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Sample records for endopeptidase develop disorders

  1. Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis-Based Computer-Aided Molecular Design

    Science.gov (United States)

    2009-11-01

    simulations; (4) synthesis and evaluation of the molecules from Step 2 or 3 (e.g., synthesizing and testing AHP). From synthetic chemistry point of view...2000) Synthesis of 6H-indolo [2,3-b][1,6]naphthyridines and related compounds as the 5-Aza analogues of ellipticine alkaloids . J Org Chem 65: 7977–7983...Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis -Based Computer-Aided Molecular Design

  2. Potent new small-molecule inhibitor of botulinum neurotoxin serotype A endopeptidase developed by synthesis-based computer-aided molecular design.

    Directory of Open Access Journals (Sweden)

    Yuan-Ping Pang

    2009-11-01

    Full Text Available Botulinum neurotoxin serotype A (BoNTA causes a life-threatening neuroparalytic disease known as botulism. Current treatment for post exposure of BoNTA uses antibodies that are effective in neutralizing the extracellular toxin to prevent further intoxication but generally cannot rescue already intoxicated neurons. Effective small-molecule inhibitors of BoNTA endopeptidase (BoNTAe are desirable because such inhibitors potentially can neutralize the intracellular BoNTA and offer complementary treatment for botulism. Previously we reported a serotype-selective, small-molecule BoNTAe inhibitor with a K(i (app value of 3.8+/-0.8 microM. This inhibitor was developed by lead identification using virtual screening followed by computer-aided optimization of a lead with an IC(50 value of 100 microM. However, it was difficult to further improve the lead from micromolar to even high nanomolar potency due to the unusually large enzyme-substrate interface of BoNTAe. The enzyme-substrate interface area of 4,840 A(2 for BoNTAe is about four times larger than the typical protein-protein interface area of 750-1,500 A(2. Inhibitors must carry several functional groups to block the unusually large interface of BoNTAe, and syntheses of such inhibitors are therefore time-consuming and expensive. Herein we report the development of a serotype-selective, small-molecule, and competitive inhibitor of BoNTAe with a K(i value of 760+/-170 nM using synthesis-based computer-aided molecular design (SBCAMD. This new approach accounts the practicality and efficiency of inhibitor synthesis in addition to binding affinity and selectivity. We also report a three-dimensional model of BoNTAe in complex with the new inhibitor and the dynamics of the complex predicted by multiple molecular dynamics simulations, and discuss further structural optimization to achieve better in vivo efficacy in neutralizing BoNTA than those of our early micromolar leads. This work provides new insight

  3. Induced-fit Mechanism for Prolyl Endopeptidase

    Energy Technology Data Exchange (ETDEWEB)

    Li, Min; Chen, Changqing; Davies, David R.; Chiu, Thang K. (NIH); (LSU); (Chinese Aca. Sci.)

    2010-11-15

    Prolyl peptidases cleave proteins at proline residues and are of importance for cancer, neurological function, and type II diabetes. Prolyl endopeptidase (PEP) cleaves neuropeptides and is a drug target for neuropsychiatric diseases such as post-traumatic stress disorder, depression, and schizophrenia. Previous structural analyses showing little differences between native and substrate-bound structures have suggested a lock-and-key catalytic mechanism. We now directly demonstrate from seven structures of Aeromonus punctata PEP that the mechanism is instead induced fit: the native enzyme exists in a conformationally flexible opened state with a large interdomain opening between the {beta}-propeller and {alpha}/{beta}-hydrolase domains; addition of substrate to preformed native crystals induces a large scale conformational change into a closed state with induced-fit adjustments of the active site, and inhibition of this conformational change prevents substrate binding. Absolute sequence conservation among 28 orthologs of residues at the active site and critical residues at the interdomain interface indicates that this mechanism is conserved in all PEPs. This finding has immediate implications for the use of conformationally targeted drug design to improve specificity of inhibition against this family of proline-specific serine proteases.

  4. Disordered follicle development

    Science.gov (United States)

    Chang, R. Jeffrey; Cook-Andersen, Heidi

    2013-01-01

    Alterations of ovarian follicle morphology and function have been well documented in women with PCOS. These include increased numbers of growing preantral follicles, failure of follicle growth beyond the mid-antral stage, evidence of granulosa call degeneration, and theca cell hyperplasia. Functional abnormalities include paradoxical granulosa cell hyperresponsiveness to FSH which is clinically linked to ovarian hyperstimulation during ovulation induction. In addition, there is likely a primary theca cell defect that accounts for the majority of excess androgen production in this disorder. The precise mechanisms responsible for altered follicle function are not completely clear. However, several factors appear to influence normal advancement of follicle development as well as impair ovarian steroidogenesis. These include intra- as well as extraovarian influences that distort normal ovarian growth and disrupt steroid production by follicle cells. PMID:22874072

  5. Drug development for neurodevelopmental disorders

    DEFF Research Database (Denmark)

    Berry-Kravis, Elizabeth M; Lindemann, Lothar; Jønch, Aia E

    2018-01-01

    Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong cognitive and behavioural deficits and represent a major public health burden. FXS is the most frequent monogenic form of intellectual disability and autism, and the underlying pathophysiology linked to its causal ge......, FMR1, has been the focus of intense research. Key alterations in synaptic function thought to underlie this neurodevelopmental disorder have been characterized and rescued in animal models of FXS using genetic and pharmacological approaches. These robust preclinical findings have led...... to the implementation of the most comprehensive drug development programme undertaken thus far for a genetically defined neurodevelopmental disorder, including phase IIb trials of metabotropic glutamate receptor 5 (mGluR5) antagonists and a phase III trial of a GABAB receptor agonist. However, none of the trials has...... been able to unambiguously demonstrate efficacy, and they have also highlighted the extent of the knowledge gaps in drug development for FXS and other neurodevelopmental disorders. In this Review, we examine potential issues in the previous studies and future directions for preclinical and clinical...

  6. Child development and personality disorder.

    Science.gov (United States)

    Cohen, Patricia

    2008-09-01

    The evidence is surprisingly strong that even early adolescent personality disorders or elevated personality disorder symptoms have a broad range of negative effects well into adulthood, for the most part comparable to or even larger than those of Axis I disorders. Current evidence suggests that the most severe long-term prognosis is associated with borderline and schizotypal PDs and elevated symptoms. And of course, childhood conduct disorder is in a peculiar status, disappearing in adulthood to be manifest as a very severe disorder-antisocial PD-in a minority of those with the adolescent disorder.

  7. Multiple forms of endopeptidase activity from jojoba seeds.

    Science.gov (United States)

    Wolf, M J; Storey, R D

    1990-01-01

    The cotyledons of 27 day post-germination jojoba seedlings (Simmondsia chinensis) contained five distinct endopeptidase activities separable by DEAE Bio-Gel and CM-cellulose ion exchange chromatography. The endopeptidases were purified 108- to 266-fold and their individuality was confirmed by activity-specific assays in native acrylamide gels along with differences in their Mr and catalytic properties. The five endopeptidases, which showed activity on model substrates and protein, were named EP Ia, EP Ib, EP II, EP III and EP IV. EP Ia was a serine proteinase with a pH optimum of ca 8 and Mr of 58,000. EP Ib, II and III were discrete cysteine proteinases showing pH optima of ca 6.8, 6.0 and 5.4 and Mr of 41,000, 47,000 and 35,000 respectively. EP IV was an aspartic acid proteinase with a ca pH optimum of 3.5 and Mr of 33,000.

  8. Disorders of brain development and phakomatosis

    International Nuclear Information System (INIS)

    Merhemis, Z.

    2006-01-01

    Full text: Disorders of brain development and phakomatosis are resulting from disturbed embryonic-foetal development One third of all major embryological anomalies involve CNS, and over 2000 different anomalies have been described. Anomalies of the brain often cause foetal and neonatal death, and mental and physical retardation in pediatric group. The majority of disorders of brain development and phakomatosis are idiopathic, and most of them are not hereditary or familial. Ultrasonography plays the important role in screening foetal and neonatal brain, but after closure of fontanels it is difficult to find the acoustic window. CT has limited contrast resolution, and disadvantage exposing infant to ionizing radiation. It is helpful to demonstrate the presence of calcifications. MR imaging has proved to be a diagnostic tool of major importance in children with disorders of brain development and phakomatosis. The excellent grey/white matter differentiation and multiplanar imaging capabilities of MR allow a systematic analysis of the brain. Disorders occurring in the first 4 weeks of gestation: Disorders of neural tube closure; Chiari malformation; Cephaloceles; Dermoid/Epidermoid. Disorders occurring between 5 and 10 weeks of gestation: Holoprosencephaly; Septo-optic dysplasia; Diencephalic cyst; Dandy Walker complex; Mega cistern magna. Disorders occurring between 2 and 5 months of gestation: Disorders of sulcation and cellular migration; Lissencephaly; Pachigyria; Schizencephaly; Heterotopias; Megaencephaly; Polymicrogyria; Porencephaly; Arachnoid cyst. Corpus callosum anomalies. Phakomatosis: Neurocutaneous Syndromes Neurofibromatosis Type 1 and 2; Tuberous Sclerosis; von Hippel-Lindau disease; Studge-Weber sy; Osler-Weber- Rendu sy

  9. Genetics Home Reference: 46,XX testicular disorder of sex development

    Science.gov (United States)

    ... 46,XX testicular disorder of sex development 46,XX testicular disorder of sex development Printable PDF Open ... to view the expand/collapse boxes. Description 46,XX testicular disorder of sex development is a condition ...

  10. Isolation of prolyl endopeptidase inhibitory peptides from a sodium caseinate hydrolysate.

    Science.gov (United States)

    Hsieh, Cheng-Hong; Wang, Tzu-Yuan; Hung, Chuan-Chuan; Hsieh, You-Liang; Hsu, Kuo-Chiang

    2016-01-01

    Prolyl endopeptidase (PEP) has been associated with neurodegenerative disorders, and the PEP inhibitors can restore the memory loss caused by amnesic compounds. In this study, we investigated the PEP inhibitory activity of the enzymatic hydrolysates from various food protein sources, and isolated and identified the PEP inhibitory peptides. The hydrolysate obtained from sodium caseinate using bromelain (SC/BML) displayed the highest inhibitory activity of 86.8% at 5 mg mL(-1) in the present study, and its IC50 value against PEP was 0.77 mg mL(-1). The F-5 fraction by RP-HPLC (reversed-phase high performance liquid chromatography) from SC/BML showed the highest PEP inhibition rate of 88.4%, and 9 peptide sequences were identified. The synthetic peptides (1245.63-1787.94 Da) showed dose-dependent inhibition effects on PEP as competitive inhibitors with IC50 values between 29.8 and 650.5 μM. The results suggest that the peptides derived from sodium caseinate have the potential to be PEP inhibitors.

  11. Production and characterization of two major Aspergillus oryzae secreted prolyl endopeptidases able to efficiently digest proline-rich peptides of gliadin.

    Science.gov (United States)

    Eugster, Philippe J; Salamin, Karine; Grouzmann, Eric; Monod, Michel

    2015-12-01

    Prolyl endopeptidases are key enzymes in the digestion of proline-rich proteins. Fungal extracts rich in prolyl endopeptidases produced by a species such as Aspergillus oryzae used in food fermentation would be of particular interest for the development of an oral enzyme therapy product in patients affected by intolerance to gluten. Two major A. oryzae secreted prolyl endopeptidases of the MEROPS S28 peptidase family, AoS28A and AoS28B, were identified when this fungus was grown at acidic pH in a medium containing soy meal protein or wheat gliadin as the sole source of nitrogen. AoS28B was produced by 12 reference A. oryzae strains used in food fermentation. AoS28A was secreted by six of these 12 strains. This protease is the orthologue of the previously characterized Aspergillus fumigatus (AfuS28) and Aspergillus niger (AN-PEP) prolyl endopeptidases which are encoded by genes with a similar intron-exon structure. Large amounts of secreted AoS28A and AoS28B were obtained by gene overexpression in A. oryzae. AoS28A and AoS28B are endoproteases able to cleave N-terminally blocked proline substrates. Both enzymes very efficiently digested the proline-rich 33-mer of gliadin, the most representative immunotoxic peptide deriving from gliadin, with some differences in terms of specificity and optimal pH. Digestion of the gliadin peptide in short peptides with both enzymes was found to occur from its N terminus.

  12. Presence and expression of hydrogenase specific C-terminal endopeptidases in cyanobacteria

    Directory of Open Access Journals (Sweden)

    Lindblad Peter

    2003-05-01

    Full Text Available Abstract Background Hydrogenases catalyze the simplest of all chemical reactions: the reduction of protons to molecular hydrogen or vice versa. Cyanobacteria can express an uptake, a bidirectional or both NiFe-hydrogenases. Maturation of those depends on accessory proteins encoded by hyp-genes. The last maturation step involves the cleavage of a ca. 30 amino acid long peptide from the large subunit by a C-terminal endopeptidase. Until know, nothing is known about the maturation of cyanobacterial NiFe-hydrogenases. The availability of three complete cyanobacterial genome sequences from strains with either only the uptake (Nostoc punctiforme ATCC 29133/PCC 73102, only the bidirectional (Synechocystis PCC 6803 or both NiFe-hydrogenases (Anabaena PCC 7120 prompted us to mine these genomes for hydrogenase maturation related genes. In this communication we focus on the presence and the expression of the NiFe-hydrogenases and the corresponding C-terminal endopeptidases, in the three strains mentioned above. Results We identified genes encoding putative cyanobacterial hydrogenase specific C-terminal endopeptidases in all analyzed cyanobacterial genomes. The genes are not part of any known hydrogenase related gene cluster. The derived amino acid sequences show only low similarity (28–41% to the well-analyzed hydrogenase specific C-terminal endopeptidase HybD from Escherichia coli, the crystal structure of which is known. However, computational secondary and tertiary structure modeling revealed the presence of conserved structural patterns around the highly conserved active site. Gene expression analysis shows that the endopeptidase encoding genes are expressed under both nitrogen-fixing and non-nitrogen-fixing conditions. Conclusion Anabaena PCC 7120 possesses two NiFe-hydrogenases and two hydrogenase specific C-terminal endopeptidases but only one set of hyp-genes. Thus, in contrast to the Hyp-proteins, the C-terminal endopeptidases are the only known

  13. [Psychomotor development and its disorders: between normal and pathological development].

    Science.gov (United States)

    Vericat, Agustina; Bibiana Orden, Alicia

    2013-10-01

    This article discusses some aspects of psychomotor development and its disorders, with special emphasis on psychomotor retardation. Diagnostic classifications of psychomotor problems, such as DSM-IV and CIE-10, are referred to and their advantages and disadvantages are analyzed. The concept of normality as a synonym for the statistical mean in the context of psychomotor disorders is also analyzed in order to consider its dynamic and variability, thereby avoiding the normality/pathology opposition, while some issues, such as the social and cultural aspects, are highlighted, making it possible to rethink the universality and relativity of psychomotor development.

  14. cDNA cloning of porcine brain prolyl endopeptidase and identification of the active-site seryl residue

    Energy Technology Data Exchange (ETDEWEB)

    Rennex, D.; Hemmings, B.A.; Hofsteenge, J.; Stone, S.R. (Friedrich Miescher-Institut, Basel (Switzerland))

    1991-02-26

    Prolyl endopeptidase is a cytoplasmic serine protease. The enzyme was purified from porcine kidney, and oligonucleotides based on peptide sequences from this protein were used to isolate a cDNA clone from a porcine brain library. This clone contained the complete coding sequence of prolyl endopeptidase and encoded a polypeptide with a molecular mass of 80751 Da. The deduced amino acid sequence of prolyl endopeptidase showed no sequence homology with other known serine proteases. ({sup 3}H)Diisopropyl fluorophosphate was used to identify the active-site serine of prolyl endopeptidase. One labeled peptide was isolated and sequenced. The sequence surrounding the active-site serine was Asn-Gly-Gly-Ser-Asn-Gly-Gly. This sequence is different from the active-site sequences of other known serine proteases. This difference and the lack of overall homology with the known families of serine proteases suggest that prolyl endopeptidase represents a new type of serine protease.

  15. Lack of genetic association of neutral endopeptidase (NEP) with complex regional pain syndrome (CRPS).

    Science.gov (United States)

    Huehne, Kathrin; Schaal, Ute; Leis, Stefan; Uebe, Steffen; Gosso, M Florencia; van den Maagdenberg, Arn M J M; Maihöfner, Christian; Birklein, Frank; Rautenstrauss, Bernd; Winterpacht, Andreas

    2010-03-12

    Complex regional pain syndrome (CRPS) is a condition that is characterized by severe pain and exaggerated neurogenic inflammation, which may develop after injury or surgery. Neurogenic inflammation is mediated by neuropeptides, such as calcitonin gene-related peptide (CGRP) and substance P (SP) that are released from nociceptors. Genetic factors may play a role in CRPS as was suggested by the occurrence of familial cases and several genetic association studies investigating mainly the human leukocyte antigen (HLA) system. Here we investigated the role of neutral endopeptidase (NEP), a key enzyme in neuropeptide catabolism. NEP dysfunction resulting in reduced inactivation of neuropeptides may be a possible pathomechanism in CRPS. To this end, we tested a GT-repeat polymorphism in the NEP promoter region as well as 18 tag-SNPs in six linkage disequilibrium (LD) blocks in the NEP gene region in 320 CRPS patients and 376 controls. No significant genetic association was observed. Thus, we conclude that the NEP gene does not seem to be a major risk factor for CRPS. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  16. Molecular mechanisms in disorders of gonadal development

    OpenAIRE

    Norling, Ameli

    2014-01-01

    “Hur många barn får jag när jag blir stor?” Controlling fertility, or rather infertility, is a common problem for couples nowadays where approximately 10% experience infertility. This thesis focuses on the rare conditions leading to infertility in which the gonads have either failed to develop properly, or prematurely lost their function. The overall aim of this thesis was to identify and study candidate genes in gonadal disorders of sex development (DSD) and primary o...

  17. Precursors to the Development of Anxiety Disorders in Young Children with Autism Spectrum Disorder

    Science.gov (United States)

    2017-12-01

    children -autism- spectrum-disorder C. Technologies or techniques Nothing to Report D. Inventions, patent applications, and/or licenses Nothing to Report...AWARD NUMBER: W81XWH-14-1-0526 TITLE: Precursors to the Development of Anxiety Disorders in Young Children with Autism Spectrum Disorder...TITLE AND SUBTITLE Precursors to the Development of Anxiety Disorders in Young Children with Autism Spectrum Disorder 5a. CONTRACT NUMBER 5b

  18. [Pragmatics in autism spectrum disorder: recent developments].

    Science.gov (United States)

    Kissine, Mikhail; Clin, Elise; de Villiers, Jessica

    2016-10-01

    Autism spectrum disorder (ASD) is characterized by primary pragmatic difficulties, out of step with verbal and non-verbal developmental level. This selective survey paper addresses three recent domains of research on pragmatic functions in autism. First, we provide an up-to-date discussion of how lack of sensitivity to social cues impacts early acquisition of words. Second, we review recent findings on the comprehension of non-literal language, pointing to a more refined clinical reality. Third, we describe recent developments in the study of conversation skills in autism. © 2016 médecine/sciences – Inserm.

  19. Inhibition of [gamma]-endorphin generating endopeptidase activity of rat brain by peptides: Structure activity relationship

    NARCIS (Netherlands)

    Lebouille, J.L.M.; Visser, W.H.; Hendriks, R.W.; Nispen, J.W. van; Greven, H.M.; Burbach, J.P.H.

    1985-01-01

    Gamma-Endorphin generating endopeptidase (gammaEGE) activity is an enzyme activity which converts beta-endorphin into gamma-endorphin and beta-endorphin-(18–31). The inhibitory potency on gammaEGE activity of neuropeptides and analogues or fragments of neuropeptides was tested. Dynorphin-(1–13)

  20. Chromosomal Location by Use of Trisomics and New Alleles of an Endopeptidase in Zea Mays

    DEFF Research Database (Denmark)

    Nielsen, Gunnar Gissel; Scandalios, John G.

    1974-01-01

    An association was found earlier between the Ep1 gene locus coding for an endopeptidase and the endosperm color gene Y1 on chromosome 6 of Zea mays. By employing primary trisomics we have unequivocally placed the Ep1 gene on chromosome 6, closely linked to the Y1 locus. Additionally we describe new...

  1. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

    DEFF Research Database (Denmark)

    Wong, Mei Mei Jaslyn Elizabeth; Midtgaard, Søren Roi; Gysel, Kira

    2015-01-01

    of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering...

  2. Concurrent neutral endopeptidase and ACE inhibition in experimental heart failure: renal and hormonal effects

    DEFF Research Database (Denmark)

    Helin, K

    1993-01-01

    Neutral endopeptidase (NEP) inhibitors have been shown to strengthen the effects of endogenous atrial natriuretic peptide (ANP). It has been well documented that angiotensin I-converting enzyme (ACE) inhibitors act beneficially in chronic congestive heart failure (CHF). In the present study, renal...

  3. Precursors to the Development of Anxiety Disorders in Young Children with Autism Spectrum Disorder

    Science.gov (United States)

    2017-12-01

    AWARD NUMBER: W81XWH-14-1-0527 TITLE: Precursors to the Development of Anxiety Disorders in Young Children with Autism Spectrum Disorder...2017 4. TITLE AND SUBTITLE Precursors to the Development of Anxiety Disorders in Young Children with Autism Spectrum Disorder 5a. CONTRACT NUMBER 5b...neurophysiological, and observational measures. Initial findings indicate that children with ASD who have clinically significant sensory are at increased risk for

  4. Recent developments in esophageal motor disorders.

    Science.gov (United States)

    Beaumont, Hanneke; Boeckxstaens, Guy

    2007-07-01

    Every year more insight into the pathogenesis and treatment of esophageal motor disorders is obtained. This review highlights some interesting literature published in this area during the last year. Longitudinal and circular muscle contractions act in a well coordinated fashion to allow normal peristalsis. Techniques such as intraluminal impedance, high-resolution manometry and intraluminal ultrasound provide useful additional information on esophageal function both in the normal and abnormal situation. The dynamics of the gastroesophageal junction can be studied with a newly developed probe, and the mechanism behind transient lower esophageal sphincter relaxations is still being unravelled. New manometric criteria for nutcracker esophagus have been proposed, whereas further evidence is reported supporting an association between diabetes mellitus and cardiovascular disease and esophageal dysmotility and spasm, respectively. Finally, several long-term follow-up results of surgical myotomy and pneumodilatation have been reported. Due to the perfection of esophageal measuring techniques, our knowledge of esophageal function continues to increase. The studies reviewed here provide interesting information on the pathogenesis and treatment of several esophageal motor disorders.

  5. Development of Antisocial Personality Disorder in Detained Youths: The Predictive Value of Mental Disorders

    Science.gov (United States)

    Washburn, Jason J.; Romero, Erin Gregory; Welty, Leah J.; Abram, Karen M.; Teplin, Linda A.; McClelland, Gary M.; Paskar, Leah D.

    2007-01-01

    Antisocial personality disorder (APD) is a serious public and mental health concern. Understanding how well conduct disorder (CD) and other mental disorders predict the development of APD among youths involved in the juvenile justice system is critical for prevention. The authors used a stratified random sample of 1,112 detained youths to examine…

  6. Suppression of asparaginyl endopeptidase attenuates breast cancer-induced bone pain through inhibition of neurotrophin receptors.

    Science.gov (United States)

    Yao, Peng; Ding, Yuanyuan; Han, Zhenkai; Mu, Ying; Hong, Tao; Zhu, Yongqiang; Li, Hongxi

    2017-01-01

    Objective Cancer-induced bone pain is a common clinical problem in breast cancer patients with bone metastasis. However, the mechanisms driving cancer-induced bone pain are poorly known. Recent studies show that a novel protease, asparaginyl endopeptidase (AEP) plays crucial roles in breast cancer metastasis and progression. We aim to determine the functions and targeted suppress of AEP in a mouse model of breast cancer-induced bone pain. Methods Breast cancer cells with AEP knocked-down or overexpression were constructed and implanted into the intramedullary space of the femur to induce pain-like behavior in mice. AEP-specific inhibitors or purified AEP proteins were further used in animal model. The histological characters of femur and pain ethological changes were measured. The expressions of AEP and neurotrophin receptors (p75NTR and TrkA) in dorsal root ganglion and spinal cord were examined. Results Femur radiographs and histological analysis revealed that cells with AEP knocked-down reduced bone destruction and pain behaviors. However, cells with AEP overexpression elevated bone damage and pain behaviors. Further, Western blot results found that the expressions of p75NTR and TrkA in dorsal root ganglions and spinal cords were reduced in mice inoculated with AEP knocked-down cells. Targeted suppression of AEP with specific small compounds significantly reduced the bone pain while purified recombinant AEP proteins increased bone pain. Conclusions AEP aggravate the development of breast cancer bone metastasis and bone pain by increasing the expression of neurotrophin receptors. AEP might be an effective target for treatment of breast cancerinduced bone pain.

  7. Developing Undergraduate Coursework in Autism Spectrum Disorders

    Science.gov (United States)

    Masterson, Tracy Loye; Dimitriou, Francine; Turko, Kristine; McPartland, James

    2014-01-01

    With rates of autism spectrum disorders (ASD) continuing to rise alongside improvements in early identification and treatment, service providers are in great demand. Providing undergraduate students with opportunities for education and applied experiences with autism spectrum disorders (ASD) can help fill a valuable niche in the autism community.…

  8. Colocalization of neurotensin receptors and of the neurotensin-degrading enzyme endopeptidase 24-16 in primary cultures of neurons

    International Nuclear Information System (INIS)

    Chabry, J.; Checler, F.; Vincent, J.P.; Mazella, J.

