvement of a third. The primary outcome was cardiometabolic disorders, including cardiovascular disease (coronary heart disease and stroke), diabetes, and metabolic syndrome. A meta-analysis assessed the risk of developing cardiometabolic disorders by comparing the highest and lowest level of chocolate consumption. From 4576 references seven studies met the inclusion criteria (including 114,009 participants). None of the studies was a randomised trial, six were cohort studies, and one a cross sectional study. Large variation was observed between these seven studies for measurement of chocolate consumption, methods, and outcomes evaluated. Five of the seven studies reported a beneficial association between higher levels of chocolate consumption and the risk of cardiometabolic disorders. The highest levels of chocolate consumption were associated with a 37% reduction in cardiovascular disease (relative risk 0.63 (95% confidence interval 0.44 to 0.90)) and a 29% reduction in stroke compared with the lowest levels. Based on observational evidence, levels of chocolate consumption seem to be associated with a substantial reduction in the risk of cardiometabolic disorders. Further experimental studies are required to confirm a potentially beneficial effect of chocolate consumption.

  9. Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Desdoits-Lethimonier, Christèle; Mackey, Abigail L

    2018-01-01

    Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects...... with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig...... and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby...

  10. Major depressive disorder, panic disorder, and post-traumatic stress disorder in Korean subway drivers.

    Science.gov (United States)

    Kim, Hyoung-Ryoul; Yim, Hyeon Woo; Jo, Sun-Jin; Choi, Bongkyoo; Jeong, Seung Hee; Lee, Kang Sook; Park, Jong-Ik; Chang, Sung Man

    2013-05-01

    The purposes of this study are to investigate the prevalence of major depressive disorder, panic disorder, and post-traumatic stress disorder (PTSD) in Korean subway drivers, and find the association between these disorders and the drivers' person-under-train (PUT) experiences. A total of 826 subway drivers who participated in a cross-sectional work and health survey were included for this study. The Korean version of the Composite International Diagnostic Interview 2.1 was applied to assess major depressive disorder, panic disorder, and PTSD. The date of PUT, whether victim died, and how many PUTs the drivers experienced were asked using a structured questionnaire. The standardized prevalence ratios (SPRs) for lifetime prevalence of panic disorder and PTSD in subway drivers were 13.3 (95 % confidence interval [CI] 6.6-22.4) and 2.1 (95 % CI 1.1-3.4), respectively. In lifetime prevalence, after adjusting for age, education, income, and working career, the drivers who experienced PUT had significantly higher risks for panic disorder (odds ratio [OR] = 4.2, 95 % CI 1.2-16.6) and PTSD (OR = 4.4, 95 % CI 1.3-16.4). In 1-year prevalence, the drivers who experienced PUT had a significantly higher risk for PTSD (OR = 11.7, 95 % CI 1.9-225.8). There was no significant value of SPR and OR in major depressive disorder. This study suggests that Korean subway drivers are at higher risk for panic disorder and PTSD compared to the general population, and PUT experience is associated with panic disorder and PTSD. Drivers who have experienced PUT should be treated quickly, sympathetically, and sensitively by a psychological professional and their colleagues, so they can return to work soon.

  11. Speech and Communication Disorders

    Science.gov (United States)

    ... to being completely unable to speak or understand speech. Causes include Hearing disorders and deafness Voice problems, ... or those caused by cleft lip or palate Speech problems like stuttering Developmental disabilities Learning disorders Autism ...

  12. Orofacial manifestations of hematological disorders: Anemia and hemostatic disorders

    Directory of Open Access Journals (Sweden)

    Titilope A Adeyemo

    2011-01-01

    Full Text Available The aim of this paper is to review the literature and identify orofacial manifestations of hematological diseases, with particular reference to anemias and disorders of hemostasis. A computerized literature search using MEDLINE was conducted for published articles on orofacial manifestations of hematological diseases, with emphasis on anemia. Mesh phrases used in the search were: oral diseases AND anaemia; orofacial diseases AND anaemia; orofacial lesions AND anaemia; orofacial manifestations AND disorders of haemostasis. The Boolean operator "AND" was used to combine and narrow the searches. Anemic disorders associated with orofacial signs and symptoms include iron deficiency anemia, Plummer-Vinson syndrome, megaloblastic anemia, sickle cell anemia, thalassaemia and aplastic anemia. The manifestations include conjunctiva and facial pallor, atrophic glossitis, angular stomatitis, dysphagia, magenta tongue, midfacial overgrowth, osteoclerosis, osteomyelitis and paraesthesia/anesthesia of the mental nerve. Orofacial petechiae, conjunctivae hemorrhage, nose-bleeding, spontaneous and post-traumatic gingival hemorrhage and prolonged post-extraction bleeding are common orofacial manifestations of inherited hemostatic disorders such as von Willebrand′s disease and hemophilia. A wide array of anemic and hemostatic disorders encountered in internal medicine has manifestations in the oral cavity and the facial region. Most of these manifestations are non-specific, but should alert the hematologist and the dental surgeon to the possibilities of a concurrent disease of hemopoiesis or hemostasis or a latent one that may subsequently manifest itself.

  13. Adult Attention-Deficit / Hyperactivity Disorder (ADHD)

    Science.gov (United States)

    Adult attention-deficit/hyperactivity disorder (ADHD) Overview Adult attention-deficit/hyperactivity disorder (ADHD) is a mental health disorder that includes a combination of persistent problems, such as difficulty paying attention, ...

  14. Tourette's disorder and other tic disorders in DSM-5: a comment.

    Science.gov (United States)

    Roessner, Veit; Hoekstra, Pieter J; Rothenberger, Aribert

    2011-02-01

    Classification of tic disorders will be revised in the forthcoming edition of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5). We do not support the suggestion to move tic disorders to "Anxiety and Obsessive-Compulsive Disorders", if the section "Disorders Usually First Diagnosed in Infancy, Childhood, or Adolescence" is not retained. Other than that, most proposed changes of the criteria for tic disorders contain a number of welcome improvements, e.g., the more unified definition of tics including the removal of the term "stereotyped" and the better capture of the temporal pattern of tics (e.g., removal of the maximum 3 months criterion for a tic-free period in chronic tic disorders). But, unfortunately there are some inconsistencies in detail, e.g., the unification of diagnostic criteria for tic disorders had not been consistently pursued in transient tic disorder. In sum, the proposed DSM-5 criteria could be seen as an important step forward particularly in clinical routine. However, continued research is needed to justify the existing and proposed classification of tic disorders as well as to better clarify what other changes should be made in the DSM-5 and beyond.

  15. The cerebellum and psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Joseph ePhillips

    2015-05-01

    Full Text Available The cerebellum has been considered for a long time to play a role solely in motor coordination. However, studies over the past two decades have shown that the cerebellum also plays a key role in many motor, cognitive, and emotional processes. In addition, studies have also shown that the cerebellum is implicated in many psychiatric disorders including attention deficit hyperactivity disorder, autism spectrum disorders, schizophrenia, bipolar disorder, major depressive disorder and anxiety disorders. In this review, we discuss existing studies reporting cerebellar dysfunction in various psychiatric disorders. We will also discuss future directions for studies linking the cerebellum to psychiatric disorders.

  16. Plants traditionally used in age-related brain disorders (dementia): an ethanopharmacological survey.

    Science.gov (United States)

    Natarajan, Suganthy; Shunmugiah, Karutha Pandian; Kasi, Pandima Devi

    2013-04-01

    Epidemiological studies have shown that despite mortality due to communicable diseases, poverty and human conflicts, the incidence of dementia increases in the developing world in tandem with the ageing population. Although some FDA approved drugs are available for the treatment of dementia, the outcomes are often unsatisfactory. In traditional practices of medicine, numerous plants have been used to treat cognitive disorders, including neurodegenerative diseases such as Alzheimer's disease (AD) and other memory-related disorders. In western medicine most of the drugs used for the treatment of neurodegenerative disorders are derived from plant sources. This article reviews plants and their active constituents that have been used for their reputed cognitive-enhancing and antidementia effects. A literature survey in Science Direct, Pubmed, and Google Scholar was performed to gather information regarding drug discovery from plants sources for the treatment of congnitive disorders and dementia. More than forty herbal remedies were identified with cholinesterase inhibitory, anti-inflammatory, or antioxidant activities. Bioactive compounds include alkaloids, flavonoids, steroids, saponins, terpenoids, and essential oils. About eleven herbal plants with multipotent activity against AD are discussed. Literature surveys show that most of the research has been conducted on herbal remedies effect on cholinesterase inhibitory and antioxidant activities. Studies regarding the effect of herbal drugs on β-secretase inhibitory activity and antiaggregation property are lacking. This review provides leads for identifying potential new drugs from plant sources for the treatment of neurodegenerative disorders.

  17. Climate Change, Human Rights, and Social Justice.

    Science.gov (United States)

    Levy, Barry S; Patz, Jonathan A

    2015-01-01

    The environmental and health consequences of climate change, which disproportionately affect low-income countries and poor people in high-income countries, profoundly affect human rights and social justice. Environmental consequences include increased temperature, excess precipitation in some areas and droughts in others, extreme weather events, and increased sea level. These consequences adversely affect agricultural production, access to safe water, and worker productivity, and, by inundating land or making land uninhabitable and uncultivatable, will force many people to become environmental refugees. Adverse health effects caused by climate change include heat-related disorders, vector-borne diseases, foodborne and waterborne diseases, respiratory and allergic disorders, malnutrition, collective violence, and mental health problems. These environmental and health consequences threaten civil and political rights and economic, social, and cultural rights, including rights to life, access to safe food and water, health, security, shelter, and culture. On a national or local level, those people who are most vulnerable to the adverse environmental and health consequences of climate change include poor people, members of minority groups, women, children, older people, people with chronic diseases and disabilities, those residing in areas with a high prevalence of climate-related diseases, and workers exposed to extreme heat or increased weather variability. On a global level, there is much inequity, with low-income countries, which produce the least greenhouse gases (GHGs), being more adversely affected by climate change than high-income countries, which produce substantially higher amounts of GHGs yet are less immediately affected. In addition, low-income countries have far less capability to adapt to climate change than high-income countries. Adaptation and mitigation measures to address climate change needed to protect human society must also be planned to protect

  18. Relationship of personality disorders to the course of major depressive disorder in a nationally representative sample.

    Science.gov (United States)

    Skodol, Andrew E; Grilo, Carlos M; Keyes, Katherine M; Geier, Timothy; Grant, Bridget F; Hasin, Deborah S

    2011-03-01

    The purpose of this study was to examine the effects of specific personality disorder comorbidity on the course of major depressive disorder in a nationally representative sample. Data were drawn from 1,996 participants in a national survey. Participants who met criteria for major depressive disorder at baseline in face-to-face interviews (in 2001-2002) were reinterviewed 3 years later (in 2004-2005) to determine persistence and recurrence. Predictors included all DSM-IV personality disorders. Control variables included demographic characteristics, other axis I disorders, family and treatment histories, and previously established predictors of the course of major depressive disorder. A total of 15.1% of participants had persistent major depressive disorder, and 7.3% of those who remitted had a recurrence. Univariate analyses indicated that avoidant, borderline, histrionic, paranoid, schizoid, and schizotypal personality disorders all elevated the risk for persistence. With axis I comorbidity controlled, all personality disorders except histrionic personality disorder remained significant. With all other personality disorders controlled, borderline and schizotypal disorders remained significant predictors. In final, multivariate analyses that controlled for age at onset of major depressive disorder, the number of previous episodes, duration of the current episode, family history, and treatment, borderline personality disorder remained a robust predictor of major depressive disorder persistence. Neither personality disorders nor other clinical variables predicted recurrence. In this nationally representative sample of adults with major depressive disorder, borderline personality disorder robustly predicted persistence, a finding that converges with recent clinical studies. Personality psychopathology, particularly borderline personality disorder, should be assessed in all patients with major depressive disorder, considered in prognosis, and addressed in treatment.

  19. Does monosodium glutamate really cause headache? : a systematic review of human studies

    OpenAIRE

    Obayashi, Yoko; Nagamura, Yoichi

    2016-01-01

    Although monosodium glutamate (MSG) is classified as a causative substance of headache in the International Classification of Headache Disorders 3rd edition (ICHD-III beta), there is no literature in which causal relationship between MSG and headache was comprehensively reviewed. We performed systematic review of human studies which include the incidence of headache after an oral administration of MSG. An analysis was made by separating the human studies with MSG administration with or withou...

  20. Pathophysiological Role of Neuroinflammation in Neurodegenerative Diseases and Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Heeok Hong

    2016-05-01

    Full Text Available Brain diseases and disorders such as Alzheimer disease, Parkinson disease, depression, schizophrenia, autism, and addiction lead to reduced quality of daily life through abnormal thoughts, perceptions, emotional states, and behavior. While the underlying mechanisms remain poorly understood, human and animal studies have supported a role of neuroinflammation in the etiology of these diseases. In the central nervous system, an increased inflammatory response is capable of activating microglial cells, leading to the release of pro-inflammatory cytokines including interleukin (IL-1β, IL-6, and tumor necrosis factor-α. In turn, the pro-inflammatory cytokines aggravate and propagate neuroinflammation, degenerating healthy neurons and impairing brain functions. Therefore, activated microglia may play a key role in neuroinflammatory processes contributing to the pathogenesis of psychiatric disorders and neurodegeneration.

  1. Chromatin Remodeling BAF (SWI/SNF Complexes in Neural Development and Disorders

    Directory of Open Access Journals (Sweden)

    Godwin Sokpor

    2017-08-01

    Full Text Available The ATP-dependent BRG1/BRM associated factor (BAF chromatin remodeling complexes are crucial in regulating gene expression by controlling chromatin dynamics. Over the last decade, it has become increasingly clear that during neural development in mammals, distinct ontogenetic stage-specific BAF complexes derived from combinatorial assembly of their subunits are formed in neural progenitors and post-mitotic neural cells. Proper functioning of the BAF complexes plays critical roles in neural development, including the establishment and maintenance of neural fates and functionality. Indeed, recent human exome sequencing and genome-wide association studies have revealed that mutations in BAF complex subunits are linked to neurodevelopmental disorders such as Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, Kleefstra's syndrome spectrum, Hirschsprung's disease, autism spectrum disorder, and schizophrenia. In this review, we focus on the latest insights into the functions of BAF complexes during neural development and the plausible mechanistic basis of how mutations in known BAF subunits are associated with certain neurodevelopmental disorders.

  2. Chromatin Remodeling BAF (SWI/SNF) Complexes in Neural Development and Disorders

    Science.gov (United States)

    Sokpor, Godwin; Xie, Yuanbin; Rosenbusch, Joachim; Tuoc, Tran

    2017-01-01

    The ATP-dependent BRG1/BRM associated factor (BAF) chromatin remodeling complexes are crucial in regulating gene expression by controlling chromatin dynamics. Over the last decade, it has become increasingly clear that during neural development in mammals, distinct ontogenetic stage-specific BAF complexes derived from combinatorial assembly of their subunits are formed in neural progenitors and post-mitotic neural cells. Proper functioning of the BAF complexes plays critical roles in neural development, including the establishment and maintenance of neural fates and functionality. Indeed, recent human exome sequencing and genome-wide association studies have revealed that mutations in BAF complex subunits are linked to neurodevelopmental disorders such as Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, Kleefstra's syndrome spectrum, Hirschsprung's disease, autism spectrum disorder, and schizophrenia. In this review, we focus on the latest insights into the functions of BAF complexes during neural development and the plausible mechanistic basis of how mutations in known BAF subunits are associated with certain neurodevelopmental disorders. PMID:28824374

  3. Chromatin Remodeling BAF (SWI/SNF) Complexes in Neural Development and Disorders.

    Science.gov (United States)

    Sokpor, Godwin; Xie, Yuanbin; Rosenbusch, Joachim; Tuoc, Tran

    2017-01-01

    The ATP-dependent BRG1/BRM associated factor (BAF) chromatin remodeling complexes are crucial in regulating gene expression by controlling chromatin dynamics. Over the last decade, it has become increasingly clear that during neural development in mammals, distinct ontogenetic stage-specific BAF complexes derived from combinatorial assembly of their subunits are formed in neural progenitors and post-mitotic neural cells. Proper functioning of the BAF complexes plays critical roles in neural development, including the establishment and maintenance of neural fates and functionality. Indeed, recent human exome sequencing and genome-wide association studies have revealed that mutations in BAF complex subunits are linked to neurodevelopmental disorders such as Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, Kleefstra's syndrome spectrum, Hirschsprung's disease, autism spectrum disorder, and schizophrenia. In this review, we focus on the latest insights into the functions of BAF complexes during neural development and the plausible mechanistic basis of how mutations in known BAF subunits are associated with certain neurodevelopmental disorders.

  4. Polygenic risk for five psychiatric disorders and cross-disorder and disorder-specific neural connectivity in two independent populations.

    Science.gov (United States)

    Wang, Tianqi; Zhang, Xiaolong; Li, Ang; Zhu, Meifang; Liu, Shu; Qin, Wen; Li, Jin; Yu, Chunshui; Jiang, Tianzi; Liu, Bing

    2017-01-01

    Major psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), autism (AUT), bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SZ), are highly heritable and polygenic. Evidence suggests that these five disorders have both shared and distinct genetic risks and neural connectivity abnormalities. To measure aggregate genetic risks, the polygenic risk score (PGRS) was computed. Two independent general populations (N = 360 and N = 323) were separately examined to investigate whether the cross-disorder PGRS and PGRS for a specific disorder were associated with individual variability in functional connectivity. Consistent altered functional connectivity was found with the bilateral insula: for the left supplementary motor area and the left superior temporal gyrus with the cross-disorder PGRS, for the left insula and right middle and superior temporal lobe associated with the PGRS for autism, for the bilateral midbrain, posterior cingulate, cuneus, and precuneus associated with the PGRS for BD, and for the left angular gyrus and the left dorsolateral prefrontal cortex associated with the PGRS for schizophrenia. No significant functional connectivity was found associated with the PGRS for ADHD and MDD. Our findings indicated that genetic effects on the cross-disorder and disorder-specific neural connectivity of common genetic risk loci are detectable in the general population. Our findings also indicated that polygenic risk contributes to the main neurobiological phenotypes of psychiatric disorders and that identifying cross-disorder and specific functional connectivity related to polygenic risks may elucidate the neural pathways for these disorders.

  5. [Consensus statement on metabolic disorders and cardiovascular risks in patients with human immunodeficiency virus].

    Science.gov (United States)

    Polo Rodríguez, Rosa; Galindo Puerto, María José; Dueñas, Carlos; Gómez Candela, Carmen; Estrada, Vicente; Villar, Noemí G P; Locutura, Jaime; Mariño, Ana; Pascua, Javier; Palacios, Rosario; von Wichmman, Miguel Ángel; Álvarez, Julia; Asensi, Victor; Lopez Aldeguer, José; Lozano, Fernando; Negredo, Eugenia; Ortega, Enrique; Pedrol, Enric; Gutiérrez, Félix; Sanz Sanz, Jesús; Martínez Chamorro, Esteban

    2015-01-01

    This consensus document is an update of metabolic disorders and cardiovascular risk (CVR) guidelines for HIV-infected patients. This document has been approved by an expert panel of GEAM, SPNS and GESIDA after reviewing the results of efficacy and safety of clinical trials, cohort and pharmacokinetic studies published in biomedical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendation strength and the evidence in which they are supported are based on the GRADE system. A healthy lifestyle is recommended, no smoking and at least 30min of aerobic exercise daily. In diabetic patients the same treatment as non-HIV infected patients is recommended. HIV patients with dyslipidemia should be considered as high CVR, thus its therapeutic objective is an LDL less than 100mg/dL. The antihypertensive of ACE inhibitors and ARAII families are better tolerated and have a lower risk of interactions. In HIV-patients with diabetes or metabolic syndrome and elevated transaminases with no defined etiology, the recommended is to rule out a hepatic steatosis Recommendations for action in hormone alterations are also updated. These new guidelines update previous recommendations regarding all those metabolic disorders involved in CVR. Hormone changes and their management and the impact of metabolic disorders on the liver are also included. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  6. Microendophenotypes of psychiatric disorders: phenotypes of psychiatric disorders at the level of molecular dynamics, synapses, neurons, and neural circuits.

    Science.gov (United States)

    Kida, S; Kato, T

    2015-01-01

    Psychiatric disorders are caused not only by genetic factors but also by complicated factors such as environmental ones. Moreover, environmental factors are rarely quantitated as biological and biochemical indicators, making it extremely difficult to understand the pathological conditions of psychiatric disorders as well as their underlying pathogenic mechanisms. Additionally, we have actually no other option but to perform biological studies on postmortem human brains that display features of psychiatric disorders, thereby resulting in a lack of experimental materials to characterize the basic biology of these disorders. From these backgrounds, animal, tissue, or cell models that can be used in basic research are indispensable to understand biologically the pathogenic mechanisms of psychiatric disorders. In this review, we discuss the importance of microendophenotypes of psychiatric disorders, i.e., phenotypes at the level of molecular dynamics, neurons, synapses, and neural circuits, as targets of basic research on these disorders.

  7. A review of attention-deficit/hyperactivity disorder complicated by symptoms of oppositional defiant disorder or conduct disorder.

    Science.gov (United States)

    Connor, Daniel F; Steeber, Jennifer; McBurnett, Keith

    2010-06-01

    Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder with significant functional impairment. ADHD is frequently complicated by oppositional symptoms, which are difficult to separate from comorbidity with oppositional defiant disorder, conduct disorder, and aggressive symptoms. This review addresses the impact of oppositional symptoms on ADHD, disease course, functional impairment, clinical management, and treatment response. Oppositional defiant disorder or conduct disorder may be comorbid in more than half of ADHD cases and are more common with the combined than with the inattentive ADHD subtype. Comorbid symptoms of oppositional defiant disorder and conduct disorder in patients with ADHD can have a significant impact on the course and prognosis for these patients and may lead to differential treatment response to both behavioral and pharmacologic treatments. Assessment of oppositional symptoms is an essential part of ADHD screening and diagnosis and should include parental, as well as educator, input. Although clinical evidence remains limited, some stimulant and nonstimulant medications have shown effectiveness in treating both core ADHD symptoms and oppositional symptoms. Oppositional symptoms are a key consideration in ADHD management, although the optimum approach to treating ADHD complicated by such symptoms remains unclear. Future research should focus on the efficacy and safety of various behavioral and medication regimens, as well as longitudinal studies to further clarify the relationships between ADHD, oppositional defiant disorder, and conduct disorder.