    1990-01-01

    This paper compares the localization of neurotensin receptors and of endopeptidase 24-16, a peptidase likely involved in the inactivation of neurotensin in primary cultures of neurons. Neurotensin binding sites were radiolabeled with 125 I-Tyr3-neurotensin, whereas endopeptidase 24-16 was stained by immunohistochemical techniques using a monospecific polyclonal antibody. Endopeptidase 24-16 is present in 80-85% of the nondifferentiated neurons. The proportion of immunoreactive neurons decreased during maturation to reach 35-40% after 4-8 d of culture. By contrast, neurotensin receptors were not detectable in nondifferentiated cells and appear during maturation. Specific 125 I-Tyr3-neurotensin labeling is maximal after 4 d of culture and is located on about 10% of differentiated neurons. Double-labeling experiments show that about 90% of cortical, hypothalamic, and mesencephalic neurons bearing the neurotensin receptor also contained endopeptidase 24-16, supporting the hypothesis that one of the functions of endopeptidase 24-16 is the physiological inactivation of neurotensin. However, the presence of endopeptidase 24-16 on numerous neurons that do not contain neurotensin receptors also suggests that the enzyme could be involved in the degradation and/or maturation of other neuropeptides

  9. Early, Real-Time Medical Diagnosis of Botulism by Endopeptidase-Mass Spectrometry.

    Science.gov (United States)

    Rosen, Osnat; Feldberg, Liron; Gura, Sigalit; Brosh-Nissimov, Tal; Guri, Alex; Zimhony, Oren; Shapiro, Eli; Beth-Din, Adi; Stein, Dana; Ozeri, Eyal; Barnea, Ada; Turgeman, Amram; Ben David, Alon; Schwartz, Arieh; Elhanany, Eytan; Diamant, Eran; Yitzhaki, Shmuel; Zichel, Ran

    2015-12-15

    Botulinum toxin was detected in patient serum using Endopeptidase-mass-spectrometry assay, although all conventional tests provided negative results. Antitoxin was administered, resulting in patient improvement. Implementing this highly sensitive and rapid assay will improve preparedness for foodborne botulism and deliberate exposure. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Jaslyn E. M. M. [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Midtgaard, Søren Roi [University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark); Gysel, Kira [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Thygesen, Mikkel B.; Sørensen, Kasper K.; Jensen, Knud J. [University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark); Stougaard, Jens; Thirup, Søren; Blaise, Mickaël, E-mail: mickael.blaise@cpbs.cnrs.fr [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark)

    2015-03-01

    The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

  11. Recent developments in esophageal motor disorders

    NARCIS (Netherlands)

    Beaumont, Hanneke; Boeckxstaens, Guy

    2007-01-01

    PURPOSE OF REVIEW: Every year more insight into the pathogenesis and treatment of esophageal motor disorders is obtained. This review highlights some interesting literature published in this area during the last year. RECENT FINDINGS: Longitudinal and circular muscle contractions act in a well

  12. Gene Expression of Lytic Endopeptidases AlpA and AlpB from Lysobacter sp. XL1 in Pseudomonads.

    Science.gov (United States)

    Tsfasman, Irina M; Lapteva, Yulia S; Krasovskaya, Ludmila A; Kudryakova, Irina V; Vasilyeva, Natalia V; Granovsky, Igor E; Stepnaya, Olga A

    2015-01-01

    Development of an efficient expression system for (especially secreted) bacterial lytic enzymes is a complicated task due to the specificity of their action. The substrate for such enzymes is peptidoglycan, the main structural component of bacterial cell walls. For this reason, expression of recombinant lytic proteins is often accompanied with lysis of the producing bacterium. This paper presents data on the construction of an inducible system for expression of the lytic peptidases AlpA and AlpB from Lysobacter sp. XL1 in Pseudomonas fluorescens Q2-87, which provides for the successful secretion of these proteins into the culture liquid. In this system, the endopeptidase gene under control of the T7lac promoter was integrated into the bacterial chromosome, as well as the Escherichia coli lactose operon repressor protein gene. The T7 pol gene under lac promoter control, which encodes the phage T7 RNA polymerase, is maintained in Pseudomonas cells on the plasmids. Media and cultivation conditions for the recombinant strains were selected to enable the production of AlpA and AlpB by a simple purification protocol. Production of recombinant lytic enzymes should contribute to the development of new-generation antimicrobial drugs whose application will not be accompanied by selection of resistant microorganisms. © 2015 S. Karger AG, Basel.

  13. Psychosocial and psychosexual aspects of disorders of sex development

    NARCIS (Netherlands)

    Cohen-Kettenis, P.T.

    2010-01-01

    Psychosocial aspects of the treatment of disorders of sex development (DSDs) concern gender assignment, information management and communication, timing of medical interventions, consequences of surgery, and sexuality. Although outcome is often satisfactory, a variety of medical and psychosocial

  14. Fine motor skills development of children with autism sepctrum disorder.

    OpenAIRE

    Marešová, Petra

    2010-01-01

    My diploma thesis topic is Fine motor skills development of children with autism spectrum disorder. The objective of this document is to create a well arranged group of exercises and structured tasks aimed to develop fine motor skills of children at pre-school age with autism spectrum disorder. Theoretical part of this diploma thesis contains basic information related to autism and various details about motor skills. Practical section describes individual jobs and structured tasks used for fi...

  15. IrAE - An asparaginyl endopeptidase (legumain) in the gut of the hard tick Ixodes ricinus

    Czech Academy of Sciences Publication Activity Database

    Sojka, Daniel; Hajdušek, Ondřej; Dvořák, J.; Sajid, M.; Franta, Zdeněk; Schneider, E. L.; Craik, C. S.; Vancová, Marie; Burešová, Veronika; Bogyo, M.; Sexton, K. B.; McKerrow, J. H.; Caffrey, C. R.; Kopáček, Petr

    2007-01-01

    Roč. 37, č. 7 (2007), s. 713-724 ISSN 0020-7519 R&D Projects: GA ČR GA206/06/0865; GA AV ČR IAA6022307; GA MŠk(CZ) LC06009; GA ČR GD524/03/H133 Grant - others:GA MŠk(CZ) FRVŠ 3646/2005; NIH(US) AI35707 Institutional research plan: CEZ:AV0Z60220518 Source of funding: V - iné verejné zdroje Keywords : asparaginyl endopeptidase * tick gut, * blood digestion Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.392, year: 2007

  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. Development and validation of the Stirling Eating Disorder Scales.

    Science.gov (United States)

    Williams, G J; Power, K G; Miller, H R; Freeman, C P; Yellowlees, A; Dowds, T; Walker, M; Parry-Jones, W L

    1994-07-01

    The development and reliability/validity check of an 80-item, 8-scale measure for use with eating disorder patients is presented. The Stirling Eating Disorder Scales (SEDS) assess anorexic dietary behavior, anorexic dietary cognitions, bulimic dietary behavior, bulimic dietary cognitions, high perceived external control, low assertiveness, low self-esteem, and self-directed hostility. The SEDS were administered to 82 eating disorder patients and 85 controls. Results indicate that the SEDS are acceptable in terms of internal consistency, reliability, group validity, and concurrent validity.

  18. Characterization of the glutamate-specific endopeptidase from Bacillus licheniformis expressed in Escherichia coli.

    Science.gov (United States)

    Ye, Wei; Wang, Haiying; Ma, Yi; Luo, Xiaochun; Zhang, Weimin; Wang, Jufang; Wang, Xiaoning

    2013-10-10

    Glutamate-specific endopeptidase from Bacillus licheniformis (GSE-BL) is widely used in peptide recovery and synthesis because of its unique substrate specificity. However, the mechanism underlying its specificity is still not thoroughly understood. In this study, the roles of the prosegment and key amino acids involved in the proteolytic activity of GSE-BL were investigated. Loss of the GSE-BL prosegment severely restricted enzymatic activity toward Z-Phe-Leu-Glu-pNA. A homologous model of GSE-BL revealed that it contains the catalytic triad "His47, Asp96 and Ser 167", which was further confirmed by site-directed mutagenesis. In vitro mutagenesis further indicated that Val2, Arg89 and His190 are essential for enzymatic activity toward Z-Phe-Leu-Glu-pNA. Moreover, the catalytic efficiency of Phe57Ala GSE-BL toward Z-Phe-Leu-Glu-pNA was 50% higher than that of the native mature GSE-BL. This is the first study to fully elucidate the key amino acids for proteolytic activity of GSE-BL. Mature GSE-BL could be obtained through self-cleavage alone when Lys at -1 position was replaced by Glu, providing a new strategy for the preparation of mature GSE-BL. This study yielded some valuable insights into the substrate specificity of glutamate-specific endopeptidase, establishing a foundation for broadening the applications of GSE-BL. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. DEVELOPMENT AND DISORDERS OF SPEECH IN CHILDHOOD.

    Science.gov (United States)

    KARLIN, ISAAC W.; AND OTHERS

    THE GROWTH, DEVELOPMENT, AND ABNORMALITIES OF SPEECH IN CHILDHOOD ARE DESCRIBED IN THIS TEXT DESIGNED FOR PEDIATRICIANS, PSYCHOLOGISTS, EDUCATORS, MEDICAL STUDENTS, THERAPISTS, PATHOLOGISTS, AND PARENTS. THE NORMAL DEVELOPMENT OF SPEECH AND LANGUAGE IS DISCUSSED, INCLUDING THEORIES ON THE ORIGIN OF SPEECH IN MAN AND FACTORS INFLUENCING THE NORMAL…

  20. Development and Validation of the Minnesota Borderline Personality Disorder Scale

    Science.gov (United States)

    Bornovalova, Marina A.; Hicks, Brian M.; Patrick, Christopher J.; Iacono, William G.; McGue, Matt

    2011-01-01

    Although large epidemiological data sets can inform research on the etiology and development of borderline personality disorder (BPD), they rarely include BPD measures. In some cases, however, proxy measures can be constructed using instruments already in these data sets. In this study, the authors developed and validated a self-report measure of…

  1. Development of Rostral Prefrontal Cortex and Cognitive and Behavioural Disorders

    Science.gov (United States)

    Dumontheil, Iroise; Burgess, Paul W.; Blakemore, Sarah-Jayne

    2008-01-01

    Information on the development and functions of rostral prefrontal cortex (PFC), or Brodmann area 10, has been gathered from different fields, from anatomical development to functional neuroimaging in adults, and put forward in relation to three particular cognitive and behavioural disorders. Rostral PFC is larger and has a lower cell density in…

  2. Nutritional Disorders and the Development of Young Children: A Bibliography.

    Science.gov (United States)

    Erickson, Joan Good

    This bibliography on nutritional disorders and child development is directed towards early childhood professionals outside the field of nutrition. The main topic covered pertains to malnutrition and undernutrition as it relates to mental/intellectual/cognitive development of children from the fetal stage through the early childhood years. Included…

  3. CLONING AND SEQUENCING OF THE GENE FOR A LACTOCOCCAL ENDOPEPTIDASE, AN ENZYME WITH SEQUENCE SIMILARITY TO MAMMALIAN ENKEPHALINASE

    NARCIS (Netherlands)

    Mierau, Igor; Tan, Paris S.T.; Haandrikman, Alfred J.; Kok, Jan; Leenhouts, Kees J.; Konings, Wil N.; Venema, Gerard

    The gene specifying an endopeptidase of Lactococcus lactis, named pepO, was cloned from a genomic library of L. lactis subsp. cremoris P8-247 in lambdaEMBL3 and was subsequently sequenced. pepO is probably the last gene of an operon encoding the binding-protein-dependent oligopeptide transport

  4. 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

    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. 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. 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. 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. The reader will be able to: (1) identify the difficulties in studying disordered speech motor development; (2) describe the differences in speech motor characteristics between SSD and subtype CAS; (3) describe the different types of learning that occur in the sensory-motor system during babbling and early speech acquisition; (4) identify the neural control subsystems involved in speech production; (5) describe the potential role of auditory self-monitoring in developmental speech disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Crystal structure of a catalytically active, non-toxic endopeptidase derivative of Clostridium botulinum toxin A.

    Science.gov (United States)

    Masuyer, Geoffrey; Thiyagarajan, Nethaji; James, Peter L; Marks, Philip M H; Chaddock, John A; Acharya, K Ravi

    2009-03-27

    Botulinum neurotoxins (BoNTs) modulate cholinergic nerve terminals to result in neurotransmitter blockade. BoNTs consists of catalytic (LC), translocation (Hn) and cell-binding domains (Hc). The binding function of the Hc domain is essential for BoNTs to bind the neuronal cell membrane, therefore, removal of the Hc domain results in a product that retains the endopeptidase activity of the LC but is non-toxic. Thus, a molecule consisting of LC and Hn domains of BoNTs, termed LHn, is a suitable molecule for engineering novel therapeutics. The structure of LHA at 2.6 A reported here provides an understanding of the structural implications and challenges of engineering therapeutic molecules that combine functional properties of LHn of BoNTs with specific ligand partners to target different cell types.

  6. Sociological Factors in the Development of Eating Disorders.

    Science.gov (United States)

    Nagel, K. L.; Jones, Karen H.

    1992-01-01

    Reviews sociocultural, socioeconomic, and sex-related factors which contribute to development of eating disorders. Recommends that professionals help adolescents resist societal pressure to conform to unrealistic standards of appearance and provide guidance on nutrition, realistic body ideals, and achievement of self-esteem, self-efficacy,…

  7. Consanguinity and Disorders of Sexual Developments in the Sudan ...

    African Journals Online (AJOL)

    Background: Consanguinity is very common in the Sudanese society. There is a lack of studies on consanguinity and its impact on genetic diseases in Sudan. In this study we correlated Disorders of Sexual developments (DSDs), as an example of genetic conditions, in relation with consanguinity. Material and Methods: A ...

  8. The Development of Siblings' Understanding of Autism Spectrum Disorders.

    Science.gov (United States)

    Glasberg, Beth A.

    2000-01-01

    Sixty-three siblings (and their parents) of individuals with autism or related disorders were interviewed to determine their cognitive sophistication about autism. Although children's reasoning became more mature with age, it tended to develop at a delayed rate compared to norms for illness concepts. Parents tended to overestimate their child's…

  9. Group Development for Students with Emotional/Behavioral Disorders.

    Science.gov (United States)

    Rockwell, Sylvia; Guetzloe, Eleanor

    1996-01-01

    This article addresses effective techniques for teaching students with emotional disturbances and/or behavior disorders in group settings. Three stages of group development are described with specific teaching strategies for each stage identified and related to Maslow's hierarchy of needs, including needs for safety and trust, belonging and…

  10. Risk Factors for the Development of Metabolic Disorders: A Review ...

    African Journals Online (AJOL)

    External factors impact on the hormones and enzymes which trigger development of metabolic disorders. The aim of this review was to highlight major hormonal and enzymatic factors that differentially predispose males and females to obesity, diabetes mellitus and hypertension. The research was a literaturebased ...

  11. AmpH, a bifunctional DD-endopeptidase and DD-carboxypeptidase of Escherichia coli.

    Science.gov (United States)

    González-Leiza, Silvia M; de Pedro, Miguel A; Ayala, Juan A

    2011-12-01

    In Escherichia coli, low-molecular-mass penicillin-binding proteins (LMM PBPs) are important for correct cell morphogenesis. These enzymes display DD-carboxypeptidase and/or dd-endopeptidase activities associated with maturation and remodeling of peptidoglycan (PG). AmpH has been classified as an AmpH-type class C LMM PBP, a group closely related to AmpC β-lactamases. AmpH has been associated with PG recycling, although its enzymatic activity remained uncharacterized until now. Construction and purification of His-tagged AmpH from E. coli permitted a detailed study of its enzymatic properties. The N-terminal export signal of AmpH is processed, but the protein remains membrane associated. The PBP nature of AmpH was demonstrated by its ability to bind the β-lactams Bocillin FL (a fluorescent penicillin) and cefmetazole. In vitro assays with AmpH and specific muropeptides demonstrated that AmpH is a bifunctional DD-endopeptidase and DD-carboxypeptidase. Indeed, the enzyme cleaved the cross-linked dimers tetrapentapeptide (D45) and tetratetrapeptide (D44) with efficiencies (k(cat)/K(m)) of 1,200 M(-1) s(-1) and 670 M(-1) s(-1), respectively, and removed the terminal D-alanine from muropeptides with a C-terminal D-Ala-D-Ala dipeptide. Both DD-peptidase activities were inhibited by 40 μM cefmetazole. AmpH also displayed a weak β-lactamase activity for nitrocefin of 1.4 × 10(-3) nmol/μg protein/min, 1/1,000 the rate obtained for AmpC under the same conditions. AmpH was also active on purified sacculi, exhibiting the bifunctional character that was seen with pure muropeptides. The wide substrate spectrum of the DD-peptidase activities associated with AmpH supports a role for this protein in PG remodeling or recycling.

  12. 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

  13. Structural basis for type VI secreted peptidoglycan dl-endopeptidase function, specificity and neutralization in Serratia marcescens

    Energy Technology Data Exchange (ETDEWEB)

    Srikannathasan, Velupillai; English, Grant [University of Dundee, Dundee DD1 5EH, Scotland (United Kingdom); Bui, Nhat Khai [Newcastle University, Newcastle upon Tyne NE2 4HH (United Kingdom); Trunk, Katharina; O’Rourke, Patrick E. F.; Rao, Vincenzo A. [University of Dundee, Dundee DD1 5EH, Scotland (United Kingdom); Vollmer, Waldemar [Newcastle University, Newcastle upon Tyne NE2 4HH (United Kingdom); Coulthurst, Sarah J., E-mail: s.j.coulthurst@dundee.ac.uk; Hunter, William N., E-mail: s.j.coulthurst@dundee.ac.uk [University of Dundee, Dundee DD1 5EH, Scotland (United Kingdom)

    2013-12-01

    Crystal structures of type VI secretion system-associated immunity proteins, a peptidoglycan endopeptidase and a complex of the endopeptidase and its cognate immunity protein are reported together with assays of endopeptidase activity and functional assessment. Some Gram-negative bacteria target their competitors by exploiting the type VI secretion system to extrude toxic effector proteins. To prevent self-harm, these bacteria also produce highly specific immunity proteins that neutralize these antagonistic effectors. Here, the peptidoglycan endopeptidase specificity of two type VI secretion-system-associated effectors from Serratia marcescens is characterized. These small secreted proteins, Ssp1 and Ssp2, cleave between γ-d-glutamic acid and l-meso-diaminopimelic acid with different specificities. Ssp2 degrades the acceptor part of cross-linked tetratetrapeptides. Ssp1 displays greater promiscuity and cleaves monomeric tripeptides, tetrapeptides and pentapeptides and dimeric tetratetra and tetrapenta muropeptides on both the acceptor and donor strands. Functional assays confirm the identity of a catalytic cysteine in these endopeptidases and crystal structures provide information on the structure–activity relationships of Ssp1 and, by comparison, of related effectors. Functional assays also reveal that neutralization of these effectors by their cognate immunity proteins, which are called resistance-associated proteins (Raps), contributes an essential role to cell fitness. The structures of two immunity proteins, Rap1a and Rap2a, responsible for the neutralization of Ssp1 and Ssp2-like endopeptidases, respectively, revealed two distinct folds, with that of Rap1a not having previously been observed. The structure of the Ssp1–Rap1a complex revealed a tightly bound heteromeric assembly with two effector molecules flanking a Rap1a dimer. A highly effective steric block of the Ssp1 active site forms the basis of effector neutralization. Comparisons with Ssp2–Rap2

  14. Structural basis for type VI secreted peptidoglycan dl-endopeptidase function, specificity and neutralization in Serratia marcescens

    International Nuclear Information System (INIS)

    Srikannathasan, Velupillai; English, Grant; Bui, Nhat Khai; Trunk, Katharina; O’Rourke, Patrick E. F.; Rao, Vincenzo A.; Vollmer, Waldemar; Coulthurst, Sarah J.; Hunter, William N.

    2013-01-01

    Crystal structures of type VI secretion system-associated immunity proteins, a peptidoglycan endopeptidase and a complex of the endopeptidase and its cognate immunity protein are reported together with assays of endopeptidase activity and functional assessment. Some Gram-negative bacteria target their competitors by exploiting the type VI secretion system to extrude toxic effector proteins. To prevent self-harm, these bacteria also produce highly specific immunity proteins that neutralize these antagonistic effectors. Here, the peptidoglycan endopeptidase specificity of two type VI secretion-system-associated effectors from Serratia marcescens is characterized. These small secreted proteins, Ssp1 and Ssp2, cleave between γ-d-glutamic acid and l-meso-diaminopimelic acid with different specificities. Ssp2 degrades the acceptor part of cross-linked tetratetrapeptides. Ssp1 displays greater promiscuity and cleaves monomeric tripeptides, tetrapeptides and pentapeptides and dimeric tetratetra and tetrapenta muropeptides on both the acceptor and donor strands. Functional assays confirm the identity of a catalytic cysteine in these endopeptidases and crystal structures provide information on the structure–activity relationships of Ssp1 and, by comparison, of related effectors. Functional assays also reveal that neutralization of these effectors by their cognate immunity proteins, which are called resistance-associated proteins (Raps), contributes an essential role to cell fitness. The structures of two immunity proteins, Rap1a and Rap2a, responsible for the neutralization of Ssp1 and Ssp2-like endopeptidases, respectively, revealed two distinct folds, with that of Rap1a not having previously been observed. The structure of the Ssp1–Rap1a complex revealed a tightly bound heteromeric assembly with two effector molecules flanking a Rap1a dimer. A highly effective steric block of the Ssp1 active site forms the basis of effector neutralization. Comparisons with Ssp2–Rap2

  15. Gender identity in disorders of sex development: review article.

    Science.gov (United States)

    Yang, Jennifer H; Baskin, Laurence S; DiSandro, Michael

    2010-01-01

    Many concerns have been raised regarding the treatment and long-term outcome of infants born with complex genital anomalies. Debate among clinicians, psychologists, ethicists, and patient advocate groups regarding the optimal management of these individuals is ongoing. Although determining the most appropriate gender is a difficult task, this review will help clarify some of the issues at hand. A literature review which addresses the challenges of advising families about gender identity in infants and children with disorders of sex development. The evidence for endocrine effects on neurobiological development with regard to sexual behavior is compelling, although the existing outcome studies are largely anecdotal and somewhat contradictory. Gender assignment in infants born with a disorder of sex development remains only one of the many difficult decisions faced by both the treatment team and the family. Improved long-term follow-up of these patients will provide much needed feedback on previous and contemporary management. 2010 Elsevier Inc. All rights reserved.

  16. Transactional processes in the development of adult personality disorder symptoms.

    Science.gov (United States)

    Carlson, Elizabeth A; Ruiz, Sarah K

    2016-08-01

    The development of adult personality disorder symptoms, including transactional processes of relationship representational and behavioral experience from infancy to early adolescence, was examined using longitudinal data from a risk sample (N = 162). Significant preliminary correlations were found between early caregiving experience and adult personality disorder symptoms and between representational and behavioral indices across time and adult symptomatology. Significant correlations were also found among diverse representational assessments (e.g., interview, drawing, and projective narrative) and between concurrent representational and observational measures of relationship functioning. Path models were analyzed to investigate the combined relations of caregiving experience in infancy; relationship representation and experience in early childhood, middle childhood, and early adolescence; and personality disorder symptoms in adulthood. The hypothesized model representing interactive contributions of representational and behavioral experience represented the data significantly better than competing models representing noninteractive contributions. Representational and behavioral indicators mediated the link between early caregiving quality and personality disorder symptoms. The findings extend previous studies of normative development and support an organizational developmental view that early relationship experiences contribute to socioemotional maladaptation as well as adaptation through the progressive transaction of mutually informing expectations and experience.

  17. Disorder of Sexual Development and Congenital Heart Defect in 47XYY: Clinical Disorder or Coincidence?

    Directory of Open Access Journals (Sweden)

    Hanane Latrech

    2015-01-01

    Full Text Available Background. 47XYY syndrome is a rare sex chromosome variation characterized by an additional Y chromosome. Most patients with 47XYY karyotype have normal phenotype. This disorder seems associated with a higher risk of developing behavioral and cognitive problems, tall stature, and infertility in adulthood. Sexual development disorder is a rare finding. We report a first case with an abnormal left coronary artery originating from the pulmonary artery in a 47XYY patient. Case. A one-month-old child was referred for ectopic testis and micropenis. Physical examination revealed facial dysmorphia, micropenis, and curvature of the penis with nonpalpable testis. Laboratory tests showed decreased total testosterone and anti-Mullerian hormone (AMH levels. Blood karyotyping revealed a 47XYY chromosomal formula. At the age of 3 months, the patient developed dyspnea and tachycardia. Echocardiography revealed an anomalous left coronary artery from pulmonary artery with left ventricular dysfunction requiring surgical revascularization by direct reimplantation of the left coronary artery system. Our second case was a 3-year-old child referred for hypospadias with nonpalpable left testicle. Physical examination showed hypertelorism. Blood karyotyping revealed a 47XYY chromosomal formula. Conclusion. To our knowledge, this is the first case of 47XYY syndrome associated with this congenital heart malformation and a sexual development disorder.

  18. Cloning and expression analysis of genes encoding lytic endopeptidases L1 and L5 from Lysobacter sp. strain XL1.

    Science.gov (United States)

    Lapteva, Y S; Zolova, O E; Shlyapnikov, M G; Tsfasman, I M; Muranova, T A; Stepnaya, O A; Kulaev, I S; Granovsky, I E

    2012-10-01

    Lytic enzymes are the group of hydrolases that break down structural polymers of the cell walls of various microorganisms. In this work, we determined the nucleotide sequences of the Lysobacter sp. strain XL1 alpA and alpB genes, which code for, respectively, secreted lytic endopeptidases L1 (AlpA) and L5 (AlpB). In silico analysis of their amino acid sequences showed these endopeptidases to be homologous proteins synthesized as precursors similar in structural organization: the mature enzyme sequence is preceded by an N-terminal signal peptide and a pro region. On the basis of phylogenetic analysis, endopeptidases AlpA and AlpB were assigned to the S1E family [clan PA(S)] of serine peptidases. Expression of the alpA and alpB open reading frames (ORFs) in Escherichia coli confirmed that they code for functionally active lytic enzymes. Each ORF was predicted to have the Shine-Dalgarno sequence located at a canonical distance from the start codon and a potential Rho-independent transcription terminator immediately after the stop codon. The alpA and alpB mRNAs were experimentally found to be monocistronic; transcription start points were determined for both mRNAs. The synthesis of the alpA and alpB mRNAs was shown to occur predominantly in the late logarithmic growth phase. The amount of alpA mRNA in cells of Lysobacter sp. strain XL1 was much higher, which correlates with greater production of endopeptidase L1 than of L5.

  19. NMR and photo-CIDNP studies of human proinsulin and prohormone processing intermediates with application to endopeptidase recognition

    International Nuclear Information System (INIS)

    Weiss, M.A.; Frank, B.H.; Heiney, R.; Pekar, A.; Khait, I.; Neuringer, L.J.; Shoelson, S.E.

    1990-01-01

    The proinsulin-insulin system provides a general model for the proteolytic processing of polypeptide hormones. Two proinsulin-specific endopeptidases have been defined, a type I activity that cleaves the B-chain/C-peptide junction (Arg 31 -Arg 32 ) and a type II activity that cleaves the C-peptide/A-chain junction (Lys 64 -Arg 65 ). These endopeptidases are specific for their respective dibasic target sites; not all such dibasic sites are cleaved, however, and studies of mutant proinsulins have demonstrated that additional sequence or structural features are involved in determining substrate specificity. To define structural elements required for endopeptidase recognition, the authors have undertaken comparative 1 H NMR and photochemical dynamic nuclear polarization (photo-CIDNP) studies of human proinsulin, insulin, and split proinsulin analogues as models or prohormone processing intermediates. The overall conformation of proinsulin is observed to be similar to that of insulin, and the connecting peptide is largely unstructured. In the 1 H NMR spectrum of proinsulin significant variation is observed in the line widths of insulin-specific amide resonances, reflecting exchange among conformational substrates; similar exchange is observed in insulin and is not damped by the connecting peptide. The aromatic 1 H NMR resonances of proinsulin are assigned by analogy to the spectrum of insulin, and assignments are verified by chemical modification. These results suggest that a stable local structure is formed at the CA junction, which influences insulin-specific packing interactions. They propose that this structure (designated the CA knuckle) provides a recognition element for type II proinsulin endopeptidase

  20. 46,XX T testicular disorder of sex development. Case report.