  8. Treatment of Schizoaffective Disorder

    OpenAIRE

    Cascade, Elisa; Kalali, Amir H.; Buckley, Peter

    2009-01-01

    In this article, we investigate the range of treatments prescribed for schizoaffective disorder. The data show that the majority of those treated, 87 percent, receive two or more pharmaceutical classes. From a therapeutic class perspective, 93 percent of schizoaffective disorder patients receive an antipsychotic, 48 percent receive a mood disorder treatment, and 42 percent receive an antidepressant. An expert commentary is also included.

  9. On human self-domestication, psychiatry, and eugenics

    Directory of Open Access Journals (Sweden)

    Brüne Martin

    2007-10-01

    Full Text Available Abstract The hypothesis that anatomically modern homo sapiens could have undergone changes akin to those observed in domesticated animals has been contemplated in the biological sciences for at least 150 years. The idea had already plagued philosophers such as Rousseau, who considered the civilisation of man as going against human nature, and eventually "sparked over" to the medical sciences in the late 19th and early 20th century. At that time, human "self-domestication" appealed to psychiatry, because it served as a causal explanation for the alleged degeneration of the "erbgut" (genetic material of entire populations and the presumed increase of mental disorders. Consequently, Social Darwinists emphasised preventing procreation by people of "lower genetic value" and positively selecting favourable traits in others. Both tendencies culminated in euthanasia and breeding programs ("Lebensborn" during the Nazi regime in Germany. Whether or not domestication actually plays a role in some anatomical changes since the late Pleistocene period is, from a biological standpoint, contentious, and the currently resurrected debate depends, in part, on the definitional criteria applied. However, the example of human self-domestication may illustrate that scientific ideas, especially when dealing with human biology, are prone to misuse, particularly if "is" is confused with "ought", i.e., if moral principles are deduced from biological facts. Although such naturalistic fallacies appear to be banned, modern genetics may, at least in theory, pose similar ethical problems to medicine, including psychiatry. In times during which studies into the genetics of psychiatric disorders are scientifically more valued than studies into environmental causation of disorders (which is currently the case, the prospects of genetic therapy may be tempting to alter the human genome in patients, probably at costs that no-one can foresee. In the case of "self-domestication", it

  10. Cytokines in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Vinberg, Maj; Vedel Kessing, Lars

    2012-01-01

    BACKGROUND: Current research and hypothesis regarding the pathophysiology of bipolar disorder suggests the involvement of immune system dysfunction that is possibly related to disease activity. Our objective was to systematically review evidence of cytokine alterations in bipolar disorder according...... to affective state. METHODS: We conducted a systemtic review of studies measuring endogenous cytokine concentrations in patients with bipolar disorder and a meta-analysis, reporting results according to the PRISMA statement. RESULTS: Thirteen studies were included, comprising 556 bipolar disorder patients...

  11. Zebrafish models for the functional genomics of neurogenetic disorders.

    Science.gov (United States)

    Kabashi, Edor; Brustein, Edna; Champagne, Nathalie; Drapeau, Pierre

    2011-03-01

    In this review, we consider recent work using zebrafish to validate and study the functional consequences of mutations of human genes implicated in a broad range of degenerative and developmental disorders of the brain and spinal cord. Also we present technical considerations for those wishing to study their own genes of interest by taking advantage of this easily manipulated and clinically relevant model organism. Zebrafish permit mutational analyses of genetic function (gain or loss of function) and the rapid validation of human variants as pathological mutations. In particular, neural degeneration can be characterized at genetic, cellular, functional, and behavioral levels. Zebrafish have been used to knock down or express mutations in zebrafish homologs of human genes and to directly express human genes bearing mutations related to neurodegenerative disorders such as spinal muscular atrophy, ataxia, hereditary spastic paraplegia, amyotrophic lateral sclerosis (ALS), epilepsy, Huntington's disease, Parkinson's disease, fronto-temporal dementia, and Alzheimer's disease. More recently, we have been using zebrafish to validate mutations of synaptic genes discovered by large-scale genomic approaches in developmental disorders such as autism, schizophrenia, and non-syndromic mental retardation. Advances in zebrafish genetics such as multigenic analyses and chemical genetics now offer a unique potential for disease research. Thus, zebrafish hold much promise for advancing the functional genomics of human diseases, the understanding of the genetics and cell biology of degenerative and developmental disorders, and the discovery of therapeutics. This article is part of a Special Issue entitled Zebrafish Models of Neurological Diseases. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders

    Directory of Open Access Journals (Sweden)

    Alberto J Lopez

    2015-04-01

    Full Text Available It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, schizophrenia, and Autism Spectrum Disorder. Together, these human developmental and intellectual disability disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.

  13. Familial circadian rhythm disorder in the diurnal primate, Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    Irina V Zhdanova

    Full Text Available In view of the inverse temporal relationship of central clock activity to physiological or behavioral outputs in diurnal and nocturnal species, understanding the mechanisms and physiological consequences of circadian disorders in humans would benefit from studies in a diurnal animal model, phylogenetically close to humans. Here we report the discovery of the first intrinsic circadian disorder in a family of diurnal non-human primates, the rhesus monkey. The disorder is characterized by a combination of delayed sleep phase, relative to light-dark cycle, mutual desynchrony of intrinsic rhythms of activity, food intake and cognitive performance, enhanced nighttime feeding or, in the extreme case, intrinsic asynchrony. The phenotype is associated with normal length of intrinsic circadian period and requires an intact central clock, as demonstrated by an SCN lesion. Entrainment to different photoperiods or melatonin administration does not eliminate internal desynchrony, though melatonin can temporarily reinstate intrinsic activity rhythms in the animal with intrinsic asynchrony. Entrainment to restricted feeding is highly effective in animals with intrinsic or SCN lesion-induced asynchrony. The large isolated family of rhesus macaques harboring the disorder provides a powerful new tool for translational research of regulatory circuits underlying circadian disorders and their effective treatment.

  14. Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders.

    Science.gov (United States)

    López, Alberto J; Wood, Marcelo A

    2015-01-01

    It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability (ID) disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF) complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NBS), schizophrenia, and Autism Spectrum Disorder (ASD). Together, these human developmental and ID disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and ID disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.

  15. Anatomy and Cell Biology of Autism Spectrum Disorder : Lessons from Human Genetics

    NARCIS (Netherlands)

    Kleijer, Kristel T E; Huguet, Guillaume; Tastet, Julie; Bourgeron, Thomas; Burbach, J P H

    2017-01-01

    Until recently autism spectrum disorder (ASD) was regarded as a neurodevelopmental condition with unknown causes and pathogenesis. In the footsteps of the revolution of genome technologies and genetics, and with its high degree of heritability, ASD became the first neuropsychiatric disorder for

  16. Functional imaging of neurotransmitter systems in movement disorders

    Energy Technology Data Exchange (ETDEWEB)

    Ilgin, N. [Ankara, Gazi Univ. Medical School (Turkey). Dept. of Nuclear Medicine

    1998-09-01

    PET and SPECT enable the direct measurement of components of the dopaminergic and other systems in the living human brain and offer unique opportunity for the in vivo quantification on the dopaminergic function in PD and other movement disorders. The need to establish the early and differential diagnosis of PD is increasingly important given the recent evidence that early pharmacologic intervention may slow progression of this progressive degenerative disease. Accordingly, imaging with PET and SPECT using specific neuro markers has been increasingly important to biochemically identify the loss of specific neurotransmitters, their synthesizing enzymes and their receptors in movement disorders. Through the parallel development of new radiotracers, kinetic models and better instruments, PET and SPECT technology is enabling investigation of increasingly more complex aspects of the human brain neurotransmitter systems. This paper summarizes the results of different PET-SPECT studies used to evaluate the various elements of the dopamine system in the human brain with PET and intends to introduce the newly emerging specific tracers and their applications to clinical research in movement disorders.

  17. Functional imaging of neurotransmitter systems in movement disorders

    International Nuclear Information System (INIS)

    Ilgin, N.

    1998-01-01

    PET and SPECT enable the direct measurement of components of the dopaminergic and other systems in the living human brain and offer unique opportunity for the in vivo quantification on the dopaminergic function in PD and other movement disorders. The need to establish the early and differential diagnosis of PD is increasingly important given the recent evidence that early pharmacologic intervention may slow progression of this progressive degenerative disease. Accordingly, imaging with PET and SPECT using specific neuro markers has been increasingly important to biochemically identify the loss of specific neurotransmitters, their synthesizing enzymes and their receptors in movement disorders. Through the parallel development of new radiotracers, kinetic models and better instruments, PET and SPECT technology is enabling investigation of increasingly more complex aspects of the human brain neurotransmitter systems. This paper summarizes the results of different PET-SPECT studies used to evaluate the various elements of the dopamine system in the human brain with PET and intends to introduce the newly emerging specific tracers and their applications to clinical research in movement disorders

  18. Sleep disorders in children

    OpenAIRE

    Montgomery, Paul; Dunne, Danielle

    2007-01-01

    Sleep disorders may affect 20-30% of young children, and include excessive daytime sleepiness, problems getting to sleep (dysomnias), or undesirable phenomena during sleep (parasomnias), such as sleep terrors, and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders. Other risk factors include the child being the first born, having a difficult temperament or having had colic, and increased maternal responsiveness.

  19. Sleep disorders in children

    OpenAIRE

    Bruni, Oliveiero; Novelli, Luana

    2010-01-01

    Sleep disorders may affect between 20% and 30% of young children, and include problems getting to sleep (dyssomnias) or undesirable phenomena during sleep (parasomnias), such as sleep terrors and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders. Other risk factors include the child being the first born, having a difficult temperament or having had colic, and increased maternal responsiveness.

  20. Immortalization of human myogenic progenitor cell clone retaining multipotentiality

    International Nuclear Information System (INIS)

    Hashimoto, Naohiro; Kiyono, Tohru; Wada, Michiko R.; Shimizu, Shirabe; Yasumoto, Shigeru; Inagawa, Masayo

    2006-01-01

    Human myogenic cells have limited ability to proliferate in culture. Although forced expression of telomerase can immortalize some cell types, telomerase alone delays senescence of human primary cultured myogenic cells, but fails to immortalize them. In contrast, constitutive expression of both telomerase and the E7 gene from human papillomavirus type 16 immortalizes primary human myogenic cells. We have established an immortalized primary human myogenic cell line preserving multipotentiality by ectopic expression of telomerase and E7. The immortalized human myogenic cells exhibit the phenotypic characteristics of their primary parent, including an ability to undergo myogenic, osteogenic, and adipogenic terminal differentiation under appropriate culture conditions. The immortalized cells will be useful for both basic and applied studies aimed at human muscle disorders. Furthermore, immortalization by transduction of telomerase and E7 represents a useful method by which to expand human myogenic cells in vitro without compromising their ability to differentiate

  1. Animal Models of Post-Traumatic Stress Disorder and Recent Neurobiological Insights

    Science.gov (United States)

    Whitaker, Annie M.; Gilpin, Nicholas W.; Edwards, Scott

    2014-01-01

    Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder characterized by the intrusive re-experiencing of past trauma, avoidant behavior, enhanced fear, and hyperarousal following a traumatic event in vulnerable populations. Preclinical animal models do not replicate the human condition in its entirety, but seek to mimic symptoms or endophenotypes associated with PTSD. Although many models of traumatic stress exist, few adequately capture the complex nature of the disorder and the observed individual variability in susceptibility of humans to develop PTSD. In addition, various types of stressors may produce different molecular neuroadaptations that likely contribute to the various behavioral disruptions produced by each model, although certain consistent neurobiological themes related to PTSD have emerged. For example, animal models report traumatic stress- and trauma reminder-induced alterations in neuronal activity in the amygdala and prefrontal cortex, in agreement with the human PTSD literature. Models have also provided a conceptual framework for the often observed combination of PTSD and co-morbid conditions such as alcohol use disorder (AUD). Future studies will continue to refine preclinical PTSD models in hopes of capitalizing on their potential to deliver new and more efficacious treatments for PTSD and associated psychiatric disorders. PMID:25083568

  2. Movement disorders in hereditary ataxias.

    Science.gov (United States)

    Garcia Ruiz, Pedro J; Mayo, David; Hernandez, Jaime; Cantarero, Susana; Ayuso, Carmen

    2002-10-15

    Movement disorders are well known features of some dominant hereditary ataxias (HA), specially SCA3/Machado-Joseph disease and dentatorubropallidolusyan atrophy. However, little is known about the existence and classification of movement disorders in other dominant and recessive ataxias. We prospectively studied the presence of movement disorders in patients referred for HA over the last 3 years. Only those patients with a confirmed family history of ataxia were included. We studied 84 cases of HA, including 46 cases of recessive and 38 cases of dominant HA. Thirty out of 46 cases of recessive HA could be classified as: Friedreich ataxia (FA), 29 cases; vitamin E deficiency, 1 case. Twenty-three out of 38 cases of dominant HA could be classified as: SCA 2, 4 cases; SCA 3, 8 cases; SCA 6, 4 cases; SCA 7, 6 cases and SCA 8, 1 case. We observed movement disorders in 20/38 (52%) patients with dominant HA and 25/46 (54%) cases with recessive HA, including 16 patients (16/29) with FA. In general, postural tremor was the most frequent observed movement disorder (27 cases), followed by dystonia (22 cases). Five patients had akinetic rigid syndrome, and in 13 cases, several movement disorders coexisted. Movement disorders are frequent findings in HA, not only in dominant HA but also in recessive HA. Copyright 2002 Elsevier Science B.V.

  3. Islamic perspectives on human cloning.

    Science.gov (United States)

    Sadeghi, Mahmoud

    2007-01-01

    The present paper seeks to assess various views from Islamic jurists relating to human cloning, which is one of the controversial topics in the recent past. Taking Islamic jurisprudence principles, such as the rule of necessity for self preservation and respect for human beings, the rule of la darar wa la dirar ('the necessity to refrain from causing harm to oneself and others') and the rule of usr wa haraj, one may indicate that if human cloning could not be prohibited, as such, it could still be opposed because it gives way to various harmful consequences, which include family disorder, chaos in the clone's family relationships, physical and mental diseases for clones and suffering of egg donors and surrogate mothers. However with due attention to the fact that the reasons behind the prohibition of abortion only restrict the destruction of human embryos in their post-implantation stages, human cloning for biomedical research and exploitation of stem cells from cloned embryos at the blastocyst stage for therapeutic purposes would be acceptable.

  4. Hematopoietic Stem Cell Therapy as a Counter-Measure for Human Exploration of Deep Space

    Science.gov (United States)

    Ohi, S.; Roach, A.-N.; Ramsahai, S.; Kim, B. C.; Fitzgerald, W.; Riley, D. A.; Gonda, S. R.

    2004-01-01

    Human exploration of deep space depends, in part, on our ability to counter severe/invasive disorders that astronauts experience in space environments. The known symptoms include hematological/cardiac abnormalities,bone and muscle losses, immunodeficiency, neurological disorders, and cancer. Exploiting the extraordinary plasticity of hematopoietic stem cells (HSCs), which differentiate not only to all types of blood cells, but also to various tissues, we have advanced a hypothesis that ome of the space-caused disorders maybe amenable to hematopoietis stem cell therapy(HSCT) so as to maintain promote human exploration of deep space. Using mouse models of human anemia beta-thaiassemia) as well as spaceflight (hindlimb unloading system), we have obtained feasibility results of HSCT for space anemia, muscle loss, and immunodeficiency. For example, in the case of HSCT for muscle loss, the beta-galactosidese marked HSCs were detected in the hindlimbs of unloaded mouse following transplantation by -X-gal wholemaunt staining procedure. Histochemicaland physical analyses indicated structural contribution of HSCs to the muscle. HSCT for immunodeficiency was investigated ising beta-galactosidese gene-tagged Escherichia coli as the infectious agent. Results of the X-gal staining procedure indicated the rapeutic role of the HSCT. To facilitate the HSCT in space, growth of HSCs were optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

  5. Temporomandibular disorders and migraine headache

    OpenAIRE

    Demarin, Vida; Bašić Kes, Vanja

    2010-01-01

    Migraine headache and temporomandibular disorders show significant overlap in the area or distribution of pain, the gender prevalence and age distribution. Temporomandibular disorders may cause headaches per se, worsen existent primary headaches, and add to the burden of headache disorders. The patients with combined migraine and tension-type headaches had a higher prevelance of temporomandibular disorders. Evidence supporting a close relationship include the increased masticatory...

  6. Women's sexual pain disorders.

    Science.gov (United States)

    van Lankveld, Jacques J D M; Granot, Michal; Weijmar Schultz, Willibrord C M; Binik, Yitzchak M; Wesselmann, Ursula; Pukall, Caroline F; Bohm-Starke, Nina; Achtrari, Chahin

    2010-01-01

    Women's sexual pain disorders include dyspareunia and vaginismus and there is need for state-of-the-art information in this area. To update the scientific evidence published in 2004, from the 2nd International Consultation on Sexual Medicine pertaining to the diagnosis and treatment of women's sexual pain disorders. An expert committee, invited from six countries by the 3rd International Consultation, was comprised of eight researchers and clinicians from biological and social science disciplines, for the purpose of reviewing and grading the scientific evidence on nosology, etiology, diagnosis, and treatment of women's sexual pain disorders. Expert opinion was based on grading of evidence-based medical literature, extensive internal committee discussion, public presentation, and debate. Results. A comprehensive assessment of medical, sexual, and psychosocial history is recommended for diagnosis and management. Indications for general and focused pelvic genital examination are identified. Evidence-based recommendations for assessment of women's sexual pain disorders are reviewed. An evidence-based approach to management of these disorders is provided. Continued efforts are warranted to conduct research and scientific reporting on the optimal assessment and management of women's sexual pain disorders, including multidisciplinary approaches.

  7. Disordered gambling and co-morbidity of psychiatric disorders among college students: an examination of problem drinking, anxiety and depression.

    Science.gov (United States)

    Martin, Ryan J; Usdan, Stuart; Cremeens, Jennifer; Vail-Smith, Karen

    2014-06-01

    We assessed the occurrence of co-morbid psychiatric disorders (i.e., problem drinking, anxiety, and depression) among college students who met the threshold for disordered gambling. The participants included a large sample of undergraduate students (n = 1,430) who were enrolled in an introductory health course at a large, southeastern university in Spring 2011 and completed an online assessment that included scales to assess disordered gambling, problem drinking, anxiety, and depression. We calculated screening scores, computed prevalence rates for each disorder, and calculated Pearson correlations and Chi square tests to examine correlations and co-morbid relationships between the four disorders. Analyses indicated that all disorders were significantly associated (p students who experience disordered gambling (and other psychiatric disorders) are at increased risk of experiencing co-occurring disorders, it might be useful for college health professionals to concurrently screen and intervene for co-occurring disorders.

  8. Relationship of Personality Disorders to the Course of Major Depressive Disorder in a Nationally Representative Sample

    Science.gov (United States)

    Skodol, Andrew E.; Grilo, Carlos M.; Keyes, Katherine; Geier, Timothy; Grant, Bridget F.; Hasin, Deborah S.

    2011-01-01

    Objective The purpose of this study was to examine the effects of specific personality disorder co-morbidity on the course of major depressive disorder in a nationally-representative sample. Method Data were drawn from 1,996 participants in a national survey. Participants who met criteria for major depressive disorder at baseline in face-to-face interviews (2001–2002) were re-interviewed three years later (2004–2005) to determine persistence and recurrence. Predictors included all DSM-IV personality disorders. Control variables included demographic characteristics, other Axis I disorders, family and treatment histories, and previously established predictors of the course of major depressive disorder. Results 15.1% of participants had persistent major depressive disorder and 7.3% of those who remitted had a recurrence. Univariate analyses indicated that avoidant, borderline, histrionic, paranoid, schizoid, and schizotypal personality disorders all elevated the risk for persistence. With Axis I co-morbidity controlled, all but histrionic personality disorder remained significant. With all other personality disorders controlled, borderline and schizotypal remained significant predictors. In final, multivariate analyses that controlled for age at onset of major depressive disorder, number of previous episodes, duration of current episode, family history, and treatment, borderline personality disorder remained a robust predictor of major depressive disorder persistence. Neither personality disorders nor other clinical variables predicted recurrence. Conclusions In this nationally-representative sample of adults with major depressive disorder, borderline personality disorder robustly predicted persistence, a finding that converges with recent clinical studies. Personality psychopathology, particularly borderline personality disorder, should be assessed in all patients with major depressive disorder, considered in prognosis, and addressed in treatment. PMID:21245088

  9. Induction of Skin-Derived Precursor Cells from Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Sugiyama-Nakagiri, Yoriko; Fujimura, Tsutomu; Moriwaki, Shigeru

    2016-01-01

    The generation of full thickness human skin from dissociated cells is an attractive approach not only for treating skin diseases, but also for treating many systemic disorders. However, it is currently not possible to obtain an unlimited number of skin dermal cells. The goal of this study was to develop a procedure to produce skin dermal stem cells from induced pluripotent stem cells (iPSCs). Skin-derived precursor cells (SKPs) were isolated as adult dermal precursors that could differentiate into both neural and mesodermal progenies and could reconstitute the dermis. Thus, we attempted to generate SKPs from iPSCs that could reconstitute the skin dermis. Human iPSCs were initially cultured with recombinant noggin and SB431542, an inhibitor of activin/nodal and TGFβ signaling, to induce neural crest progenitor cells. Those cells were then treated with SKP medium that included CHIR99021, a WNT signal activator. The induction efficacy from neural crest progenitor cells to SKPs was more than 97%. No other modifiers tested were able to induce those cells. Those human iPSC-derived SKPs (hiPSC-SKPs) showed a similar gene expression signature to SKPs isolated from human skin dermis. Human iPSC-SKPs differentiated into neural and mesodermal progenies, including adipocytes, skeletogenic cell types and Schwann cells. Moreover, they could be induced to follicular type keratinization when co-cultured with human epidermal keratinocytes. We here provide a new efficient protocol to create human skin dermal stem cells from hiPSCs that could contribute to the treatment of various skin disorders.