    Science.gov (United States)

    Pastor Guzmán, José María; Pastor Navarro, Hector; Quintanilla Mata, María Luisa; Carrión López, Pedro; Martínez Ruíz, Jesús; Martínez Sanchiz, Carlos; Perán Teruel, Miguel; Virseda Rodríguez, Julio Antonio

    2011-06-01

    We present a case of X-Y translocation with male phenotype (46,XX testicular disorder of sex development) and review the literature. Disorders of sex development with mismatch of genetic, gonadal and phenotypic sex are quite rare, and some are due to genetic or chromosomal abnormalities. The karyotype was investigated by a cytogenetic study of peripheral blood (phytohemagglutinin-timulated lymphocyte culture over 72 hours). G-banding analysis of 25 metaphases showed a 46,XX chromosome constitution (46 chromosomes with XX sexual composition). Fluorescence in situ hybridization (FISH) analysis with probes for X centromeres and the sex-determining region of the Y chromosome (SRY) (testis-determining factor gene) showed two X chromosomes. The analysis also showed the SRY signal in the telomeric region of the short arm of one of the chromosomes. In recent years, a number of other genes involved in disorders of sex development in animals and humans have also been identified. Genetic defects in the peptide hormone receptors, members of the steroid receptor superfamily, and other transcription factors, as well as any of a series of enzymes and cofactors involved in steroid biosynthesis can cause abnormal determination and differentiation. Although chromosomal abnormalities are rarely present in patients with apparently normal external genitalia, they should be considered in urology consultations by adolescents and adults, particularly in the investigation of gynecomastia or infertility.

  1. Destructin-1 is a collagen-degrading endopeptidase secreted by Pseudogymnoascus destructans, the causative agent of white-nose syndrome.

    Science.gov (United States)

    O'Donoghue, Anthony J; Knudsen, Giselle M; Beekman, Chapman; Perry, Jenna A; Johnson, Alexander D; DeRisi, Joseph L; Craik, Charles S; Bennett, Richard J

    2015-06-16

    Pseudogymnoascus destructans is the causative agent of white-nose syndrome, a disease that has caused the deaths of millions of bats in North America. This psychrophilic fungus proliferates at low temperatures and targets hibernating bats, resulting in their premature arousal from stupor with catastrophic consequences. Despite the impact of white-nose syndrome, little is known about the fungus itself or how it infects its mammalian host. P. destructans is not amenable to genetic manipulation, and therefore understanding the proteins involved in infection requires alternative approaches. Here, we identify hydrolytic enzymes secreted by P. destructans, and use a novel and unbiased substrate profiling technique to define active peptidases. These experiments revealed that endopeptidases are the major proteolytic activities secreted by P. destructans, and that collagen, the major structural protein in mammals, is actively degraded by the secretome. A serine endopeptidase, hereby-named Destructin-1, was subsequently identified, and a recombinant form overexpressed and purified. Biochemical analysis of Destructin-1 showed that it mediated collagen degradation, and a potent inhibitor of peptidase activity was identified. Treatment of P. destructans-conditioned media with this antagonist blocked collagen degradation and facilitated the detection of additional secreted proteolytic activities, including aminopeptidases and carboxypeptidases. These results provide molecular insights into the secretome of P. destructans, and identify serine endopeptidases that have the clear potential to facilitate tissue invasion and pathogenesis in the mammalian host.

  2. Comorbid ADHD and mental health disorders: are these children more likely to develop reading disorders?

    Science.gov (United States)

    Levy, Florence; Young, Deidra J; Bennett, Kelly S; Martin, Neilson C; Hay, David A

    2013-03-01

    While attention-deficit/hyperactivity disorder (ADHD) has been associated with both internalizing and externalizing childhood behaviour disorders, the specific relationship of these comorbid disorders to ADHD and reading problems is less well defined. The present study analysed data from the Australian Twin ADHD Project, which utilized DSM-IV-based ratings of ADHD, separation anxiety disorder, generalized anxiety disorder, depression, conduct disorder, and oppositional defiant disorder for twins and siblings aged 6 to 18 years. While differences between children with and without ADHD were demonstrated for those with separation anxiety disorder, generalized anxiety disorder, depression, conduct disorder, oppositional defiant disorder and a reading disorder, for all age groups, regression analysis of ADHD diagnostic subtypes by age and reading disorder showed that only generalized anxiety disorder remained significant after controlling for ADHD subtypes. Analysis of the mean reading disorder scores in children with and without ADHD showed that children with conduct disorder had significantly more reading problems, as did children with multiple comorbid disorders. In summary, both age and ADHD diagnosis were associated with variations in these comorbid disorders, and multiple comorbid disorders were associated with greater reading impairment.

  3. Radical scavenging, prolyl endopeptidase inhibitory, and antimicrobial potential of a cultured Himalayan lichen Cetrelia olivetorum.

    Science.gov (United States)

    Savale, Swapnil Anil; Pol, Chaitrali Satish; Khare, Roshni; Verma, Neeraj; Gaikwad, Subhash; Mandal, Bapi; Behera, Bhaskar C

    2016-01-01

    Lichens are source of natural bioactive compounds which are traditionally used to cure a variety of ailments. The objective of this study is to assess free radical scavenging, prolyl endopeptidase inhibitory (PEPI), and antimicrobial potential of a high altitude lichen species Cetrelia olivetorum (Nyl.) W. L. Culb. & C. F. Culb (Parmeliaceae). Lichen C. olivetorum has been cultured in vitro, and optimized culture conditions were implemented in bioreactor to obtain high quantity of biomass for the study of radical scavenging, PEPI, and antimicrobial activities. Radical scavenging activity of methanol extract of Cetrelia olivetorum (MECO) was tested at 100 µg/mL, PEPI activity at 25 and 50 µg/mL, and antimicrobial activity at 5, 25, 50, and 100 µg/mL conc. All the biological activities of natural thallus extract and its derived culture extract were evaluated spectrophotometrically. Murashige and Skoog medium supplemented with 3% glucose and 100 ppb indole-3-butyric acid (IBA) supported biomass growth at flask level and yielded 5.095 g biomass in bioreactor. MECO of both the cultured and the natural lichen exhibited half inhibiting concentration (IC50) for radical scavenging activities in the range of 50-60 µg/mL, whereas the IC50 value of standard antioxidants was found to be in the range of 12-29 µg/mL. The IC50 value of lichen extract for PEPI activity was 144-288 µg/mL, whereas the IC50 value of standard prolyl endopeptidase inhibitor, Z-pro-prolinal, was 57.73 µg/mL. As far as the antimicrobial activity of MECO is concerned, minimum inhibitory concentration (MIC) value of lichen extracts against tested microorganisms was obtained in the range of 50-104 µg/mL and found to be more effective than commercially available standard erythromycin. Murashige and Skoog medium containing IBA was found to be suitable for maximum biomass production of C. olivetorum under bioreactor conditions. The cultured lichen biomass extract also showed

  4. The epigenetic switches for neural development and psychiatric disorders.

    Science.gov (United States)

    Lv, Jingwen; Xin, Yongjuan; Zhou, Wenhao; Qiu, Zilong

    2013-07-20

    The most remarkable feature of the nervous system is that the development and functions of the brain are largely reshaped by postnatal experiences, in joint with genetic landscapes. The nature vs. nurture argument reminds us that both genetic and epigenetic information is indispensable for the normal function of the brain. The epigenetic regulatory mechanisms in the central nervous system have been revealed over last a decade. Moreover, the mutations of epigenetic modulator genes have been shown to be implicated in neuropsychiatric disorders, such as autism spectrum disorders. The epigenetic study has initiated in the neuroscience field for a relative short period of time. In this review, we will summarize recent discoveries about epigenetic regulation on neural development, synaptic plasticity, learning and memory, as well as neuropsychiatric disorders. Although the comprehensive view of how epigenetic regulation contributes to the function of the brain is still not completed, the notion that brain, the most complicated organ of organisms, is profoundly shaped by epigenetic switches is widely accepted. Copyright © 2013. Published by Elsevier Ltd.

  5. Critical developments in the assessment of personality disorder.

    Science.gov (United States)

    Tyrer, Peter; Coombs, Natalie; Ibrahimi, Fatema; Mathilakath, Anand; Bajaj, Priya; Ranger, Maja; Rao, Bharti; Din, Raana

    2007-05-01

    The assessment of personality disorder is currently inaccurate, largely unreliable, frequently wrong and in need of improvement. To describe the errors inherent in the current systems and to indicate recent ways of improving personality assessment. Historical review, description of recent developments, including temporal stability, and of studies using document-derived assessment. Studies of interrater agreement and accuracy of diagnosis in complex patients with independently established personality status using document-derived assessment (PAS-DOC) with a four personality cluster classification, showed very good agreement between raters for the flamboyant cluster B group of personalities, generally good agreement for the anxious/dependent cluster C group and inhibited (obsessional) cluster D group, but only fair agreement for the withdrawn cluster A group. Overall diagnostic accuracy was 71%. Personality function or diathesis, a fluctuating state, is a better description than personality disorder. The best form of assessment is one that uses longitudinal repeated measures using a four-dimensional system.

  6. Parents' Strategies to Elicit Autobiographical Memories in Autism Spectrum Disorders, Developmental Language Disorders and Typically Developing Children

    Science.gov (United States)

    Goldman, Sylvie; DeNigris, Danielle

    2015-01-01

    Conversations about the past support the development of autobiographical memory. Parents' strategies to elicit child's participation and recall during past event conversations were compared across three school-age diagnostic groups: autism spectrum disorder (ASD, n = 11), developmental language disorders (n = 11) and typically developing (TD,…

  7. Attitudes towards "disorders of sex development" nomenclature among affected individuals.

    Science.gov (United States)

    Johnson, Emilie K; Rosoklija, Ilina; Finlayson, Courtney; Chen, Diane; Yerkes, Elizabeth B; Madonna, Mary Beth; Holl, Jane L; Baratz, Arlene B; Davis, Georgiann; Cheng, Earl Y

    2017-12-01

    Although now commonly used in medicine, the updated "disorders of sex development" (DSD) nomenclature formally introduced in 2006 has never been universally accepted by members of the affected community, particularly advocacy groups. Use of this nomenclature by medical professionals may unintentionally negatively affect access to healthcare and research for individuals with DSD conditions. Among individuals affected by various DSD diagnoses, this study sought to (1) evaluate attitudes towards potentially controversial DSD terminology, (2) determine potential impact of terminology on how affected individuals access healthcare, and (3) explore alternate terms. A web-based survey was developed in collaboration with the AIS-DSDSG (Androgen Insensitivity Syndrome-DSD Support Group) leadership. AIS-DSDSG members (caregivers and affected individuals) were surveyed about attitudes towards DSD, potential impact on healthcare utilization, and alternate terms. A qualitative analysis of reasons for using/avoiding specific terms was performed. Surveys were completed by 202 out of 580 (35%) AIS-DSDSG members (61% affected, 39% caregivers; 16% non-gender binary; age range of affected individuals 0-86 years). Only 24% use disorder of sex development to describe themselves/their child. A majority (69%) had a negative emotional experience because of clinical use of nomenclature; 81% changed their care because of it. Preferred and non-preferred terms for clinical care and research are illustrated in the figure. Preferred diagnostic terms were intersex, variation in sex development, and difference of sex development (55%, 52%, and 50% liked/strongly liked, respectively). Disorder of sex development was not preferred (17% liked/strongly liked). About one-third reported that they would not attend a clinic named the Disorder of Sex Development Clinic. Overall, 81% provided qualitative comments; flexible terminology use was a key theme. These study findings are consistent with previous

  8. Impact on infants' cognitive development of antenatal exposure to iron deficiency disorder and common mental disorders.

    Directory of Open Access Journals (Sweden)

    Thach Duc Tran

    Full Text Available OBJECTIVES: The aim of this study was to examine the effects of antenatal exposure to iron deficiency anemia (IDA and common mental disorders (CMD on cognitive development of 6 months old infants in a developing country. METHODS: A prospective population-based study in a rural province in Vietnam, which enrolled pregnant women at 12-20 weeks gestation and followed them up with their infants until six months postpartum. Criteria for IDA were Hb 30 years and primiparity had an indirect adverse effect on infants' Bayley cognitive scores. CONCLUSIONS: These findings suggest that antenatal IDA and CMD both have adverse effects on child cognitive development, which if unrecognized and unaddressed are likely to be lasting. It is crucial that both these risks are considered by policy makers, clinicians, and researchers seeking to improve child cognitive function in developing countries.

  9. Prolyl Endopeptidase (PREP) is Associated With Male Reproductive Functions and Gamete Physiology in Mice.

    Science.gov (United States)

    Dotolo, Raffaele; Kim, Jung Dae; Pariante, Paolo; Minucci, Sergio; Diano, Sabrina

    2016-03-01

    Prolyl endopeptidase (PREP) is a serine protease which has been implicated in many biological processes, such as the maturation and degradation of peptide hormones and neuropeptides, learning and memory, cell proliferation and differentiation, and glucose metabolism. A small number of reports have also suggested PREP participation in both male and female reproduction-associated processes. In the present work, we examined PREP distribution in male germ cells and studied the effects of its knockdown (Prep(gt/gt)) on testis and sperm in adult mice. The protein is expressed and localized in elongating spermatids and luminal spermatozoa of wild type (wt) mice, as well as Sertoli, Leydig, and peritubular cells. PREP is also expressed in the head and midpiece of epididymal spermatozoa, whereas the remaining tail region shows a weaker signal. Furthermore, testis weight, histology of seminiferous tubules, and epididymal sperm parameters were assessed in wt and Prep(gt/gt) mice: wild type testes have larger average tubule and lumen diameter; in addition, lumenal composition of seminiferous tubules is dissimilar between wt and Prep(gt/gt), as the percentage of spermiated tubules is much higher in wt. Finally, total sperm count, sperm motility, and normal morphology are also higher in wt than in Prep(gt/gt). These results show for the first time that the expression of PREP could be necessary for a correct reproductive function, and suggest that the enzyme may play a role in mouse spermatogenesis and sperm physiology. © 2015 Wiley Periodicals, Inc.

  10. A comprehensive review of the pharmacodynamics, pharmacokinetics and clinical effects of the neutral endopeptidase inhibitor racecadotril

    Directory of Open Access Journals (Sweden)

    Marion eEberlin

    2012-05-01

    Full Text Available Racecadotril, via its active metabolite thiorphan, is an inhibitor of the enzyme neutral endopeptidase (NEP, EC 3.4.24.11, thereby increasing exposure to NEP including enkephalins and atrial natriuretic peptide. Upon oral administration racecadotril is rapidly and effectively converted into the active metabolite thiorphan, which does not cross the blood-brain-barrier. Racecadotril has mainly been tested in animal models and patients of three therapeutic areas. As an analgesic the effects of racecadotril across animal models were inconsistent. In cardiovascular diseases such as hypertension or congestive heart failure results from animal studies were promising, probably related to increased exposure to atrial natriuretic peptide, but clinical results have not shown substantial therapeutic benefit over existing treatment options in cardiovascular disease. In contrast, racecadotril was consistently effective in animal models and patients with various forms of acute diarrhea by inhibiting pathologic (but not basal secretion from the gut without changing gastro-intestinal transit time or motility. This included studies in both adults and children. In direct comparative studies with loperamide in adults and children, racecadotril was at least as effective but exhibited fewer adverse events in most studies, particularly less rebound constipation. Several guidelines recommend the use of racecadotril as addition to oral rehydration treatment in children with acute diarrhea.

  11. Rab9-dependent retrograde transport and endosomal sorting of the endopeptidase furin

    Science.gov (United States)

    Chia, Pei Zhi Cheryl; Gasnereau, Isabelle; Lieu, Zi Zhao; Gleeson, Paul A.

    2011-01-01

    The endopeptidase furin and the trans-Golgi network protein TGN38 are membrane proteins that recycle between the TGN and plasma membrane. TGN38 is transported by a retromer-dependent pathway from early endosomes to the TGN, whereas the intracellular transport of furin is poorly defined. Here we have identified the itinerary and transport requirements of furin. Using internalisation assays, we show that furin transits the early and late endosomes en route to the TGN. The GTPase Rab9 and the TGN golgin GCC185, components of the late endosome-to-TGN pathway, were required for efficient TGN retrieval of furin. By contrast, TGN38 trafficking was independent of Rab9 and GCC185. To identify the sorting signals for the early endosome-to-TGN pathway, the trafficking of furin–TGN38 chimeras was investigated. The diversion of furin from the Rab9-dependent late-endosome-to-TGN pathway to the retromer-dependent early-endosome-to-TGN pathway required both the transmembrane domain and cytoplasmic tail of TGN38. We present evidence to suggest that the length of the transmembrane domain is a contributing factor in endosomal sorting. Overall, these data show that furin uses the Rab9-dependent pathway from late endosomes and that retrograde transport directly from early endosomes is dependent on both the transmembrane domain and the cytoplasmic tail. PMID:21693586

  12. Enzymatic and Structural Characterization of the Major Endopeptidase in the Venus Flytrap Digestion Fluid*

    Science.gov (United States)

    Risør, Michael W.; Thomsen, Line R.; Sanggaard, Kristian W.; Nielsen, Tania A.; Thøgersen, Ida B.; Lukassen, Marie V.; Rossen, Litten; Garcia-Ferrer, Irene; Guevara, Tibisay; Scavenius, Carsten; Meinjohanns, Ernst; Gomis-Rüth, F. Xavier; Enghild, Jan J.

    2016-01-01

    Carnivorous plants primarily use aspartic proteases during digestion of captured prey. In contrast, the major endopeptidases in the digestive fluid of the Venus flytrap (Dionaea muscipula) are cysteine proteases (dionain-1 to -4). Here, we present the crystal structure of mature dionain-1 in covalent complex with inhibitor E-64 at 1.5 Å resolution. The enzyme exhibits an overall protein fold reminiscent of other plant cysteine proteases. The inactive glycosylated pro-form undergoes autoprocessing and self-activation, optimally at the physiologically relevant pH value of 3.6, at which the protective effect of the pro-domain is lost. The mature enzyme was able to efficiently degrade a Drosophila fly protein extract at pH 4 showing high activity against the abundant Lys- and Arg-rich protein, myosin. The substrate specificity of dionain-1 was largely similar to that of papain with a preference for hydrophobic and aliphatic residues in subsite S2 and for positively charged residues in S1. A tentative structure of the pro-domain was obtained by homology modeling and suggested that a pro-peptide Lys residue intrudes into the S2 pocket, which is more spacious than in papain. This study provides the first analysis of a cysteine protease from the digestive fluid of a carnivorous plant and confirms the close relationship between carnivorous action and plant defense mechanisms. PMID:26627834

  13. Adenovirus type 2 endopeptidase: an unusual phosphoprotein enzyme matured by autocatalysis

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, P.K.; Flint, S.J.

    1987-02-01

    A 19-kDa protein, present in low copy number in purified adenovirus type 2, has been characterized. Several criteria were used to establish that this protein is neither a degradation product of the known structural proteins of the virion nor a minor, unusually modified, form of protein VII. This 19-kDa protein, unlike other virion proteins, possesses alkali-resistant phosphoamino acids. Analysis by partial proteolysis indicated that it is related to a 23-kDa phosphoprotein present in H2ts-1 virions assembled in infected cells maintained at 39/sup 0/C. Affinity labeling with (/sup 3/H)diisopropyl fluorophosphate showed that the 19-kDa protein contains the active site for a serine protease. The authors, therefore, conclude that the 19-kDa protein is the active form of the adenovirus-encoded endopeptidase, defined by the H2ts-1 mutation, and is synthesized as a 23-kDa precursor that appears to mature by autocatalysis.

  14. Current models of care for disorders of sex development

    DEFF Research Database (Denmark)

    Kyriakou, Andreas; Dessens, Arianne; Bryce, Jillian

    2016-01-01

    BACKGROUND: To explore the current models of practice in centres delivering specialist care for children with disorders of sex development (DSD), an international survey of 124 clinicians, identified through DSDnet and the I-DSD Registry, was performed in the last quarter of 2014. RESULTS: A total...... by 14 (19 %) centres. In addition to complex biochemistry and molecular genetic investigations, 40 clinicians (51 %) also had access to next generation sequencing. A genetic test was reported to be more preferable than biochemical tests for diagnosing 5-alpha reductase deficiency and 17-beta...

  15. Disorders of sex development in Indonesia: The course of psychological development in late identified patients

    NARCIS (Netherlands)

    A. Ediati (Annastasia)

    2014-01-01

    markdownabstract__Abstract__ In individuals with a disorder of sex development (DSD), prenatal development into male or female has deviated. Consequently, the child is born with anomalies of the genital tract and may have ambiguous sex characteristics. In Western countries, identification and

  16. Actigraph measures discriminate pediatric bipolar disorder from attention-deficit/hyperactivity disorder and typically developing controls.

    Science.gov (United States)

    Faedda, Gianni L; Ohashi, Kyoko; Hernandez, Mariely; McGreenery, Cynthia E; Grant, Marie C; Baroni, Argelinda; Polcari, Ann; Teicher, Martin H

    2016-06-01

    Distinguishing pediatric bipolar disorder (BD) from attention-deficit hyperactivity disorder (ADHD) can be challenging. Hyperactivity is a core feature of both disorders, but severely disturbed sleep and circadian dysregulation are more characteristic of BD, at least in adults. We tested the hypothesis that objective measures of activity, sleep, and circadian rhythms would help differentiate pediatric subjects with BD from ADHD and typically developing controls. Unmedicated youths (N = 155, 97 males, age 5-18) were diagnosed using DSM-IV criteria with Kiddie-SADS PL/E. BD youths (n = 48) were compared to typically developing controls (n = 42) and children with ADHD (n = 44) or ADHD plus comorbid depressive disorders (n = 21). Three-to-five days of minute-to-minute belt-worn actigraph data (Ambulatory Monitoring Inc.), collected during the school week, were processed to yield 28 metrics per subject, and assessed for group differences with analysis of covariance. Cross-validated machine learning algorithms were used to determine the predictive accuracy of a four-parameter model, with measures reflecting sleep, hyperactivity, and circadian dysregulation, plus Indic's bipolar vulnerability index (VI). There were prominent group differences in several activity measures, notably mean 5 lowest hours of activity, skewness of diurnal activity, relative circadian amplitude, and VI. A predictive support vector machine model discriminated bipolar from non-bipolar with mean accuracy of 83.1 ± 5.4%, ROC area of 0.781 ± 0.071, kappa of 0.587 ± 0.136, specificity of 91.7 ± 5.3%, and sensitivity of 64.4 ± 13.6%. Objective measures of sleep, circadian rhythmicity, and hyperactivity were abnormal in BD. Wearable sensor technology may provide bio-behavioral markers that can help differentiate children with BD from ADHD and healthy controls. © 2016 Association for Child and Adolescent Mental Health.

  17. Risk of developing major depressive disorder and anxiety disorders among adolescents and adults with atopic dermatitis: a nationwide longitudinal study.

    Science.gov (United States)

    Cheng, Chih-Ming; Hsu, Ju-Wei; Huang, Kai-Lin; Bai, Ya-Mei; Su, Tung-Ping; Li, Cheng-Ta; Yang, Albert C; Chang, Wen-Han; Chen, Tzeng-Ji; Tsai, Shih-Jen; Chen, Mu-Hong

    2015-06-01

    Previous cross-sectional studies have suggested a comorbid association between atopic dermatitis (AD) and depressive disorder as well as anxiety disorders, but the temporal relationship was not determined. Using the Taiwan National Health Insurance Research Database, 8208 AD patients aged 12 and older without psychiatric history and age-/sex-matched (1:1) controls between 1998 and 2008 were enrolled in our study and followed to the end of 2011. Subjects who developed major depression, any depressive disorder, and anxiety disorders during the follow-up were identified. The Cox regression analysis after adjusting for demographic data and atopic comorbidities demonstrated that patients with AD had an elevated risk of developing major depression (hazard ratio [HR]: 6.56, 95% confidence interval [CI]: 3.64-11.84), any depressive disorder (HR: 5.44, 95% CI: 3.99-7.44), and anxiety disorders (HR: 3.57, 95% CI: 2.55-4.98). Stratified by age group, both adolescents and adults with AD were prone to developing major depression (HR: 4.26, 95% CI: 1.39-13.13; HR: 7.56, 95% CI: 3.75-15.23), any depressive disorder (HR: 4.38, 95% CI: 2.09-9.18; HR: 5.66, 95% CI: 4.01-7.99), and anxiety disorders (HR: 5.40, 95% CI: 2.02-14.39; HR: 3.36, 95% CI: 2.38-4.80). AD in both adolescence and adulthood increased the risk of developing major depression, any depressive disorder, and anxiety disorders in later life. Further studies would be required to clarify the possible underlying mechanism between AD and depression as well as anxiety disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. CEREBELLUM: LINKS BETWEEN DEVELOPMENT, DEVELOPMENTAL DISORDERS AND MOTOR LEARNING

    Directory of Open Access Journals (Sweden)

    Mario U Manto

    2012-01-01

    Full Text Available The study of the links and interactions between development and motor learning has noticeable implications for the understanding and management of neurodevelopmental disorders. This is particularly relevant for the cerebellum which is critical for sensorimotor learning. The olivocerebellar pathway is a key pathway contributing to learning of motor skills. Its developmental maturation and remodelling are being unravelled. Advances in genetics have led to major improvements in our appraisal of the genes involved in cerebellar development, especially studies in mutant mice. Cerebellar neurogenesis is compartmentalized in relationship with neurotransmitter fate. The Engrailed-2 gene is a major actor of the specification of cerebellar cell types and late embryogenic morphogenesis. Math1, expressed by the rhombic lip (RL, is required for the genesis of glutamatergic neurons. Mutants deficient for the transcription factor Ptf1a display a lack of Purkinje cells and gabaergic interneurons. Rora gene contributes to the developmental signalling between granule cells and Purkinje neurons. The expression profile of SHH (Sonic hedgehog in postnatal stages determines the final size/shape of the cerebellum. Genes affecting the development impact upon the physiological properties of the cerebellar circuits. For instance, receptors are developmentally regulated and their action interferes directly with developmental processes. Another field of research which is expanding relates to very preterm neonates. They are at risk for cerebellar lesions, which may themselves impair the developmental events. Very preterm neonates often show sensori-motor deficits, highlighting another major link between impaired development and learning deficiencies. Pathways playing a critical role in cerebellar development are likely to become therapeutical targets for several neurodevelopmental disorders.

  19. Motor development of children with attention deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Francisco Rosa Neto

    2015-09-01

    Full Text Available Objective:To compare both global and specific domains of motor development of children with attention deficit hyperactivity disorder (ADHD with that of typically developing children.Methods:Two hundred children (50 children with clinical diagnoses of ADHD, according to the DSM-IV-TR and 150 typically developing controls, aged 5 to 10 years, participated in this cross-sectional study. The Motor Development Scale was used to assess fine and global motricity, balance, body schema, and spatial and temporal organization.Results:Between-group testing revealed statistically significant differences between the ADHD and control groups for all domains. The results also revealed a deficit of nearly two years in the motor development of children with ADHD compared with the normative sample.Conclusion:The current study shows that ADHD is associated with a delay in motor development when compared to typically developing children. The results also suggested difficulties in certain motor areas for those with ADHD. These results may point to plausible mechanisms underlying the relationship between ADHD and motor difficulties.

  20. Psychosocial implications of disorders of sex development treatment for parents.

    Science.gov (United States)

    Wisniewski, Amy B

    2017-01-01

    Historically, studies of caregivers of children with disorders of sex development (DSD) have been limited. Recent data reveal that parents of young children with DSD report increased stress, anxiety, depression, and decreased quality of life in ways that are similar to parents of children with other types of chronic illnesses. Also similar to other chronic illnesses of childhood, parents of children with DSD exhibit overprotective parenting and perceive their child as being vulnerable. These emotions and behaviors exhibited by parents are concerning as they may limit an affected child's emotional and social development over time. Perhaps, more unique to the situation of DSD is the perceived, or real, child-focused stigma experienced by parents of children with DSD. Interventions to improve parents' psychosocial adaptation to their child's medical condition, including coaching in how to discuss their child's condition in a manner that makes them feel safe and supported, are needed to optimize outcomes for families.

  1. Stimulant treatment for attention-deficit hyperactivity disorder and risk of developing substance use disorder

    NARCIS (Netherlands)

    Groenman, A.P.; Oosterlaan, J.; Rommelse, N.N.J.; Franke, B.; Greven, C.U.; Hoekstra, P.J.; Hartman, C.A.; Luman, M.; Roeyers, H.; Oades, R.D.; Sergeant, J.A.; Buitelaar, J.K.; Faraone, S.V.

    2013-01-01

    BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is linked to increased risk for substance use disorders and nicotine dependence. AIMS: To examine the effects of stimulant treatment on subsequent risk for substance use disorder and nicotine dependence in a prospective longitudinal ADHD

  2. Stimulant treatment for attention-deficit hyperactivity disorder and risk of developing substance use disorder

    NARCIS (Netherlands)

    Groenman, Annabeth P.; Oosterlaan, Jaap; Rommelse, Nanda N. J.; Franke, Barbara; Greven, Corina U.; Hoekstra, Pieter J.; Hartman, Catharina A.; Luman, Marjolein; Roeyers, Herbert; Oades, Robert D.; Sergeant, Joseph A.; Buitelaar, Jan K.; Faraone, Stephen V.

    Background Attention-deficit hyperactivity disorder (ADHD) is linked to increased risk for substance use disorders and nicotine dependence. Aims To examine the effects of stimulant treatment on subsequent risk for substance use disorder and nicotine dependence in a prospective longitudinal ADHD

  3. Stimulant treatment for attention-deficit hyperactivity disorder and risk of developing substance use disorder.

    NARCIS (Netherlands)

    Groenman, A.P.; Oosterlaan, J.; Rommelse, N.; Franke, B.; Greven, C.U.; Hoekstra, P.J.; Hartman, C.A.; Luman, M.; Roeyers, H.; Oades, R.D.; Sergeant, J.A.; Buitelaar, J.K.; Faraone, S.V.

    2013-01-01

    Background: Attention-deficit hyperactivity disorder (ADHD) is linked to increased risk for substance use disorders and nicotine dependence. Aims: To examine the effects of stimulant treatment on subsequent risk for substance use disorder and nicotine dependence in a prospective longitudinal ADHD

  4. Rational redesign of neutral endopeptidase binding to merlin and moesin proteins

    Science.gov (United States)

    Niv, Masha Y; Iida, Katsuyuki; Zheng, Rong; Horiguchi, Akio; Shen, Ruoqian; Nanus, David M

    2009-01-01

    Neutral endopeptidase (NEP) is a 90- to 110-kDa cell-surface peptidase that is normally expressed by numerous tissues but whose expression is lost or reduced in a variety of malignancies. The anti-tumorigenic function of NEP is mediated not only by its catalytic activity but also through direct protein–protein interactions of its cytosolic region with several binding partners, including Lyn kinase, PTEN, and ezrin/radixin/moesin (ERM) proteins. We have previously shown that mutation of the K19K20K21 basic cluster in NEPs' cytosolic region to residues QNI disrupts binding to the ERM proteins. Here we show that the ERM-related protein merlin (NF2) does not bind NEP or its cytosolic region. Using experimental data, threading, and sequence analysis, we predicted the involvement of moesin residues E159Q160 in binding to the NEP cytosolic domain. Mutation of these residues to NL (to mimic the corresponding N159L160 residues in the nonbinder merlin) disrupted moesin binding to NEP. Mutation of residues N159L160Y161K162M163 in merlin to the corresponding moesin residues resulted in NEP binding to merlin. This engineered NEP peptide–merlin interaction was diminished by the QNI mutation in NEP, supporting the role of the NEP basic cluster in binding. We thus identified the region of interaction between NEP and moesin, and engineered merlin into a NEP-binding protein. These data form the basis for further exploration of the details of NEP-ERM binding and function. PMID:19388049

  5. A neuroprotective brain-penetrating endopeptidase fusion protein ameliorates Alzheimer disease pathology and restores neurogenesis.

    Science.gov (United States)

    Spencer, Brian; Verma, Inder; Desplats, Paula; Morvinski, Dinorah; Rockenstein, Ed; Adame, Anthony; Masliah, Eliezer

    2014-06-20

    Alzheimer disease (AD) is characterized by widespread neurodegeneration throughout the association cortex and limbic system, deposition of amyloid-β peptide (Aβ) in the neuropil and around the blood vessels, and formation of neurofibrillary tangles. The endopeptidase neprilysin has been successfully used to reduce the accumulation of Aβ following intracranial viral vector delivery or ex vivo manipulated intracranial delivery. These therapies have relied on direct injections into the brain, whereas a clinically desirable therapy would involve i.v. infusion of a recombinant enzyme. We previously characterized a recombinant neprilysin that contained a 38-amino acid brain-targeting domain. Recombinant cell lines have been generated expressing this brain-targeted enzyme (ASN12). In this report, we characterize the ASN12 recombinant protein for pharmacology in a mouse as well as efficacy in two APPtg mouse models of AD. The recombinant ASN12 transited to the brain with a t½ of 24 h and accumulated to 1.7% of injected dose at 24 h following i.v. delivery. We examined pharmacodynamics in the tg2576 APPtg mouse with the prion promoter APP695 SWE mutation and in the Line41 mThy1 APP751 mutation mouse. Treatment of either APPtg mouse resulted in reduced Aβ, increased neuronal synapses, and improved learning and memory. In addition, the Line41 APPtg mice showed increased levels of C-terminal neuropeptide Y fragments and increased neurogenesis. These results suggest that the recombinant brain-targeted neprilysin, ASN12, may be an effective treatment for AD and warrant further investigation in clinical trials. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Development of the lower urinary tract and its functional disorders

    Directory of Open Access Journals (Sweden)

    Peco-Antić Amira

    2015-01-01

    Full Text Available A normal development of lower urinary tract function control evolves from involuntary bladder empting (incontinence during infancy to daytime urinary continence, and finally a successful day and night continence that is generally achieved by the 5th to 7th year of age. This gradual process primarily depends on the progressive maturation of the neural control of the lower urinary tract, but it is also influenced by behavioral training that evolves through social support. Functional voiding disorders (bladder dysfunction are common problems during childhood. They are present in 5-15 % of general pediatric population, and in one-fifth of school-age children or in over one-third of patients of the pediatric urologist or nephrologist. More than half of children with bladder dysfunction have vesicoureteral reflux, and more than two-thirds have recurrent urinary tract infections. There is also a frequent association of bladder dysfunction with constipation and encopresis (dysfunctional elimination syndrome. Bladder dysfunction may cause a permanent damage to the upper urinary tract and kidneys. In addition, urinary incontinence, as the most common manifestation of bladder dysfunction can be the cause of major stress in schoolage children and have a negative effect on the child’s feeling of self-esteem. Thus, a timely detection and treatment of this group of disorders in children is highly significant.

  7. Anterior Cortical Development During Adolescence in Bipolar Disorder.

    Science.gov (United States)

    Najt, Pablo; Wang, Fei; Spencer, Linda; Johnston, Jennifer A Y; Cox Lippard, Elizabeth T; Pittman, Brian P; Lacadie, Cheryl; Staib, Lawrence H; Papademetris, Xenophon; Blumberg, Hilary P

    2016-02-15

    Increasing evidence supports a neurodevelopmental model for bipolar disorder (BD), with adolescence as a critical period in its development. Developmental abnormalities of anterior paralimbic and heteromodal frontal cortices, key structures in emotional regulation processes and central in BD, are implicated. However, few longitudinal studies have been conducted, limiting understanding of trajectory alterations in BD. In this study, we performed longitudinal neuroimaging of adolescents with and without BD and assessed volume changes over time, including changes in tissue overall and within gray and white matter. Larger decreases over time in anterior cortical volumes in the adolescents with BD were hypothesized. Gray matter decreases and white matter increases are typically observed during adolescence in anterior cortices. It was hypothesized that volume decreases over time in BD would reflect alterations in those processes, showing larger gray matter contraction and decreased white matter expansion. Two high-resolution magnetic resonance imaging scans were obtained approximately 2 years apart for 35 adolescents with bipolar I disorder (BDI) and 37 healthy adolescents. Differences over time between groups were investigated for volume overall and specifically for gray and white matter. Relative to healthy adolescents, adolescents with BDI showed greater volume contraction over time in a region including insula and orbitofrontal, rostral, and dorsolateral prefrontal cortices (p adolescence in BDI in anterior cortices, including altered developmental trajectories of anterior gray and white matter. Published by Elsevier Inc.

  8. Association between language development and auditory processing disorders

    Directory of Open Access Journals (Sweden)

    Caroline Nunes Rocha-Muniz

    2014-06-01

    Full Text Available INTRODUCTION: It is crucial to understand the complex processing of acoustic stimuli along the auditory pathway ;comprehension of this complex processing can facilitate our understanding of the processes that underlie normal and altered human communication. AIM: To investigate the performance and lateralization effects on auditory processing assessment in children with specific language impairment (SLI, relating these findings to those obtained in children with auditory processing disorder (APD and typical development (TD. MATERIAL AND METHODS: Prospective study. Seventy-five children, aged 6-12 years, were separated in three groups: 25 children with SLI, 25 children with APD, and 25 children with TD. All went through the following tests: speech-in-noise test, Dichotic Digit test and Pitch Pattern Sequencing test. RESULTS: The effects of lateralization were observed only in the SLI group, with the left ear presenting much lower scores than those presented to the right ear. The inter-group analysis has shown that in all tests children from APD and SLI groups had significantly poorer performance compared to TD group. Moreover, SLI group presented worse results than APD group. CONCLUSION: This study has shown, in children with SLI, an inefficient processing of essential sound components and an effect of lateralization. These findings may indicate that neural processes (required for auditory processing are different between auditory processing and speech disorders.

  9. Rapid degradation of D- and L-succinimide-containing peptides by a post-proline endopeptidase from human erythrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Momand, J.; Clarke, S.

    1987-12-01

    The authors have been interested in the metabolic fate of proteins containing aspartyl succinimide (Asu) residues. These residues can be derived from the spontaneous rearrangement of Asp and Asn residues and from the spontaneous demethylation of enzymatically methylated L-isoAsp and D-Asp residues. Incubation of the synthetic hexapeptide N-Ac-Val-Tyr-Pro-Asu-Gly-Ala with the cytosolic fraction of human erythrocytes resulted in rapid cleavage of the prolyl-aspartyl succinimide bond producing the tripeptide N-Ac-Val-Try-Pro. The rate of this reaction is equal for both L- and D-Asu-containing peptides and is 10-fold greater that the rate of cleavage of a corresponding peptide containing a normal Pro-Asp linkage. When the aspartyl succinimide ring was replaced with an isoaspartyl residue, the cleavage rate was about 5 times that of the normal Pro-Asp peptide. The tripeptide-producing activity copurified on DEAE-cellulose chromatography with an activity that cleaves N-carbobenzoxy-Gly-Pro-4-methylcoumarin-7-amide, a post-proline endopeptidase substrate. These two activities were both inhibited by an antiserum to rat brain post-proline endopeptidase, and it appears that they are catalyzed by the same enzyme. This enzyme has a molecular weight of approximately 80,000 and is covalently labeled and inhibited by (/sup 3/H) diisopropyl fluorophosphate. The facile cleavage of the succinimide- and isoaspartyl-containing peptides by this post-proline endopeptidase suggests that it may play a role in the metabolism of peptides containing altered aspartyl residues.

  10. Neutral endopeptidase-resistant C-type natriuretic peptide variant represents a new therapeutic approach for treatment of fibroblast growth factor receptor 3-related dwarfism.

    Science.gov (United States)

    Wendt, Daniel J; Dvorak-Ewell, Melita; Bullens, Sherry; Lorget, Florence; Bell, Sean M; Peng, Jeff; Castillo, Sianna; Aoyagi-Scharber, Mika; O'Neill, Charles A; Krejci, Pavel; Wilcox, William R; Rimoin, David L; Bunting, Stuart

    2015-04-01

    Achondroplasia (ACH), the most common form of human dwarfism, is caused by an activating autosomal dominant mutation in the fibroblast growth factor receptor-3 gene. Genetic overexpression of C-type natriuretic peptide (CNP), a positive regulator of endochondral bone growth, prevents dwarfism in mouse models of ACH. However, administration of exogenous CNP is compromised by its rapid clearance in vivo through receptor-mediated and proteolytic pathways. Using in vitro approaches, we developed modified variants of human CNP, resistant to proteolytic degradation by neutral endopeptidase, that retain the ability to stimulate signaling downstream of the CNP receptor, natriuretic peptide receptor B. The variants tested in vivo demonstrated significantly longer serum half-lives than native CNP. Subcutaneous administration of one of these CNP variants (BMN 111) resulted in correction of the dwarfism phenotype in a mouse model of ACH and overgrowth of the axial and appendicular skeletons in wild-type mice without observable changes in trabecular and cortical bone architecture. Moreover, significant growth plate widening that translated into accelerated bone growth, at hemodynamically tolerable doses, was observed in juvenile cynomolgus monkeys that had received daily subcutaneous administrations of BMN 111. BMN 111 was well tolerated and represents a promising new approach for treatment of patients with ACH. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Disorders of sex development presenting as unilateral cryptorchidism

    DEFF Research Database (Denmark)

    Ostergren, Peter; Juul, Anders; Azawi, Nessn H

    2013-01-01

    Abstract Disorders of sex development (DSD) present in different forms but, in most cases, with visible anomalies of the external genitalia. The diagnosis of DSD can have a vast impact on an individual; in addition to concerns about fertility and a higher risk of neoplasia, it may have severe...... psychosocial impact on the patient. This report presents two apparently healthy cases referred for operation because of unilateral undescended testis. In these two patients, uterine remnants were found during the operation, and underlying DSD conditions were unexpectedly diagnosed. One patient had a 45,X/46,XY...... mosaic karyotype, while the second patient had persistent müllerian duct syndrome, probably due to an anti-müllerian hormone receptor defect. Both conditions are extremely rare, but the findings reinforce that DSD should be considered in patients with cryptorchidism, especially if other clinical signs...

  12. Breastfeeding may protect from developing attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Mimouni-Bloch, Aviva; Kachevanskaya, Anna; Mimouni, Francis Benjamin; Shuper, Avinoam; Raveh, Eyal; Linder, Nehama

    2013-08-01

    Breastfeeding has a positive influence on physical and mental development. Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder with major social, familial, and academic influences. The present study aimed to evaluate whether ADHD is associated with a shorter duration of breastfeeding. In this retrospective matched study, children 6-12 years old diagnosed at Schneider's Children Medical Center (Petach Tikva, Israel) with ADHD between 2008 and 2009 were compared with two control groups. The first one consisted of healthy (no ADHD) siblings of ADHD children; the second control group consisted of children without ADHD who consulted at the otolaryngology clinic. A constructed questionnaire about demographic, medical, and perinatal findings, feeding history during the first year of life, and a validated adult ADHD screening questionnaire were given to both parents of every child in each group. In children later diagnosed as having ADHD, 43% were breastfed at 3 months of age compared with 69% in the siblings group and 73% in the control non-related group (p=0.002). By 6 months of age 29% of ADHD children were breastfed compared with 50% in the siblings group and 57% in the control non-related group (p=0.011). A stepwise logistic regression that included the variables found to be significant in univariate analysis demonstrated a significant association between ADHD and lack of breastfeeding at 3 months of age, maternal age at birth, male gender, and parental divorce. Children with ADHD were less likely to breastfeed at 3 months and 6 months of age than children in the two control groups. We speculate that breastfeeding may have a protective effect from developing ADHD later in childhood.

  13. Impact on infants' cognitive development of antenatal exposure to iron deficiency disorder and common mental disorders.

    Science.gov (United States)

    Tran, Thach Duc; Biggs, Beverley-Ann; Tran, Tuan; Simpson, Julie Anne; Hanieh, Sarah; Dwyer, Terence; Fisher, Jane

    2013-01-01

    The aim of this study was to examine the effects of antenatal exposure to iron deficiency anemia (IDA) and common mental disorders (CMD) on cognitive development of 6 months old infants in a developing country. A prospective population-based study in a rural province in Vietnam, which enrolled pregnant women at 12-20 weeks gestation and followed them up with their infants until six months postpartum. Criteria for IDA were Hb cognitive development was assessed by Bayley Scales of Infant and Toddler Development, 3rd Ed. Path analyses were performed to determine the direct and indirect, partly or fully mediated, causal effects of the antenatal exposures. A total of 497 pregnant women were recruited, of those 378 women provided complete data which were included in the analyses. Statistically significant direct adverse effects of persistent antenatal IDA (estimated difference of -11.62 points; 95% CI -23.01 to -0.22) and antenatal CMD (-4.80 points; 95% CI: -9.40 to -0.20) on infant Bayley cognitive scores at six months were found. Higher birthweight, household wealth, and self-rated sufficient supply of breastmilk were associated with higher cognitive scores. Maternal age >30 years and primiparity had an indirect adverse effect on infants' Bayley cognitive scores. These findings suggest that antenatal IDA and CMD both have adverse effects on child cognitive development, which if unrecognized and unaddressed are likely to be lasting. It is crucial that both these risks are considered by policy makers, clinicians, and researchers seeking to improve child cognitive function in developing countries.

  14. Impact on Infants’ Cognitive Development of Antenatal Exposure to Iron Deficiency Disorder and Common Mental Disorders

    Science.gov (United States)

    Tran, Thach Duc; Biggs, Beverley-Ann; Tran, Tuan; Simpson, Julie Anne; Hanieh, Sarah; Dwyer, Terence; Fisher, Jane

    2013-01-01

    Objectives The aim of this study was to examine the effects of antenatal exposure to iron deficiency anemia (IDA) and common mental disorders (CMD) on cognitive development of 6 months old infants in a developing country. Methods A prospective population-based study in a rural province in Vietnam, which enrolled pregnant women at 12–20 weeks gestation and followed them up with their infants until six months postpartum. Criteria for IDA were Hb cognitive development was assessed by Bayley Scales of Infant and Toddler Development, 3rd Ed. Path analyses were performed to determine the direct and indirect, partly or fully mediated, causal effects of the antenatal exposures. Results A total of 497 pregnant women were recruited, of those 378 women provided complete data which were included in the analyses. Statistically significant direct adverse effects of persistent antenatal IDA (estimated difference of −11.62 points; 95% CI −23.01 to −0.22) and antenatal CMD (−4.80 points; 95% CI: −9.40 to −0.20) on infant Bayley cognitive scores at six months were found. Higher birthweight, household wealth, and self-rated sufficient supply of breastmilk were associated with higher cognitive scores. Maternal age >30 years and primiparity had an indirect adverse effect on infants’ Bayley cognitive scores. Conclusions These findings suggest that antenatal IDA and CMD both have adverse effects on child cognitive development, which if unrecognized and unaddressed are likely to be lasting. It is crucial that both these risks are considered by policy makers, clinicians, and researchers seeking to improve child cognitive function in developing countries. PMID:24086390

  15. Operative treatment and avascular necrosis of the hip development disorder.

    Science.gov (United States)

    Gavrankapetanović, Ismet; Hadžimehmedagić, Amel; Papović, Adnan; Baždar, Elvir

    2014-07-01

    The purpose of this research was (1) to evaluate the consequences of an operative treatment of hip developmental disorder in children, (2) to evaluate the significance of hip vascular supply in children through indirect radiological signs, such as morphological changes on femoral head, and to classify them with standard classification methods, and (3) to analyse the research results and make a recommendation for the following treatment dilemma: when is the optimal time for an operative treatment of a hip development disorder? The research is a retrospective and observational analysis based on the classification of indirect radiological signs of local vascular disorder by the Bucholz-Ogden's scale. Materials used for this research are medical records of treated patients at the Clinic for Orthopaedics and Traumatology of the Sarajevo University Clinical Centre. Using a random selection, two groups of 30 patients with hip development disorder were formed. The first group was comprised of patients aged six to 18 months and the second group of patients aged 18-60 months. The medical records used for this research included all necessary anamnestic details and postoperative state treatments with clinical findings and regular radiological check-up findings that include the presence or absence of the ossification nucleus as well as its position. All patients underwent surgery with the same operative technique. Data analysis points include the state at the beginning of the treatment, the postoperative state, the state at discharge as well as control findings that followed the development of the proximal femoral part up to 72 months on average. The analysis covered data such as age, sex, family anamnestic data, clinical findings and radiological findings regarding the femoral head morphology (appearance, size, shape, position and indirect signs showing lack of vascular supply). In addition, data analysis included the types of any previous conservative or operative treatments

  16. Penile Dysmorphic Disorder: Development of a Screening Scale.

    Science.gov (United States)

    Veale, David; Miles, Sarah; Read, Julie; Troglia, Andrea; Carmona, Lina; Fiorito, Chiara; Wells, Hannah; Wylie, Kevan; Muir, Gordon

    2015-11-01

    Penile dysmorphic disorder (PDD) is shorthand for men diagnosed with body dysmorphic disorder, in whom the size or shape of the penis is their main, if not their exclusive, preoccupation causing significant shame or handicap. There are no specific measures for identifying men with PDD compared to men who are anxious about the size of their penis but do not have PDD. Such a measure might be helpful for treatment planning, reducing unrealistic expectations, and measuring outcome after any psychological or physical intervention. Our aim was, therefore, to validate a specific measure, termed the Cosmetic Procedure Screening Scale for PDD (COPS-P). Eighty-one male participants were divided into three groups: a PDD group (n = 21), a small penis anxiety group (n = 37), and a control group (n = 23). All participants completed the COPS-P as well as standardized measures of depression, anxiety, social phobia, body image, quality of life, and erectile function. Penis size was also measured. The final COPS-P was based on nine items. The scale had good internal reliability and significant convergent validity with measures of related constructs. It discriminated between the PDD group, the small penis anxiety group, and the control group. This is the first study to develop a scale able to discriminate between those with PDD and men anxious about their size who did not have PDD. Clinicians and researchers may use the scale as part of an assessment for men presenting with anxiety about penis size and as an audit or outcome measure after any intervention for this population.

  17. Development of social anxiety disorder secondary to attention deficit/hyperactivity disorder (the developmental hypothesis).

    Science.gov (United States)

    Koyuncu, Ahmet; Alkın, Tunç; Tükel, Raşit

    2018-04-01

    Social anxiety disorder (SAD) may develop secondary to childhood attention deficit/hyperactivity (ADHD) in a subgroup of the patients with SAD. Patients pass through a number of identifiable stages of developmental pathways to SAD as they grow up. Patients with ADHD have maladaptive behaviours in social settings due to the symptoms of ADHD. These behaviours are criticized by their parents and social circle; they receive insults, humiliation and bullying. After each aversive incident, the individual feels shame and guilt. A vicious cycle emerges. The patients then develop social fears and a cognitive inhibition that occurs in social situations. The inhibition increases gradually as the fear persists and the individual becomes withdrawn. Patients start to monitor themselves and to focus on others' feedback. Finally, performative social situations become extremely stimulating for them and may trigger anxiety/panic attacks. If this hypothesis is proven, treatment of 'patients with SAD secondary to ADHD' should focus on the primary disease. © 2016 John Wiley & Sons Australia, Ltd.