  10. Cell based-gene delivery approaches for the treatment of spinal cord injury and neurodegenerative disorders.

    Science.gov (United States)

    Taha, Masoumeh Fakhr

    2010-03-01

    Cell based-gene delivery has provided an important therapeutic strategy for different disorders in the recent years. This strategy is based on the transplantation of genetically modified cells to express specific genes and to target the delivery of therapeutic factors, especially for the treatment of cancers and neurological, immunological, cardiovascular and heamatopoietic disorders. Although, preliminary reports are encouraging, and experimental studies indicate functionally and structurally improvements in the animal models of different disorders, universal application of this strategy for human diseases requires more evidence. There are a number of parameters that need to be evaluated, including the optimal cell source, the most effective gene/genes to be delivered, the optimal vector and method of gene delivery into the cells and the most efficient route for the delivery of genetically modified cells into the patient. Also, some obstacles have to be overcome, including the safety and usefulness of the approaches and the stability of the improvements. Here, recent studies concerning with the cell-based gene delivery for spinal cord injury and some neurodegenerative disorders such as amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease are briefly reviewed, and their exciting consequences are discussed.

  11. Human brain evolution and the "Neuroevolutionary Time-depth Principle:" Implications for the Reclassification of fear-circuitry-related traits in DSM-V and for studying resilience to warzone-related posttraumatic stress disorder.

    Science.gov (United States)

    Bracha, H Stefan

    2006-07-01

    The DSM-III, DSM-IV, DSM-IV-TR and ICD-10 have judiciously minimized discussion of etiologies to distance clinical psychiatry from Freudian psychoanalysis. With this goal mostly achieved, discussion of etiological factors should be reintroduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). A research agenda for the DSM-V advocated the "development of a pathophysiologically based classification system". The author critically reviews the neuroevolutionary literature on stress-induced and fear circuitry disorders and related amygdala-driven, species-atypical fear behaviors of clinical severity in adult humans. Over 30 empirically testable/falsifiable predictions are presented. It is noted that in DSM-IV-TR and ICD-10, the classification of stress and fear circuitry disorders is neither mode-of-acquisition-based nor brain-evolution-based. For example, snake phobia (innate) and dog phobia (overconsolidational) are clustered together. Similarly, research on blood-injection-injury-type-specific phobia clusters two fears different in their innateness: 1) an arguably ontogenetic memory-trace-overconsolidation-based fear (hospital phobia) and 2) a hardwired (innate) fear of the sight of one's blood or a sharp object penetrating one's skin. Genetic architecture-charting of fear-circuitry-related traits has been challenging. Various, non-phenotype-based architectures can serve as targets for research. In this article, the author will propose one such alternative genetic architecture. This article was inspired by the following: A) Nesse's "Smoke-Detector Principle", B) the increasing suspicion that the "smooth" rather than "lumpy" distribution of complex psychiatric phenotypes (including fear-circuitry disorders) may in some cases be accounted for by oligogenic (and not necessarily polygenic) transmission, and C) insights from the initial sequence of the chimpanzee genome and comparison with the human genome by the Chimpanzee Sequencing

  12. Precursor or sequela: pathological disorders in people with Internet addiction disorder.

    Directory of Open Access Journals (Sweden)

    Guangheng Dong

    Full Text Available BACKGROUND: This study aimed to evaluate the roles of pathological disorders in Internet addiction disorder and identify the pathological problems in IAD, as well as explore the mental status of Internet addicts prior to addiction, including the pathological traits that may trigger Internet addiction disorder. METHODS AND FINDINGS: 59 students were measured by Symptom CheckList-90 before and after they became addicted to the Internet. A comparison of collected data from Symptom Checklist-90 before Internet addiction and the data collected after Internet addiction illustrated the roles of pathological disorders among people with Internet addiction disorder. The obsessive-compulsive dimension was found abnormal before they became addicted to the Internet. After their addiction, significantly higher scores were observed for dimensions on depression, anxiety, hostility, interpersonal sensitivity, and psychoticism, suggesting that these were outcomes of Internet addiction disorder. Dimensions on somatisation, paranoid ideation, and phobic anxiety did not change during the study period, signifying that these dimensions are not related to Internet addiction disorder. CONCLUSIONS: We can not find a solid pathological predictor for Internet addiction disorder. Internet addiction disorder may bring some pathological problems to the addicts in some ways.

  13. Eating Disorders in Adolescents

    Directory of Open Access Journals (Sweden)

    Beena Johnson

    2015-10-01

    Full Text Available According to International Classification of Diseases by World Health Organization, eating disorders are behavioural syndromes associated with physiological disturbances [1]. Eating disorders include anorexia nervosa, atypical anorexia nervosa, bulimia nervosa, atypical bulimia nervosa, overeating associated with other psychological disturbances and vomiting associated with other psychological disturbances [1]. Maladaptive eating pattern and inadequate physical activity are seen in adolescents with eating disorders and obesity [2]. Those with comorbid eating disorder and obesity have a poorer prognosis and are at higher risk for future medical problems.

  14. Including pathogen risk in life cycle assessment of wastewater management. 2. Quantitative comparison of pathogen risk to other impacts on human health.

    Science.gov (United States)

    Heimersson, Sara; Harder, Robin; Peters, Gregory M; Svanström, Magdalena

    2014-08-19

    Resource recovery from sewage sludge has the potential to save natural resources, but the potential risks connected to human exposure to heavy metals, organic micropollutants, and pathogenic microorganisms attract stakeholder concern. The purpose of the presented study was to include pathogen risks to human health in life cycle assessment (LCA) of wastewater and sludge management systems, as this is commonly omitted from LCAs due to methodological limitations. Part 1 of this article series estimated the overall pathogen risk for such a system with agricultural use of the sludge, in a way that enables the results to be integrated in LCA. This article (part 2) presents a full LCA for two model systems (with agricultural utilization or incineration of sludge) to reveal the relative importance of pathogen risk in relation to other potential impacts on human health. The study showed that, for both model systems, pathogen risk can constitute an important part (in this study up to 20%) of the total life cycle impacts on human health (expressed in disability adjusted life years) which include other important impacts such as human toxicity potential, global warming potential, and photochemical oxidant formation potential.

  15. Connectivity analysis is essential to understand neurological disorders

    Directory of Open Access Journals (Sweden)

    James Rowe

    2010-09-01

    Full Text Available Neurological and neuropsychiatric disorders are major causes of morbidity worldwide. A systems level analysis including functional and structural neuroimaging is particularly useful when the pathology leads to disorders of higher order cognitive functions in human patients. However, an analysis that is restricted to regional effects is impoverished and insensitive, compared to the analysis of distributed brain networks. We discuss the issues to consider when choosing an appropriate connectivity method, and compare the results from several different methods that are relevant to fMRI and PET data. These include psychophysiological interactions in general linear models, structural equation modeling, dynamic causal modeling and independent components analysis. The advantages of connectivity analysis are illustrated with a range of structural and neurodegenerative brain disorders. We illustrate the sensitivity of these methods to the presence or severity of disease and/or treatment, even where analyses of voxel-wise activations are insensitive. However, functional and structural connectivity methods should be seen as complementary to, not a substitute for, other imaging and behavioral approaches. The functional relevance of changes in connectivity, to motor or cognitive performance, are considered alongside the complex relationship between structural and functional changes with neuropathology. Finally some of the problems associated with connectivity analysis are discussed. We suggest that the analysis of brain connectivity is an essential complement to the analysis of regionally specific dysfunction, in order to understand neurological and neuropsychiatric disease, and to evaluate the mechanisms of effective therapies.

  16. A Review of Sleep Disorder Diagnosis by Electromyogram Signal Analysis.

    Science.gov (United States)

    Shokrollahi, Mehrnaz; Krishnan, Sridhar

    2015-01-01

    Sleep and sleep-related problems play a role in a large number of human disorders and affect every field of medicine. It is estimated that 50 to 70 million Americans suffer from a chronic sleep disorder, which hinders their daily life, affects their health, and confers a significant economic burden to society. The negative public health consequences of sleep disorders are enormous and could have long-term effects, including increased risk of hypertension, diabetes, obesity, heart attack, stroke and in some cases death. Polysomnographic modalities can monitor sleep cycles to identify disrupted sleep patterns, adjust the treatments, increase therapeutic options and enhance the quality of life of recording the electroencephalogram (EEG), electromyogram (EMG) and electrocardiogram (ECG). Although the skills acquired by medical facilitators are quite extensive, it is just as important for them to have access to an assortment of technologies and to further improve their monitoring and treatment capabilities. Computer-aided analysis is one advantageous technique that could provide quantitative indices for sleep disorder screening. Evolving evidence suggests that Parkinson's disease may be associated with rapid eye movement sleep behavior disorder (RBD). With this article, we are reviewing studies that are related to EMG signal analysis for detection of neuromuscular diseases that result from sleep movement disorders. As well, the article describes the recent progress in analysis of EMG signals using temporal analysis, frequency-domain analysis, time-frequency, and sparse representations, followed by the comparison of the recent research.

  17. Hepatitis C infection in patients with hereditary bleeding disorders: epidemiology, natural history, and management.

    Science.gov (United States)

    Papadopoulos, Nikolaos; Argiana, Vasiliki; Deutsch, Melanie

    2018-01-01

    Hereditary bleeding disorders include a group of diseases with abnormalities of coagulation. Prior to 1990, infection with hepatitis C virus (HCV) was mainly transmitted via pooled plasma products as a treatment for hereditary bleeding disorders. Anti-HCV positivity in these patients may be as high as >70% in some areas, while some of them have also been coinfected with human immunodeficiency virus. Since about 20% of HCV-infected patients clear the infection naturally, chronic HCV infection represents a significant health problem in this group of patients. Mortality due to chronic HCV infection is estimated to be >10 times higher in patients with hemophilia than in the general population, and is mainly due to liver cirrhosis and hepatocellular carcinoma. The antiviral treatment of HCV in patients with hereditary bleeding disorders is not different from that of any other infected patients. Nevertheless, many patients with hereditary bleeding disorders have declined (Peg)interferon-based treatment because of side effects. In recent years, multiple orally administrated direct-acting antivirals (DAAs) have been approved for HCV treatment. Unfortunately, there is not much experience from treating these patients with DAA regimens, as major studies and real-life data did not include adequate numbers of patients with inherited hemorrhagic disorders. However, the available data indicate that DAAs have an excellent safety profile with a sustained virological response rate of >90%.

  18. Treatment of Schizoaffective Disorder

    Science.gov (United States)

    2009-01-01

    In this article, we investigate the range of treatments prescribed for schizoaffective disorder. The data show that the majority of those treated, 87 percent, receive two or more pharmaceutical classes. From a therapeutic class perspective, 93 percent of schizoaffective disorder patients receive an antipsychotic, 48 percent receive a mood disorder treatment, and 42 percent receive an antidepressant. An expert commentary is also included. PMID:19724749

  19. The Comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD in Children and Arabic Speech Sound Disorder

    Directory of Open Access Journals (Sweden)

    Ruaa Osama Hariri

    2016-04-01

    Full Text Available Children with Attention-Deficiency/Hyperactive Disorder (ADHD often have co-existing learning disabilities and developmental weaknesses or delays in some areas including speech (Rief, 2005. Seeing that phonological disorders include articulation errors and other forms of speech disorders, studies pertaining to children with ADHD symptoms who demonstrate signs of phonological disorders in their native Arabic language are lacking. The purpose of this study is to provide a description of Arabic language deficits and to present a theoretical model of potential associations between phonological language deficits and ADHD. Dodd and McCormack’s (1995 four subgroups classification of speech disorder and the phonological disorders pertaining to the Arabic language provided by a Saudi Institute for Speech and Hearing are examined within the theoretical framework. Since intervention may improve articulation and focuses a child’s attention on the sound structure of words, findings in this study are based on the assumption that children with ADHD may acquire phonology for their Arabic language in the same way, and following the same developmental stages as intelligible children. Both quantitative and qualitative analyses have proven that the ADHD group analyzed in this study had indeed failed to acquire most of their Arabic consonants as they should have. Keywords: speech sound disorder, attention-deficiency/hyperactive, developmental disorder, phonological disorder, language disorder/delay, language impairment

  20. Physical disorders among Southeast Asian refugee outpatients with psychiatric disorders.

    Science.gov (United States)

    Ta, K; Westermeyer, J; Neider, J

    1996-09-01

    The study assessed the prevalence and duration of axis III physical disorders and the resulting level of disability among Southeast Asian refugee outpatients with axis I psychiatric disorders. A total of 266 consecutive patients who were evaluated in a psychiatric outpatient clinic were assessed for the presence of axis III conditions through questions about physical symptoms, a medical history and review of records, physical examination, and laboratory screening. The sample included 158 Hmong, 58 Laotian, 43 Vietnamese, and seven Cambodian patients. Fifty-five percent of the patients had one or more axis III disorders, most of which were chronic and were not associated with extreme disability. Neurological conditions were most common, and the sequelae of war-related trauma were prominent. No associations were found between the presence of axis III conditions and age, gender, marital status, or ethnic group. In 48 cases, the axis III condition may have caused or exacerbated the axis I condition. Routine medical history and a physical examination, including a neurological examination, are recommended for all psychiatric patients, including outpatients.

  1. Sleep and Eating Disorders.

    Science.gov (United States)

    Allison, Kelly C; Spaeth, Andrea; Hopkins, Christina M

    2016-10-01

    Insomnia is related to an increased risk of eating disorders, while eating disorders are related to more disrupted sleep. Insomnia is also linked to poorer treatment outcomes for eating disorders. However, over the last decade, studies examining sleep and eating disorders have relied on surveys, with no objective measures of sleep for anorexia nervosa or bulimia nervosa, and only actigraphy data for binge eating disorder. Sleep disturbance is better defined for night eating syndrome, where sleep efficiency is reduced and melatonin release is delayed. Studies that include objectively measured sleep and metabolic parameters combined with psychiatric comorbidity data would help identify under what circumstances eating disorders and sleep disturbance produce an additive effect for symptom severity and for whom poor sleep would increase risk for an eating disorder. Cognitive behavior therapy for insomnia may be a helpful addition to treatment of those with both eating disorder and insomnia.

  2. Generalized Anxiety Disorder and Social Anxiety Disorder, but Not Panic Anxiety Disorder, Are Associated with Higher Sensitivity to Learning from Negative Feedback: Behavioral and Computational Investigation

    OpenAIRE

    Khdour, Hussain Y.; Abushalbaq, Oday M.; Mughrabi, Ibrahim T.; Imam, Aya F.; Gluck, Mark A.; Herzallah, Mohammad M.; Moustafa, Ahmed A.

    2016-01-01

    Anxiety disorders, including generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic anxiety disorder (PAD), are a group of common psychiatric conditions. They are characterized by excessive worrying, uneasiness, and fear of future events, such that they affect social and occupational functioning. Anxiety disorders can alter behavior and cognition as well, yet little is known about the particular domains they affect. In this study, we tested the cognitive correlates of me...

  3. Neurobiology of comorbid post-traumatic stress disorder and alcohol-use disorder

    Science.gov (United States)

    Gilpin, N. W.; Weiner, J. L.

    2016-01-01

    Post-traumatic stress disorder (PTSD) and alcohol-use disorder (AUD) are highly comorbid in humans. Although we have some understanding of the structural and functional brain changes that define each of these disorders, and how those changes contribute to the behavioral symptoms that define them, little is known about the neurobiology of comorbid PTSD and AUD, which may be due in part to a scarcity of adequate animal models for examining this research question. The goal of this review is to summarize the current state-of-the-science on comorbid PTSD and AUD. We summarize epidemiological data documenting the prevalence of this comorbidity, review what is known about the potential neurobiological basis for the frequent co-occurrence of PTSD and AUD and discuss successes and failures of past and current treatment strategies. We also review animal models that aim to examine comorbid PTSD and AUD, highlighting where the models parallel the human condition, and we discuss the strengths and weaknesses of each model. We conclude by discussing key gaps in our knowledge and strategies for addressing them: in particular, we (1) highlight the need for better animal models of the comorbid condition and better clinical trial design, (2) emphasize the need for examination of subpopulation effects and individual differences and (3) urge cross-talk between basic and clinical researchers that is reflected in collaborative work with forward and reverse translational impact. PMID:27749004

  4. Neurobiology of comorbid post-traumatic stress disorder and alcohol-use disorder.

    Science.gov (United States)

    Gilpin, N W; Weiner, J L

    2017-01-01

    Post-traumatic stress disorder (PTSD) and alcohol-use disorder (AUD) are highly comorbid in humans. Although we have some understanding of the structural and functional brain changes that define each of these disorders, and how those changes contribute to the behavioral symptoms that define them, little is known about the neurobiology of comorbid PTSD and AUD, which may be due in part to a scarcity of adequate animal models for examining this research question. The goal of this review is to summarize the current state-of-the-science on comorbid PTSD and AUD. We summarize epidemiological data documenting the prevalence of this comorbidity, review what is known about the potential neurobiological basis for the frequent co-occurrence of PTSD and AUD and discuss successes and failures of past and current treatment strategies. We also review animal models that aim to examine comorbid PTSD and AUD, highlighting where the models parallel the human condition, and we discuss the strengths and weaknesses of each model. We conclude by discussing key gaps in our knowledge and strategies for addressing them: in particular, we (1) highlight the need for better animal models of the comorbid condition and better clinical trial design, (2) emphasize the need for examination of subpopulation effects and individual differences and (3) urge cross-talk between basic and clinical researchers that is reflected in collaborative work with forward and reverse translational impact. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  5. [Neuropsychological assessment in conversion disorder].

    Science.gov (United States)

    Demır, Süleyman; Çelıkel, Feryal Çam; Taycan, Serap Erdoğan; Etıkan, İlker

    2013-01-01

    Conversion disorder is characterized by functional impairment in motor, sensory, or neurovegetative systems that cannot be explained by a general medical condition. Diagnostic systems emphasize the absence of an organic basis for the dysfunction observed in conversion disorder. Nevertheless, there is a growing body of data on the specific functional brain correlates of conversion symptoms, particularly those obtained via neuroimaging and neurophysiological assessment. The present study aimed to determine if there are differences in measures of cognitive functioning between patients with conversion disorder and healthy controls. The hypothesis of the study was that the patients with conversion disorder would have poorer neurocognitive performance than the controls. The patient group included 43 patients diagnosed as conversion disorder and other psychiatric comorbidities according to DSM-IV-TR. Control group 1 included 44 patients diagnosed with similar psychiatric comorbidities, but not conversion diosorder, and control group 2 included 43 healthy individuals. All participants completed a sociodemographic questionnaire and were administered the SCID-I and a neuropsychological test battery of 6 tests, including the Serial Digit Learning Test (SDLT), Auditory Verbal Learning Test (AVLT), Wechsler Memory Scale, Stroop Color Word Interference Test, Benton Judgment of Line Orientation Test (BJLOT), and Cancellation Test. The patient group had significantly poorer performance on the SDLT, AVLT, Stroop Color Word Interference Test, and BJLOT than both control groups. The present findings highlight the differences between the groups in learning and memory, executive and visuospatial functions, and attention, which seemed to be specific to conversion disorder.

  6. Assessment of Elderlies Sleep Disorders and Different Confronts Methods Among Them

    Directory of Open Access Journals (Sweden)

    Monir Nobahar

    2007-07-01

    Full Text Available Objectives: Sleep is one of the essential needs for human and every disorder in during of sleep causes psychological problem and decreased person>s ability. Although sleep disorders occur in every of ages. Elderly person usually has very problem for satisfied sleep. The aim of this study was to estimate prevalence of sleep disorders and confront methods of those in elderly persons in Semnan city. Methods & Materials: This is a descriptive analytical research. 200 elderly residents of Semnan were selected through rundomical sampling. Sleep disorders was assessment with questioner and interviewer that include of sleep disorders (Dissomnia, Parasomnia and confront methods (Behavioral, Cognitive, sleep hygiene and drug therapy. Results: Data indicated that prevalence of dissomnia was 67% and prevalence of insomnia was 61% that the most problem were in all stage of sleep (early, intermittent and end. Prevalence of Parasomnia was 29% that more of those (14% had night terror. In the part of confront methods of sleep disorders, 57% used of behavioral therapy. The most of that (25% were concentration of the limb before the sleep and 95.5% of them comprehension of cognitive methods. The most of that (26% were comprehension of effect of age on sleep. 100% of them orientation of sleep hygiene and the most of that (39% were orientation with 4 choose of sleep hygiene. 20% of them used of drug therapy. Conclusion: Finding above indicate that high prevalence of sleep disorders in elderly in Semnan, need supervised and widespread program for promoting awareness among population about sleep disorders and confront methods of those.

  7. The International Communication Project: Raising global awareness of communication as a human right.

    Science.gov (United States)

    Mulcair, Gail; Pietranton, Arlene A; Williams, Cori

    2018-02-01

    Communication as a human right is embedded within Article 19 of the Universal Declaration of Human Rights; however, there is a need to raise global awareness of the communication needs of those with communication disorders. In 2014, the six national speech-language and audiology professional bodies that comprise the Mutual Recognition Agreement (MRA) launched the International Communication Project (ICP) to help raise awareness of communication disorders around the world. Since its inception, the project has engaged close to 50 organisations from diverse regions, and has undertaken a number of initiatives, including development of the Universal Declaration of Communication Rights. A consultancy report was commissioned to inform ICP efforts to influence international policy bodies. As a result, the current focus of the ICP is to identify opportunities to influence the policies of organisations such as the World Health Organization, the United Nations and World Bank to more explicitly acknowledge and address communication as a human right. This commentary paper describes the work of the ICP to date, with an emphasis on the place of communication disorders in current international policy and potential pathways for advocacy.