  18. Auditory-Motor Interactions in Pediatric Motor Speech Disorders: Neurocomputational Modeling of Disordered Development

    NARCIS (Netherlands)

    Terband, H.R.; Maassen, B.A.M.; 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

  19. Auditory-motor interactions in pediatric motor speech disorders: Neurocomputational modeling of disordered development

    NARCIS (Netherlands)

    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

  20. Prospective associations of early-onset Axis I disorders with developing eating disorders

    NARCIS (Netherlands)

    Sihvola, Elina; Keski-Rahkonen, Anna; Dick, Danielle M.; Hoek, Hans W.; Raevuori, Anu; Rose, Richard J.; Pulkkinen, Lea; Marttunen, Mauri; Kaprio, Jaakko

    2009-01-01

    Objective: The purpose of this study is to analyze the developmental relationships of adolescent-onset Axis I mental disorders and eating disorders (EDs). Method: One thousand three hundred eighteen adolescent twins born from 1983 to 1987 completed a professionally administered semistructured

  1. Characterization of a gut-associated asparaginyl endopeptidase of Clonorchis sinensis.

    Science.gov (United States)

    Kang, Jung-Mi; Lee, Jinyoung; Ju, Hye-Lim; Ju, Jung Won; Kim, Jong-Hyun; Pak, Jhang Ho; Kim, Tong-Soo; Hong, Yeonchul; Sohn, Woon-Mok; Na, Byoung-Kuk

    2015-06-01

    Asparaginyl endopeptidases (AEP: EC 3.4.22.34) are a family of cysteine proteases classified into the MEROPS clan CD, family C13. In this study, we characterized the biochemical and antigenic properties of an AEP of Clonorchis sinensis (CsAEP). The recombinant CsAEP showed hydrolytic activity at pH values ranging from acidic to neutral with optimum activity at pH 6.0. While the recombinant CsAEP was stable at neutral pHs, it was unstable at acidic pHs and resulted in loss of enzymatic activity. The recombinant enzyme was effectively inhibited by iodoacetic acid and N-ethylmaleimide, but not by E-64. The partially purified native CsAEP showed biochemical properties similar to the recombinant enzyme. Native CsAEP is likely to be cleaved into an N-terminal mature enzyme and a C-terminal fragment via autocatalytic activation at acidic pHs. Polyclonal antibody raised against the recombinant CsAEP recognized three forms of CsAEP, proenzyme, the N-terminal mature enzyme and the C-terminal fragment, in the worm extract (WE) of C. sinensis. However, only the C-terminal fragment was mainly found in the excretory and secretory (ES) products of the parasite. Strong CsAEP activity was found in the WE, but only a trace level of CsAEP activity was detected in the ES products of the parasite. CsAEP was expressed in various developmental stages of C. sinensis, from metacercariae to adults, and was found to be localized in the intestine of the parasite as well as in intestinal contents. Sera from rats experimentally infected with C. sinensis reacted with CsAEP beginning 4 weeks after infection. These results suggest that CsAEP is a gut-associated enzyme synthesized in the intestine of C. sinensis and subsequently secreted into the intestinal lumen of the parasite. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Histone Deacetylases in Bone Development and Skeletal Disorders

    Science.gov (United States)

    Bradley, Elizabeth W.; Carpio, Lomeli R.; van Wijnen, Andre J.; McGee-Lawrence, Meghan E.; Westendorf, Jennifer J.

    2015-01-01

    Histone deacetylases (Hdacs) are conserved enzymes that remove acetyl groups from lysine side chains in histones and other proteins. Eleven of the 18 Hdacs encoded by the human and mouse genomes depend on Zn2+ for enzymatic activity, while the other 7, the sirtuins (Sirts), require NAD2+. Collectively, Hdacs and Sirts regulate numerous cellular and mitochondrial processes including gene transcription, DNA repair, protein stability, cytoskeletal dynamics, and signaling pathways to affect both development and aging. Of clinical relevance, Hdacs inhibitors are United States Food and Drug Administration-approved cancer therapeutics and are candidate therapies for other common diseases including arthritis, diabetes, epilepsy, heart disease, HIV infection, neurodegeneration, and numerous aging-related disorders. Hdacs and Sirts influence skeletal development, maintenance of mineral density and bone strength by affecting intramembranous and endochondral ossification, as well as bone resorption. With few exceptions, inhibition of Hdac or Sirt activity though either loss-of-function mutations or prolonged chemical inhibition has negative and/or toxic effects on skeletal development and bone mineral density. Specifically, Hdac/Sirt suppression causes abnormalities in physiological development such as craniofacial dimorphisms, short stature, and bone fragility that are associated with several human syndromes or diseases. In contrast, activation of Sirts may protect the skeleton from aging and immobilization-related bone loss. This knowledge may prolong healthspan and prevent adverse events caused by epigenetic therapies that are entering the clinical realm at an unprecedented rate. In this review, we summarize the general properties of Hdacs/Sirts and the research that has revealed their essential functions in bone forming cells (e.g., osteoblasts and chondrocytes) and bone resorbing osteoclasts. Finally, we offer predictions on future research in this area and the utility of

  3. Ethical challenges in developing drugs for psychiatric disorders.

    Science.gov (United States)

    Carrier, Felix; Banayan, David; Boley, Randy; Karnik, Niranjan

    2017-05-01

    As the classification of mental disorders advances towards a disease model as promoted by the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC), there is hope that a more thorough neurobiological understanding of mental illness may allow clinicians and researchers to determine treatment efficacy with less diagnostic variability. This paradigm shift has presented a variety of ethical issues to be considered in the development of psychiatric drugs. These challenges are not limited to informed consent practices, industry funding, and placebo use. The consideration for alternative research models and quality of research design also present ethical challenges in the development of psychiatric drugs. The imperatives to create valid and sound research that justify the human time, cost, risk and use of limited resources must also be considered. Clinical innovation, and consideration for special populations are also important aspects to take into account. Based on the breadth of these ethical concerns, it is particularly important that scientific questions regarding the development of psychiatric drugs be answered collaboratively by a variety of stakeholders. As the field expands, new ethical considerations will be raised with increased focus on genetic markers, personalized medicine, patient-centered outcomes research, and tension over funding. We suggest that innovation in trial design is necessary to better reflect practices in clinical settings and that there must be an emphasized focus on expanding the transparency of consent processes, regard for suicidality, and care in working with special populations to support the goal of developing sound psychiatric drug therapies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. THE CORRELATION OF PARENTING STYLE WITH COGNITIVE DEVELOPMENT IN CHILDREN WITH ATTENTION DEFICIT HYPERACTIVITY DISORDER

    OpenAIRE

    Fitri Genisti; Ni Komang Sukra Andini; Ni Luh Gede Puspita Yanti

    2018-01-01

    Background: Child development is a very important phase, which children learn various skills as future generations in the future. Disorders that can impede child development process of Attention Deficit Hyperactivity Disorder (ADHD). Children with ADHD have problems with cognitive abilities, of which about 20-60% of them have learning disorders. The efforts to support cognitive development in ADHD children is to approach the child's environment through parenting parents. Objective: This s...

  5. Etiological Diagnosis of Undervirilized Male / XY Disorder of Sex Development

    International Nuclear Information System (INIS)

    Atta, I.; Ibrahim, M.; Parkash, A.; Lone, S. W.; Khan, Y. N.; Raza, J.

    2014-01-01

    Objective: To do clinical, hormonal and chromosomal analysis in undervirilized male / XY disorder of sex development and to make presumptive etiological diagnosis according to the new Disorder of Sex Development (DSD) classification system. Study Design: Case series. Place and Duration of Study: Endocrine Unit at National Institute of Child Health, Karachi, Pakistan, from January 2007 to December 2012. Methodology: Patients of suspected XY DSD / undervirilized male visiting endocrine clinic were enrolled in the study. Criteria suggested XY DSD include overt genital ambiguity, apparent female/male genitalia with inguinal/labial mass, apparent male genitalia with unilateral or bilateral non-palpable testes, micropenis and isolated hypospadias or with undescended testis. The older children who had delayed puberty were also evaluated with respect to DSD. As a part of evaluation of XY DSD, abdominopelvic ultrasound, karyotype, hormone measurement (testosterone, FSH, LH), FISH analysis with SRY probing, genitogram, laparoscopy, gonadal biopsy and HCG stimulation test were performed. Frequencies and percentages applied on categorical data whereas mean, median, standard deviation were calculated for continuous data. Results: A total of 187 patients met the criteria of XY DSD. Age ranged from 1 month to 15 years, 55 (29.4%) presented in infancy, 104 (55.6%) between 1 and 10 years and 28 (15%) older than 10 years. Twenty five (13.4%) were raised as female and 162 as (86.6%) male. The main complaints were ambiguous genitalia, unilateral cryptorchidism, bilateral cryptorchidism, micropenis, delayed puberty, hypospadias, female like genitalia with gonads, inguinal mass. The karyotype was 46 XY in 183 (97.9%), 46 XX in 2 (1.1%), 47 XXY in 1 (0.5%), 45 X/46 XY in 1 (0.5%) patient. HCG stimulation test showed low testosterone response in 43 (23 %), high testosterone response in 62 (33.2%), partial testosterone response in 32 (17.1%) and normal testosterone response in 50 (26

  6. Motor Skill Abilities in Toddlers with Autistic Disorder, Pervasive Developmental Disorder-Not Otherwise Specified, and Atypical Development

    Science.gov (United States)

    Matson, Johnny L.; Mahan, Sara; Fodstad, Jill C.; Hess, Julie A.; Neal, Daniene

    2010-01-01

    Motor skills were assessed in 397 toddlers, and it was demonstrated that atypically developing toddlers exhibited significantly greater motor skill abilities than toddlers with autistic disorder. No significant difference on gross or fine motor skill abilities were found between atypically developing toddlers and toddlers with pervasive…

  7. Disorders of sex development: a new definition and classification.

    Science.gov (United States)

    Hughes, Ieuan A

    2008-02-01

    A newborn infant with ambiguous genitalia is a complex enough problem to unravel without any further clouding by confusing terms. The nomenclature 'intersex', 'hermaphrodite' and 'pseudohermaphrodite' is anachronistic, unhelpful, and perceived to be pejorative by some affected families. In its place, a consensus statement recommends the term 'disorder of sex development' (DSD), a generic definition encompassing any problem noted at birth where the genitalia are atypical in relation to the chromosomes or gonads. The karyotype is used as a prefix to define the category of DSD, replacing the arcane terminology of male or female pseudohermaphroditism (now known as XY DSD or XX DSD, respectively). The new nomenclature has spawned a simple and logical classification of the causes of DSD. In this chapter new facets of gonadal dysgenesis and novel defects in steroid biosynthesis are reviewed in relation to the DSD classification, and options for early, non-invasive fetal sexing are described. Future research to determine many causes of DSD will benefit from the use of this universal language of scientific communication.

  8. The role of sleep and sleep disorders in the development, diagnosis, and management of neurocognitive disorders.

    OpenAIRE

    Michelle A Miller

    2015-01-01

    It is becoming increasingly apparent that sleep plays an important role in the maintenance, disease prevention, repair and restoration of both mind and body. The sleep and wake cycles are controlled by the pacemaker activity of the superchiasmic nucleus in the hypothalamus but can be disrupted by diseases of the nervous system causing disordered sleep. A lack of sleep has been associated with an increase in all–cause mortality. Likewise, sleep disturbances and sleep disorders may disrupt neu...

  9. Environmental factors in the development of autism spectrum disorders.

    Science.gov (United States)

    Sealey, L A; Hughes, B W; Sriskanda, A N; Guest, J R; Gibson, A D; Johnson-Williams, L; Pace, D G; Bagasra, O

    2016-03-01

    Autism spectrum disorders (ASD) are highly heterogeneous developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication, and obsessive/stereotyped patterns of behavior and repetitive movements. Social interaction impairments are the most characteristic deficits in ASD. There is also evidence of impoverished language and empathy, a profound inability to use standard nonverbal behaviors (eye contact, affective expression) to regulate social interactions with others, difficulties in showing empathy, failure to share enjoyment, interests and achievements with others, and a lack of social and emotional reciprocity. In developed countries, it is now reported that 1%-1.5% of children have ASD, and in the US 2015 CDC reports that approximately one in 45 children suffer from ASD. Despite the intense research focus on ASD in the last decade, the underlying etiology remains unknown. Genetic research involving twins and family studies strongly supports a significant contribution of environmental factors in addition to genetic factors in ASD etiology. A comprehensive literature search has implicated several environmental factors associated with the development of ASD. These include pesticides, phthalates, polychlorinated biphenyls, solvents, air pollutants, fragrances, glyphosate and heavy metals, especially aluminum used in vaccines as adjuvant. Importantly, the majority of these toxicants are some of the most common ingredients in cosmetics and herbicides to which almost all of us are regularly exposed to in the form of fragrances, face makeup, cologne, air fresheners, food flavors, detergents, insecticides and herbicides. In this review we describe various scientific data to show the role of environmental factors in ASD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. The influence of genes and environment on the development of bipolar disorder: A twin study

    OpenAIRE

    Vonk, Ronald

    2016-01-01

    Bipolar disorder (or manic-depressive disorder) is a severe mood disorder in which episodes of (hypo) mania (e.g. elevated mood en hyperactivity) and depression (e.g. decreased mood and reduced activity) alternate with periods of normal mood and functioning. Genetic factors as well as environmental factors play a role in the development of bipolar disorder. A serious problem for bipolar disorder is a delay of several years between the first mood episode(s) and the diagnosis. Afterwards it can...

  11. Poverty and common mental disorders in developing countries.

    Science.gov (United States)

    Patel, Vikram; Kleinman, Arthur

    2003-01-01

    A review of English-language journals published since 1990 and three global mental health reports identified 11 community studies on the association between poverty and common mental disorders in six low- and middle-income countries. Most studies showed an association between indicators of poverty and the risk of mental disorders, the most consistent association being with low levels of education. A review of articles exploring the mechanism of the relationship suggested weak evidence to support a specific association with income levels. Factors such as the experience of insecurity and hopelessness, rapid social change and the risks of violence and physical ill-health may explain the greater vulnerability of the poor to common mental disorders. The direct and indirect costs of mental ill-health worsen the economic condition, setting up a vicious cycle of poverty and mental disorder. Common mental disorders need to be placed alongside other diseases associated with poverty by policy-makers and donors. Programmes such as investment in education and provision of microcredit may have unanticipated benefits in reducing the risk of mental disorders. Secondary prevention must focus on strengthening the ability of primary care services to provide effective treatment.

  12. The HOPE (Helping to Outline Paediatric Eating Disorders) Project: development and debut of a paediatric clinical eating disorder registry

    Science.gov (United States)

    2013-01-01

    Background The HOPE (Helping to Outline Paediatric Eating Disorders) Project is an ongoing registry study made up of a sequential cross-sectional sample prospectively recruited over 17 years, and is designed to answer empirical questions about paediatric eating disorders. This paper introduces the HOPE Project, describes the registry sample to-date, and discusses future directions and challenges and accomplishments. The project and clinical service were established in a tertiary academic hospital in Western Australia in 1996 with a service development grant. Research processes were inbuilt into the initial protocols and data collection was maintained in the following years. Recognisable progress with the research agenda accelerated only when dedicated research resources were obtained. The registry sample consists of consecutive children and adolescents assessed at the eating disorder program from 1996 onward. Standardised multidisciplinary data collected from family intake interview, parent and child clinical interviews, medical review, parent, child and teacher psychometric assessments, and inpatient admission records populate the HOPE Project database. Results The registry database to-date contains 941 assessments, of whom 685 met DSM-IV diagnostic criteria for an eating disorder at admission. The majority of the sample were females (91%) from metropolitan Perth (83%). The cases with eating disorders consist of eating disorders not otherwise specified (68%), anorexia nervosa (25%) and bulimia nervosa (7%). Among those with eating disorders, a history of weight loss since illness onset was almost universal (96%) with fear of weight gain (71%) common, and the median duration of illness was 8 months. Conclusions Over the next five years and more, we expect that the HOPE Project will make a strong scientific contribution to paediatric eating disorders research and will have important real-world applications to clinical practice and policy as the research unfolds

  13. Atypical development of spontaneous social cognition in autism spectrum disorders.

    Science.gov (United States)

    Senju, Atsushi

    2013-02-01

    Individuals with autism spectrum disorders (ASD) have profound impairment in the development of social interaction and communication. However, it is also known that some 'high-functioning' individuals with ASD show apparently typical capacity to process social information in a controlled experimental settings, despite their difficulties in daily life. The current paper overviews the spontaneous social cognition, spontaneous processing of social information in the absence of explicit instruction or task demand, in individuals with ASD. Three areas of the researches, false belief attribution, imitation/mimicry, and eye gaze processing, have been reviewed. The literatures suggest that high-functioning individuals with ASD (a) do not spontaneously attribute false belief to others, even though they can easily do so when explicitly instructed, (b) can imitate others' goal-directed actions under explicit instruction and show spontaneous mimicry of others' actions when they attend to the action, but are less likely to show spontaneous mimicry without the task structure to navigate attention to others' action and (c) can process others' gaze direction and shift attention to others' gaze directions, but fail to spontaneously attend to another person's eyes in social and communicative context, and less likely to be prompted to respond in response to perceived eye contact. These results are consistent with the claim that individuals with ASD do not spontaneously attend to socially relevant information, even though they can easily process the same information when their attention is navigated towards it. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  14. Unbiased identification of patients with disorders of sex development.

    Directory of Open Access Journals (Sweden)

    David A Hanauer

    Full Text Available Disorders of sex development (DSD represent a collection of rare diseases that generate substantial controversy regarding best practices for diagnosis and treatment. A significant barrier preventing a better understanding of how patients with these conditions should be evaluated and treated, especially from a psychological standpoint, is the lack of systematic and standardized approaches to identify cases for study inclusion. Common approaches include "hand-picked" subjects already known to the practice, which could introduce bias. We implemented an informatics-based approach to identify patients with DSD from electronic health records (EHRs at three large, academic children's hospitals. The informatics approach involved comprehensively searching EHRs at each hospital using a combination of structured billing codes as an initial filtering strategy followed by keywords applied to the free text clinical documentation. The informatics approach was implemented to replicate the functionality of an EHR search engine (EMERSE available at one of the hospitals. At the two hospitals that did not have EMERSE, we compared case ascertainment using the informatics method to traditional approaches employed for identifying subjects. Potential cases identified using all approaches were manually reviewed by experts in DSD to verify eligibility criteria. At the two institutions where both the informatics and traditional approaches were applied, the informatics approach identified substantially higher numbers of potential study subjects. The traditional approaches yielded 14 and 28 patients with DSD, respectively; the informatics approach yielded 226 and 77 patients, respectively. The informatics approach missed only a few cases that the traditional approaches identified, largely because those cases were known to the study team, but patient data were not in the particular children's hospital EHR. The use of informatics approaches to search electronic documentation

  15. Disorders of sex development: a study of 194 cases

    Directory of Open Access Journals (Sweden)

    R Walia

    2018-02-01

    Full Text Available Objective: To study the clinical profile and the management of patients with disorders of sex development (DSD. Design and setting: Retrospective study from a tertiary care hospital of North India. Methods and patients: One hundred ninety-four patients of DSD registered in the Endocrine clinic of Postgraduate Institute of Medical Education and Research, Chandigarh between 1995 and 2014 were included. Results: One hundred and two patients (52.5% had 46,XY DSD and seventy-four patients (38.1% had 46,XX DSD. Sex chromosome DSD was identified in seven (3.6% patients. Of 102 patients with 46,XY DSD, 32 (31.4% had androgen insensitivity syndrome and 26 (25.5% had androgen biosynthetic defect. Of the 74 patients with 46,XX DSD, 52 (70.27% had congenital adrenal hyperplasia (CAH and eight (10.8% had ovotesticular DSD. Five patients with sex chromosome DSD had mixed gonadal dysgenesis. Excluding CAH, majority of the patients (90% presented in the post-pubertal period. One-fourth of the patients with simple virilising CAH were reared as males because of strong male gender identity and behaviour and firm insistence by the parents. Corrective surgeries were performed in twenty patients (20% of 46,XY DSD without hormonal evaluation prior to the presentation. Conclusion: Congenital adrenal hyperplasia is the most common DSD in the present series. Most common XY DSD is androgen insensitivity syndrome, while CAH is the most common XX DSD. Delayed diagnosis is a common feature, and corrective surgeries are performed without seeking a definite diagnosis.

  16. The influence of school on whether girls develop eating disorders.

    Science.gov (United States)

    Bould, Helen; De Stavola, Bianca; Magnusson, Cecilia; Micali, Nadia; Dal, Henrik; Evans, Jonathan; Dalman, Christina; Lewis, Glyn

    2016-04-01

    Clinical anecdote suggests that rates of eating disorders (ED) vary between schools. Given their high prevalence and mortality, understanding risk factors is important. We hypothesised that rates of ED would vary between schools, and that school proportion of female students and proportion of parents with post-high school education would be associated with ED, after accounting for individual characteristics. Multilevel analysis of register-based, record-linkage data on 55 059 females born in Stockholm County, Sweden, from 1983, finishing high school in 2002-10. Outcome was clinical diagnosis of an ED, or attendance at a specialist ED clinic, aged 16-20 years. The 5-year cumulative incidence of ED diagnosis aged 16-20 years was 2.4%. Accounting for individual risk factors, with each 10% increase in the proportion of girls at a school, the odds ratio for ED was 1.07 (1.01 to 1.13), P = 0.018. With each 10% increase in the proportion of children with at least one parent with post-high school education, the odds ratio for ED was 1.14 (1.09 to 1.19), P < 0.0001. Predicted probability of an average girl developing an ED was 1.3% at a school with 25% girls where 25% of parents have post-high school education, and 3.3% at a school with 75% girls where 75% of parents have post-high school education. Rates of ED vary between schools; this is not explained by individual characteristics. Girls at schools with high proportions of female students, and students with highly educated parents, have higher odds of ED regardless of individual risk factors. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.

  17. Relationships between Psychosocial Development and Personality Disorder Symptomatology in Late Adolescents.

    Science.gov (United States)

    Johnson, Jeffrey G.

    1993-01-01

    Studied the extent to which psychosocial development thorough the first 5 stages of E. H. Erikson's theory of personality development is associated with personality disorder symptoms, using 106 undergraduates. Negative resolutions of stages one through five may predict the presence of personality disorder symptomatology during late adolescence.…

  18. Disorder effects in topological states: Brief review of the recent developments

    International Nuclear Information System (INIS)

    Wu Binglan; Zhou Jiaojiao; Jiang Hua; Song Juntao

    2016-01-01

    Disorder inevitably exists in realistic samples, manifesting itself in various exotic properties for the topological states. In this paper, we summarize and briefly review the work completed over the last few years, including our own, regarding recent developments in several topics about disorder effects in topological states. For weak disorder, the robustness of topological states is demonstrated, especially for both quantum spin Hall states with Z 2 = 1 and size induced nontrivial topological insulators with Z 2 = 0. For moderate disorder, by increasing the randomness of both the impurity distribution and the impurity induced potential, the topological insulator states can be created from normal metallic or insulating states. These phenomena and their mechanisms are summarized. For strong disorder, the disorder causes a metal–insulator transition. Due to their topological nature, the phase diagrams are much richer in topological state systems. Finally, the trends in these areas of disorder research are discussed. (topical review)

  19. Multidisciplinary Management of Disorders of Sex Development in Indonesia, A Prototype in Developing Country

    Directory of Open Access Journals (Sweden)

    Nurin Aisyiyah Listyasari

    2017-06-01

    Full Text Available ABSTRACT Background : Disorder of sex development (DSD patients require comprehensive management to improve quality of life. A standardized management protocol for patients in Indonesia is not yet available resulting in patients infrequently received a proper diagnosis. This study reported a multidisciplinary management DSD in Indonesia based on minimal diagnostic facilities and expertise in developing country. Objectives : The purpose of the study is to review the management of DSD patients in Indonesia relates to providing appropriate gender assignment and to improving patients quality of life. Methodology : We analyzed the records of DSD patient admitted to the division of Human Genetics Center for Biomedical Research (CEBIOR Faculty of Medicine Diponegoro University, Semarang, Indonesia from May 2004 - December 2015. Data were collected and analyzed for physical examination, family pedigree karyotyping, hormonal assays and  psychosocial.  Other examination such as ultrasonography, Xray and Cytoscopy were also recorded for selected cases. Bimonthly, Sexual Adjustment Team (SAT meeting was recorded. Results : From the total 617 DSD cases we found 426 cases (69,04 % with 46, XY DSD, 117 cases (18,96% with 46,XX DSD and 74 cases (12% with sex chromosome DSD. Most of the patients in the group of 46, XY DSD are Unknown Male Undervirilization (UMU with 256 cases (60.09%. As the majority cases of 46, XX DSD was Congenital Adrenal Hyperplasia with 81 cases (69.23%. The remaining cases were Androgen Action Disorder (AAD with 140 cases (32.86%, 46, XY DSD Gonadal Dysgenesis with 30 cases (7.04%, Androgen Excess Disorders with 3 cases (2.56%, Defect of Mullerian Development with 19 cases (16,24%, 3 cases (2.56% of Androgen Excess and 3 cases (2.56% of 46, XX Gonadal Dysgenesis. Conclusion : Comprehensive management for DSD Patients help patient in diagnosis, gender assignment and support patient to improve quality of life. This multidisciplinary of

  20. Discovery, cloning and characterisation of proline specific prolyl endopeptidase, a gluten degrading thermo-stable enzyme from Sphaerobacter thermophiles

    DEFF Research Database (Denmark)

    Shetty, Radhakrishna; Vestergaard, Mike; Jessen, Flemming

    2017-01-01

    processes occur at elevated temperature. We present in this paper, the discovery, cloning and characterisation of a novel recombinant thermostable gluten degrading enzyme, a proline specific prolyl endoprotease (PEP) from Sphaerobacter thermophiles. The molecular mass of the prolyl endopeptidase......Gluten free products have emerged during the last decades, as a result of a growing public concern and technological advancements allowing gluten reduction in food products. One approach is to use gluten degrading enzymes, typically at low or ambient temperatures, whereas many food production...... was estimated to be 77 kDa by using SDS-PAGE. Enzyme activity assays with a synthetic dipeptide Z-Gly-Pro-p-nitroanilide as the substrate revealed that the enzyme had optimal activity at pH 6.6 and was most active from pH 5.0-8.0. The optimum temperature was 63 °C and residual activity after one hour incubation...

  1. Sensory Symptoms in Children with Autism Spectrum Disorder, Other Developmental Disorders and Typical Development: A Longitudinal Study

    Science.gov (United States)

    McCormick, Carolyn; Hepburn, Susan; Young, Gregory S.; Rogers, Sally J.

    2016-01-01

    Sensory symptoms are prevalent in autism spectrum disorder but little is known about the early developmental patterns of these symptoms. This study examined the development of sensory symptoms and the relationship between sensory symptoms and adaptive functioning during early childhood. Three groups of children were followed across three time…

  2. Mechanisms shaping the development of personality and personality disorders in children and adolescents.

    Science.gov (United States)

    Lenkiewicz, Kamila; Srebnicki, Tomasz; Bryńska, Anita

    2016-01-01

    Until the end of the nineties last century personality disorders could not be diagnosed before the age of eighteen. Nevertheless, the results of studies published in the last decade have revealed that personality disorders can be observed in children and adolescents and that personality disorders diagnosed in adult patients had been present as early as in childhood. The knowledge of possible mechanisms shaping personality disorders in childhood is unsatisfactory and needs to be expanded. Developmental psychology explains the development of abnormal personality through inappropriate attachment patterns and abnormal transitions between developmental phases. Genetic and temperamental factors are also important in the aetiology of personality disorders as well as early maladaptive schemas resulting from personal experiences and interactions with others. The aim of this article is to review the current knowledge on the mechanisms shaping the development of personality and personality disorders in childhood and adolescence.

  3. Early adolescent substance use as a risk factor for developing conduct disorder and depression symptoms.

    Science.gov (United States)

    Wymbs, Brian T; McCarty, Carolyn A; Mason, W Alex; King, Kevin M; Baer, John S; Vander Stoep, Ann; McCauley, Elizabeth

    2014-03-01

    Conduct disorder and depression symptoms are well-established risk factors for substance use during adolescence. However, few investigations have examined whether early substance use increases adolescents' risk of developing conduct disorder/depression symptoms. Using the Developmental Pathways Project sample of 521 middle school students (51.6% male), we tested whether substance use (indicated by alcohol and marijuana use, and use-related impairment) in 8th and 9th grade increased risk of conduct disorder and depression symptoms in 9th and 12th grade over and above prior symptoms. We examined whether associations between substance use and conduct disorder/depression symptoms were consistent across self- or parent-reported symptoms and whether associations were moderated by gender. Analyses indicated that, over and above prior symptoms, elevated substance use in 8th grade predicted elevated conduct disorder symptoms in 9th grade, and substance use in 9th grade predicted conduct disorder symptoms in 12th grade. In contrast, substance use failed to predict later depression symptoms independent of prior symptoms. These findings were consistent across self- and parent-reported conduct disorder/depression symptoms. With one exception (association between substance use in 8th grade and self-reported conduct disorder symptoms in 9th grade), relations between early substance use and later conduct disorder symptoms did not differ between boys and girls. Study findings underscore the unique contribution of substance use during early adolescence to the development of conduct disorder symptoms by late adolescence.

  4. Comparing service use and costs among adolescents with autism spectrum disorders, special needs and typical development.

    Science.gov (United States)

    Barrett, Barbara; Mosweu, Iris; Jones, Catherine Rg; Charman, Tony; Baird, Gillian; Simonoff, Emily; Pickles, Andrew; Happé, Francesca; Byford, Sarah

    2015-07-01

    Autism spectrum disorder is a complex condition that requires specialised care. Knowledge of the costs of autism spectrum disorder, especially in comparison with other conditions, may be useful to galvanise policymakers and leverage investment in education and intervention to mitigate aspects of autism spectrum disorder that negatively impact individuals with the disorder and their families. This article describes the services and associated costs for four groups of individuals: adolescents with autistic disorder, adolescents with other autism spectrum disorders, adolescents with other special educational needs and typically developing adolescents using data from a large, well-characterised cohort assessed as part of the UK Special Needs and Autism Project at the age of 12 years. Average total costs per participant over 6 months were highest in the autistic disorder group (£11,029), followed by the special educational needs group (£9268), the broader autism spectrum disorder group (£8968) and the typically developing group (£2954). Specialised day or residential schooling accounted for the vast majority of costs. In regression analysis, lower age and lower adaptive functioning were associated with higher costs in the groups with an autism spectrum disorder. Sex, ethnicity, number of International Classification of Diseases (10th revision) symptoms, autism spectrum disorder symptom scores and levels of mental health difficulties were not associated with cost. © The Author(s) 2014.

  5. Development and Psychometric Properties of A Screening Tool for Assessing Developmental Coordination Disorder in Adults

    OpenAIRE

    Clark, Carol J.

    2013-01-01

    Background: Developmental Coordination Disorder (DCD) is a neurodevelopmental disorder affecting motor coordination. Evidence suggests this disorder persists into adulthood and may be associated with biomechanical dysfunction and pain. We report on the development and initial validation of a questionnaire to assess for DCD in adults. Methods: An initial item pool (13 items) was derived from the American Psychiatric Association criteria and World Health Organisation definition for DCD. An expe...

  6. Disordered Money Behaviors: Development of the Klontz Money Behavior Inventory

    Directory of Open Access Journals (Sweden)

    Brad T Klontz

    2012-06-01

    Full Text Available Much of the existing literature on financial behavior focuses on basic money management tasks (e.g., balancing a checkbook. However, it can be equally important to identify problematic financial behaviors that can sabotage one’s financial health. The purpose of this study was to create an assessment tool that can be used by mental health and financial professionals to identify disordered money behaviors that may impede on progress towards one’s financial goals. This study asked 422 respondents to indicate their agreement with disordered money behaviors, including compulsive buying, pathological gambling, compulsive hoarding, workaholism, financial enabling, financial dependence, financial denial, and financial enmeshment, which were correlated with demographic characteristics and financial outcomes. The results identified eight subscales derived from 68 disordered money behavior items. All eight subscales were found to have high reliability in measuring disordered behaviors, and six were associated with negative financial health indicators (e.g. less net worth, less income, and/or more revolving credit.

  7. Predicting Friendship Quality in Autism Spectrum Disorders and Typical Development

    Science.gov (United States)

    Bauminger, Nirit; Solomon, Marjorie; Rogers, Sally J.

    2010-01-01

    The role played by social relationship variables (attachment security; mother-child relationship qualities) and social-cognitive capacities (theory of mind) was examined in both observed friendship behaviors and in children's descriptions of friendships (age 8-12) with high functioning children with autism spectrum disorders (HFASD) (n = 44) and…

  8. Risk of developing depressive disorders following rheumatoid arthritis: a nationwide population-based study.

    Directory of Open Access Journals (Sweden)

    Shu-Li Wang

    Full Text Available BACKGROUND & AIMS: To evaluate the risk of depressive disorders among rheumatoid arthritis (RA by using the Taiwan National Health Insurance Research Database (NHIRD. METHODS: We conducted a retrospective study of a matched cohort of 18 285 participants (3 657 RA patients and 14 628 control patients who were selected from the NHIRD. Patients were observed for a maximum of 10 years to determine the rates of newly diagnosed depressive disorders, and Cox regression was used to identify the risk factors associated with depressive disorders in RA patients. RESULTS: During the 10-year follow-up period, 205 (11.2 per 1000 person-years RA patients and 384 (5.1 per 1000 person-years control patients were diagnosed with depressive disorders. In RA patients, most depressive disorders (n = 163, 80% developed with five years of being diagnosed with RA. The incidence risk ratio of depressive disorders between RA patients and control patients was 2.20 (95% confidence interval [CI], 1.84-2.61, P<.001. After adjusting for age, sex, and comorbidities, RA patients were 2.06 times more likely to develop depressive disorders (95% CI, 1.73-2.44, P<.001 compared with the control patients. Hyperthyroidism (HR = 1.67 was an independent risk factor for depressive disorders in patients with RA. CONCLUSIONS: The likelihood of developing depressive disorders is greater among RA patients than among patients without RA. Symptoms of depression should be sought in patients with RA.

  9. 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

  10. Identifying Dieters Who Will Develop an Eating Disorder: A Prospective, Population-Based Study

    Science.gov (United States)

    Fairburn, Christopher G.; Cooper, Zafra; Doll, Helen A.; Davies, Beverley A.

    2010-01-01

    Objective The aims of the study were to identify the characteristics of the dieters most at risk of subsequently developing an eating disorder and to evaluate the feasibility of using a brief questionnaire to identify such dieters in advance. Method A general population cohort of 2,992 young women who were dieting was identified. On four occasions over the subsequent 2 years, this cohort was sent a questionnaire concerning eating habits and attitudes. Participants whose responses suggested that they had developed an eating disorder were interviewed to establish their true case status. The baseline questionnaires of those who did and did not subsequently develop an eating disorder were compared to identify features that predicted future case status. Results One hundred four of the dieters developed an eating disorder of clinical severity during the 2 years of follow-up. Their baseline questionnaire scores differed in many respects from those who had not developed an eating disorder. Items associated with developing an eating disorder were selected by using three different statistical methods. A simple case-predicting instrument based on one of five items scoring above an optimal cut point had a sensitivity of 71% and a specificity of 72% (overall efficiency of 72%). Conclusions Dieters who will develop an eating disorder within the next 2 years have distinctive features. It is feasible to identify them in advance with reasonable efficiency with a brief questionnaire. This questionnaire could be incorporated into routine health assessments, thereby identifying those at high risk. PMID:16330587

  11. A cost of illness study of children with high-functioning autism spectrum disorders and comorbid anxiety disorders as compared to clinically anxious and typically developing children

    NARCIS (Netherlands)

    van Steensel, F.J.A.; Dirksen, C.D.; Bögels, S.M.

    2013-01-01

    The study’s aim was to estimate the societal costs of children with high-functioning ASD and comorbid anxiety disorder(s) (ASD + AD-group; n = 73), and to compare these costs to children with anxiety disorders (AD-group; n = 34), and typically developing children (controls; n = 87). Mean total costs

  12. The association between school exam grades and subsequent development of bipolar disorder

    DEFF Research Database (Denmark)

    Pedersen, Steffie Damgaard; Østergaard, Søren Dinesen; Petersen, Liselotte

    2018-01-01

    and bipolar I disorder (BD-I) has not been studied. Therefore, we aimed to study the association between school exam grades and subsequent development of BD and BD-I while adjusting for parental history of mental disorder. METHODS: We conducted a register-based nationwide cohort study following 505 688......OBJECTIVE: Prior studies have indicated that both high and low school grades are associated with development of bipolar disorder (BD), but these studies have not adjusted for parental history of mental disorder, which is a likely confounder. Furthermore, the association between school grades...... individuals born in Denmark between 1987 and 1995. We investigated the association between school exam grades and development of BD or BD-I with a Cox model adjusting for family history of mental disorder and other potential confounders. RESULTS: During follow-up, 900 individuals were diagnosed with BD...

  13. Parents’ Strategies to Elicit Autobiographical Memories in Autism Spectrum Disorders, Developmental Language Disorders and Typically Developing Children

    Science.gov (United States)

    Goldman, Sylvie; DeNigris, Danielle

    2014-01-01

    Conversations about the past support the development of autobiographical memory. Parents’ strategies to elicit child's participation and recall during past event conversations were compared across three school-age diagnostic groups: autism spectrum disorder (ASD, n = 11), developmental language disorders (n = 11) and typically developing (TD, n = 11). We focused on the prevalence of directives versus enrichment of events. Groups did not differ in number of events, length, and total turns. However, parents of children with ASD produced more direct questions, corrections, and unrelated turns than parents of TD children. Results highlight how parents adjusted their conversational style to their child's communication difficulties to maximize interactions and how these strategies may affect the development of personal conversations. PMID:25312278

  14. Parents' strategies to elicit autobiographical memories in autism spectrum disorders, developmental language disorders and typically developing children.

    Science.gov (United States)

    Goldman, Sylvie; DeNigris, Danielle

    2015-05-01

    Conversations about the past support the development of autobiographical memory. Parents' strategies to elicit child's participation and recall during past event conversations were compared across three school-age diagnostic groups: autism spectrum disorder (ASD, n = 11), developmental language disorders (n = 11) and typically developing (TD, n = 11). We focused on the prevalence of directives versus enrichment of events. Groups did not differ in number of events, length, and total turns. However, parents of children with ASD produced more direct questions, corrections, and unrelated turns than parents of TD children. Results highlight how parents adjusted their conversational style to their child's communication difficulties to maximize interactions and how these strategies may affect the development of personal conversations.

  15. Clock Genes and Altered Sleep-Wake Rhythms: Their Role in the Development of Psychiatric Disorders.

    Science.gov (United States)

    Charrier, Annaëlle; Olliac, Bertrand; Roubertoux, Pierre; Tordjman, Sylvie

    2017-04-29

    In mammals, the circadian clocks network (central and peripheral oscillators) controls circadian rhythms and orchestrates the expression of a range of downstream genes, allowing the organism to anticipate and adapt to environmental changes. Beyond their role in circadian rhythms, several studies have highlighted that circadian clock genes may have a more widespread physiological effect on cognition, mood, and reward-related behaviors. Furthermore, single nucleotide polymorphisms in core circadian clock genes have been associated with psychiatric disorders (such as autism spectrum disorder, schizophrenia, anxiety disorders, major depressive disorder, bipolar disorder, and attention deficit hyperactivity disorder). However, the underlying mechanisms of these associations remain to be ascertained and the cause-effect relationships are not clearly established. The objective of this article is to clarify the role of clock genes and altered sleep-wake rhythms in the development of psychiatric disorders (sleep problems are often observed at early onset of psychiatric disorders). First, the molecular mechanisms of circadian rhythms are described. Then, the relationships between disrupted circadian rhythms, including sleep-wake rhythms, and psychiatric disorders are discussed. Further research may open interesting perspectives with promising avenues for early detection and therapeutic intervention in psychiatric disorders.

  16. Clock Genes and Altered Sleep–Wake Rhythms: Their Role in the Development of Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Annaëlle Charrier

    2017-04-01

    Full Text Available In mammals, the circadian clocks network (central and peripheral oscillators controls circadian rhythms and orchestrates the expression of a range of downstream genes, allowing the organism to anticipate and adapt to environmental changes. Beyond their role in circadian rhythms, several studies have highlighted that circadian clock genes may have a more widespread physiological effect on cognition, mood, and reward-related behaviors. Furthermore, single nucleotide polymorphisms in core circadian clock genes have been associated with psychiatric disorders (such as autism spectrum disorder, schizophrenia, anxiety disorders, major depressive disorder, bipolar disorder, and attention deficit hyperactivity disorder. However, the underlying mechanisms of these associations remain to be ascertained and the cause–effect relationships are not clearly established. The objective of this article is to clarify the role of clock genes and altered sleep–wake rhythms in the development of psychiatric disorders (sleep problems are often observed at early onset of psychiatric disorders. First, the molecular mechanisms of circadian rhythms are described. Then, the relationships between disrupted circadian rhythms, including sleep–wake rhythms, and psychiatric disorders are discussed. Further research may open interesting perspectives with promising avenues for early detection and therapeutic intervention in psychiatric disorders.

  17. Intermittent explosive disorder: development of integrated research criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

    Science.gov (United States)

    Coccaro, Emil F

    2011-01-01

    This study was designed to develop a revised diagnostic criteria set for intermittent explosive disorder (IED) for consideration for inclusion in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). This revised criteria set was developed by integrating previous research criteria with elements from the current DSM-IV set of diagnostic criteria. Evidence supporting the reliability and validity of IED-IR ("IED Integrated Criteria") in a new and well-characterized group of subjects with personality disorder is presented. Clinical, phenomenologic, and diagnostic data from 201 individuals with personality disorder were reviewed. All IED diagnoses were assigned using a best-estimate process (eg, kappa for IED-IR >0.85). In addition, subjects meeting IED-IR criteria had higher scores on dimensional measures of aggression and had lower global functioning scores than non-IED-IR subjects, even when related variables were controlled. The IED-IR criteria were more sensitive than the DSM-IV criteria only in identifying subjects with significant impulsive-aggressive behavior by a factor of 16. We conclude that the IED-IR criteria can be reliably applied and have sufficient validity to warrant consideration as DSM-V criteria for IED. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Non-Verbal Psychotherapy of Deaf Children with Disorders in Personality Development.

    Science.gov (United States)

    Zalewska, Marina

    1989-01-01

    Discussed are principles of nonverbal therapy for deaf children with disorders in the development of self, and the possible existence of a relationship between lack of auditory experiences in deaf children and disorders in mother-child bonding. A case study presents a three-year-old deaf boy successfully treated through a nonverbal…

  19. Word Problem Solving of Students with Autistic Spectrum Disorders and Students with Typical Development

    Science.gov (United States)

    Bae, Young Seh

    2013-01-01

    Mathematical Word Problem Solving of Students with Autistic Spectrum Disorders and Students with Typical Development Young Seh Bae This study investigated mathematical word problem solving and the factors associated with the solution paths adopted by two groups of participants (N=40), students with autism spectrum disorders (ASDs) and typically…

  20. Developing scales measuring disorder-specific intolerance of uncertainty (DSIU) : a new perspective on transdiagnostic

    NARCIS (Netherlands)

    Thibodeau, Michel A; Carleton, R Nicholas; McEvoy, Peter M; Zvolensky, Michael J; Brandt, Charles P; Boelen, Paul A; Mahoney, Alison E J; Deacon, Brett J; Asmundson, Gordon J G

    Intolerance of uncertainty (IU) is a construct of growing prominence in literature on anxiety disorders and major depressive disorder. Existing measures of IU do not define the uncertainty that respondents perceive as distressing. To address this limitation, we developed eight scales measuring

  1. Social Analogical Reasoning in School-Aged Children with Autism Spectrum Disorder and Typically Developing Peers

    Science.gov (United States)

    Green, Adam E.; Kenworthy, Lauren; Gallagher, Natalie M.; Antezana, Ligia; Mosner, Maya G.; Krieg, Samantha; Dudley, Katherina; Ratto, Allison; Yerys, Benjamin E.

    2017-01-01

    Analogical reasoning is an important mechanism for social cognition in typically developing children, and recent evidence suggests that some forms of analogical reasoning may be preserved in autism spectrum disorder. An unanswered question is whether children with autism spectrum disorder can apply analogical reasoning to social information. In…

  2. Initial Development of a Measure of Emotional Dysregulation for Individuals with Cluster B Personality Disorders

    Science.gov (United States)

    Newhill, Christina E.; Mulvey, Edward P.; Pilkonis, Paul A.

    2004-01-01

    Individuals with DSM-IV Cluster B personality disorders are at particular risk of violence toward self or others. Emotional dysregulation is likely to be a factor in such incidents and is a central issue addressed in therapies with personality-disordered individuals. This article reports findings from a study that developed an original 18-item…

  3. Development of Anxiety Disorders in a Traumatized Pediatric Population: A Preliminary Longitudinal Evaluation

    Science.gov (United States)

    Cortes, Adriana M.; Saltzman, Kassey M.; Weems, Carl F.; Regnault, Heather P.; Reiss, Allan L.; Carrion, Victor G.

    2005-01-01

    Objective: The current study was conducted to determine if post-traumatic stress disorder (PTSD) symptomatology predicted later development of non-PTSD anxiety disorders in children and adolescents victimized by interpersonal trauma. Methods: Thirty-four children with a history of interpersonal trauma and no initial diagnosis of anxiety disorder…

  4. Using Qualitative Methods to Guide Scale Development for Anxiety in Youth with Autism Spectrum Disorder

    Science.gov (United States)

    Bearss, Karen; Taylor, Christopher A.; Aman, Michael G.; Whittemore, Robin; Lecavalier, Luc; Miller, Judith; Pritchett, Jill; Green, Bryson; Scahill, Lawrence

    2016-01-01

    Anxiety is common in youth with autism spectrum disorder. Despite this common co-occurrence, studies targeting anxiety in this population are hindered by the under-developed state of measures in youth with autism spectrum disorder. Content validity (the extent to which an instrument measures the domain of interest) and an instrument's relevance to…

  5. Injuries in Children with Autism Spectrum Disorder: Study to Explore Early Development (SEED)

    Science.gov (United States)

    DiGuiseppi, Carolyn; Levy, Susan E.; Sabourin, Katherine R.; Soke, Gnakub N.; Rosenberg, Steven; Lee, Li-Ching; Moody, Eric; Schieve, Laura A.

    2018-01-01

    This study examined caregiver-reported medically-attended injuries among 30-68 month old children with autism spectrum disorder (ASD) compared to general population (POP) and non-ASD developmental disorders (DD) controls in the Study to Explore Early Development. Injuries were common in ASD cases (32.3%) as well as POP (30.2%) and DD (27.8%)…

  6. Orphan drugs in development for urea cycle disorders: current perspectives

    OpenAIRE

    Häberle, Johannes; McCandless,Shawn

    2014-01-01

    Johannes Häberle,1 Shawn E McCandless2 1Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland; 2Center for Human Genetics, University Hospitals Case Medical Center, and Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA Abstract: The urea cycle disorders are caused by deficiency of one of the six hepatic enzymes or two transporters involved in detoxification of am...

  7. Social Anxiety Disorder in Swedish Adolescents : Prevalence, Victimization & Development

    OpenAIRE

    Green-Landell, Malin

    2010-01-01

    Human beings are social creatures. Accordingly, fear of social situations can be severely disabling. Social anxiety disorder (SAD) is characterized by excessive fear of negative evaluation in social or performance situations. SAD has an early onset and often goes undetected an untreated. Descriptive studies on non‐clinical samples are required in order to find ways to prevent SAD and associated consequences. This thesis aimed at examining epidemiological variables of SAD in adolescence which ...

  8. Drug Repurposing Is a New Opportunity for Developing Drugs against Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Hyeong-Min Lee

    2016-01-01

    Full Text Available Better the drugs you know than the drugs you do not know. Drug repurposing is a promising, fast, and cost effective method that can overcome traditional de novo drug discovery and development challenges of targeting neuropsychiatric and other disorders. Drug discovery and development targeting neuropsychiatric disorders are complicated because of the limitations in understanding pathophysiological phenomena. In addition, traditional de novo drug discovery and development are risky, expensive, and time-consuming processes. One alternative approach, drug repurposing, has emerged taking advantage of off-target effects of the existing drugs. In order to identify new opportunities for the existing drugs, it is essential for us to understand the mechanisms of action of drugs, both biologically and pharmacologically. By doing this, drug repurposing would be a more effective method to develop drugs against neuropsychiatric and other disorders. Here, we review the difficulties in drug discovery and development in neuropsychiatric disorders and the extent and perspectives of drug repurposing.

  9. Early brain enlargement and elevated extra-axial fluid in infants who develop autism spectrum disorder.

    Science.gov (United States)

    Shen, Mark D; Nordahl, Christine W; Young, Gregory S; Wootton-Gorges, Sandra L; Lee, Aaron; Liston, Sarah E; Harrington, Kayla R; Ozonoff, Sally; Amaral, David G

    2013-09-01

    Prospective studies of infants at risk for autism spectrum disorder have provided important clues about the early behavioural symptoms of autism spectrum disorder. Diagnosis of autism spectrum disorder, however, is not currently made until at least 18 months of age. There is substantially less research on potential brain-based differences in the period between 6 and 12 months of age. Our objective in the current study was to use magnetic resonance imaging to identify any consistently observable brain anomalies in 6-9 month old infants who would later develop autism spectrum disorder. We conducted a prospective infant sibling study with longitudinal magnetic resonance imaging scans at three time points (6-9, 12-15, and 18-24 months of age), in conjunction with intensive behavioural assessments. Fifty-five infants (33 'high-risk' infants having an older sibling with autism spectrum disorder and 22 'low-risk' infants having no relatives with autism spectrum disorder) were imaged at 6-9 months; 43 of these (27 high-risk and 16 low-risk) were imaged at 12-15 months; and 42 (26 high-risk and 16 low-risk) were imaged again at 18-24 months. Infants were classified as meeting criteria for autism spectrum disorder, other developmental delays, or typical development at 24 months or later (mean age at outcome: 32.5 months). Compared with the other two groups, infants who developed autism spectrum disorder (n = 10) had significantly greater extra-axial fluid at 6-9 months, which persisted and remained elevated at 12-15 and 18-24 months. Extra-axial fluid is characterized by excessive cerebrospinal fluid in the subarachnoid space, particularly over the frontal lobes. The amount of extra-axial fluid detected as early as 6 months was predictive of more severe autism spectrum disorder symptoms at the time of outcome. Infants who developed autism spectrum disorder also had significantly larger total cerebral volumes at both 12-15 and 18-24 months of age. This is the first magnetic

  10. Orphan drugs in development for urea cycle disorders: current perspectives

    Directory of Open Access Journals (Sweden)

    Häberle J

    2014-09-01

    Full Text Available Johannes Häberle,1 Shawn E McCandless2 1Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland; 2Center for Human Genetics, University Hospitals Case Medical Center, and Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA Abstract: The urea cycle disorders are caused by deficiency of one of the six hepatic enzymes or two transporters involved in detoxification of ammonia. The resulting hyperammonemia causes severe brain injury unless aggressive steps are taken to reduce the accumulation of ammonia, which is thought to be the most toxic metabolite. This review describes the current state of chronic management of urea cycle disorders, focusing on new and emerging therapies. Management strategies include the mainstay of treatment, namely dietary protein restriction and supplementation with l-arginine or l-citrulline. Several currently approved medications utilize and enhance alternative pathways of waste nitrogen excretion (sodium benzoate, sodium phenylacetate, sodium phenylbutyrate in several formulations, and glycerol phenylbutyrate, working through conjugation of the drug to either glycine (in the case of benzoate or glutamine, the products of which are excreted in the urine. Carglumic acid activates the first committed step of conversion of ammonia to urea, carbamoylphosphate synthetase, and thus effectively treats defective synthesis of the endogenous activator, N-acetylglutamate, whether due to genetic defects or biochemical inhibition of the N-acetylglutamate synthase enzyme. Approaches to neuroprotection during episodes of hyperammonemia are discussed, including the use of controlled hypothermia (brain cooling, as well as proposed, but as yet untested, pharmacologic therapies. Finally, cell-based therapies, including liver transplantation, infusion of fresh or cryopreserved hepatocytes, use of stem cells, and new approaches to gene

  11. Development of the Clinic of Endocrinology, diabetes and metabolic disorders.

    Science.gov (United States)

    Shubeska Stratrova, S

    2013-01-01

    The Clinic of Endocrinology, diabetes and metabolic disorders was founded in 1975 by Prof d-r Alexandar Plashevski. Healthcare, educational and scientific activities in the Clinic of Endocrinology are performed in its departments. The Department for hospitalized diabetic and endocrine patients consists of the metabolic and endocrine intensive care unit, the department for diagnosis and treatment of diabetics and endocrine patients, day hospital, the department for education of diabetic patients, and the national center for insulin pump therapy. The Center for Diabetes was established in 1972 by Prof d-r Dimitar Arsov. In 1975, Prof d-r Alexandar Plasheski broadened the activities of the Center for Diabetes. It was dislocated in 1980, with new accommodation outside the clinic. Since then the Center has consisted of several organized units: two specialist outpatient clinics for diabetic patients, biochemical and endocrine laboratory, sub-departments for: diabetic foot, cardiovascular diagnosis, ophthalmology, and urgent interventions. The Department of Endocrinology and Metabolic Disorders for outclinic endocrine patients was established in 1980, and it integrates the following sub-departments: thyrology, andrology, reproductive endocrinology, obesity and lipid disorders and sub-department for osteoporosis. The educational staff of the Clinic of Endocrinology organizes theoretical and practical education about Clinical Investigation and Internal Medicine with credit transfer system course of study of the Medical Faculty, Faculty of Stomatology, postgraduate studies, specializations and sub-specializations. Symposiums, 3 congresses, schools for diabetes and osteoporosis and continuous medical education were also organized. The Clinic of Endocrinology was initiator, organizer, founder and the seat of several medical associations.

  12. Estimated Risk of Developing Selected DSM-IV Disorders among 5-Year-Old Children with Prenatal Cocaine Exposure

    Science.gov (United States)

    Morrow, Connie E.; Accornero, Veronica H.; Xue, Lihua; Manjunath, Sudha; Culbertson, Jan L.; Anthony, James C.; Bandstra, Emmalee S.

    2009-01-01

    We estimated childhood risk of developing selected DSM-IV Disorders, including Attention-Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), and Separation Anxiety Disorder (SAD), in children with prenatal cocaine exposure (PCE). Children were enrolled prospectively at birth (n = 476) with prenatal drug exposures documented…

  13. Sleep Disturbance in Children and Adolescents with Disorders of Development: Its Significance and Management. Clinics in Developmental Medicine.