  8. Circadian rhythm sleep-wake disorders as predictors for bipolar disorder in patients with remitted mood disorders.

    Science.gov (United States)

    Takaesu, Yoshikazu; Inoue, Yuichi; Ono, Kotaro; Murakoshi, Akiko; Futenma, Kunihiro; Komada, Yoko; Inoue, Takeshi

    2017-10-01

    Circadian rhythm dysfunction is thought to play a key role in the pathogenesis of bipolar disorder (BD). We focused on circadian rhythm sleep-wake disorders (CRSWD) as possible predictors for bipolar disorder in patients with remitted mood disorders. One hundred four BD (41 type I and 63 type II) outpatients and 73 age- and sex-matched major depressive disorder (MDD) outpatients participated in this study. The subjects were asked to answer questionnaires including demographic variables, clinical course of the disorder, and family history of psychiatric disorders. Severity of mood status was evaluated by the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. CRSWD was diagnosed by clinical interview and sleep logs based on the International Classification of Sleep Disorders, third edition. The rate of CRSWD in BD subjects was significantly higher than that in MDD subjects (33.7% vs 9.6%; P < 0.001). A multiple logistic regression analysis revealed that comorbid CRSWD (OR = 3.35, 95% CI = 1.24 - 9.07; P = 0.018), two or more previous mood episodes within the past year (OR = 3.57, 95% CI = 1.10 - 11.63; P = 0.035), and antidepressant-related switch to mania/hypomania (OR = 10.01, 95% CI = 1.20 - 83.52; P = 0.033) were significantly associated with BD in patients with remitted mood disorders. CRSWD, as well as other factors, could be diagnostic predictors for BD in patients with remitted mood disorders. Combinations of these factors might be useful for predicting a BD diagnosis among the mood disorders in a clinical setting. Copyright © 2017. Published by Elsevier B.V.

  9. Unraveling the Neurobiology of Sleep and Sleep Disorders Using Drosophila.

    Science.gov (United States)

    Chakravarti, L; Moscato, E H; Kayser, M S

    2017-01-01

    Sleep disorders in humans are increasingly appreciated to be not only widespread but also detrimental to multiple facets of physical and mental health. Recent work has begun to shed light on the mechanistic basis of sleep disorders like insomnia, restless legs syndrome, narcolepsy, and a host of others, but a more detailed genetic and molecular understanding of how sleep goes awry is lacking. Over the past 15 years, studies in Drosophila have yielded new insights into basic questions regarding sleep function and regulation. More recently, powerful genetic approaches in the fly have been applied toward studying primary human sleep disorders and other disease states associated with dysregulated sleep. In this review, we discuss the contribution of Drosophila to the landscape of sleep biology, examining not only fundamental advances in sleep neurobiology but also how flies have begun to inform pathological sleep states in humans. © 2017 Elsevier Inc. All rights reserved.

  10. Melatonin as a Novel Interventional Candidate for Fragile X Syndrome with Autism Spectrum Disorder in Humans

    Directory of Open Access Journals (Sweden)

    Jinyoung Won

    2017-06-01

    Full Text Available Fragile X syndrome (FXS is the most common monogenic form of autism spectrum disorder (ASD. FXS with ASD results from the loss of fragile X mental retardation (fmr gene products, including fragile X mental retardation protein (FMRP, which triggers a variety of physiological and behavioral abnormalities. This disorder is also correlated with clock components underlying behavioral circadian rhythms and, thus, a mutation of the fmr gene can result in disturbed sleep patterns and altered circadian rhythms. As a result, FXS with ASD individuals may experience dysregulation of melatonin synthesis and alterations in melatonin-dependent signaling pathways that can impair vigilance, learning, and memory abilities, and may be linked to autistic behaviors such as abnormal anxiety responses. Although a wide variety of possible causes, symptoms, and clinical features of ASD have been studied, the correlation between altered circadian rhythms and FXS with ASD has yet to be extensively investigated. Recent studies have highlighted the impact of melatonin on the nervous, immune, and metabolic systems and, even though the utilization of melatonin for sleep dysfunctions in ASD has been considered in clinical research, future studies should investigate its neuroprotective role during the developmental period in individuals with ASD. Thus, the present review focuses on the regulatory circuits involved in the dysregulation of melatonin and disruptions in the circadian system in individuals with FXS with ASD. Additionally, the neuroprotective effects of melatonin intervention therapies, including improvements in neuroplasticity and physical capabilities, are discussed and the molecular mechanisms underlying this disorder are reviewed. The authors suggest that melatonin may be a useful treatment for FXS with ASD in terms of alleviating the adverse effects of variations in the circadian rhythm.

  11. Melatonin as a Novel Interventional Candidate for Fragile X Syndrome with Autism Spectrum Disorder in Humans.

    Science.gov (United States)

    Won, Jinyoung; Jin, Yunho; Choi, Jeonghyun; Park, Sookyoung; Lee, Tae Ho; Lee, Sang-Rae; Chang, Kyu-Tae; Hong, Yonggeun

    2017-06-20

    Fragile X syndrome (FXS) is the most common monogenic form of autism spectrum disorder (ASD). FXS with ASD results from the loss of fragile X mental retardation ( fmr ) gene products, including fragile X mental retardation protein (FMRP), which triggers a variety of physiological and behavioral abnormalities. This disorder is also correlated with clock components underlying behavioral circadian rhythms and, thus, a mutation of the fmr gene can result in disturbed sleep patterns and altered circadian rhythms. As a result, FXS with ASD individuals may experience dysregulation of melatonin synthesis and alterations in melatonin-dependent signaling pathways that can impair vigilance, learning, and memory abilities, and may be linked to autistic behaviors such as abnormal anxiety responses. Although a wide variety of possible causes, symptoms, and clinical features of ASD have been studied, the correlation between altered circadian rhythms and FXS with ASD has yet to be extensively investigated. Recent studies have highlighted the impact of melatonin on the nervous, immune, and metabolic systems and, even though the utilization of melatonin for sleep dysfunctions in ASD has been considered in clinical research, future studies should investigate its neuroprotective role during the developmental period in individuals with ASD. Thus, the present review focuses on the regulatory circuits involved in the dysregulation of melatonin and disruptions in the circadian system in individuals with FXS with ASD. Additionally, the neuroprotective effects of melatonin intervention therapies, including improvements in neuroplasticity and physical capabilities, are discussed and the molecular mechanisms underlying this disorder are reviewed. The authors suggest that melatonin may be a useful treatment for FXS with ASD in terms of alleviating the adverse effects of variations in the circadian rhythm.

  12. Paraneoplastic autoimmune movement disorders.

    Science.gov (United States)

    Lim, Thien Thien

    2017-11-01

    To provide an overview of paraneoplastic autoimmune disorders presenting with various movement disorders. The spectrum of paraneoplastic autoimmune disorders has been expanding with the discovery of new antibodies against cell surface and intracellular antigens. Many of these paraneoplastic autoimmune disorders manifest as a form of movement disorder. With the discovery of new neuronal antibodies, an increasing number of idiopathic or neurodegenerative movement disorders are now being reclassified as immune-mediated movement disorders. These include anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis which may present with orolingual facial dyskinesia and stereotyped movements, CRMP-5 IgG presenting with chorea, anti-Yo paraneoplastic cerebellar degeneration presenting with ataxia, anti-VGKC complex (Caspr2 antibodies) neuromyotonia, opsoclonus-myoclonus-ataxia syndrome, and muscle rigidity and episodic spasms (amphiphysin, glutamic acid decarboxylase, glycine receptor, GABA(A)-receptor associated protein antibodies) in stiff-person syndrome. Movement disorders may be a presentation for paraneoplastic autoimmune disorders. Recognition of these disorders and their common phenomenology is important because it may lead to the discovery of an occult malignancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Oligodendrocyte Injury and Pathogenesis of HIV-1-Associated Neurocognitive Disorders

    Directory of Open Access Journals (Sweden)

    Han Liu

    2016-07-01

    Full Text Available Oligodendrocytes wrap neuronal axons to form myelin, an insulating sheath which is essential for nervous impulse conduction along axons. Axonal myelination is highly regulated by neuronal and astrocytic signals and the maintenance of myelin sheaths is a very complex process. Oligodendrocyte damage can cause axonal demyelination and neuronal injury, leading to neurological disorders. Demyelination in the cerebrum may produce cognitive impairment in a variety of neurological disorders, including human immunodeficiency virus type one (HIV-1-associated neurocognitive disorders (HAND. Although the combined antiretroviral therapy has markedly reduced the incidence of HIV-1-associated dementia, a severe form of HAND, milder forms of HAND remain prevalent even when the peripheral viral load is well controlled. HAND manifests as a subcortical dementia with damage in the brain white matter (e.g., corpus callosum, which consists of myelinated axonal fibers. How HIV-1 brain infection causes myelin injury and resultant white matter damage is an interesting area of current HIV research. In this review, we tentatively address recent progress on oligodendrocyte dysregulation and HAND pathogenesis.

  14. Brain stimulation in posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Vladan Novakovic

    2011-10-01

    Full Text Available Posttraumatic stress disorder (PTSD is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT and Cranial electrotherapy stimulation (CES have both been in use for decades; transcranial magnetic stimulation (TMS, magnetic seizure therapy (MST, deep brain stimulation (DBS, transcranial Direct Current Stimulation (tDCS, and vagus nerve stimulation (VNS have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES, depression (ECT, CES, rTMS, VNS, DBS, obsessive-compulsive disorder (OCD (DBS, essential tremor, dystonia (DBS, epilepsy (DBS, VNS, Parkinson Disease (DBS, pain (CES, and insomnia (CES. To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in

  15. Application of an ex vivo cellular model of circadian variation for bipolar disorder research: a proof of concept study.

    Science.gov (United States)

    Bamne, Mikhil N; Ponder, Christine A; Wood, Joel A; Mansour, Hader; Frank, Ellen; Kupfer, David J; Young, Michael W; Nimgaonkar, Vishwajit L

    2013-09-01

    Disruption of circadian function has been observed in several human disorders, including bipolar disorder (BD). Research into these disorders can be facilitated by human cellular models that evaluate external factors (zeitgebers) that impact circadian pacemaker activity. Incorporating a firefly luciferase reporter system into human fibroblasts provides a facile, bioluminescent readout that estimates circadian phase, while leaving the cells intact. We evaluated whether this system can be adapted to clinical BD research and whether it can incorporate zeitgeber challenge paradigms. Fibroblasts from patients with bipolar I disorder (BD-I) (n = 13) and controls (n = 12) were infected ex vivo with a lentiviral reporter incorporating the promoter sequences for Bmal1, a circadian gene to drive expression of the firefly luciferase gene. Following synchronization, the bioluminescence was used to estimate period length. Phase response curves (PRCs) were also generated following forskolin challenge and the phase response patterns were characterized. Period length and PRCs could be estimated reliably from the constructs. There were no significant case-control differences in period length, with a nonsignificant trend for differences in PRCs following the phase-setting experiments. An ex vivo cellular fibroblast-based model can be used to investigate circadian function in BD-I. It can be generated from specific individuals and this could usefully complement ongoing circadian clinical research. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. A radioimmunoassay for erythropoietin: serum levels in normal human subjects and patients with hemopoietic disorders

    International Nuclear Information System (INIS)

    Rege, A.B.; Brookins, J.; Fisher, J.W.

    1982-01-01

    An RIA for Ep has been developed that is highly sensitive and specific. A homogeneous Ep preparation was labeled with 125 I by the chloramine-T method to a specific activity of 90 to 136 micro Ci/microgram and immunoreactivity of 80%. Ep antiserum, which was produced to a human urinary Ep preparation (80 U/mg of protein), was adsorbed with normal human urinary and serum proteins without any loss in sensitivity of the RIA to increase the specificity of the assay. A good correlation was seen between the RIA and the exhypoxic polycythemic mouse assay (corr. coef. 0.967; slope 1.05 and y intercept 0.75). Ep titers in sera from 175 hematologically normal human subjects exhibited a normal frequency distribution and ranged between 5.8 and 36.6 mU/ml with a mean of 14.9 +/- 4.7 (S.D.) and median of 14.3 Serum Ep titers were markedly elevated in seven patients with aplastic anemia and one patient with pure red cell aplasia (1350 to 20,640 mU/ml) and were lower than normal in two patients with polycythemia vera (8.1 and 9.4 mU/ml). The serum Ep titers in a prenephrectomy patient with chronic glomerulonephritis (32.1 mU/ml) decreased to below normal levels (9.04 mU/ml) after nephrectomy. The cord serum erythropoietin titers in 10 IDM [90.82 +/- 134.1 (S.D.) mu/ml] returned to values within the normal range (13.86 +/- 5.55) on day 3 after birth, suggesting the utility of the RIA in elucidating the role of hypoxia and/or insulin in increased erythropoiesis in IDM. The serum Ep titers in patients with anemias and polycythemias were compared to those of normal human subjects and agreed well with pathophysiologic mechanisms of these hemopoietic disorders, confirming the validity of the RIA

  17. A radioimmunoassay for erythropoietin: serum levels in normal human subjects and patients with hemopoietic disorders

    International Nuclear Information System (INIS)

    Rege, A.B.; Brookins, J.; Fisher, J.W.

    1982-01-01

    An RIA for Ep has been developed that is highly sensitive and specific. A homogeneous Ep preparation was labeled with 125 I by the chloramine-T method to a specific activity of 90 to 136 μCi/μg and immunoreactivity of 80%. Ep antiserum, which was produced to a human urinary Ep preparation (80 U/mg of protein), was adsorbed with normal human urinary and serum proteins without any loss in sensitivity of the RIA to increase the specificity of the assay. A good correlation was seen between the RIA and the exhypoxic polycythemic mouse assay (corr. coef. 0.967; slope 1.05 and ''y'' intercept 0.75). Ep titers in sera from 175 hematologically normal human subjects exhibited a normal frequency distribution and ranged between 5.8 and 36.6 mU/ml with a mean of 14.9 +/- 4.7 (S.D.) and median of 14.3. Serum Ep titers were markedly elevated in seven patients with aplastic anemia and one patient with pure red cell aplasia (1350 to 20,640 mU/ml) and were lower than normal in two patients with polycythemia vera (8.1 and 9.4 mU/ml). The serum Ep titers in a prenephrectomy patient with chronic glomerulonephritis (31.1 mU/ml) decreased to below normal levels (9.04 mU/ml) after nephrectomy. The cord serum erythropoietin titers in 10 IDM [90.82 +/- 134.1 (S.D.) mu/ml] returned to values within the normal range (13.86 +/- 5.55) on day 3 after birth, suggesting the utility of the RIA in elucidating the role of hypoxia and/or insulin in increased erythropoiesis in IDM. The serum Ep titers in patients with anemias and polycythemias were compared to those of normal human subjects and agreed well with pathophysiologic mechanisms of these hemopoietic disorders, confirming the validity of the RIA

  18. A novel description of a syndrome consisting of 7q21.3 deletion including DYNC1I1 with preserved DLX5/6 without ectrodactyly: a case report.

    Science.gov (United States)

    Ramos-Zaldívar, Héctor M; Martínez-Irías, Daniel G; Espinoza-Moreno, Nelson A; Napky-Rajo, José S; Bueso-Aguilar, Tulio A; Reyes-Perdomo, Karla G; Montes-Gambarelli, Jimena A; Euceda, Isis M; Ponce-Barahona, Aldo F; Gámez-Fernández, Carlos A; Moncada-Arita, Wilberg A; Palomo-Bermúdez, Victoria A; Jiménez-Faraj, Julia E; Hernández-Padilla, Amanda G; Olivera, Denys A; Robertson, Kevin J; Leiva-Sanchez, Luis A; Herrera-Paz, Edwin Francisco

    2016-06-13

    Chromosomal region 7q21.3 comprises approximately 5.2 mega base pairs that include genes DLX5/6, SHFM1, and DYNC1I1 associated with split hand/split foot malformation 1. So far, there are reports of eight families with deletion of DYNC1I1 and preserved DLX5/6 associated with ectrodactyly. From these families, only three patients did not present ectrodactyly and, unlike our patient, no other cases have been described as having craniofacial dysmorphology, mitral valve prolapse, kyphoscoliosis, inguinal herniae, or personality disorder. There is no designation described in the literature for patients with syndromic manifestations without ectrodactyly, which hinders diagnosis. We report the case of a 44-year-old mestizo (combined European and Amerindian descent) man with a 3191 kilo base pairs deletion and International System for Human Cytogenetic Nomenclature array 7q21.3 (93,389,222-96,579,845)x1. Clinical manifestations included micrognathia, retrognathia, wormian bones, auditory canal stenosis, depressed nasal bridge, epicanthal fold, fullness of upper eyelid, long philtrum, low-set ears, sensorineural hearing loss, kyphoscoliosis, bilateral inguinal herniae, mild mitral valve prolapse, and paranoid personality disorder. His isolated DNA was analyzed using a CytoScan HD Microarray system. Chromosome Analysis Suite software was utilized for the microarray analysis. All copy number changes were determined using the human genome build 19 (hg19/NCBI build 37). Cases of deletions within chromosome 7q21.3 that include the split hand/split foot malformation 1 region represent a diagnostic challenge when not presenting ectrodactyly despite being syndromic. Due to the heterogeneity of the region, a better method to group and classify these patients is needed to facilitate their clinical diagnosis. For this purpose, we suggest that patients with 7q21.3 deletion including DYNC1I1 and preserved DLX5/6 without ectrodactyly, accompanied by craniofacial dysmorphology

  19. Digested disorder: Quarterly intrinsic disorder digest (April-May-June, 2013).

    Science.gov (United States)

    DeForte, Shelly; Reddy, Krishna D; Uversky, Vladimir N

    2013-01-01

    The current literature on intrinsically disordered proteins is overwhelming. To keep interested readers up to speed with this literature, we continue a "Digested Disorder" project and represent a series of reader's digest type articles objectively representing the research papers and reviews on intrinsically disordered proteins. The only 2 criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the period of April, May, and June of 2013. The papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings.

  20. Engineering of Systematic Elimination of a Targeted Chromosome in Human Cells.

    Science.gov (United States)

    Sato, Hiroshi; Kato, Hiroki; Yamaza, Haruyoshi; Masuda, Keiji; Nguyen, Huong Thi Nguyen; Pham, Thanh Thi Mai; Han, Xu; Hirofuji, Yuta; Nonaka, Kazuaki

    2017-01-01

    Embryonic trisomy leads to abortion or congenital genetic disorders in humans. The most common autosomal chromosome abnormalities are trisomy of chromosomes 13, 18, and 21. Although alteration of gene dosage is thought to contribute to disorders caused by extra copies of chromosomes, genes associated with specific disease phenotypes remain unclear. To generate a normal cell from a trisomic cell as a means of etiological analysis or candidate therapy for trisomy syndromes, we developed a system to eliminate a targeted chromosome from human cells. Chromosome 21 was targeted by integration of a DNA cassette in HeLa cells that harbored three copies of chromosome 21. The DNA cassette included two inverted loxP sites and a herpes simplex virus thymidine kinase (HSV-tk) gene. This system causes missegregation of chromosome 21 after expression of Cre recombinase and subsequently enables the selection of cells lacking the chromosome by culturing in a medium that includes ganciclovir (GCV). Cells harboring only two copies of chromosome 21 were efficiently induced by transfection of a Cre expression vector, indicating that this approach is useful for eliminating a targeted chromosome.

  1. Systematic review of the neurobiological relevance of chemokines to psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Michael eStuart

    2015-09-01

    Full Text Available Psychiatric disorders are highly prevalent and disabling conditions of increasing public health relevance. Much recent research has focused on the role of cytokines in the pathophysiology of psychiatric disorders; however the related family of immune proteins designated chemokines has been relatively neglected. Chemokines were originally identified as having chemotactic function on immune cells, however recent evidence has begun to elucidate novel, brain-specific functions of these proteins of relevance to the mechanisms of psychiatric disorders. A systematic review of both human and animal literature in the PubMed and Google Scholar databases was undertaken. After application of all inclusion and exclusion criteria, 157 references were remained for the review. Some early mechanistic evidence does associate select chemokines with the neurobiological processes, including neurogenesis, modulation of the neuroinflammatory response, regulation of the HPA axis, and modulation of neurotransmitter systems. This early evidence however does not clearly demonstrate any specificity for a certain psychiatric disorder, but is primarily relevant to mechanisms which are shared across disorders. Notable exceptions include CCL11 which has recently been shown to impair hippocampal function in aging - of distinct relevance to Alzheimer’s disease and depression in the elderly, and prenatal exposure to CXCL8 that may disrupt early neurodevelopmental periods predisposing to schizophrenia. Pro-inflammatory chemokines, such as CCL2, CCL7, CCL8, CCL12, CCL13, have been shown to drive chemotaxis of pro-inflammatory cells to the inflamed or injured CNS. Likewise, CX3CL has been implicated in promoting glial cells activation, proinflammatory cytokines secretion, expression of ICAM-1 and recruitment of CD4+ T-cells into the CNS during neuroinflammatory processes. With further translational research, chemokines may present novel diagnostic and/or therapeutic targets in

  2. Systematic Review of the Neurobiological Relevance of Chemokines to Psychiatric Disorders.

    Science.gov (United States)

    Stuart, Michael J; Singhal, Gaurav; Baune, Bernhard T

    2015-01-01

    Psychiatric disorders are highly prevalent and disabling conditions of increasing public health relevance. Much recent research has focused on the role of cytokines in the pathophysiology of psychiatric disorders; however, the related family of immune proteins designated chemokines has been relatively neglected. Chemokines were originally identified as having chemotactic function on immune cells; however, recent evidence has begun to elucidate novel, brain-specific functions of these proteins of relevance to the mechanisms of psychiatric disorders. A systematic review of both human and animal literature in the PubMed and Google Scholar databases was undertaken. After application of all inclusion and exclusion criteria, 157 references were remained for the review. Some early mechanistic evidence does associate select chemokines with the neurobiological processes, including neurogenesis, modulation of the neuroinflammatory response, regulation of the hypothalamus-pituitary-adrenal axis, and modulation of neurotransmitter systems. This early evidence however does not clearly demonstrate any specificity for a certain psychiatric disorder, but is primarily relevant to mechanisms which are shared across disorders. Notable exceptions include CCL11 that has recently been shown to impair hippocampal function in aging - of distinct relevance to Alzheimer's disease and depression in the elderly, and pre-natal exposure to CXCL8 that may disrupt early neurodevelopmental periods predisposing to schizophrenia. Pro-inflammatory chemokines, such as CCL2, CCL7, CCL8, CCL12, and CCL13, have been shown to drive chemotaxis of pro-inflammatory cells to the inflamed or injured CNS. Likewise, CX3CL has been implicated in promoting glial cells activation, pro-inflammatory cytokines secretion, expression of ICAM-1, and recruitment of CD4+ T-cells into the CNS during neuroinflammatory processes. With further translational research, chemokines may present novel diagnostic and

  3. The downside of strong emotional memories: how human memory-related genes influence the risk for posttraumatic stress disorder--a selective review.

    Science.gov (United States)

    Wilker, Sarah; Elbert, Thomas; Kolassa, Iris-Tatjana

    2014-07-01

    A good memory for emotionally arousing experiences may be intrinsically adaptive, as it helps the organisms to predict safety and danger and to choose appropriate responses to prevent potential harm. However, under conditions of repeated exposure to traumatic stressors, strong emotional memories of these experiences can lead to the development of trauma-related disorders such as posttraumatic stress disorder (PTSD). This syndrome is characterized by distressing intrusive memories that can be so intense that the survivor is unable to discriminate past from present experiences. This selective review on the role of memory-related genes in PTSD etiology is divided in three sections. First, we summarize studies indicating that the likelihood to develop PTSD depends on the cumulative exposure to traumatic stressors and on individual predisposing risk factors, including a substantial genetic contribution to PTSD risk. Second, we focus on memory processes supposed to be involved in PTSD etiology and present evidence for PTSD-associated alterations in both implicit (fear conditioning, fear extinction) and explicit memory for emotional material. This is supplemented by a brief description of structural and functional alterations in memory-relevant brain regions in PTSD. Finally, we summarize a selection of studies indicating that genetic variations found to be associated with enhanced fear conditioning, reduced fear extinction or better episodic memory in human experimental studies can have clinical implications in the case of trauma exposure and influence the risk of PTSD development. Here, we focus on genes involved in noradrenergic (ADRA2B), serotonergic (SLC6A4), and dopaminergic signaling (COMT) as well as in the molecular cascades of memory formation (PRKCA and WWC1). This is supplemented by initial evidence that such memory-related genes might also influence the response rates of exposure-based psychotherapy or pharmacological treatment of PTSD, which underscores the

  4. Subcortical pathways: Towards a better understanding of auditory disorders.

    Science.gov (United States)

    Felix, Richard A; Gourévitch, Boris; Portfors, Christine V

    2018-05-01

    Hearing loss is a significant problem that affects at least 15% of the population. This percentage, however, is likely significantly higher because of a variety of auditory disorders that are not identifiable through traditional tests of peripheral hearing ability. In these disorders, individuals have difficulty understanding speech, particularly in noisy environments, even though the sounds are loud enough to hear. The underlying mechanisms leading to such deficits are not well understood. To enable the development of suitable treatments to alleviate or prevent such disorders, the affected processing pathways must be identified. Historically, mechanisms underlying speech processing have been thought to be a property of the auditory cortex and thus the study of auditory disorders has largely focused on cortical impairments and/or cognitive processes. As we review here, however, there is strong evidence to suggest that, in fact, deficits in subcortical pathways play a significant role in auditory disorders. In this review, we highlight the role of the auditory brainstem and midbrain in processing complex sounds and discuss how deficits in these regions may contribute to auditory dysfunction. We discuss current research with animal models of human hearing and then consider human studies that implicate impairments in subcortical processing that may contribute to auditory disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. At the crossroads: the intersection of substance use disorders, anxiety disorders, and posttraumatic stress disorder.

    Science.gov (United States)

    Ruglass, Lesia M; Lopez-Castro, Teresa; Cheref, Soumia; Papini, Santiago; Hien, Denise A

    2014-11-01

    The co-occurrence of substance use disorders with anxiety disorders and/or posttraumatic stress disorder has been widely documented and when compared to each disorder alone, consistently linked to increased risk for a host of negative outcomes including greater impairment, poorer treatment response, and higher rates of symptom relapse. This article focuses on recent advances in the understanding and effective treatment of this common and highly complex comorbidity. Prevalence and epidemiological data are introduced, followed by a review of contemporary models of etiology and associative pathways. Conceptualizations of effective treatment approaches are discussed alongside evidence from the past decade of clinical research trials. Highlighted are ongoing questions regarding the benefit of sequential, parallel, and integrated approaches and the necessity of further investigation into the mechanisms underlying treatment efficacy. Lastly, recent contributions from neuroscience research are offered as a promising bridge for the development and testing of novel, interdisciplinary treatment approaches.

  6. Binge-Eating Disorder: Between Eating Disorders and Obesity? A Cognitive-Behavioral Perspective

    OpenAIRE

    Gempeler Rueda, Juanita

    2005-01-01

    Abstract This article reviews the available literature on binge-eating disorder, currently included in the DSM IV as an Eating Disorder NOS. Its inclusion in the DSM V is under discussion. Conceptualization of this disorder is examined, as well as implications for clinical interventions from a cognitive-behavioral perspective. Resumen El presente artículo tiene por objeto revisar la bibliografía actualizada disponible sobre el tema del trastorno por atracones de la alimentación, que hasta ...

  7. Signs of mood and anxiety disorders in chimpanzees.

    Directory of Open Access Journals (Sweden)

    Hope R Ferdowsian

    Full Text Available BACKGROUND: In humans, traumatic experiences are sometimes followed by psychiatric disorders. In chimpanzees, studies have demonstrated an association between traumatic events and the emergence of behavioral disturbances resembling posttraumatic stress disorder (PTSD and depression. We addressed the following central question: Do chimpanzees develop posttraumatic symptoms, in the form of abnormal behaviors, which cluster into syndromes similar to those described in human mood and anxiety disorders? METHODOLOGY/PRINCIPAL FINDINGS: In phase 1 of this study, we accessed case reports of chimpanzees who had been reportedly subjected to traumatic events, such as maternal separation, social isolation, experimentation, or similar experiences. We applied and tested DSM-IV criteria for PTSD and major depression to published case reports of 20 chimpanzees identified through PrimateLit. Additionally, using the DSM-IV criteria and ethograms as guides, we developed behaviorally anchored alternative criteria that were applied to the case reports. A small number of chimpanzees in the case studies met DSM-IV criteria for PTSD and depression. Measures of inter-rater reliability, including Fleiss' kappa and percentage agreement, were higher with use of the alternative criteria for PTSD and depression. In phase 2, the alternative criteria were applied to chimpanzees living in wild sites in Africa (n = 196 and chimpanzees living in sanctuaries with prior histories of experimentation, orphanage, illegal seizure, or violent human conflict (n = 168. In phase 2, 58% of chimpanzees living in sanctuaries met the set of alternative criteria for depression, compared with 3% of chimpanzees in the wild (p = 0.04, and 44% of chimpanzees in sanctuaries met the set of alternative criteria for PTSD, compared with 0.5% of chimpanzees in the wild (p = 0.04. CONCLUSIONS/SIGNIFICANCE: Chimpanzees display behavioral clusters similar to PTSD and depression in their key

  8. Children with Autism Spectrum Disorders Make a Fruit Salad with Probo, the Social Robot: An Interaction Study

    Science.gov (United States)

    Simut, Ramona E.; Vanderfaeillie, Johan; Peca, Andreea; Van de Perre, Greet; Vanderborght, Bram

    2016-01-01

    Social robots are thought to be motivating tools in play tasks with children with autism spectrum disorders. Thirty children with autism were included using a repeated measurements design. It was investigated if the children's interaction with a human differed from the interaction with a social robot during a play task. Also, it was examined if…

  9. Resilience in patients with psychotic disorder.

    Science.gov (United States)

    Bozikas, V; Parlapani, E

    2016-01-01

    The recovery movement differentiated clinical, which is related to disorder's symptoms, from personal recovery, which is outlined by a subjectively defined wellness state, characterised by hope and self-management. Schizophrenia research has long focused on risk factors and symptoms. The recovery movement triggered a focus shift from psychopathology towards better adjustment and growth despite living with schizophrenia. The recovery movement flourished parallel with positive psychology, the scientific study of ordinary human strengths and virtues investigating human motives and potentials. Understanding of human strengths could contribute to prevention or lessening of psychiatric disorders' devastating consequences, since optimism, sense of personal control and many other positive processes promote psychological health. Lately, the concepts of positive psychology have been implemented in schizophrenia research. Positive self-appraisals moderated suicidal ideation, even when patients experienced high levels of hopelessness.1 Additionally, among other factors, better self-images, internal locus of control (i.e. the perception that events in one's life relate to one's actions) and emphasis on personal efforts predicted a more favourable outcome in functioning of unmedicated patients.2 The concept of "resilience" is closely related to positive psychology. The American Psychological Association defines resilience as ''the process of adapting well in the face of adversity, trauma, threats or significant sources of stress''. The concept of resilience includes rebound from adversity.3 Determinants of resilience include biological, psychological, social and cultural factors that interact in a complex manner. The major manifestations of personal resilience are social competence, problem solving, autonomy and sense of purpose.5 Personality strengths that relate to resilience include high self-esteem, extroversion and optimism. Internal assets and personal competencies

  10. Restoring function in major depressive disorder: A systematic review.

    Science.gov (United States)

    Sheehan, David V; Nakagome, Kazuyuki; Asami, Yuko; Pappadopulos, Elizabeth A; Boucher, Matthieu

    2017-06-01

    Functional impairment contributes to significant disability and economic burden in major depressive disorder (MDD). Treatment response is measured by improvement in depressive symptoms, but functional improvement often lags behind symptomatic improvement. Residual deficits are associated with relapse of depressive symptoms. A literature search was conducted using the following terms: "major depressive disorder," "functional impairment," "functional outcomes," "recovery of function," "treatment outcome," "outcome assessment," "social functioning," "presenteeism," "absenteeism," "psychiatric status rating scales," and "quality of life." Search limits included publication date (January 1, 1995 to August 31, 2016), English language, and human clinical trials. Controlled, acute-phase, nonrecurrent MDD treatment studies in adults were included if a functional outcome was measured at baseline and endpoint. The qualitative analysis included 35 controlled studies. The Sheehan Disability Scale was the most commonly used functional assessment. Antidepressant treatments significantly improved functional outcomes. Early treatment response predicted functional improvement, while baseline disease severity did not. Clinical studies utilized various methodologies and assessments for functional impairment, and were not standardized or adequately powered. The lack of synchronicity between symptomatic and functional improvement highlights an unmet need for MDD. Treatment guided by routine monitoring of symptoms and functionality may minimize residual functional impairments. Copyright © 2017. Published by Elsevier B.V.

  11. Non-neoplastic disorders of the esophagus

    International Nuclear Information System (INIS)

    Hong, Min Ji; Kim, Young Tong

    2013-01-01

    Non-neoplastic disorders of the esophagus include esophagitis, esophageal diverticulum, esophageal injury, foreign body, fistulous formation between the esophagus and the surrounding structures and mucocele. Since these disorders have variable symptoms and radiologic findings, it needs to differentiated from other disorders other than esophageal diseases. Being knowledgeable of CT findings suggest that these disorders can help diagnose non-neoplastic disorders of the esophagus. The purpose of this pictorial essay is to review the CT appearance of non-neoplastic disorders of the esophagus.

  12. Tic disorders.

    Science.gov (United States)

    Martino, Davide; Mink, Jonathan W

    2013-10-01

    Primary tic disorders are complex, multifactorial disorders in which tics are accompanied by other sensory features and an array of comorbid behavioral disorders. Secondary tics are proportionally much less frequent, but their etiology is diverse. This review aims to guide clinicians in the recognition of the phenomenology, pathophysiology, and treatment of these disorders. Advances include greater phenomenologic insights, particularly of nonmotor (sensory) features; increased knowledge of disease mechanisms, particularly coming from neuropsychological, functional imaging, pathologic, and animal model studies; growing evidence on the efficacy of alpha-2 agonists and the newer generation of dopamine-modulating agents; and recent strides in the evaluation of cognitive-behavioral therapy and deep brain stimulation surgery. The correct diagnostic approach to tic disorders requires accurate historical gathering, a thorough neurologic examination, and detailed definition of the patient's psychopathologic profile. Treatment should always begin with individualized psychoeducational strategies. Although pharmacologic treatments remain beneficial for most patients, cognitive-behavioral treatments have thus far shown promising efficacy. Deep brain stimulation surgery should still be limited to adult patients refractory to pharmacotherapy and cognitive-behavioral therapy.

  13. Thought Disorder in Preschool Children with Attention Deficit/Hyperactivity Disorder (ADHD).

    Science.gov (United States)

    Hutchison, Amanda K; Kelsay, Kimberly; Talmi, Ayelet; Noonan, Kate; Ross, Randal G

    2016-08-01

    Preschool identification of and intervention for psychiatric symptoms has the potential for lifelong benefits. However, preschool identification of thought disorder, a symptom associated with long term risk for social and cognitive dysfunction, has received little attention with previous work limited to examining preschoolers with severe emotional and behavioral dysregulation. Using story-stem methodology, 12 children with ADHD and 12 children without ADHD, ages 4.0-6.0 years were evaluated for thought disorder. Thought disorder was reliably assessed (Cronbach's alpha = .958). Children with ADHD were significantly more likely than children without ADHD to exhibit thought disorder (75 vs 25 %; Fischer's Exact Test = .0391). Thought disorder can be reliably assessed in preschool children and is present in preschool children with psychiatric illness including preschool children with ADHD. Thought disorder may be identifiable in preschool years across a broad range of psychiatric illnesses and thus may be an appropriate target of intervention.

  14. [A case of major depressive disorder barely distinguishable from narcissistic personality disorder].

    Science.gov (United States)

    Saito, Shinnosuke; Kobayashi, Toshiyuki; Kato, Satoshi

    2013-01-01

    The recent increase in cases of depression with a narcissistic tendency, especially among young individuals, has been pointed out. When the narcissistic tendency is conspicuous, patients may be treated for a personality disorder or pervasive developmental disorder, and not for a mood disorder. A case is described of a man in his late twenties who developed depression due to his failure in research work and job hunting, and, after a time, due to the break off of his engagement with his fiancée, manifested with narcissistic symptoms including an exaggerated opinion of himself, a sense of entitlement, interpersonal exploitation, lack of empathy, strong feelings of envy, and an extrapunitive tendency. He was regarded at the start of treatment as having narcissistic personality disorder. However, persevering treatment, mainly with supportive psychotherapy and pharmacotherapy including antidepressants (high dose of maprotiline combined with low dose of mirtazapine), sodium valprote and aripiprazole, finally improved not only his depressive symptoms, but also the symptoms regarded as a deriving from a personality disorder. He presented fierce anger and aggression regarded as a mixed state, and showed the rapid improvement in his depressive state after hospitalization, which we considered to show potential bipolarity. We diagnosed the patient with narcissistic depression, emphasizing the aspect which suggested a mood disorder, such as the episodic presence of narcissistic symptoms as long as a depressive state resided, his circular, recursive discourse, and his potential bipolarity. To accurately evaluate the aspect of mood disorders which patients appearing to show personality disorders have, it is considered useful to grasp a patient's condition from the viewpoint of a personality structure and viable dynamics. From a therapeutic standpoint, we suggest the importance of simple but persevering psychotherapy and a sufficient quantity of antidepressant medication for

  15. Eating disorders in women

    Science.gov (United States)

    Sharan, Pratap; Sundar, A. Shyam

    2015-01-01

    Eating disorders, especially anorexia nervosa and bulimia nervosa have been classically described in young females in Western population. Recent research shows that they are also seen in developing countries including India. The classification of eating disorders has been expanded to include recently described conditions like binge eating disorder. Eating disorders have a multifactorial etiology. Genetic factor appear to play a major role. Recent advances in neurobiology have improved our understanding of these conditions and may possibly help us develop more effective treatments in future. Premorbid personality appears to play an important role, with differential predisposition for individual disorders. The role of cultural factors in the etiology of these conditions is debated. Culture may have a pathoplastic effect leading to non-conforming presentations like the non fat-phobic form of anorexia nervosa, which are commonly reported in developing countries. With rapid cultural transformation, the classical forms of these conditions are being described throughout the world. Diagnostic criteria have been modified to accommodate for these myriad presentations. Treatment of eating disorders can be quite challenging, given the dearth of established treatments and poor motivation/insight in these conditions. Nutritional rehabilitation and psychotherapy remains the mainstay of treatment, while pharmacotherapy may be helpful in specific situations. PMID:26330646

  16. The applications of pharmacogenomics to neurological disorders.

    Science.gov (United States)

    Gilman, C; McSweeney, C; Mao, Y

    2014-01-01

    The most common neurological disorders, including neurodegenerative diseases and psychiatric disorders, have received recent attention with regards to pharmacogenomics and personalized medicine. Here, we will focus on a neglected neurodegenerative disorder, cerebral ischemic stroke (CIS), and highlight recent advances in two disorders, Parkinson's disease (PD) and Alzheimer's diseases (AD), that possess both similar and distinct mechanisms in regards to potential therapeutic targets. In the first part of this review, we will focus primarily on mechanisms that are somewhat specific to each disorder which are involved in neurodegeneration (i.e., protease pathways, calcium homeostasis, reactive oxygen species regulation, DNA repair mechanisms, neurogenesis regulation, mitochondrial function, etc.). In the second part of this review, we will discuss the applications of the genome-wide technology on pharmacogenomics of mental illnesses including schizophrenia (SCZ), autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and obsessive compulsive disorder (OCD).

  17. A rat model of post-traumatic stress disorder reproduces the hippocampal deficits seen in the human syndrome

    Directory of Open Access Journals (Sweden)

    Sonal eGoswami

    2012-06-01

    Full Text Available Despite recent progress, the causes and pathophysiology of post-traumatic stress disorder (PTSD remain poorly understood, partly because of ethical limitations inherent to human studies. One approach to circumvent this obstacle is to study PTSD in a valid animal model of the human syndrome. In one such model, extreme and long-lasting behavioral manifestations of anxiety develop in a subset of Lewis rats after exposure to an intense predatory threat that mimics the type of life-and-death situation known to precipitate PTSD in humans. This study aimed to assess whether the hippocampus-associated deficits observed in the human syndrome are reproduced in this rodent model. Prior to predatory threat, different groups of rats were each tested on one of three object recognition memory tasks that varied in the types of contextual clues (i.e. that require the hippocampus or not the rats could use to identify novel items. After task completion, the rats were subjected to predatory threat and, one week later, tested on the elevated plus maze. Based on their exploratory behavior in the plus maze, rats were then classified as resilient or PTSD-like and their performance on the pre-threat object recognition tasks compared. The performance of PTSD-like rats was inferior to that of resilient rats but only when subjects relied on an allocentric frame of reference to identify novel items, a process thought to be critically dependent on the hippocampus. Therefore, these results suggest that even prior to trauma, PTSD-like rats show a deficit in hippocampal-dependent functions, as reported in twin studies of human PTSD.

  18. A rat model of post-traumatic stress disorder reproduces the hippocampal deficits seen in the human syndrome.

    Science.gov (United States)

    Goswami, Sonal; Samuel, Sherin; Sierra, Olga R; Cascardi, Michele; Paré, Denis

    2012-01-01

    Despite recent progress, the causes and pathophysiology of post-traumatic stress disorder (PTSD) remain poorly understood, partly because of ethical limitations inherent to human studies. One approach to circumvent this obstacle is to study PTSD in a valid animal model of the human syndrome. In one such model, extreme and long-lasting behavioral manifestations of anxiety develop in a subset of Lewis rats after exposure to an intense predatory threat that mimics the type of life-and-death situation known to precipitate PTSD in humans. This study aimed to assess whether the hippocampus-associated deficits observed in the human syndrome are reproduced in this rodent model. Prior to predatory threat, different groups of rats were each tested on one of three object recognition memory tasks that varied in the types of contextual clues (i.e., that require the hippocampus or not) the rats could use to identify novel items. After task completion, the rats were subjected to predatory threat and, one week later, tested on the elevated plus maze (EPM). Based on their exploratory behavior in the plus maze, rats were then classified as resilient or PTSD-like and their performance on the pre-threat object recognition tasks compared. The performance of PTSD-like rats was inferior to that of resilient rats but only when subjects relied on an allocentric frame of reference to identify novel items, a process thought to be critically dependent on the hippocampus. Therefore, these results suggest that even prior to trauma PTSD-like rats show a deficit in hippocampal-dependent functions, as reported in twin studies of human PTSD.

  19. Stigmatizing attitudes differ across mental health disorders: a comparison of stigma across eating disorders, obesity, and major depressive disorder.

    Science.gov (United States)

    Ebneter, Daria S; Latner, Janet D

    2013-04-01

    The aim of the current article was to compare stigmatizing attitudes toward eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED), with stigma toward another weight-related condition (obesity) and a non-weight-related mental disorder (major depressive disorder [MDD]). Participants (N = 447) read five vignettes describing a woman with AN, BN, BED, obesity, or MDD and responded to questionnaires examining stigmatizing attitudes. The targets with EDs were blamed more for their condition than the targets with MDD, whereas persons with obesity were held more responsible for their condition than any other target. On the other hand, the target with MDD was perceived as more impaired than any other target. Lack of self-discipline was attributed more to the development of BED and obesity than to any other condition. Stigmatizing attitudes vary across mental health disorders, and future research should aim to specifically target stigmatizing beliefs to reduce and prevent discrimination toward mental health disorders and obesity.