    Science.gov (United States)

    Stores, Gregory, Ed.; Wiggs, Luci, Ed.

    The 30 papers in this collection are arranged in five sections which address general issues, neurodevelopmental disorders, other neurological conditions, non-neurological pediatric disorders, and psychiatric disorders. The papers are: (1) "Sleep Disturbance: A Serious, Widespread, Yet Neglected Problem in Disorders of Development"…

  14. Thoughts on the nature of identity: how disorders of sex development inform clinical research about gender identity disorders.

    Science.gov (United States)

    Reiner, William G; Reiner, D Townsend

    2012-01-01

    Disorders of sex development (DSD), like gender dysphoria, are conditions with major effects on child sexuality and identity, as well as sexual orientation. Each may in some cases lead to change of gender from that assigned neonatally. These similarities-and the conditions' differences-provide a context for reviewing the articles in this issue about clinical approaches to children with gender dysphoria, in relation to assessment, intervention, and ethics.

  15. Social determinants of mental disorders and the Sustainable Development Goals: a systematic review of reviews.

    Science.gov (United States)

    Lund, Crick; Brooke-Sumner, Carrie; Baingana, Florence; Baron, Emily Claire; Breuer, Erica; Chandra, Prabha; Haushofer, Johannes; Herrman, Helen; Jordans, Mark; Kieling, Christian; Medina-Mora, Maria Elena; Morgan, Ellen; Omigbodun, Olayinka; Tol, Wietse; Patel, Vikram; Saxena, Shekhar

    2018-04-01

    Mental health has been included in the UN Sustainable Development Goals. However, uncertainty exists about the extent to which the major social determinants of mental disorders are addressed by these goals. The aim of this study was to develop a conceptual framework for the social determinants of mental disorders that is aligned with the Sustainable Development Goals, to use this framework to systematically review evidence regarding these social determinants, and to identify potential mechanisms and targets for interventions. We did a systematic review of reviews using a conceptual framework comprising demographic, economic, neighbourhood, environmental events, and social and culture domains. We included 289 articles in the final Review. This study sheds new light on how the Sustainable Development Goals are relevant for addressing the social determinants of mental disorders, and how these goals could be optimised to prevent mental disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Cognitive Analysis of 9 to 11-Year-Old Children With Intellectual Development Disorders

    Directory of Open Access Journals (Sweden)

    Kauliņa Anda

    2017-12-01

    Full Text Available Cognitive development significantly influences efficiency and results of child’s understanding and comprehension of the world. Attention and cognition play a significant role to ensure academic achievement and success. Attention is essential for purposeful planning of action and systematic work. Attention is necessary to follow the study material and for physical survival in everyday life. Cognition is significant in decision making and evaluating possible outcomes, being especially important in children with cognitive development disorders. The aim of the present study was to find out the peculiarities of the cognitive processes in 9 to 11-year-old children with cognitive development disorders. Previous literature suggests that children with intellectual development disorders are at increased risk of general cognitive disorders. To test this assumption and establish cognitive abilities in children with intellectual development disorders, the following subtests of the Vienna Test System (VTS were used: CPM/S2 (Raven's Coloured Progressive Matrices, B19 (Double Labyrinth Test and WAFF (Perception and Attention Functions: Focused Attention. VTS is one of the leading computer-based psychophysiological testing systems in Europe. In addition to testing, behavioural observations were also carried out. Study results reveal that children with a shared diagnosis are not as similar when it comes to cognition and attention. Not all children within the sample group exhibited reduced attention and concentration, although the whole participant sample was diagnosed with intellectual development disorder. Meanwhile, risk factors hindering normal cognitive development were identified.

  17. Molecular underpinnings of prefrontal cortex development in rodents provide insights into the etiology of neurodevelopmental disorders.

    Science.gov (United States)

    Schubert, D; Martens, G J M; Kolk, S M

    2015-07-01

    The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcription factors, guidance cues and other regulatory molecules and requires the intricate and temporal orchestration of a number of developmental processes. Disturbance or failure of any of these processes causing neurodevelopmental abnormalities within the PFC may contribute to several of the cognitive deficits seen in patients with neurodevelopmental disorders. In this review, we elaborate on the specific processes underlying prefrontal development, such as induction and patterning of the prefrontal area, proliferation, migration and axonal guidance of medial prefrontal progenitors, and their eventual efferent and afferent connections. We furthermore integrate for the first time the available knowledge from genome-wide studies that have revealed genes linked to neurodevelopmental disorders with experimental molecular evidence in rodents. The integrated data suggest that the pathogenic variants in the neurodevelopmental disorder-associated genes induce prefrontal cytoarchitectonical impairments. This enhances our understanding of the molecular mechanisms of prefrontal (mis)development underlying the four major neurodevelopmental disorders in humans, that is, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder and schizophrenia, and may thus provide clues for the development of novel therapies.

  18. The influence of contemporary education on the development of narcissistic disorders

    OpenAIRE

    Černe, Neža

    2013-01-01

    The thesis takes a look at the phenomenon of narcissistic personality disorders, with the main focus on the role of contemporary education in their development. In this respect, we analyse how relations from the early childhood influence the development of such disorders. At the beginning, I introduce the myth of Narcissus, followed by the main theories of narcissism, since a definition of narcissism cannot leave out psychoanalysis. We continue with a definition of permissive education, wh...

  19. Gambling disorder in adolescents: prevalence, new developments, and treatment challenges

    Directory of Open Access Journals (Sweden)

    Floros GD

    2018-03-01

    Full Text Available Georgios D Floros 2nd Department of Psychiatry, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece Abstract: Research on adolescence gambling over the past twenty years has revealed significant incidence and prevalence rates and highlighted the possible negative effects on an adolescent’s well-being. Several risk and protective factors have also been identified. Over the course of the past few years, technological advances have heralded the advent of new avenues for gambling as well as new opportunities to gamble without any direct monetary exchange. This review article examines those established trends as well as the new issues that we are faced with, in order to accurately portray the current challenges in research, prevention, and treatment. Keywords: adolescence, gambling disorder

  20. Development and validation of an Eating Disorders Symptom Impact Scale (EDSIS for carers of people with eating disorders

    Directory of Open Access Journals (Sweden)

    Hankins Matthew

    2008-04-01

    Full Text Available Abstract Background Family members of relatives with eating disorders experience high levels of distress due to the difficulties in their care giving role. However no measures have been developed to measure the specific impact that an individual with an eating disorder has on family life. The aim of this study was to develop a measure to assess the specific caregiving burden of both anorexia nervosa and bulimia nervosa. A secondary aim was to examine whether this measure was sensitive to change. Methods A new scale, the Eating Disorders Symptom Impact Scale (EDSIS, was generated by a panel of clinicians and researchers based upon quantitative and qualitative work with carers and reviewed by a panel of "expert carers". A cross-sectional study was conducted among carers of relatives with an eating disorder to examine the properties of the new scale. In addition, participants from an ongoing pre-and-post design study completed several self-report questionnaires to assess the sensitivity of the EDSIS to change. Results A sample of 196 carers of relatives with an eating disorder aged 25–68 compted the scale. A 24-item EDSIS scale was derived with four factors: nutrition, guilt, dysregulated behaviour and social isolation. These explained 58.4% of the variance in carer distress. Reliability was acceptable (Cronbach's alpha ranged from 0.84 to 0.90. The convergent validity of the EDSIS subscales was moderately supported by correlations with a general caregiving measure (Experience of Caregiving Inventory (ECI, r = 0.42 to 0.60, psychological distress (General Health Questionnaire (GHQ-12, r = 0.33 and perceived functioning of the relative (Children Global Assessment Scale (CGAS, r = -30. A sample of 57 primary caregivers completed pre-post intervention assessments and the overall scale (t = 2.3, p Conclusion The EDSIS instrument has good psychometric properties and may be of value to assess the impact of eating disorder symptoms on family members. It

  1. Coexistence of Trisomy 13 and SRY (-) XX Ovotesticular Disorder of Sex Development.

    Science.gov (United States)

    Ürel Demir, Gizem; Doğan, Özlem Akgün; Şimşek Kiper, Pelin Özlem; Utine, Gülen Eda; Boduroğlu, Koray; Gucer, Safak; Alikaşifoğlu, Mehmet

    2017-12-01

    Ovotesticular disorder of sex development (OT-DSD) is a rare disorder of sexual differentiation characterized by the presence of both testicular and ovarian tissue in an individual and the majority of cases have been reported with 46,XX karyotype. In 46,XX cases, testicular differentiation may occur due to the translocation of SRY to the X chromosome or to an autosome. Herein, we present a female newborn with a combination of trisomy 13 and SRY (-) XX OT-DSD. Trisomy 13 is a relatively common and well-known chromosomal disorder in which disorders of sexual differentiation are not frequent. In the absence of SRY, overexpression of pro-testis genes, or decreased expression of pro-ovarian/anti-testis genes have been suggested as underlying mechanisms of testicular formation. The findings in this patient were suggestive of an underlying genomic disorder associated with FGF9 and/or SPRY2.

  2. An Examination of Participants Who Develop an Eating Disorder Despite Completing an Eating Disorder Prevention Program: Implications for Improving the Yield of Prevention Efforts

    Science.gov (United States)

    Stice, Eric; Rohde, Paul

    2014-01-01

    Numerous trials provide support for the Body Project, an eating disorder prevention program wherein young women with body image concerns critique the thin ideal. Despite medium to large effects, some participants subsequently develop an eating disorder, suggesting that intervention or recruitment procedures could be improved. This study investigated baseline and acute intervention predictors of DSM-5 eating disorder development during a 3-year follow-up among Body Project participants. Combined data from two trials compare participants who experienced eating disorder onset during follow-up (n=20) to those who did not (n=216). Participants who did versus did not develop an eating disorder started the intervention with higher eating disorder symptoms (η2=0.08), negative affect (η2=0.06), thin-ideal internalization (η2=0.02), and body dissatisfaction (η2=0.02); the same baseline predictors of eating disorder onset emerged in controls. Attenuated pre–post reductions in eating disorder symptoms (η2=0.01) predicted eating disorder onset but not after controlling for baseline levels. Given that Body Project and control participants who later developed an eating disorder started with initial elevations in risk factors and eating disorder symptoms, it might be useful to develop a more intensive variant of this program for those exhibiting greater risk at baseline and to deliver the prevention program earlier to prevent initial escalation of risk. The fact that nonresponders also showed greater negative affect and eating disorder symptoms suggests that it might be useful to add activities to improve affect and increase dissonance about disordered eating. PMID:25342026

  3. Development of functional gastrointestinal disorders after Giardia lamblia infection

    Directory of Open Access Journals (Sweden)

    Hanevik Kurt

    2009-04-01

    Full Text Available Abstract Background Functional gastrointestinal disorders (FGID may occur following acute gastroenteritis. This long-term complication has previously not been described after infection with the non-invasive protozoan Giardia lamblia. This study aims to characterize persistent abdominal symptoms elicited by Giardia infection according to Rome II criteria and symptoms scores. Methods Structured interview and questionnaires 12–30 months after the onset of Giardia infection, and at least 6 months after Giardia eradication, among 82 patients with persisting abdominal symptoms elicited by the Giardia infection. All had been evaluated to exclude other causes. Results We found that 66 (80.5% of the 82 patients had symptoms consistent with irritable bowel syndrome (IBS and 17 (24.3% patients had functional dyspepsia (FD according to Rome II criteria. IBS was sub classified into D-IBS (47.0%, A-IBS (45.5% and C-IBS (7.6%. Bloating, diarrhoea and abdominal pain were reported to be most severe. Symptoms exacerbation related to specific foods were reported by 45 (57.7% patients and to physical or mental stress by 34 (44.7% patients. Conclusion In the presence of an IBS-subtype pattern consistent with post-infectious IBS (PI-IBS, and in the absence of any other plausible causes, we conclude that acute Giardia infection may elicit functional gastrointestinal diseases with food and stress related symptoms similar to FGID patients in general.

  4. Psychological disorders and ecological factors affect the development of executive functions: Some perspectives

    Directory of Open Access Journals (Sweden)

    Rafika ZEBDI

    2016-12-01

    Full Text Available The links between deficits in executive functions (EF (e.g., mental flexibility, inhibition capacities..., and some psychological disorders (e.g., anxiety and depressive disorders has been investigated in the past decades or so. Observations evidenced that some deficits in working memory, planning, and mental flexibility were highly correlated with anxiety and depressive disorders. The majority of studies focused on adults’ population, whereas it seems important to adopt a developmental perspective to fully understand the dynamic of these EF/psychological disorders relations. We suggest two axis on which to focus in future research: (i relations between EF and anxiety traits through development; and (ii the possible role of external factors such as parent-child relationships on the development of EF.

  5. Psychological Disorders and Ecological Factors Affect the Development of Executive Functions: Some Perspectives.

    Science.gov (United States)

    Zebdi, Rafika; Goyet, Louise; Pinabiaux, Charlotte; Guellaï, Bahia

    2016-01-01

    The links between deficits in executive functions (EFs) (e.g., mental flexibility, inhibition capacities, etc.) and some psychological disorders (e.g., anxiety and depressive disorders) have been investigated in the past decades or so. Observations evidenced that some deficits in working memory, planning, and mental flexibility were highly correlated with anxiety and depressive disorders. The majority of studies focused on adults' population, whereas it seems important to adopt a developmental perspective to fully understand the dynamic relation of these EF/psychological disorders. We suggest to focus on the following two axes in future research: (i) relations between EF and anxiety traits through development and (ii) the possible role of external factors such as parent-child relationships on the development of EF.

  6. Increased risk of developing stroke for patients with major affective disorder--a registry study

    DEFF Research Database (Denmark)

    Nilsson, Flemming M; Kessing, Lars V

    2004-01-01

    and cerebrovascular diseases in hospitalised patients. The main finding of this study was that patients with depression severe enough to be hospitalised, seem to be at an increased risk of developing cerebrovascular disease. The hazard ratio of getting a diagnosis of stroke after initially having been discharged......Only a few studies have evaluated depressive disorder as a risk factor for cerebrovascular disease. In a hospital discharge register with nation-wide coverage of all hospitals in Denmark we used linkage between the somatic and psychiatric registries to study comorbidity between affective disorders...... with a diagnosis of depression was found to be 1.22 (95% Confidence Interval: 1.06-1.41). In the group of patients with manic/bipolar disorder no association was found concerning development of stroke. In elderly with first time depression admitted to hospital, neurological disorders should be carefully evaluated...

  7. Effects of UPR and ERAD pathway on the prolyl endopeptidase production in Pichia pastoris by controlling of nitrogen source.

    Science.gov (United States)

    Wang, Xiao-Dong; Jiang, Ting; Yu, Xiao-Wei; Xu, Yan

    2017-07-01

    Prolyl endopeptidase (PEP) is very useful in various industries, while the high cost of enzyme production remains a major obstacle for its industrial applications. Pichia pastoris has been used for the PEP production; however, the fermentation process has not be investigated and little is known about the impact of excessive PEP production on the host cell physiology. Here, we optimized the nitrogen source to improve the PEP expression level and further evaluated the cellular response including UPR and ERAD. During methanol induction phase the PEP activity (1583 U/L) was increased by 1.48-fold under the optimized nitrogen concentration of NH 4 + (300 mmol/L) and casamino acids [1.0% (w/v)] in a 3-L bioreactor. Evaluated by RT-PCR the UPR and ERAD pathways were confirmed to be activated. Furthermore, a strong decrease of ERAD-related gene transcription was observed with the addition of nitrogen source, which contributed to a higher PEP expression level.

  8. Psychosexual Development in Adolescents and Adults with Disorders of Sex Development-Results from the German Clinical Evaluation Study

    NARCIS (Netherlands)

    Jurgensen, M.; Kleinemeier, E.; Lux, A.; Steensma, T.D.; Cohen-Kettenis, P.T.; Hiort, O.; Thyen, U.; Kohler, B.

    2013-01-01

    Introduction. Both biological and psychosocial factors influence psychosexual development. High levels of pre- and postnatal androgens lead to more male-typical behavior. So far, the influence of androgens on gender identity and sexual orientation is unclear. Disorders of sex development (DSDs) are

  9. A Comparison of the Development of Audiovisual Integration in Children with Autism Spectrum Disorders and Typically Developing Children

    Science.gov (United States)

    Taylor, Natalie; Isaac, Claire; Milne, Elizabeth

    2010-01-01

    This study aimed to investigate the development of audiovisual integration in children with Autism Spectrum Disorder (ASD). Audiovisual integration was measured using the McGurk effect in children with ASD aged 7-16 years and typically developing children (control group) matched approximately for age, sex, nonverbal ability and verbal ability.…

  10. Behavioral Own-Body-Transformations in Children and Adolescents With Typical Development, Autism Spectrum Disorder, and Developmental Coordination Disorder

    Directory of Open Access Journals (Sweden)

    Soizic Gauthier

    2018-05-01

    Full Text Available Background: In motor imitation, taking a partner's perspective often involves a mental body transformation from an embodied, ego-centered viewpoint to a disembodied, hetero-centered viewpoint. Impairments of both own-body-transformation (OBT and abnormalities in visual-spatial processing have been reported in patients with neurodevelopmental disorders including autism spectrum disorder (ASD. In the context of a visual-motor interactive task, studying OBT impairments while disentangling the contribution of visual-spatial impairments associated with motor coordination problems has not been investigated.Methods: 85 children and adolescents (39 controls with typical development, TD; 29 patients with ASD; 17 patients with developmental coordination disorder, DCD, aged 6–19 years, participated in a behavioral paradigm in which participants interacted with a virtual tightrope walker (TW standing and moving with him. The protocol enables to distinguish ego-centered and hetero-centered perspectives.Results: We show that (1 OBT was possible but difficult for children with neurodevelopmental disorders, as well as for TD children, when the task required the participant to perform a mental rotation in order to adopt a hetero-centered perspective. (2 Using multivariate models, hetero-centered perspective score was significantly associated with age, TW orientation, latency, and diagnosis. ASD and TD groups' performances were close and significantly correlated with age. However, it was not the case for DCD, since this group was specifically handicapped by visual-spatial impairments. (3 ASD and DCD did not perform similarly: motor performance as shown by movement amplitude was better in DCD than ASD. ASD motor response was more ambiguous and hardly readable.Conclusion: Changing perspective in a spatial environment is possible for patients with ASD although delayed compared with TD children. In patients with DCD, their visual-spatial impairments negatively

  11. Headache Disorders May Be a Risk Factor for the Development of New Onset Hypothyroidism.

    Science.gov (United States)

    Martin, Andrew T; Pinney, Susan M; Xie, Changchun; Herrick, Robert L; Bai, Yun; Buckholz, Jeanette; Martin, Vincent T

    2017-01-01

    To determine whether headache disorders are a risk factor for the development of new onset hypothyroidism. Past studies have reported associations between headache disorders and hypothyroidism, but the directionality of the association is unknown. This was a longitudinal retrospective cohort study using data from the Fernald Medical Monitoring Program (FMMP). Residents received physical examinations and thyroid function testing every 3 years during the 20 year program. Residents were excluded from the cohort if there was evidence of past thyroid disease or abnormal thyroid function tests at the first office visit. A diagnosis of a headache disorder was established by self-report of "frequent headaches," use of any headache-specific medication, or a physician diagnosis of a headache disorder. The primary outcome measure was new onset hypothyroidism defined as the initiation of thyroid replacement therapy or TSH ≥ 10 without thyroid medication. A Cox survival analysis with time dependent variables were used for the model. Headache disorders, age, sex, body mass index, income, smoking, narcotic use, and hypothyroidism-producing medications were independent variables in the model. Data from 8412 residents enrolled in the FMMP were used in the current study. Headache disorders were present in about 26% of the residents and new onset hypothyroidism developed in ∼7%. The hazard ratio for the development of new onset hypothyroidism was 1.21 (95% CI = 1.001, 1.462) for those with headache disorders. Headache disorders may be associated with an increased risk for the development of new onset hypothyroidism. © 2016 American Headache Society.

  12. The development of a research agenda for substance use disorders diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V).

    Science.gov (United States)

    Saunders, John B; Schuckit, Marc A

    2006-09-01

    This paper describes the background to the establishment of the Substance Use Disorders Workgroup, which was charged with developing the research agenda for the development of the next edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM). It summarizes 18 articles that were commissioned to inform that process. A preliminary list of research topics, developed at the DSM-V Launch Conference in 2004, led to the identification of subjects that were subject to formal presentations and detailed discussion at the Substance Use Disorders Conference in February 2005. The 18 articles presented in this supplement examine: (1) categorical versus dimensional diagnoses; (2) the neurobiological basis of substance use disorders; (3) social and cultural perspectives; (4) the crosswalk between DSM-IV and the International Classification of Diseases Tenth Revision (ICD-10); (5) comorbidity of substance use disorders and mental health disorders; (6) subtypes of disorders; (7) issues in adolescence; (8) substance-specific criteria; (9) the place of non-substance addictive disorders; and (10) the available research resources. In the final paper a broadly based research agenda for the development of diagnostic concepts and criteria for substance use disorders is presented.

  13. [Changes and disorders in voluntary saccades during development and aging].

    Science.gov (United States)

    Hikosaka, O

    1997-05-01

    We examined age-dependent changes in voluntary eye movements in normal subjects (age : 5-76) using a visually guided saccade (V-saccade) task and a memory guided saccade (M-saccade) task. Changes were more evident in M-saccades. The latencies were long in children (people (> 50 y.o.). Both young children and elderly people tended to break fixation by making a saccade to the cue stimulus that indicated the future target position. On the other hand, both young children and elderly people tended to be slow in making M-saccade promptly after the central fixation point went off. Thus, they had difficulties both in suppressing unnecessary saccades and in initiating saccades based on memory. Interestingly, similar difficulties were observed, in exaggerated forms, in patients in basal ganglia disorders, such as Parkinson's disease, juvenile parkinsonism, dopa-responsive dystonia, and hereditary progressive dystonia with marked diurnal fluctuation. These findings were consistent with the known functions of the basal ganglia which have been revealed by physiological studies using trained monkeys. The substantia nigra pars reticulata exerts tonic inhibitory influences over the superior colliculus, thereby preventing excitatory inputs from triggering unnecessary saccades. The tonic inhibition, however, is removed by a phasic inhibition largely originating in the caudate nucleus. Thus, inhibition and disinhibition are key mechanisms of the basal ganglia. In fact, experimental manipulations of these serial inhibitory pathway in the basal ganglia led either to the difficulty in initiation of saccades, especially M-saccades, or to the difficulty in suppressing unnecessary saccades. These comparisons suggest that the functions of the basal ganglia are immature in young children while they become deteriorated in elderly people.

  14. Impact of early adolescent anxiety disorders on self-esteem development from adolescence to young adulthood

    Science.gov (United States)

    Maldonado, Lizmarie; Huang, Yangxin; Chen, Ren; Kasen, Stephanie; Cohen, Patricia; Chen, Henian

    2013-01-01

    Purpose To examine the association between early adolescent anxiety disorders and self-esteem development from early adolescence to young adulthood. Methods Self-esteem was measured at mean ages 13, 16 and 22 for 821 participants from the Children in the Community Study, a population-based longitudinal cohort. Anxiety disorders were measured at mean age 13 years. Multilevel growth models were employed to analyze the change in self-esteem from early adolescence to young adulthood and to evaluate whether adolescent anxiety disorders predict both average and slope of self-esteem development. Results Self-esteem increased during adolescence and continued to increase in young adulthood. Girls had lower average self-esteem than boys, but this difference disappeared when examining the effect of anxiety. Adolescents with anxiety disorder had lower self-esteem, on average, compared with healthy adolescents (effect size (ES) =−0.35, pself-esteem (ES=−0.30, pself-esteem from adolescence to young-adulthood ( =−0.1, pself-esteem development. Conclusions All but one of the assessed adolescent anxiety disorders were related to lower self-esteem, with social phobia having the greatest impact. OCD predicted a decline in self-esteem trajectory with age. The importance of raising self-esteem in adolescents with anxiety and other mental disorders is discussed. PMID:23648133

  15. Development and initial evaluation of Transdiagnostic Behavior Therapy (TBT) for veterans with affective disorders.

    Science.gov (United States)

    Gros, Daniel F

    2014-12-15

    Considerable attention has focused on the growing need for evidence-based psychotherapy for veterans with affective disorders within the Department of Veteran Affairs. Despite, and possibly due to, the large number of evidence-based protocols available, several obstacles remain in their widespread delivery within Veterans Affairs Medical Centers. In part as an effort to address these concerns, newer transdiagnostic approaches to psychotherapy have been developed to provide a single treatment that is capable of addressing several, related disorders. The goal of the present investigation was to develop and evaluate a transdiagnostic psychotherapy, Transdiagnostic Behavior Therapy (TBT), in veterans with affective disorders. Study 1 provided initial support for transdiagnostic presentation of evidence-based psychotherapy components in veterans with principal diagnoses of affective disorders (n=15). These findings were used to inform the development of the TBT protocol. In Study 2, an initial evaluation of TBT was completed in a second sample of veterans with principal diagnoses of affective disorders (n=29). The findings of Study 2 demonstrated significant improvements in symptoms of depression, anxiety, stress, posttraumatic stress, and related impairment across participants with various principal diagnoses. Together, the investigation provided preliminary support for effectiveness of TBT in veterans with affective disorders. Published by Elsevier Ireland Ltd.