  20. Characteristics of binge eating disorder in relation to diagnostic criteria

    Directory of Open Access Journals (Sweden)

    Wilfley DE

    2016-08-01

    Full Text Available Denise E Wilfley,1 Leslie Citrome,2 Barry K Herman3 1Department of Psychiatry, Washington University School of Medicine, St Louis, MO, 2Department of Psychiatry & Behavioral Sciences, New York Medical College, Valhalla, NY, 3Global Medical Affairs, Shire, Lexington, MA, USA Abstract: The objective of this review was to examine the evidentiary basis for binge eating disorder (BED with reference to the Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition (DSM-5 diagnostic criteria for BED. A PubMed search restricted to titles and abstracts of English-language reviews, meta-analyses, clinical trials, randomized controlled trials, journal articles, and letters using human participants was conducted on August 7, 2015, using keywords that included “binge eating disorder,” DSM-5, DSM-IV, guilt, shame, embarrassment, quantity, psychological, behavior, and “shape and weight concerns.” Of the 257 retrieved publications, 60 publications were considered relevant to discussions related to DSM-5 diagnostic criteria and were included in the current review, and 20 additional references were also included on the basis of the authors’ knowledge and/or on a review of the reference lists from relevant articles obtained through the literature search. Evidence supports the duration/frequency criterion for BED and the primary importance of loss of control and marked distress in identifying individuals with BED. Although overvaluation of shape/weight is not a diagnostic criterion, its relationship to the severity of BED psychopathology may identify a unique subset of individuals with BED. Additionally, individuals with BED often exhibit a clinical profile consisting of psychiatric (eg, mood, obsessive–compulsive, and impulsive disorders and medical (eg, gastrointestinal symptoms, metabolic syndrome, and type 2 diabetes comorbidities and behavioral profiles (eg, overconsumption of calories outside of a binge eating episode and emotional

  1. Animal Models of Speech and Vocal Communication Deficits Associated With Psychiatric Disorders.

    Science.gov (United States)

    Konopka, Genevieve; Roberts, Todd F

    2016-01-01

    Disruptions in speech, language, and vocal communication are hallmarks of several neuropsychiatric disorders, most notably autism spectrum disorders. Historically, the use of animal models to dissect molecular pathways and connect them to behavioral endophenotypes in cognitive disorders has proven to be an effective approach for developing and testing disease-relevant therapeutics. The unique aspects of human language compared with vocal behaviors in other animals make such an approach potentially more challenging. However, the study of vocal learning in species with analogous brain circuits to humans may provide entry points for understanding this human-specific phenotype and diseases. We review animal models of vocal learning and vocal communication and specifically link phenotypes of psychiatric disorders to relevant model systems. Evolutionary constraints in the organization of neural circuits and synaptic plasticity result in similarities in the brain mechanisms for vocal learning and vocal communication. Comparative approaches and careful consideration of the behavioral limitations among different animal models can provide critical avenues for dissecting the molecular pathways underlying cognitive disorders that disrupt speech, language, and vocal communication. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Fluvoxamine in the treatment of anxiety disorders

    OpenAIRE

    Irons, Jane

    2005-01-01

    Fluvoxamine is a selective-serotonin reuptake inhibitor (SSRI) that has proved effective in large double-blind, randomized, controlled trials involving patients with social anxiety disorder (SAD), obsessive-compulsive disorder (OCD), and panic disorder. Improvements have also been demonstrated in patients with post-traumatic stress disorder, as well as those with a range of obsessive-compulsive spectrum disorders including binge eating disorder, bulimia nervosa, pathological gambling, and bod...

  3. A critical role for glycine transporters in hyperexcitability disorders

    Directory of Open Access Journals (Sweden)

    Robert J Harvey

    2008-03-01

    Full Text Available Defects in mammalian glycinergic neurotransmission result in a complex motor disorder characterized by neonatal hypertonia and an exaggerated startle refl ex, known as hyperekplexia (OMIM 149400. This affects newborn children and is characterized by noise or touch-induced seizures that result in muscle stiffness and breath-holding episodes. Although rare, this disorder can have serious consequences, including brain damage and/or sudden infant death. The primary cause of hyperekplexia is missense and nonsense mutations in the glycine receptor (GlyR α1 subunit gene (GLRA1 on chromosome 5q33.1, although we have also discovered rare mutations in the genes encoding the GlyR β subunit (GLRB and the GlyR clustering proteins gephyrin (GPNH and collybistin (ARHGEF9. Recent studies of the Na+ /Cl--dependent glycine transporters GlyT1 and GlyT2 using mouse knockout models and human genetics have revealed that mutations in GlyT2 are a second major cause of hyperekplexia, while the phenotype of the GlyT1 knockout mouse resembles a devastating neurological disorder known as glycine encephalopathy (OMIM 605899. These findings highlight the importance of these transporters in regulating the levels of synaptic glycine.

  4. Characteristics of binge eating disorder in relation to diagnostic criteria

    Science.gov (United States)

    Wilfley, Denise E; Citrome, Leslie; Herman, Barry K

    2016-01-01

    The objective of this review was to examine the evidentiary basis for binge eating disorder (BED) with reference to the Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition (DSM-5) diagnostic criteria for BED. A PubMed search restricted to titles and abstracts of English-language reviews, meta-analyses, clinical trials, randomized controlled trials, journal articles, and letters using human participants was conducted on August 7, 2015, using keywords that included “binge eating disorder,” DSM-5, DSM-IV, guilt, shame, embarrassment, quantity, psychological, behavior, and “shape and weight concerns.” Of the 257 retrieved publications, 60 publications were considered relevant to discussions related to DSM-5 diagnostic criteria and were included in the current review, and 20 additional references were also included on the basis of the authors’ knowledge and/or on a review of the reference lists from relevant articles obtained through the literature search. Evidence supports the duration/frequency criterion for BED and the primary importance of loss of control and marked distress in identifying individuals with BED. Although overvaluation of shape/weight is not a diagnostic criterion, its relationship to the severity of BED psychopathology may identify a unique subset of individuals with BED. Additionally, individuals with BED often exhibit a clinical profile consisting of psychiatric (eg, mood, obsessive–compulsive, and impulsive disorders) and medical (eg, gastrointestinal symptoms, metabolic syndrome, and type 2 diabetes) comorbidities and behavioral profiles (eg, overconsumption of calories outside of a binge eating episode and emotional eating). Future revisions of the BED diagnostic criteria should consider the inclusion of BED subtypes, perhaps based on the overvaluation of shape/weight, and an evidence-based reassessment of severity criteria. PMID:27621631

  5. Acid-Base and Electrolyte Disorders in Patients with and without Chronic Kidney Disease: An Update.

    Science.gov (United States)

    Dhondup, Tsering; Qian, Qi

    2017-12-01

    Kidneys play a pivotal role in the maintenance and regulation of acid-base and electrolyte homeostasis, which is the prerequisite for numerous metabolic processes and organ functions in the human body. Chronic kidney diseases compromise the regulatory functions, resulting in alterations in electrolyte and acid-base balance that can be life-threatening. In this review, we discuss the renal regulations of electrolyte and acid-base balance and several common disorders including metabolic acidosis, alkalosis, dysnatremia, dyskalemia, and dysmagnesemia. Common disorders in chronic kidney disease are also discussed. The most recent and relevant advances on pathophysiology, clinical characteristics, diagnosis, and management of these conditions have been incorporated.

  6. The Perils of "Adjustment Disorder" as a Diagnostic Category

    Science.gov (United States)

    Daniels, John

    2009-01-01

    "Adjustment disorder" occupies a peculiar position in the diagnostic system of the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000) straddling the boundary between normal and abnormal psychology. A more human-centered approach in counseling offers a defense of "normal" adjustment as…

  7. Temporal Assessment of Mental Disorders, Smoking, and Hazardous Drinking in United States Troops Deployed in Support of the Operations in Iraq and Afghanistan

    Science.gov (United States)

    2012-04-26

    drinking may have occurred, since the questionnaire includes only two of ten questions of Alcohol Use Disorders Identification Test (AUDIT).44 The degree...Psychiatric disorders and stages of smoking. Biol Psychiatry. 2004;55(1):69-76. 30. Romberger DJ, Grant K. Alcohol consumption and smoking...from human genetic studies. Mol Psychiatry. 2010;15(6):574-588. 44. Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the

  8. Digested disorder: Quarterly intrinsic disorder digest (January/February/March, 2013).

    Science.gov (United States)

    Uversky, Vladimir N

    2013-01-01

    The current literature on intrinsically disordered proteins is blooming. A simple PubMed search for "intrinsically disordered protein OR natively unfolded protein" returns about 1,800 hits (as of June 17, 2013), with many papers published quite recently. To keep interested readers up to speed with this literature, we are starting a "Digested Disorder" project, which will encompass a series of reader's digest type of publications aiming at the objective representation of the research papers and reviews on intrinsically disordered proteins. The only two criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest covers papers published during the period of January, February and March of 2013. The papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings.

  9. LYMPHOPROLIFERATIVE SYNDROMES ASSOCIATED WITH HUMAN HERPESVIRUS-6A AND HUMAN HERPESVIRUS-6B

    Directory of Open Access Journals (Sweden)

    Eva Eliassen

    2018-05-01

    Full Text Available Human herpesvirus 6A and 6B (HHV-6A and HHV-6B have been noted since their discovery for their T-lymphotropism. Although it has proven difficult to determine the extent to which HHV-6A and HHV-6B are involved in the pathogenesis of many diseases, evidence suggests that primary infection and reactivation of both viruses may induce or contribute to the progression of several lymphoproliferative disorders, ranging from benign to malignant and including infectious mononucleosis-like illness, drug induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS, and nodular sclerosis Hodgkin’s lymphoma. Herein, we discuss the conditions associated with the lymphoproliferative capacity of HHV-6, as well as the potential mechanisms behind them. Continued exploration on this topic may add to our understanding of the interactions between HHV-6 and the immune system and may open the doors to more accurate diagnosis and treatment of certain lymphoproliferative disorders.

  10. Digested disorder: Quarterly intrinsic disorder digest (July-August-September, 2013).

    Science.gov (United States)

    Reddy, Krishna D; DeForte, Shelly; Uversky, Vladimir N

    2014-01-01

    The current literature on intrinsically disordered proteins grows fast. To keep interested readers up to speed with this literature, we continue a "Digested Disorder" project and represent a new issue of reader's digest of the research papers and reviews on intrinsically disordered proteins. The only 2 criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the third quarter of 2013; i.e., during the period of June, July, and September of 2013. Similar to previous issues, the papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings.

  11. New techniques for positron emission tomography in the study of human neurological disorders

    International Nuclear Information System (INIS)

    Kuhl, D.E.

    1989-11-01

    This progress report represents a summary of our performance during the two year period following initial start-up of these research activities at Michigan. Productivity has been excellent; already over 47 papers and abstracts have been published or accepted for publication from this still young program. They represent significant contributions to extending the technology of positron emission tomography in the study of human neurological disorders. Our focus is to develop more cost effective and efficient means for producing new functionally specific tracers and simpler, less expensive, means for acquiring and interpreting quantitative data. These improved processes are required for the future growth of PET as a sophisticated research tool and for the transfer of this technology to clinical use. Our approach concentrates on two separate yet related areas, radiosynthesis and data analysis. In subproject 1, Drs. Jewett and Mulholland have introduced innovative methods for improving 11C and 18F synthetic processes. In Subproject 2, Dr. Hutchins has laid the foundations for an objective analysis of the limitations and opportunities for quantifying regional PET data. In Subproject 3, Dr. Koeppe has extended rapid techniques for parameter estimation in kinetic modeling of new ligands. Finally, in Subproject 4, Dr. Frey has applied kinetic analysis to ligand tracing of the cholinergic neurotransmitter system in animal and human brain. These DOE supported studies have direct impact on clinical research here and elsewhere which is expected to improve diagnosis and treatment of degenerative neurological diseases, mental illness and brain tumors. 47 refs., 7 figs., 4 tabs

  12. Putaminal mosaic visualized by tyrosine hydroxylase immunohistochemistry in the human neostriatum.

    Directory of Open Access Journals (Sweden)

    Ryoma eMorigaki

    2016-04-01

    Full Text Available Among the basal ganglia-thalamocortical circuits, the putamen plays a critical role in the ‘motor’ circuits that control voluntary movements and motor learning. The human neostriatum comprises two functional subdivisions known as the striosome (patch and matrix compartments. Accumulating evidence suggests that compartment-specific dysregulations of dopamine activity might be involved in the disease-specific pathology and symptoms of human striatal diseases including movement disorders. This study was undertaken to examine whether or how striatal dopaminergic innervations are organized into the compartmentalized architecture found in the putamen of adult human brains. For this purpose, we used a highly sensitive immunohistochemistry technique to identify tyrosine hydroxylase (TH, EC 1.14.16.2, a marker for striatal dopaminergic axons and terminals, in formalin-fixed paraffin-embedded tissues obtained from autopsied human brains. Herein, we report that discrete compartmentalization of TH-labeled innervations occurs in the putamen, as in the caudate nucleus, with a higher density of TH labeling in the matrix compared to the striosomes. Our results provide anatomical evidence to support the hypothesis that compartment-specific dysfunction of the striosome-matrix dopaminergic systems might contribute to the genesis of movement disorders.

  13. The Human Bathtub: Safety and Risk Predictions Including the Dynamic Probability of Operator Errors

    International Nuclear Information System (INIS)

    Duffey, Romney B.; Saull, John W.

    2006-01-01

    Reactor safety and risk are dominated by the potential and major contribution for human error in the design, operation, control, management, regulation and maintenance of the plant, and hence to all accidents. Given the possibility of accidents and errors, now we need to determine the outcome (error) probability, or the chance of failure. Conventionally, reliability engineering is associated with the failure rate of components, or systems, or mechanisms, not of human beings in and interacting with a technological system. The probability of failure requires a prior knowledge of the total number of outcomes, which for any predictive purposes we do not know or have. Analysis of failure rates due to human error and the rate of learning allow a new determination of the dynamic human error rate in technological systems, consistent with and derived from the available world data. The basis for the analysis is the 'learning hypothesis' that humans learn from experience, and consequently the accumulated experience defines the failure rate. A new 'best' equation has been derived for the human error, outcome or failure rate, which allows for calculation and prediction of the probability of human error. We also provide comparisons to the empirical Weibull parameter fitting used in and by conventional reliability engineering and probabilistic safety analysis methods. These new analyses show that arbitrary Weibull fitting parameters and typical empirical hazard function techniques cannot be used to predict the dynamics of human errors and outcomes in the presence of learning. Comparisons of these new insights show agreement with human error data from the world's commercial airlines, the two shuttle failures, and from nuclear plant operator actions and transient control behavior observed in transients in both plants and simulators. The results demonstrate that the human error probability (HEP) is dynamic, and that it may be predicted using the learning hypothesis and the minimum

  14. A psychology of the human brain-gut-microbiome axis.

    Science.gov (United States)

    Allen, Andrew P; Dinan, Timothy G; Clarke, Gerard; Cryan, John F

    2017-04-01

    In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain-gut-microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress-related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain-gut-microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain-gut-microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology.

  15. A psychology of the human brain–gut–microbiome axis

    Science.gov (United States)

    Allen, Andrew P.; Dinan, Timothy G.; Clarke, Gerard

    2017-01-01

    Abstract In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain–gut–microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress‐related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain–gut–microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain–gut–microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain–gut–microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain–gut–microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology. PMID:28804508

  16. Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders

    Science.gov (United States)

    Devinsky, Orrin; Cilio, Maria Roberta; Cross, Helen; Fernandez-Ruiz, Javier; French, Jacqueline; Hill, Charlotte; Katz, Russell; Di Marzo, Vincenzo; Jutras-Aswad, Didier; Notcutt, William George; Martinez-Orgado, Jose; Robson, Philip J.; Rohrback, Brian G.; Thiele, Elizabeth; Whalley, Benjamin; Friedman, Daniel

    2015-01-01

    Objective To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regards to their relevance to epilepsy and other selected neuropsychiatric disorders. Methods We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology and data from studies with animal models and human subjects. Results Cannabis has been used to treat disease since ancient times. Δ9-THC is the major psychoactive ingredient and cannabidiol (CBD) is the major non-psychoactive ingredient in cannabis. Cannabis and Δ9-THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. Psychotropic effects of Δ9-THC limit tolerability. CBD is anticonvulsant in many acute animal models but there is limited data in chronic models. The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of melastatin type 8 channel; the 5-HT1a receptor; the α3 and α1 glycine receptors; and the transient receptor potential of ankyrin type 1 channel. CBD has neuroprotective and anti-inflammatory effects. CBD appears to be well tolerated in humans but small and methodologically limited studies of CBD in human epilepsy have been inconclusive. More recent anecdotal reports of high-ratio CBD:Δ9-THC medical marijuana have claimed efficacy, but studies were not controlled. Significance CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction and neonatal hypoxic-ischemic encephalopathy. However, we lack data from well-powered double-blind randomized, controlled studies on the efficacy of pure CBD for any disorder. Initial dose-tolerability and double-blind randomized, controlled studies focusing on target intractable epilepsy populations such as patients with

  17. Somatic Symptom and Related Disorders

    Science.gov (United States)

    ... A headache may mean a brain tumor. Body dysmorphic disorder occurs when a person becomes obsessed with ... body. Common concerns for people who have body dysmorphic disorder include: wrinkles hair loss weight gain size ...

  18. Derivation of HVR1, HVR2 and HVR3 human embryonic stem cell lines from IVF embryos after preimplantation genetic diagnosis (PGD) for monogenic disorder

    OpenAIRE

    Abdelkrim Hmadcha; Yolanda Aguilera; Maria Dolores Lozano-Arana; Nuria Mellado; Javier Sánchez; Cristina Moya; Luis Sánchez-Palazón; Jose Palacios; Guillermo Antiñolo; Bernat Soria

    2016-01-01

    From 106 human blastocyts donate for research after in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD) for monogenetic disorder, 3 human embryonic stem cells (hESCs) HVR1, HVR2 and HVR3 were successfully derived. HVR1 was assumed to be genetically normal, HVR2 carrying Becker muscular dystrophy and HVR3 Hemophilia B. Despite the translocation t(9;15)(q34.3;q14) detected in HVR2, all the 3 cell lines were characterised in vitro and in vivo as normal hESCs lines and were r...

  19. Functional disorders of the anus and rectum

    OpenAIRE

    Whitehead, W; Wald, A; Diamant, N; Enck, P; Pemberton, J; Rao, S

    1999-01-01

    In this report the functional anorectal disorders, the etiology of which is currently unknown or related to the abnormal functioning of normally innervated and structurally intact muscles, are discussed. These disorders include functional fecal incontinence, functional anorectal pain, including levator ani syndrome and proctalgia fugax, and pelvic floor dyssynergia. The epidemiology of each disorder is defined and discussed, their pathophysiology is summarized and diagnostic approaches and tr...

  20. The Right to Die in Chronic Disorders of Consciousness: Can We Avoid the Slippery Slope Argument?

    Science.gov (United States)

    Calabrò, Rocco Salvatore; Naro, Antonino; De Luca, Rosaria; Russo, Margherita; Caccamo, Lory; Manuli, Alfredo; Bramanti, Alessia; Bramanti, Placido

    2016-01-01

    Managing individuals with chronic disorders of consciousness raises ethical questions about the appropriateness of maintaining life-sustaining treatments and end-of-life decisions for those who are unable to make decisions for themselves. For many years, the positions fostering the "sanctity" of human life (i.e., life is inviolable in any case) have led to maintaining life-sustaining treatments (including artificial nutrition and hydration) in patients with disorders of consciousness, allowing them to live for as long as possible. Seldom have positions that foster "dignity" of human life (i.e., everyone has the right to a worthy death) allowed for the interruption of life-sustaining treatments in some patients with disorders of consciousness. Indeed, most ethical analyses conclude that the decision to interrupt life-sustaining therapies, including artificial nutrition and hydration, should be guided by reliable information about how the patient wants or wanted to be treated and/or whether the patient wants or wanted to live in such a condition. This would be in keeping with the principles of patient-centered medicine, and would conciliate the duty of respecting both the dignity and sanctity of life and the right to a worthy death. This "right to die" has been recognized in some countries, which have legalized euthanasia and/or physician-assisted suicide, but some groups fear that legalizing end-of-life decisions for some patients may result in the inappropriate use of euthanasia, both voluntary and nonvoluntary forms (slippery slope argument) in other patients. This review describes the current opinions and ethical issues concerning end-of-life decisions in patients with disorders of consciousness, with a focus on the impact misdiagnoses of disorders of consciousness may have on end-of-life decisions, the concept of "dignity" and "sanctity" of human life in view of end-of-life decisions, and the risk of the slippery slope argument when dealing with euthanasia and

  1. Ghrelin-derived peptides: a link between appetite/reward, GH axis and psychiatric disorders ?

    Directory of Open Access Journals (Sweden)

    Alexandra eLabarthe

    2014-10-01

    Full Text Available Psychiatric disorders are often associated with metabolic and hormonal alterations, including obesity, diabetes, metabolic syndrome as well as modifications in several biological rhythms including appetite, stress, sleep-wake cycles and secretion of their corresponding endocrine regulators.Among the gastrointestinal hormones that regulate appetite and adapt the metabolism in response to nutritional, hedonic and emotional dysfunctions, at the interface between endocrine, metabolic and psychiatric disorders, ghrelin plays a unique role as the only one increasing appetite. The secretion of ghrelin is altered in several psychiatric disorders (anorexia, schizophrenia as well as in metabolic disorders (obesity and in animal models in response to emotional triggers (psychological stress, …. but the relationship between these modifications and the physiopathology of psychiatric disorders remains unclear. Recently, a large literature showed that this key metabolic/endocrine regulator is involved in stress and reward-oriented behaviors and regulates anxiety and mood. In addition, preproghrelin is a complex prohormone but the roles of the other ghrelin-derived peptides, thought to act as functional ghrelin antagonists, are largely unknown. Altered ghrelin secretion and/or signaling in psychiatric diseases are thought to participate in altered appetite, hedonic response and reward. Whether this can contribute to the mechanism responsible for the development of the disease or can help to minimize some symptoms associated with these psychiatric disorders is discussed in the present review. We will thus describe 1 the biological actions of ghrelin and ghrelin-derived peptides on food and drugs reward, anxiety and depression, and the physiological consequences of ghrelin invalidation on these parameters, 2 how ghrelin and ghrelin-derived peptides are regulated in animal models of psychiatric diseases and in human psychiatric disorders in relation with the GH

  2. Auditory-Motor Interactions in Pediatric Motor Speech Disorders: Neurocomputational Modeling of Disordered Development

    Science.gov (United States)

    Terband, H.; Maassen, B.; Guenther, F.H.; Brumberg, J.

    2014-01-01

    Background/Purpose Differentiating the symptom complex due to phonological-level disorders, speech delay and pediatric motor speech disorders is a controversial issue in the field of pediatric speech and language pathology. The present study investigated the developmental interaction between neurological deficits in auditory and motor processes using computational modeling with the DIVA model. Method In a series of computer simulations, we investigated the effect of a motor processing deficit alone (MPD), and the effect of a motor processing deficit in combination with an auditory processing deficit (MPD+APD) on the trajectory and endpoint of speech motor development in the DIVA model. Results Simulation results showed that a motor programming deficit predominantly leads to deterioration on the phonological level (phonemic mappings) when auditory self-monitoring is intact, and on the systemic level (systemic mapping) if auditory self-monitoring is impaired. Conclusions These findings suggest a close relation between quality of auditory self-monitoring and the involvement of phonological vs. motor processes in children with pediatric motor speech disorders. It is suggested that MPD+APD might be involved in typically apraxic speech output disorders and MPD in pediatric motor speech disorders that also have a phonological component. Possibilities to verify these hypotheses using empirical data collected from human subjects are discussed. PMID:24491630

  3. Body Image, Media, and Eating Disorders

    Science.gov (United States)

    Derenne, Jennifer L.; Beresin, Eugene V.

    2006-01-01

    Objective: Eating disorders, including obesity, are a major public health problem today. Throughout history, body image has been determined by various factors, including politics and media. Exposure to mass media (television, movies, magazines, Internet) is correlated with obesity and negative body image, which may lead to disordered eating. The…

  4. Acupuncture for Alcohol Use Disorder: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Na Young Shin

    2017-01-01

    Full Text Available Empirical research has produced mixed results regarding the effects of acupuncture on the treatment of alcohol use disorder in humans. Few studies have provided a comprehensive review or a systematic overview of the magnitude of the treatment effect of acupuncture on alcoholism. This study investigated the effects of acupuncture on alcohol-related symptoms and behaviors in patients with this disorder. The PubMed database was searched until 23 August 2016, and reference lists from review studies were also reviewed. Seventeen studies were identified for a full-text inspection, and seven (243 patients of these met our inclusion criteria. The outcomes assessed at the last posttreatment point and any available follow-up data were extracted from each of the studies. Our meta-analysis demonstrated that an acupuncture intervention had a stronger effect on reducing alcohol-related symptoms and behaviors than did the control intervention (g=0.67. A beneficial but weak effect of acupuncture treatment was also found in the follow-up data (g=0.29. Although our analysis showed a significant difference between acupuncture and the control intervention in patients with alcohol use disorder, this meta-analysis is limited by the small number of studies included. Thus, a larger cohort study is required to provide a firm conclusion.

  5. Normal Stress or Adjustment Disorder?

    Science.gov (United States)

    ... disorder is a type of stress-related mental illness that can affect your feelings, thoughts and behaviors. Signs and symptoms of an adjustment disorder can include: Anxiety Poor school or work performance Relationship problems Sadness ...

  6. Role of the endocannabinoid system in human brain functions relevant for psychiatric disorders

    NARCIS (Netherlands)

    Bossong, M.G.

    2012-01-01

    Impaired cognitive function is a fundamental characteristic of many psychiatric and neurological disorders such as schizophrenia or Alzheimer’s disease. The endocannabinoid (eCB) system, consisting of cannabinoid receptors and accompanying ligands, has been implicated in these disorders. In

  7. Structural Disorder Provides Increased Adaptability for Vesicle Trafficking Pathways

    Science.gov (United States)

    Tompa, Peter

    2013-01-01

    Vesicle trafficking systems play essential roles in the communication between the organelles of eukaryotic cells and also between cells and their environment. Endocytosis and the late secretory route are mediated by clathrin-coated vesicles, while the COat Protein I and II (COPI and COPII) routes stand for the bidirectional traffic between the ER and the Golgi apparatus. Despite similar fundamental organizations, the molecular machinery, functions, and evolutionary characteristics of the three systems are very different. In this work, we compiled the basic functional protein groups of the three main routes for human and yeast and analyzed them from the structural disorder perspective. We found similar overall disorder content in yeast and human proteins, confirming the well-conserved nature of these systems. Most functional groups contain highly disordered proteins, supporting the general importance of structural disorder in these routes, although some of them seem to heavily rely on disorder, while others do not. Interestingly, the clathrin system is significantly more disordered (∼23%) than the other two, COPI (∼9%) and COPII (∼8%). We show that this structural phenomenon enhances the inherent plasticity and increased evolutionary adaptability of the clathrin system, which distinguishes it from the other two routes. Since multi-functionality (moonlighting) is indicative of both plasticity and adaptability, we studied its prevalence in vesicle trafficking proteins and correlated it with structural disorder. Clathrin adaptors have the highest capability for moonlighting while also comprising the most highly disordered members. The ability to acquire tissue specific functions was also used to approach adaptability: clathrin route genes have the most tissue specific exons encoding for protein segments enriched in structural disorder and interaction sites. Overall, our results confirm the general importance of structural disorder in vesicle trafficking and

  8. Symptom patterns in dissociative identity disorder patients and the general population.

    Science.gov (United States)

    Ross, Colin A; Ness, Laura

    2010-01-01

    The authors used the Dissociative Disorders Interview Schedule to compare structured interview symptom patterns in a general population sample (N= 502) and a sample of patients with clinical diagnoses of dissociative identity disorder (N= 303). Based on the Trauma Model, the authors predicted that the patterns would be similar in the 2 samples and that symptom scores would be higher in participants reporting childhood sexual abuse in both samples. They predicted that symptom scores would be higher among women with dissociative identity disorder reporting sexual abuse than among women in the general population reporting sexual abuse, with the clinical sample reporting more severe abuse. These predictions were supported by the data. The authors conclude that symptom patterns in dissociative identity disorder are typical of the normal human response to severe, chronic childhood trauma and have ecological validity for the human race in general.

  9. Attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Meek, D C

    1990-09-01

    The attention-deficit hyperactivity disorder is a common chronic disorder of childhood. No precise definition or approach to treatment is universally accepted; however, an extensive literature exists on which to base a rational approach to management. Symptomatic treatment with stimulant medication in selected patients is effective and safe, but not curative. Successful outcome depends on multimodality therapy, involving parents, teachers, and other professionals. Associated conditions, including learning disorders and emotional disturbance, must be identified and dealt with.

  10. The eye as a window to rare endocrine disorders

    Science.gov (United States)

    Chopra, Rupali; Chander, Ashish; Jacob, Jubbin J.

    2012-01-01

    The human eye, as an organ, can offer critical clues to the diagnosis of various systemic illnesses. Ocular changes are common in various endocrine disorders such as diabetes mellitus and Graves’ disease. However there exist a large number of lesser known endocrine disorders where ocular involvement is significant. Awareness of these associations is the first step in the diagnosis and management of these complex patients. The rare syndromes involving the pituitary hypothalamic axis with significant ocular involvement include Septo-optic dysplasia, Kallman's syndrome, and Empty Sella syndrome all affecting the optic nerve at the optic chiasa. The syndromes involving the thyroid and parathyroid glands that have ocular manifestations and are rare include Mc Cune Albright syndrome wherein optic nerve decompression may occur due to fibrous dysplasia, primary hyperparathyroidism that may present as red eye due to scleritis and Ascher syndrome wherein ptosis occurs. Allgrove's syndrome, Cushing's disease, and Addison's disease are the rare endocrine syndromes discussed involving the adrenals and eye. Ocular involvement is also seen in gonadal syndromes such as Bardet Biedl, Turner's, Rothmund's, and Klinefelter's syndrome. This review also highlights the ocular manifestation of miscellaneous syndromes such as Werner's, Cockayne's, Wolfram's, Kearns Sayre's, and Autoimmune polyendocrine syndrome. The knowledge of these relatively uncommon endocrine disorders and their ocular manifestations will help an endocrinologist reach a diagnosis and will alert an ophthalmologist to seek specialty consultation of an endocrinologist when encountered with such cases. PMID:22629495

  11. Attention Deficit Hyperactivity Disorder in Preschool-Age Children.

    Science.gov (United States)

    Tandon, Mini; Pergjika, Alba

    2017-07-01

    Attention deficit hyperactivity disorder is a neurodevelopmental disorder marked by age-inappropriate deficits in attention or hyperactivity/impulsivity that interfere with functioning or development. It is highly correlated with other disorders, such as oppositional defiant disorder, conduct disorder, and mood symptoms. The etiology is multifactorial, and neuroimaging findings are nonspecific. Although assessment tools exist, there is variability among them, and historically, parent-teacher agreement has not been consistent. Treatment algorithm for attention deficit hyperactivity disorder in preschoolers includes behavioral interventions first followed by psychopharmacologic treatment when behavioral therapies fail. Other nonpharmacologic and nonbehavioral interventions are discussed including the role of exercise and nutrition. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Abundance of intrinsic structural disorder in the histone H1 subtypes.

    Science.gov (United States)

    Kowalski, Andrzej

    2015-12-01

    The intrinsically disordered proteins consist of partially structured regions linked to the unstructured stretches, which consequently form the transient and dynamic conformational ensembles. They undergo disorder to order transition upon binding their partners. Intrinsic disorder is attributed to histones H1, perceived as assemblers of chromatin structure and the regulators of DNA and proteins activity. In this work, the comparison of intrinsic disorder abundance in the histone H1 subtypes was performed both by the analysis of their amino acid composition and by the prediction of disordered stretches, as well as by identifying molecular recognition features (MoRFs) and ANCHOR protein binding regions (APBR) that are responsible for recognition and binding. Both human and model organisms-animals, plants, fungi and protists-have H1 histone subtypes with the properties typical of disordered state. They possess a significantly higher content of hydrophilic and charged amino acid residues, arranged in the long regions, covering over half of the whole amino acid residues in chain. Almost complete disorder corresponds to histone H1 terminal domains, including MoRFs and ANCHOR. Those motifs were also identified in a more ordered histone H1 globular domain. Compared to the control (globular and fibrous) proteins, H1 histones demonstrate the increased folding rate and a higher proportion of low-complexity segments. The results of this work indicate that intrinsic disorder is an inherent structural property of histone H1 subtypes and it is essential for establishing a protein conformation which defines functional outcomes affecting on DNA- and/or partner protein-dependent cell processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Connectomic intermediate phenotypes for psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Alex eFornito

    2012-04-01

    Full Text Available Psychiatric disorders are phenotypically heterogeneous entities with a complex genetic basis. To mitigate this complexity, many investigators study so-called intermediate phenotypes that putatively provide a more direct index of the physiological effects of candidate genetic risk variants than overt psychiatric syndromes. Magnetic resonance imaging (MRI is a particularly popular technique for measuring such phenotypes because it allows interrogation of diverse aspects of brain structure and function in vivo. Much of this work however, has focused on relatively simple measures that quantify variations in the physiology or tissue integrity of specific brain regions in isolation, contradicting an emerging consensus that most major psychiatric disorders do not arise from isolated dysfunction in one or a few brain regions, but rather from disturbed interactions within and between distributed neural circuits; i.e., they are disorders of brain connectivity. The recent proliferation of new MRI techniques for comprehensively mapping the entire connectivity architecture of the brain, termed the human connectome, has provided a rich repertoire of tools for understanding how genetic variants implicated in mental disorder impact distinct neural circuits. In this article, we review research using these connectomic techniques to understand how genetic variation influences the connectivity and topology of human brain networks. We highlight recent evidence from twin and imaging genetics studies suggesting that the penetrance of candidate risk variants for mental illness, such as those in SLC6A4, MAOA, ZNF804A and APOE, may be higher for intermediate phenotypes characterised at the level of distributed neural systems than at the level of spatially localised brain regions. The findings indicate that imaging connectomics provides a powerful framework for understanding how genetic risk for psychiatric disease is expressed through altered structure and function of

  14. Differences in clinical presentation between bipolar I and II disorders in the early stages of bipolar disorder

    DEFF Research Database (Denmark)

    Vinberg, Maj; Mikkelsen, Rie Lambaek; Kirkegaard, Thomas

    2017-01-01

    Aim In a naturalistic clinical study of patients in the early stages of bipolar disorders the aim was to assess differences between patients with bipolar I (BD I) and bipolar II (BD II) disorders on clinical characteristics including affective symptoms, subjective cognitive complaints, functional...... level, the presence of comorbid personality disorders and coping strategies. Methods Diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Disorders. Clinical symptoms were rated with the Young Mania Rating Scale and the Hamilton Depression Rating Scale, and functional status using...... Inventory for Stressful Situations. Results In total, 344 patients were included (BD I (n=163) and BD II (n=181). Patients with BD II presented with significantly more depressive symptoms, more cognitive complaints, lower overall functioning, and a higher prevalence of comorbid personality disorders...

  15. Resveratrol, Potential Therapeutic Interest in Joint Disorders: A Critical Narrative Review

    Directory of Open Access Journals (Sweden)

    Christelle Nguyen

    2017-01-01

    Full Text Available Trans-resveratrol (t-Res is a natural compound of a family of hydroxystilbenes found in a variety of spermatophyte plants. Because of its effects on lipids and arachidonic acid metabolisms, and its antioxidant activity, t-Res is considered as the major cardioprotective component of red wine, leading to the “French Paradox” health concept. In the past decade, research on the effects of resveratrol on human health has developed considerably in diverse fields such as cancer, neurodegenerative and cardiovascular diseases, and metabolic disorders. In the field of rheumatic disorders, in vitro evidence suggest anti-inflammatory, anti-catabolic, anti-apoptotic and anti-oxidative properties of t-Res in various articular cell types, including chondrocytes and synoviocytes, along with immunomodulation properties on T and B lymphocytes. In preclinical models of osteoarthritis and rheumatoid arthritis, resveratrol has shown joint protective effects, mainly mediated by decreased production of pro-inflammatory and pro-degradative soluble factors, and modulation of cellular and humoral responses. Herein, we comprehensively reviewed evidence supporting a potential therapeutic interest of t-Res in treating symptoms related to rheumatic disorders.

  16. Interactions between bipolar disorder and antisocial personality disorder in trait impulsivity and severity of illness.

    Science.gov (United States)

    Swann, A C; Lijffijt, M; Lane, S D; Steinberg, J L; Moeller, F G

    2010-06-01

    We investigated trait impulsivity in bipolar disorder and antisocial personality disorder (ASPD) with respect to severity and course of illness. Subjects included 78 controls, 34 ASPD, 61 bipolar disorder without Axis II disorder, and 24 bipolar disorder with ASPD, by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (SCID-I and -II). Data were analyzed using general linear model and probit analysis. Barratt Impulsiveness Scale (BIS-11) scores were higher in ASPD (effect sizes 0.5-0.8) or bipolar disorder (effect size 1.45) than in controls. Subjects with both had more suicide attempts and previous episodes than bipolar disorder alone, and more substance-use disorders and suicide attempts than ASPD alone. BIS-11 scores were not related to severity of crimes. Impulsivity was higher in bipolar disorder with or without ASPD than in ASPD alone, and higher in ASPD than in controls. Adverse effects of bipolar disorder in ASPD, but not of ASPD in bipolar disorder, were accounted for by increased impulsivity.

  17. Co-morbid anxiety disorders in bipolar disorder and major depression: familial aggregation and clinical characteristics of co-morbid panic disorder, social phobia, specific phobia and obsessive-compulsive disorder.

    Science.gov (United States)

    Goes, F S; McCusker, M G; Bienvenu, O J; Mackinnon, D F; Mondimore, F M; Schweizer, B; Depaulo, J R; Potash, J B

    2012-07-01

    Co-morbidity of mood and anxiety disorders is common and often associated with greater illness severity. This study investigates clinical correlates and familiality of four anxiety disorders in a large sample of bipolar disorder (BP) and major depressive disorder (MDD) pedigrees. The sample comprised 566 BP families with 1416 affected subjects and 675 MDD families with 1726 affected subjects. Clinical characteristics and familiality of panic disorder, social phobia, specific phobia and obsessive-compulsive disorder (OCD) were examined in BP and MDD pedigrees with multivariate modeling using generalized estimating equations. Co-morbidity between mood and anxiety disorders was associated with several markers of clinical severity, including earlier age of onset, greater number of depressive episodes and higher prevalence of attempted suicide, when compared with mood disorder without co-morbid anxiety. Familial aggregation was found with co-morbid panic and OCD in both BP and MDD pedigrees. Specific phobia showed familial aggregation in both MDD and BP families, although the findings in BP were just short of statistical significance after adjusting for other anxiety co-morbidities. We found no evidence for familiality of social phobia. Our findings suggest that co-morbidity of MDD and BP with specific anxiety disorders (OCD, panic disorder and specific phobia) is at least partly due to familial factors, which may be of relevance to both phenotypic and genetic studies of co-morbidity.

  18. Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Yamasaki Nobuyuki

    2008-09-01

    Full Text Available Abstract Elucidating the neural and genetic factors underlying psychiatric illness is hampered by current methods of clinical diagnosis. The identification and investigation of clinical endophenotypes may be one solution, but represents a considerable challenge in human subjects. Here we report that mice heterozygous for a null mutation of the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha-CaMKII+/- have profoundly dysregulated behaviours and impaired neuronal development in the dentate gyrus (DG. The behavioral abnormalities include a severe working memory deficit and an exaggerated infradian rhythm, which are similar to symptoms seen in schizophrenia, bipolar mood disorder and other psychiatric disorders. Transcriptome analysis of the hippocampus of these mutants revealed that the expression levels of more than 2000 genes were significantly changed. Strikingly, among the 20 most downregulated genes, 5 had highly selective expression in the DG. Whereas BrdU incorporated cells in the mutant mouse DG was increased by more than 50 percent, the number of mature neurons in the DG was dramatically decreased. Morphological and physiological features of the DG neurons in the mutants were strikingly similar to those of immature DG neurons in normal rodents. Moreover, c-Fos expression in the DG after electric footshock was almost completely and selectively abolished in the mutants. Statistical clustering of human post-mortem brains using 10 genes differentially-expressed in the mutant mice were used to classify individuals into two clusters, one of which contained 16 of 18 schizophrenic patients. Nearly half of the differentially-expressed probes in the schizophrenia-enriched cluster encoded genes that are involved in neurogenesis or in neuronal migration/maturation, including calbindin, a marker for mature DG neurons. Based on these results, we propose that an "immature DG" in adulthood might induce alterations in behavior and

  19. Personality Disorder in Adult Attention-Deficit/Hyperactivity Disorder: Attrition and Change During Long-term Treatment.

    Science.gov (United States)

    Gift, Thomas E; Reimherr, Frederick W; Marchant, Barrie K; Steans, Tammy A; Wender, Paul H

    2016-05-01

    Personality disorders (PDs) are commonly found in adults with attention-deficit/hyperactivity disorder (ADHD) and are associated with increased ADHD symptoms and psychosocial impairment. To assess the impact of PDs or personality traits on retention rates in ADHD trials and whether treating ADHD affects the expression of PD, data were analyzed from 2 methylphenidate trials. Assessment of PDs and personality traits included using the Wisconsin Personality Disorders Inventory IV and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Personality Disorders. Attention-deficit/hyperactivity disorder symptoms were evaluated using the Wender-Reimherr Adult Attention Deficit Disorder Scale. Major findings were that subjects with cluster A, cluster B, passive-aggressive, or more than 1 PD showed more attrition. Subjects dropping out also had more schizoid and narcissistic traits. Attention-deficit/hyperactivity disorder symptoms (p Disorders Inventory IV items that improved most, 8 resembled ADHD or oppositional defiant disorder symptoms.

  20. Macro Ergonomics Interventions and their Impact on Productivity and Reduction of Musculoskeletal disorders: Including a Case Study

    Directory of Open Access Journals (Sweden)

    N Sadra Abarqhouei

    2012-11-01

    Full Text Available   Background and aims : The present studies show that the theoretical discussions and the applications of ergonomics have not been seriously handled in our country, Iran. So, the aim of the current study was to present an appropriate method which could help in increasing the productivity and decreasing the risk factors of ergonomics in socio-technical systems.   Methods: During the present study, a theoretical model was developed to guide the “ergonomic intervention processes” and its evaluation and application was carried out for an educational organization (EO. The faculty members were selected as the subjects of statistical survey and simple random sampling was performed. The level of musculoskeletal disorders was evaluated in control and treatment groups. Comparative analysis of the obtained data was carried out using fuzzy numbers and their level of confinement.   Results: According to the results of present study with the help of ergonomic interventions, an increase in the activity of staff members, increased revenue, expansion of work with the least number of manpower and a decrease in the overall expenses was seen as compared to the base year. In addition, the analysis of questionnaires with fuzzy approach has shown that the level of musculoskeletal disorders in the experimental group was less as compared to that of control group.   Conclusion: The results obtained by the use of macro and micro ergonomic interventions (Total ergonomics have proved that these methods were successful by increasing the innovation and motivation of the staff members to solve the organizational problems as compared to the base year. The decrease of musculoskeletal disorders among the members resulted to an increase of performance in different units of the educational organization.  

  1. [Adult attention deficit/hyperactivity disorder, associated symptoms and comorbid psychiatric disorders: diagnosis and pharmacological treatment].

    Science.gov (United States)

    Paslakis, G; Schredl, M; Alm, B; Sobanski, E

    2013-08-01

    Adult attention deficit/hyperactivity disorder (ADHD) is characterised by inattention and/or hyperactivity and impulsivity and is a frequent psychiatric disorder with childhood onset. In addition to core symptoms, patients often experience associated symptoms like emotional dysregulation or low self-esteem and suffer from comorbid disorders, particularly depressive episodes, substance abuse, anxiety or sleep disorders. It is recommended to include associated symptoms and comorbid psychiatric disorders in the diagnostic set-up and in the treatment plan. Comorbid psychiatric disorders should be addressed with disorder-specific therapies while associated symptoms also often improve with treatment of the ADHD core symptoms. The most impairing psychiatric disorder should be treated first. This review presents recommendations for differential diagnosis and treatment of adult ADHD with associated symptoms and comorbid psychiatric disorders with respect to internationally published guidelines, clinical trials and expert opinions. © Georg Thieme Verlag KG Stuttgart · New York.

  2. The size and burden of mental disorders and other disorders of the brain in Europe 2010.

    Science.gov (United States)

    Wittchen, H U; Jacobi, F; Rehm, J; Gustavsson, A; Svensson, M; Jönsson, B; Olesen, J; Allgulander, C; Alonso, J; Faravelli, C; Fratiglioni, L; Jennum, P; Lieb, R; Maercker, A; van Os, J; Preisig, M; Salvador-Carulla, L; Simon, R; Steinhausen, H-C

    2011-09-01

    To provide 12-month prevalence and disability burden estimates of a broad range of mental and neurological disorders in the European Union (EU) and to compare these findings to previous estimates. Referring to our previous 2005 review, improved up-to-date data for the enlarged EU on a broader range of disorders than previously covered are needed for basic, clinical and public health research and policy decisions and to inform about the estimated number of persons affected in the EU. Stepwise multi-method approach, consisting of systematic literature reviews, reanalyses of existing data sets, national surveys and expert consultations. Studies and data from all member states of the European Union (EU-27) plus Switzerland, Iceland and Norway were included. Supplementary information about neurological disorders is provided, although methodological constraints prohibited the derivation of overall prevalence estimates for mental and neurological disorders. Disease burden was measured by disability adjusted life years (DALY). Prevalence: It is estimated that each year 38.2% of the EU population suffers from a mental disorder. Adjusted for age and comorbidity, this corresponds to 164.8million persons affected. Compared to 2005 (27.4%) this higher estimate is entirely due to the inclusion of 14 new disorders also covering childhood/adolescence as well as the elderly. The estimated higher number of persons affected (2011: 165m vs. 2005: 82m) is due to coverage of childhood and old age populations, new disorders and of new EU membership states. The most frequent disorders are anxiety disorders (14.0%), insomnia (7.0%), major depression (6.9%), somatoform (6.3%), alcohol and drug dependence (>4%), ADHD (5%) in the young, and dementia (1-30%, depending on age). Except for substance use disorders and mental retardation, there were no substantial cultural or country variations. Although many sources, including national health insurance programs, reveal increases in sick leave

  3. Radiological protection of the environment, including non-human species-views from the global nuclear industry

    International Nuclear Information System (INIS)

    Saint-Pierre, S.; RPWG

    2008-01-01

    This paper updates the WNA key messages on the RP of the environment. This paper shows that the chronology of views (2000-2008) leads to a recognition that the current RP system has provided adequate protection of people and of the environment. In early 2000s, doubts were raised on the adequacy of the RP system. Next (2002-2005), the international community forged the view that the current RP system has in practice provided appropriate standards of environmental protection, but also acknowledged that the system needs further development to fill a 'conceptual gap'. In 2005, the IAEA plan of activities on the RP of the environment formalized international developments and conditioned the future revision (if any) of current standards. During 2006-2008, ICRP issued new guidance on RP of non-human species which offers little on an assessment framework of practical use and on a compelling case for such assessments. This guidance, based on the new ICRP concept of Reference Animals and Plants, falls short in terms of environmental protection approach. A milestone study on the RP of non-human species is the SENES independent overview (2007) which 'confirmed that both people and nature have been adequately protected from radioactive releases from all kinds of nuclear sites, old and new'. This overview covers case studies for nuclear sites including some that had experienced major accidents. It derives that the earlier acknowledgement on the 'conceptual gap' appears no longer valid or at the very least, that the gap (if any) is extremely small. The RP of the environment is part of the on-going revision of the current IAEA Basic Safety Standards (BSS). We emphasize that the recently published BSS draft 1.0 in July 2008 covers (with adequacy) RP of the environment through general provisions (free of provisions to non-human species) on the assessment of environmental impact. (author)

  4. Human Cytomegalovirus Infection in Children with Tic Disorders%巨细胞病毒感染在抽动障碍中的临床意义初探

    Institute of Scientific and Technical Information of China (English)

    匡桂芳; 贺莉娜; 蒋玉红; 邓萍

    2001-01-01

    目的:探讨人巨细胞病毒(human cytomegalovirus,HCMV)感染在抽动障碍中的临床意义。方法:应用PCR基因扩增技术对66例抽动障碍患儿进行血液HCMV检测,并测定74例正常儿童作为对照。结果:抽动障碍患儿HCMV检出阳性率(26%)明显高于对照组(3%),差异有显著性(p<0.01),抽动障碍三种类型间HCMV感染阳性率无显著性差异(p>0.05)。结论:HCMV感染与抽动障碍发病有关。%Objective: To explore the situation of human cytomegalovirus (HCMV) infection in children with tic disorders. Method: The HCMV were determined in blood sample taken from 66 cases of tic disorders by polymerase chain reaction (PCR), while 74 normal children were tested either as control. Results: The positive rate in tic group (26%) was significantly higher than that of control (3%, p<0.01). There was no difference of this rate among the 3 subtypes of tic disorders. Conclusion: HCMV infection is more common in children with tic disorders and has no difference among the three subtypes.

  5. Transcription factor SP4 is a susceptibility gene for bipolar disorder.

    Directory of Open Access Journals (Sweden)

    Xianjin Zhou

    Full Text Available The Sp4 transcription factor plays a critical role for both development and function of mouse hippocampus. Reduced expression of the mouse Sp4 gene results in a variety of behavioral abnormalities relevant to human psychiatric disorders. The human SP4 gene is therefore examined for its association with both bipolar disorder and schizophrenia in European Caucasian and Chinese populations respectively. Out of ten SNPs selected from human SP4 genomic locus, four displayed significant association with bipolar disorder in European Caucasian families (rs12668354, p = 0.022; rs12673091, p = 0.0005; rs3735440, p = 0.019; rs11974306, p = 0.018. To replicate the genetic association, the same set of SNPs was examined in a Chinese bipolar case control sample. Four SNPs displayed significant association (rs40245, p = 0.009; rs12673091, p = 0.002; rs1018954, p = 0.001; rs3735440, p = 0.029, and two of them (rs12673091, rs3735440 were shared with positive SNPs from European Caucasian families. Considering the genetic overlap between bipolar disorder and schizophrenia, we extended our studies in Chinese trios families for schizophrenia. The SNP7 (rs12673091, p = 0.012 also displayed a significant association. The SNP7 (rs12673091 was therefore significantly associated in all three samples, and shared the same susceptibility allele (A across all three samples. On the other hand, we found a gene dosage effect for mouse Sp4 gene in the modulation of sensorimotor gating, a putative endophenotype for both schizophrenia and bipolar disorder. The deficient sensorimotor gating in Sp4 hypomorphic mice was partially reversed by the administration of dopamine D2 antagonist or mood stabilizers. Both human genetic and mouse pharmacogenetic studies support Sp4 gene as a susceptibility gene for bipolar disorder or schizophrenia. The studies on the role of Sp4 gene in hippocampal development may provide novel insights for the contribution of hippocampal abnormalities in these

  6. Scientific and ethical issues related to deep brain stimulation for disorders of mood, behavior, and thought.

    Science.gov (United States)

    Rabins, Peter; Appleby, Brian S; Brandt, Jason; DeLong, Mahlon R; Dunn, Laura B; Gabriëls, Loes; Greenberg, Benjamin D; Haber, Suzanne N; Holtzheimer, Paul E; Mari, Zoltan; Mayberg, Helen S; McCann, Evelyn; Mink, Sallie P; Rasmussen, Steven; Schlaepfer, Thomas E; Vawter, Dorothy E; Vitek, Jerrold L; Walkup, John; Mathews, Debra J H

    2009-09-01

    A 2-day consensus conference was held to examine scientific and ethical issues in the application of deep brain stimulation for treating mood and behavioral disorders, such as major depression, obsessive-compulsive disorder, and Tourette syndrome. The primary objectives of the conference were to (1) establish consensus among participants about the design of future clinical trials of deep brain stimulation for disorders of mood, behavior, and thought and (2) develop standards for the protection of human subjects participating in such studies. Conference participants identified 16 key points for guiding research in this growing field. The adoption of the described guidelines would help to protect the safety and rights of research subjects who participate in clinical trials of deep brain stimulation for disorders of mood, behavior, and thought and have further potential to benefit other stakeholders in the research process, including clinical researchers and device manufactures. That said, the adoption of the guidelines will require broad and substantial commitment from many of these same stakeholders.

  7. Experience of an eating disorders out-patient program in an internal medicine hospital.

    Science.gov (United States)

    García-García, Eduardo; Rocha-Velis, Ingrid; Vázquez-Velázquez, Verónica; Kaufer-Horwitz, Martha; Reynoso, Ricardo; Méndez, Juan Pablo

    2013-12-01

    The aim of this study was to develop a successful low budget out-patient program, in an internal medicine hospital, for patients presenting eating disorders in an emerging nation. A total of 144 patients were included in a 6 month intervention centered in medical support, with fortnightly medical consultations, monthly counseling by a nutritionist and by a psychiatrist and three psycho-educational courses. The Three Factor Eating Questionnaire and the Eating Disorders Inventory-2 were performed at the beginning and at the end of the study. After 6 months, more than half of the patients who completed the intervention were on remission. Substantial improvement was observed regarding the scores of both instruments after completion of the program. The outcome of this study compares favorably to previous published data of more intensive programs. These results were obtained having little infrastructure, a low budget and limited human resources, making this a suitable eating disorders program for emerging nations.

  8. Carbohydrates and the human gut microbiota.

    Science.gov (United States)

    Chassard, Christophe; Lacroix, Christophe

    2013-07-01

    Due to its scale and its important role in maintaining health, the gut microbiota can be considered as a 'new organ' inside the human body. Many complex carbohydrates are degraded and fermented by the human gut microbiota in the large intestine to both yield basic energy salvage and impact gut health through produced metabolites. This review will focus on the gut microbes and microbial mechanisms responsible for polysaccharides degradation and fermentation in the large intestine. Gut microbes and bacterial metabolites impact the host at many levels, including modulation of inflammation, and glucose and lipid metabolisms. A complex relationship occurs in the intestine between the human gut microbiota, diet and the host. Research on carbohydrates and gut microbiota composition and functionality is fast developing and will open opportunities for prevention and treatment of obesity, diabetes and other related metabolic disorders through manipulation of the gut ecosystem.

  9. Descriptive review: hormonal influences on risk for eating disorder symptoms during puberty and adolescence.

    Science.gov (United States)

    Harden, K Paige; Kretsch, Natalie; Moore, Sarah R; Mendle, Jane

    2014-11-01

    Puberty is an important period of risk for the onset of eating pathology in adolescent females. This review focuses on changes in reproductive hormones during puberty as one specific psychopathogenic mechanism. Studies of puberty and eating disorder-related phenotypes were identified using search databases and the reference sections of previous literature. Correlational studies of adult women and experimental studies of animals provide evidence for the effects of reproductive hormones on eating disorder symptoms. Very few studies of puberty, however, have directly measured or tested the effects of hormonal change in samples of human adolescents. Commonly used measures of pubertal development, such as menarche or self-reported pubertal status, are relatively poor indicators of individual differences in hormones. The extent to which puberty-related hormonal change accounts for elevated risk for disordered eating remains unclear. Future research is necessary to elucidate the specific relations between hormonal change during puberty and risk for disordered eating. In particular, there is a need for longitudinal studies with multivariate measurement of pubertal development, including direct measures of change in reproductive hormones. © 2014 Wiley Periodicals, Inc.

  10. Nonspecific eating disorders - a subjective review.

    Science.gov (United States)

    Michalska, Aneta; Szejko, Natalia; Jakubczyk, Andrzej; Wojnar, Marcin

    2016-01-01

    The aim of this paper was to characterise nonspecific eating disorders (other than anorexia nervosa and bulimia nervosa). The Medline database was searched for articles on nonspecific eating disorders. The following disorders were described: binge eating disorder (BED), pica, rumination disorder, avoidant/restrictive food intake disorder, night eating syndrome (NES), sleep-related eating disorder (SRED), bigorexia, orthorexia, focusing on diagnosis, symptoms, assessment, comorbidities, clinical implications and treatment. All of the included disorders may have dangerous consequences, both somatic and psychological. They are often comorbid with other psychiatric disorders. Approximately a few percent of general population can be diagnosed with each disorder, from 0.5-4.7% (SRED) to about 7% (orthorexia). With the growing literature on the subject and changes in DSM-5, clinicians recognise and treat those disorders more often. More studies have to be conducted in order to differentiate disorders and treat or prevent them appropriately.

  11. Personality Disorders in Later Life: Questions about the Measurement, Course, and Impact of Disorders

    Science.gov (United States)

    Oltmanns, Thomas F.; Balsis, Steve

    2011-01-01

    Lifespan perspectives have played a crucial role in shaping our understanding of many forms of psychopathology. Unfortunately, little attention has been given to personality disorders in middle adulthood and later life. Several issues are responsible for this deficiency, including difficulty applying the diagnostic criteria for personality disorders to older people and challenges in identifying appropriate samples of older participants. The goal of this review is to explore the benefits of considering older adults in the study of personality disorders. Later life offers a unique opportunity for investigators to consider links between personality pathology and consequential outcomes in people’s lives. Many domains are relevant, including health, longevity, social adjustment, marital relationships, and the experience of major life events. We review each domain and consider ways in which the study of middle-aged and older adults challenges researchers to evaluate how personality disorders in general are defined and measured. PMID:21219195

  12. Addictive Disorders in Adolescents.

    Science.gov (United States)

    Truong, Anh; Moukaddam, Nidal; Toledo, Alexander; Onigu-Otite, Edore

    2017-09-01

    Addictive disorders in youth represent a dynamic field characterized by shifting patterns of substance use and high rates of experimentation, while retaining the risky behaviors and negative outcomes associated with established drug classes. Youth/adolescents are also at the forefront of use of new technologies, and non-substance-related disorders are pertinent. These disorders present with similar pictures of impairment, and can be diagnosed following the same principles. An underlying mental disorder and the possibility of a dual diagnosis need to be assessed carefully, and optimal treatment includes psychosocial treatments with applicable pharmacologic management, the latter representing an expanding field. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. The association between obsessive compulsive disorder and obsessive compulsive personality disorder: prevalence and clinical presentation.

    Science.gov (United States)

    Gordon, Olivia M; Salkovskis, Paul M; Oldfield, Victoria B; Carter, Natalie

    2013-09-01

    The relationship between Obsessive Compulsive Disorder (OCD) and Obsessive Compulsive Personality Disorder (OCPD) has been the subject of interest for some time due to the historical assumption that OCPD causes OCD. This study systematically examined the association between OCD and OCPD in terms of prevalence and clinical presentation. The specificity of the association between OCD and OCPD was investigated relative to another axis I anxiety disorder (Panic disorder). Data for this study were drawn from measures taken at initial assessment at a specialist treatment centre for anxiety disorders. Of the 359 participants included in this study, 189 had a principal diagnosis of OCD, while 170 had a principal diagnosis of Panic disorder. Measures included SCID I and II interview modules and self-report measures of anxiety, depression, and OCD syptomatology. Significantly elevated rates of OCPD were found in OCD relative to Panic disorder. Regardless of axis I disorder, individuals with comorbid OCPD reported more severe depression relative to those without. Participants with both OCD and OCPD had greater self-reported OCD symptom severity, doubting, ordering, and hoarding symptoms at assessment relative to those without OCPD. Participants with OCD and comorbid OCPD also reported significantly higher levels of alcohol consumption. There appears to be a significant and specific association between OCD and OCPD. Co-occurring OCD and OCPD is associated with greater severity of impairment in terms of certain OCD symptoms. The significant and specific association between OCD and OCPD suggests that OCPD occurs more frequently with OCD than previously suggested. A comorbid OCPD diagnosis is associated with a greater degree of depression, regardless of axis I disorder, either OCD or Panic disorder. This is an important consideration, as depression can interfere with therapeutic progress (Foa, 1979). Participants with OCD and OCPD had greater self-reported OCD severity, along

  14. Human genetics and sleep behavior.

    Science.gov (United States)

    Shi, Guangsen; Wu, David; Ptáček, Louis J; Fu, Ying-Hui

    2017-06-01

    Why we sleep remains one of the greatest mysteries in science. In the past few years, great advances have been made to better understand this phenomenon. Human genetics has contributed significantly to this movement, as many features of sleep have been found to be heritable. Discoveries about these genetic variations that affect human sleep will aid us in understanding the underlying mechanism of sleep. Here we summarize recent discoveries about the genetic variations affecting the timing of sleep, duration of sleep and EEG patterns. To conclude, we also discuss some of the sleep-related neurological disorders such as Autism Spectrum Disorder (ASD) and Alzheimer's Disease (AD) and the potential challenges and future directions of human genetics in sleep research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. How semantic deficits in schizotypy help understand language and thought disorders in schizophrenia: a systematic and integrative review

    Directory of Open Access Journals (Sweden)

    Hélio Anderson Tonelli

    2014-04-01

    Full Text Available Introduction: Disorders of thought are psychopathological phenomena commonly present in schizophrenia and seem to result from deficits of semantic processing. Schizotypal personality traits consist of tendencies to think and behave that are qualitatively similar to schizophrenia, with greater vulnerability to such disorder. This study reviewed the literature about semantic processing deficits in samples of individuals with schizotypal traits and discussed the impact of current knowledge upon the comprehension of schizophrenic thought disorders. Studies about the cognitive performance of healthy individuals with schizotypal traits help understand the semantic deficits underlying psychotic thought disorders with the advantage of avoiding confounding factors usually found in samples of individuals with schizophrenia, such as the use of antipsychotics and hospitalizations. Methods: A search for articles published in Portuguese or English within the last 10 years on the databases MEDLINE, Web of Science, PsycInfo, LILACS and Biological Abstracts was conducted, using the keywords semantic processing, schizotypy and schizotypal personality disorder. Results: The search retrieved 44 manuscripts, out of which 11 were firstly chosen. Seven manuscripts were additionally included after reading these papers. Conclusion: The great majority of the included studies showed that schizotypal subjects might exhibit semantic processing deficits. They help clarify about the interfaces between cognitive, neurophysiological and neurochemical mechanisms underlying not only thought disorders, but also healthy human mind's creativity.

  16. Defining Features of Unhealthy Exercise Associated with Disordered Eating and Eating Disorder Diagnoses.

    Science.gov (United States)

    Holland, Lauren A; Brown, Tiffany A; Keel, Pamela K

    2014-01-01

    The current study sought to compare different features of unhealthy exercise on associations with disordered eating and their ability to identify individuals with eating disorders. A secondary aim of the study was to compare prevalence and overlap of different aspects of unhealthy exercise and potential differences in their gender distribution. Cross-sectional epidemiological study. A community-based sample of men (n=592) and women (n=1468) completed surveys of health and eating patterns, including questions regarding exercise habits and eating disorder symptoms. Compulsive and compensatory features of exercise were the best predictors of disordered eating and eating disorder diagnoses compared to exercise that was excessive in quantity. Further, compulsive and compensatory aspects of unhealthy exercise represented overlapping, yet distinct qualities in both men and women. Including the compulsive quality among the defining features of unhealthy exercise may improve identification of eating disorders, particularly in men. Results suggest that the compensatory aspect of unhealthy exercise is not adequately captured by the compulsive aspect of unhealthy exercise. Thus, interventions that target unhealthy exercise behaviors among high-risk individuals, such as athletes, may benefit from addressing both the compulsive and compensatory aspects of unhealthy exercise. Future prospective longitudinal studies will aid in determining the direction of the association between these features of unhealthy exercise and the onset of eating pathology.

  17. Exploring the Perception of Asperger's Disorder

    Science.gov (United States)

    Kite, Donna M.; Tyson, Graham A.; Gullifer, Judith M.

    2011-01-01

    With current preparation for the release of the fifth edition of the "Diagnostic and Statistical Manual of Mental Disorders" (DSM-5) in 2013, many changes have been proposed for the diagnostic criteria, including changes to the pervasive development disorder category--of which Asperger's disorder is a part. Using focus group discussions…

  18. Functional disorders of the anus and rectum

    Science.gov (United States)

    Whitehead, W; Wald, A; Diamant, N; Enck, P; Pemberton, J; Rao, S

    1999-01-01

    In this report the functional anorectal disorders, the etiology of which is currently unknown or related to the abnormal functioning of normally innervated and structurally intact muscles, are discussed. These disorders include functional fecal incontinence, functional anorectal pain, including levator ani syndrome and proctalgia fugax, and pelvic floor dyssynergia. The epidemiology of each disorder is defined and discussed, their pathophysiology is summarized and diagnostic approaches and treatment are suggested. Some suggestions for the direction of future research on these disorders are also given.


Keywords: fecal incontinence; pelvic floor dyssynergia; anismus; proctalgia fugax; levator ani syndrome; constipation; Rome II PMID:10457046

  19. Specific learning disorder: prevalence and gender differences.

    Directory of Open Access Journals (Sweden)

    Kristina Moll

    Full Text Available Comprehensive models of learning disorders have to consider both isolated learning disorders that affect one learning domain only, as well as comorbidity between learning disorders. However, empirical evidence on comorbidity rates including all three learning disorders as defined by DSM-5 (deficits in reading, writing, and mathematics is scarce. The current study assessed prevalence rates and gender ratios for isolated as well as comorbid learning disorders in a representative sample of 1633 German speaking children in 3rd and 4th Grade. Prevalence rates were analysed for isolated as well as combined learning disorders and for different deficit criteria, including a criterion for normal performance. Comorbid learning disorders occurred as frequently as isolated learning disorders, even when stricter cutoff criteria were applied. The relative proportion of isolated and combined disorders did not change when including a criterion for normal performance. Reading and spelling deficits differed with respect to their association with arithmetic problems: Deficits in arithmetic co-occurred more often with deficits in spelling than with deficits in reading. In addition, comorbidity rates for arithmetic and reading decreased when applying stricter deficit criteria, but stayed high for arithmetic and spelling irrespective of the chosen deficit criterion. These findings suggest that the processes underlying the relationship between arithmetic and reading might differ from those underlying the relationship between arithmetic and spelling. With respect to gender ratios, more boys than girls showed spelling deficits, while more girls were impaired in arithmetic. No gender differences were observed for isolated reading problems and for the combination of all three learning disorders. Implications of these findings for assessment and intervention of learning disorders are discussed.

  20. Dissociative identity disorder: a controversial diagnosis.

    Science.gov (United States)

    Gillig, Paulette Marie

    2009-03-01

    A brief description of the controversies surrounding the diagnosis of dissociative identity disorder is presented, followed by a discussion of the proposed similarities and differences between dissociative identity disorder and borderline personality disorder. The phenomenon of autohypnosis in the context of early childhood sexual trauma and disordered attachment is discussed, as is the meaning of alters or alternate personalities. The author describes recent neurosciences research that may relate the symptoms of dissociative identity disorder to demonstrable disordered attention and memory processes. A clinical description of a typical patient presentation is included, plus some recommendations for approaches to treatment.