  16. Developing a theoretical maintenance model for disordered eating in Type 1 diabetes.

    Science.gov (United States)

    Treasure, J; Kan, C; Stephenson, L; Warren, E; Smith, E; Heller, S; Ismail, K

    2015-12-01

    According to the literature, eating disorders are an increasing problem for more than a quarter of people with Type 1 diabetes and they are associated with accentuated diabetic complications. The clinical outcomes in this group when given standard eating disorder treatments are disappointing. The Medical Research Council guidelines for developing complex interventions suggest that the first step is to develop a theoretical model. To review existing literature to build a theoretical maintenance model for disordered eating in people with Type 1 diabetes. The literature in diabetes relating to models of eating disorder (Fairburn's transdiagnostic model and the dual pathway model) and food addiction was examined and assimilated. The elements common to all eating disorder models include weight/shape concern and problems with mood regulation. The predisposing traits of perfectionism, low self-esteem and low body esteem and the interpersonal difficulties from the transdiagnostic model are also relevant to diabetes. The differences include the use of insulin mismanagement to compensate for breaking eating rules and the consequential wide variations in plasma glucose that may predispose to 'food addiction'. Eating disorder symptoms elicit emotionally driven reactions and behaviours from others close to the individual affected and these are accentuated in the context of diabetes. The next stage is to test the assumptions within the maintenance model with experimental medicine studies to facilitate the development of new technologies aimed at increasing inhibitory processes and moderating environmental triggers. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

  17. Impact of early adolescent anxiety disorders on self-esteem development from adolescence to young adulthood.

    Science.gov (United States)

    Maldonado, Lizmarie; Huang, Yangxin; Chen, Ren; Kasen, Stephanie; Cohen, Patricia; Chen, Henian

    2013-08-01

    To examine the association between early adolescent anxiety disorders and self-esteem development from early adolescence through young adulthood. Self-esteem was measured at mean ages 13, 16, and 22 for 821 participants from the Children in the Community Study, a population-based longitudinal cohort. Anxiety disorders were measured at mean age 13 years. Multilevel growth models were employed to analyze the change in self-esteem from early adolescence to young adulthood and to evaluate whether adolescent anxiety disorders predict both average and slope of self-esteem development. Self-esteem increased during adolescence and continued to increase in young adulthood. Girls had lower average self-esteem than boys, but this difference disappeared when examining the effect of anxiety. Adolescents with anxiety disorder had lower self-esteem, on average, compared with healthy adolescents (effect size [ES] = -.35, p self-esteem (ES = -.30, p self-esteem from adolescence to young adulthood (β = -.1, p self-esteem development. All but one of the assessed adolescent anxiety disorders were related to lower self-esteem, with social phobia having the greatest impact. OCD predicted a decline in self-esteem trajectory with age. The importance of raising self-esteem in adolescents with anxiety and other mental disorders is discussed. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  18. DISC1 pathway in brain development: exploring therapeutic targets for major psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Atsushi eKamiya

    2012-03-01

    Full Text Available Genetic risk factors for major psychiatric disorders play key roles in neurodevelopment. Thus, exploring the molecular pathways of risk genes is important not only for understanding the molecular mechanisms underlying brain development, but also to decipher how genetic disturbances affect brain maturation and functioning relevant to major mental illnesses. During the last decade, there has been significant progress in determining the mechanisms whereby risk genes impact brain development. Nonetheless, given that the majority of psychiatric disorders have etiological complexities encompassing multiple risk genes and environmental factors, the biological mechanisms of these diseases remain poorly understood. How can we move forward in our research for discovery of the biological markers and novel therapeutic targets for major mental disorders? Here we review recent progress in the neurobiology of Disrupted in schizophrenia 1 (DISC1, a major risk gene for major mental disorders, with a particular focus on its roles in cerebral cortex development. Convergent findings implicate DISC1 as part of a large, multi-step pathway implicated in various cellular processes and signal transduction. We discuss links between the DISC1 pathway and environmental factors, such as immune/inflammatory responses, which may suggest novel therapeutic targets. Existing treatments for major mental disorders are hampered by a limited number of pharmacological targets. Consequently, elucidation of the DISC1 pathway, and its association with neuropsychiatric disorders, may offer hope for novel treatment interventions.

  19. Development of an integrated cognitive behavioral therapy for anxiety and opioid use disorder: Study protocol and methods.

    Science.gov (United States)

    McHugh, R Kathryn; Votaw, Victoria R; Barlow, David H; Fitzmaurice, Garrett M; Greenfield, Shelly F; Weiss, Roger D

    2017-09-01

    Opioid use disorder is a highly disabling psychiatric disorder, and is associated with both significant functional disruption and risk for negative health outcomes such as infectious disease and fatal overdose. Even among those who receive evidence-based pharmacotherapy for opioid use disorder, many drop out of treatment or relapse, highlighting the importance of novel treatment strategies for this population. Over 60% of those with opioid use disorder also meet diagnostic criteria for an anxiety disorder; however, efficacious treatments for this common co-occurrence have not be established. This manuscript describes the rationale and methods for a behavioral treatment development study designed to develop and test an integrated cognitive-behavioral therapy for those with co-occurring opioid use disorder and anxiety disorders. The aims of the study are (1) to develop and pilot test a new manualized cognitive behavioral therapy for co-occurring opioid use disorder and anxiety disorders, (2) to test the efficacy of this treatment relative to an active comparison treatment that targets opioid use disorder alone, and (3) to investigate the role of stress reactivity in both prognosis and recovery from opioid use disorder and anxiety disorders. Our overarching aim is to investigate whether this new treatment improves both anxiety and opioid use disorder outcomes relative to standard treatment. Identifying optimal treatment strategies for this population are needed to improve outcomes among those with this highly disabling and life-threatening disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. A Cost of Illness Study of Children with High-Functioning Autism Spectrum Disorders and Comorbid Anxiety Disorders as Compared to Clinically Anxious and Typically Developing Children

    Science.gov (United States)

    Steensel, Francisca J.; Dirksen, Carmen D.; Bögels, Susan M.

    2013-01-01

    The study's aim was to estimate the societal costs of children with high-functioning ASD and comorbid anxiety disorder(s) (ASD + AD-group; n = 73), and to compare these costs to children with anxiety disorders (AD-group; n = 34), and typically developing children (controls; n = 87). Mean total costs for the ASD + AD-group amounted €17,380 per…

  1. General Education Development (GED®) Credential Attainment, Externalizing Disorders, and Substance Use Disorders in Disconnected Emerging Adults

    Science.gov (United States)

    Bergman, Andrea; Kong, Grace; Pope, Alice

    2014-01-01

    There are many benefits for emerging adults, both financial and personal, in obtaining a General Education Development (GED®) credential (Ou, 2008). However, little is known about the correlates of GED® credential attainment in "disconnected" emerging adults attending GED® programs. Our goal was to examine whether externalizing…

  2. Antisocial peer affiliation and externalizing disorders: Evidence for Gene × Environment × Development interaction.

    Science.gov (United States)

    Samek, Diana R; Hicks, Brian M; Keyes, Margaret A; Iacono, William G; McGue, Matt

    2017-02-01

    Gene × Environment interaction contributes to externalizing disorders in childhood and adolescence, but little is known about whether such effects are long lasting or present in adulthood. We examined gene-environment interplay in the concurrent and prospective associations between antisocial peer affiliation and externalizing disorders (antisocial behavior and substance use disorders) at ages 17, 20, 24, and 29. The sample included 1,382 same-sex twin pairs participating in the Minnesota Twin Family Study. We detected a Gene × Environment interaction at age 17, such that additive genetic influences on antisocial behavior and substance use disorders were greater in the context of greater antisocial peer affiliation. This Gene × Environment interaction was not present for antisocial behavior symptoms after age 17, but it was for substance use disorder symptoms through age 29 (though effect sizes were largest at age 17). The results suggest adolescence is a critical period for the development of externalizing disorders wherein exposure to greater environmental adversity is associated with a greater expression of genetic risk. This form of Gene × Environment interaction may persist through young adulthood for substance use disorders, but it appears to be limited to adolescence for antisocial behavior.

  3. Suicide ideation and attempts in children with psychiatric disorders and typical development.

    Science.gov (United States)

    Dickerson Mayes, Susan; Calhoun, Susan L; Baweja, Raman; Mahr, Fauzia

    2015-01-01

    Children and adolescents with psychiatric disorders are at increased risk for suicide behavior. This is the first study to compare frequencies of suicide ideation and attempts in children and adolescents with specific psychiatric disorders and typical children while controlling for comorbidity and demographics. Mothers rated the frequency of suicide ideation and attempts in 1,706 children and adolescents with psychiatric disorders and typical development, 6-18 years of age. For the typical group, 0.5% had suicide behavior (ideation or attempts), versus 24% across the psychiatric groups (bulimia 48%, depression or anxiety disorder 34%, oppositional defiant disorder 33%, ADHD-combined type 22%, anorexia 22%, autism 18%, intellectual disability 17%, and ADHD-inattentive type 8%). Most alarming, 29% of adolescents with bulimia often or very often had suicide attempts, compared with 0-4% of patients in the other psychiatric groups. It is important for professionals to routinely screen all children and adolescents who have psychiatric disorders for suicide ideation and attempts and to treat the underlying psychiatric disorders that increase suicide risk.

  4. Antisocial Peer Affiliation and Externalizing Disorders: Evidence for Gene × Environment × Development Interaction

    Science.gov (United States)

    Samek, Diana R.; Hicks, Brian M.; Keyes, Margaret A.; Iacono, William G.; McGue, Matt

    2016-01-01

    Gene × environment interaction contributes to externalizing disorders in adolescence, but little is known about whether such effects are long-lasting or present in adulthood. We examined gene-environment interplay in the concurrent and prospective associations between antisocial peer affiliation and externalizing disorders (antisocial behavior and substance use disorders) at ages 17, 20, 24, and 29. The sample included 1,382 same-sex twin pairs participating in the Minnesota Twin Family Study. We detected a gene × environment interaction at age 17, such that additive genetic influences on antisocial behavior and substance use disorders were greater in the context of greater antisocial peer affiliation. This gene × environment interaction was not present for antisocial behavior symptoms after age 17, but was for substance use disorder symptoms through age 29 (though effect sizes were largest at age 17). Results suggest adolescence is a critical period for the development of externalizing disorders wherein exposure to greater environmental adversity is associated with a greater expression of genetic risk. This form of gene × environment interaction may persist through young adulthood for substance use disorders, but is limited to adolescence for antisocial behavior. PMID:27580681

  5. Disorder effects in topological states: Brief review of the recent developments

    Science.gov (United States)

    Wu, Binglan; Song, Juntao; Zhou, Jiaojiao; Jiang, Hua

    2016-11-01

    Disorder inevitably exists in realistic samples, manifesting itself in various exotic properties for the topological states. In this paper, we summarize and briefly review the work completed over the last few years, including our own, regarding recent developments in several topics about disorder effects in topological states. For weak disorder, the robustness of topological states is demonstrated, especially for both quantum spin Hall states with Z 2 = 1 and size induced nontrivial topological insulators with Z 2 = 0. For moderate disorder, by increasing the randomness of both the impurity distribution and the impurity induced potential, the topological insulator states can be created from normal metallic or insulating states. These phenomena and their mechanisms are summarized. For strong disorder, the disorder causes a metal-insulator transition. Due to their topological nature, the phase diagrams are much richer in topological state systems. Finally, the trends in these areas of disorder research are discussed. Project supported by the National Natural Science Foundation of China (Grant Nos. 11374219, 11474085, and 11534001) and the Natural Science Foundation of Jiangsu Province, China (Grant No BK20160007).

  6. Breast development and disorders in the adolescent female.

    Science.gov (United States)

    De Silva, Nirupama K

    2018-04-01

    Breast development in the female is a process that becomes noticeable during puberty, and defines a girl's transition into adulthood. Various conditions can disrupt or alter the normal development, which may lead to abnormal breast changes and features. Further, the finding of a breast mass in adolescence can be unsettling to the patient and her family. While the majority of these breast changes and/or masses tend to be benign and self-limited, the appropriate evaluation is always warranted. This chapter will focus on the normal and abnormal development of breasts. We will also discuss the evaluation and management of breast masses that can be found in the adolescent female. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Psychosocial well-being in Dutch adults with disorders of sex development

    NARCIS (Netherlands)

    de Neve-Enthoven, Nita G M; Callens, Nina; van Kuyk, Maaike; van Kuppenveld, Jet H.; Drop, Stenvert L S; Cohen-Kettenis, Peggy T.; Dessens, Arianne B.

    2016-01-01

    OBJECTIVE: Atypical sex development is associated with psychosocial vulnerability. We investigated psychosocial well-being in individuals with disorders of sex development (DSD) and hypothesized that psychosocial well-being was related to degree of genital atypicality at birth. METHODS: 120 male

  8. Maternal Gesture Use and Language Development in Infant Siblings of Children with Autism Spectrum Disorder

    Science.gov (United States)

    Talbott, Meagan R.; Nelson, Charles A.; Tager-Flusberg, Helen

    2015-01-01

    Impairments in language and communication are an early-appearing feature of autism spectrum disorders (ASD), with delays in language and gesture evident as early as the first year of life. Research with typically developing populations highlights the importance of both infant and maternal gesture use in infants' early language development.…

  9. A longitudinal study on gross motor development in children with learning disorders

    NARCIS (Netherlands)

    Westendorp, Marieke; Hartman, Esther; Houwen, Suzanne; Huijgen, Barbara C. H.; Smith, Joanne; Visscher, Chris

    This longitudinal study examined the development of gross motor skills, and sex-differences therein, in 7; to 11-years-old children with learning disorders (LD) and compared the results with typically developing children to determine the performance level of children with LD. In children with LD (n

  10. Disorders of sexual development and associated changes in the pituitary-gonadal axis in dogs.

    NARCIS (Netherlands)

    Buijtels, J.J.C.W.M.; de Gier, J.; Kooistra, H.S.; Grinwis, G.C.M.; Naan, E.C.; Zijlstra, C.; Okkens, A.C.

    2012-01-01

    Normal sexual differentiation depends on completion of chromosomal sex determination, gonadal differentiation, and development of the phenotypic sex. An irregularity in any of these three steps can lead to a disorder in sexual development (DSD). We examined nine dogs with DSD by abdominal

  11. Research Review: Constraining Heterogeneity--The Social Brain and Its Development in Autism Spectrum Disorder

    Science.gov (United States)

    Pelphrey, Kevin A.; Shultz, Sarah; Hudac, Caitlin M.; Vander Wyk, Brent C.

    2011-01-01

    The expression of autism spectrum disorder (ASD) is highly heterogeneous, owing to the complex interactions between genes, the brain, and behavior throughout development. Here we present a model of ASD that implicates an early and initial failure to develop the specialized functions of one or more of the set of neuroanatomical structures involved…

  12. Childhood life events, immune activation and the development of mood and anxiety disorders: the TRAILS study.

    Science.gov (United States)

    Jonker, I; Rosmalen, J G M; Schoevers, R A

    2017-05-02

    The experience of childhood life events is associated with higher vulnerability to develop psychiatric disorders. One of the pathways suggested to lead to this vulnerability is activation of the immune system. The aim of this study is to find out whether the association between childhood life events and the development of mood and anxiety disorders is predicted by the activation of the immune system. This study was performed in TRAILS, a large prospective population cohort, from which a subgroup was selected (N=1084, 54.3% female, mean age 19.0 (s.d., 0.6)). Childhood life events before age 16 were assessed using questionnaires at age 12, 14, 16 and 19. Immune activation was assessed at age 16 by elevated high-sensitive C-reactive protein (hsCRP) and by levels of immunoglobulin G antibodies against the herpes viruses herpes simplex virus 1, cytomegalovirus and Epstein-Barr virus. At age 19, the presence of mood and anxiety disorders was determined using the World Health Organization Composite International Diagnostic Interview Version 3.0. Regression analyses were used to study the association between life events, the inflammatory markers and mental health. We found that childhood life events score was associated with risk of mood disorders (B=0.269, P<0.001) and anxiety disorders (B=0.129, P<0.001). Childhood life events score was marginally associated with elevated hsCRP (B=0.076, P=0.006), but not with the antibody levels. This was especially due to separation trauma (P=0.015) and sexual abuse (P=0.019). Associations lost significance after correcting for lifestyle factors such as body mass index and substance abuse (P=0.042). None of the inflammatory markers were associated with development of anxiety disorders or mood disorders. In conclusion, the life event scores predicted the development of anxiety disorders and mood disorders at age 19. Life event scores were associated with elevated hsCRP, which was partly explained by lifestyle factors. Elevated hs

  13. Developing a European research network to address unmet needs in anxiety disorders.

    Science.gov (United States)

    Baldwin, David S; Pallanti, Stefano; Zwanzger, Peter

    2013-12-01

    Anxiety disorders are common, typically have an early onset, run a chronic or relapsing course, cause substantial personal distress, impair social and occupational function, reduce quality of life, and impose a substantial economic burden: they are often comorbid with major depression, bipolar disorder, schizophrenia, substance misuse and physical illness, and are associated with increased risks of suicidal behaviour. As such, anxiety disorders should be regarded as a significant public health problem. However the causes of anxiety disorders remain largely unknown, which hinders accurate diagnosis, the prediction of prognosis, and the development of refined treatment approaches. In clinical practice, many patients with anxiety disorders do not present or are not recognised, the standard of care they receive is often sub-optimal, and the effectiveness of pharmacological and psychological treatment interventions in real-world clinical practice can be disappointing. The current substantial unmet public health, clinical and research needs in anxiety disorders could be addressed in part by developing independent collaborative European networks. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. [Risk factors and development course of conduct disorder in girls; a review].

    Science.gov (United States)

    Merckx, W; Van West, D

    2016-01-01

    So far there have been relatively few studies of conduct disorder in girls. It is very important that professionals engaged in preventing and treating this disorder have a sound knowledge of the risk factors involved and of the developmental course of the disorder. To provide an overview of what is known about the risk factors and about the way in which conduct disorder develops in girls. We searched the Eric, PubMed and Medline databases for articles on conduct disorder in girls. We reviewed 41 studies and we summarised the results. Several risk factors contribute to the development of conduct disorder in girls. Just like boys, girls too can display the life-course-persistent pathway of antisocial behavior. Such girls are often associated with serious risk factors. Those with serious forms of antisocial behaviour have an increased risk of experiencing adjustment problems in later life. Future research in this area will have to concentrate on the creation of adequate prevention and treatment programs.

  15. Is ADHD an early stage in the development of borderline personality disorder?

    DEFF Research Database (Denmark)

    Storebø, Ole Jakob; Simonsen, Erik

    2014-01-01

    BACKGROUND: Several studies report associations between adults with borderline personality disorder (BPD) and a history of attention-deficit hyperactivity (ADHD) symptoms in childhood. AIMS: To explore the association between BPD and a history of ADHD in childhood. METHOD: A comprehensive search......: Most of the 15 articles showed a statistical association between ADHD and BPD. The data, most strongly provided a basis for the hypotheses that ADHD is either an early developmental stage of BPD, or that the two disorders share an environmental and genetic aetiology. Furthermore, one of the disorders...... seems to give a synergic effect, reinforce the other or complicate the disorders. In one prospective study, the risk factor for children with ADHD to develop BPD was as high as odds ratio 13.16. No studies have looked at treatment of ADHD as a mediator of the risk for BPD. CONCLUSIONS: Many studies...

  16. Assessment of Danish-speaking children’s phonological development and speech disorders

    DEFF Research Database (Denmark)

    Clausen, Marit Carolin; Fox-Boyer, Annette

    2018-01-01

    The identification of speech sounds disorders is an important everyday task for speech and language therapists (SLTs) working with children. Therefore, assessment tools are needed that are able to correctly identify and diagnose a child with a suspected speech disorder and furthermore, that provide...... of the existing speech assessments in Denmark showed that none of the materials fulfilled current recommendations identified in research literature. Therefore, the aim of this paper is to describe the evaluation of a newly constructed instrument for assessing the speech development and disorders of Danish...... with suspected speech disorder (Clausen and Fox-Boyer, in prep). The results indicated that the instrument showed strong inter-examiner reliability for both populations as well as a high content and diagnostic validity. Hence, the study showed that the LogoFoVa can be regarded as a reliable and valid tool...

  17. [The role of psychosocial work factors in the development of musculoskeletal disorders in workers].

    Science.gov (United States)

    Bugajska, Joanna; Zołnierczyk-Zreda, Dorota; Jedryka-Góral, Anna

    2011-01-01

    The aim of the study was to determine the role of psychosocial work factors in the development of musculoskeletal disorders in workers. It should be stressed that over a decade these disorders have been the subject of studies because of complaints reported not only by workers performing heavy physical work or working in awkward, forced body posture. It has also been acknowledged that stress at work caused by various psychosocial work factors can significantly influence their development. One of the models, most popular nowadays, was used in the study. It takes into account various risk factors in the etiology of cervical spine disorders. Based on this model it was shown that certain psychosocial and cultural variables (e.g., work demands and control, individual variables, individual values, work group's culture) may constitute occupational stressors and, when combined with physical load factors, may lead to stress and musculoskeletal disorders. It was also indicated that such psychosocial work factors as excessive work demands (quantitative or qualitative), inadequate control at work or lack of social support are the most frequent sources of work-related stress. The article presents the results of some prospective studies in which the role of these factors in the development of musculoskeletal disorders has been considered. Apart from work properties (factors), the role of other psychological variables was shown; these include: work involvement, perfectionism, negative affectivity or work style, which in numerous studies turned out to be important risk factors in the development of musculoskeletal disorders. Finally, potential mechanisms underlying the relationships between psychosocial factors and musculoskeletal disorders were indicated. However, it was stressed that the majority of them still require to be confirmed in future descriptive or experimental studies.

  18. Conflict monitoring and adaptation in individuals at familial risk for developing bipolar disorder.

    Science.gov (United States)

    Patino, Luis R; Adler, Caleb M; Mills, Neil P; Strakowski, Stephen M; Fleck, David E; Welge, Jeffrey A; DelBello, Melissa P

    2013-05-01

    To examine conflict monitoring and conflict-driven adaptation in individuals at familial risk for developing bipolar disorder. We recruited 24 adolescents who had a parent with bipolar disorder and 23 adolescents with healthy parents. Participants completed an arrow version of the Eriksen Flanker Task that included trials with three levels of conflict: neutral, congruent, and incongruent flanks. Differences in performance were explored based upon the level of conflict in the current and previous trials. Individuals at risk for developing bipolar disorder performed more slowly than youth with healthy parents in all trials. Analyses evaluating sequential effects revealed that at-risk subjects responded more slowly than youth of healthy parents for all trial types when preceded by an incongruent trial, for incongruent trials preceded by congruent trials, and for neutral and congruent trials when preceded by neutral trials. In contrast to the comparison group, at-risk adolescents failed to display a response time advantage for incongruent trials preceded by an incongruent trial. When removing subjects with attention-deficit hyperactivity disorder (ADHD), differences between groups in response time fell below significant level, but a difference in sequence modulation remained significant. Subjects at risk for bipolar disorder also displayed greater intra-subject response time variability for incongruent and congruent trials compared with the comparison adolescents. No differences in response accuracy were observed between groups. Adolescents at risk for developing bipolar disorder displayed specific deficits in cognitive flexibility, which might be useful as a potential marker related to the development of bipolar disorder. © 2013 John Wiley and Sons A/S. Published by Blackwell Publishing Ltd.

  19. Discovery of serum biomarkers predicting development of a subsequent depressive episode in social anxiety disorder.

    Science.gov (United States)

    Gottschalk, M G; Cooper, J D; Chan, M K; Bot, M; Penninx, B W J H; Bahn, S

    2015-08-01

    Although social anxiety disorder (SAD) is strongly associated with the subsequent development of a depressive disorder (major depressive disorder or dysthymia), no underlying biological risk factors are known. We aimed to identify biomarkers which predict depressive episodes in SAD patients over a 2-year follow-up period. One hundred sixty-five multiplexed immunoassay analytes were investigated in blood serum of 143 SAD patients without co-morbid depressive disorders, recruited within the Netherlands Study of Depression and Anxiety (NESDA). Predictive performance of identified biomarkers, clinical variables and self-report inventories was assessed using receiver operating characteristics curves (ROC) and represented by the area under the ROC curve (AUC). Stepwise logistic regression resulted in the selection of four serum analytes (AXL receptor tyrosine kinase, vascular cell adhesion molecule 1, vitronectin, collagen IV) and four additional variables (Inventory of Depressive Symptomatology, Beck Anxiety Inventory somatic subscale, depressive disorder lifetime diagnosis, BMI) as optimal set of patient parameters. When combined, an AUC of 0.86 was achieved for the identification of SAD individuals who later developed a depressive disorder. Throughout our analyses, biomarkers yielded superior discriminative performance compared to clinical variables and self-report inventories alone. We report the discovery of a serum marker panel with good predictive performance to identify SAD individuals prone to develop subsequent depressive episodes in a naturalistic cohort design. Furthermore, we emphasise the importance to combine biological markers, clinical variables and self-report inventories for disease course predictions in psychiatry. Following replication in independent cohorts, validated biomarkers could help to identify SAD patients at risk of developing a depressive disorder, thus facilitating early intervention. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. New developments in behavioral treatments for substance use disorders.

    Science.gov (United States)

    Kiluk, Brian D; Carroll, Kathleen M

    2013-12-01

    After decades of defining which behavioral treatments are effective for treating addictions, the focus has shifted to exploring how these treatments work, how best to disseminate and implement them in the community, and what underlying factors can be manipulated in order to increase the rates of treatment success. These pursuits have led to advances in our understanding of the mechanisms of treatment effects, the incorporation of technology into the delivery of current treatments and development of novel applications to support relapse prevention, as well as the inclusion of neurocognitive approaches to target the automatic and higher-order processes underlying addictive behaviors. Although such advances have the promise of leading to better treatments for more individuals, there is still much work required for these promises to be realized. The following review will highlight some of these recent developments and provide a glimpse into the future of behavioral treatments.

  1. Challenges of developing and conducting clinical trials in rare disorders.

    Science.gov (United States)

    Kempf, Lucas; Goldsmith, Jonathan C; Temple, Robert

    2018-04-01

    Rare disease drug development is a rapidly expanding field. Clinical researchers in rare diseases face many challenges when conducting trials in small populations. Disease natural history is often poorly understood and the ability to detect clinically meaningful outcomes requires understanding of their rate of occurrence and variability, both of which contribute to difficulties in powering a study. Standard trial designs are not optimized to obtain adequate safety and efficacy data from small numbers of patients, so alternative designs (enrichment, crossover, adaptive, N-of 1) need to be considered. The affected patients can be hard to identify, especially early in the course of their disease, are generally geographically dispersed, and are often children. Trials are frequently conducted on an international scale and may be subject to complex or multiple regulatory agency oversights and may be affected by local customs, cultures, and practices. A basic understanding of the FDA programs supporting development of drugs for rare diseases is provided by this review and the role of early consultation with the FDA is emphasized. Of recent FDA New Molecular Entities (NME) approvals, 41% (17 approvals) in 2014, 47% (21 approvals) in 2015, and 41% (9 approvals) in 2016 were for rare disease indications. Through effective interactions and collaborations with physicians, institutions, and patient groups, sponsors have been successful in bringing new treatments to market for individuals affected by rare diseases. Challenges to drug development have been overcome through the focused efforts of patients/families, non-profit patient advocacy groups, drug developers, and regulatory authorities. © 2017 Wiley Periodicals, Inc.

  2. Control psychophysical children’s development under the correction movement disorder

    Directory of Open Access Journals (Sweden)

    B O Bukhovets

    2016-02-01

      Abstract   This article deals with the problem of determining the effectiveness of the method Bobath, as the main methods of psychophysical condition correction of children with movement disorders. Given the drawbacks of the proposed test detailed rating scale of psychomotor development of children "Map test of motor abilities of children" was adapted and implemented together with the Munich diagnostic testing cards of mental skills and motor abilities of children. The basis of the experiment became the evaluation of basic motor skills in certain positions and determine the true psychophysical age at the beginning and at the end of the course on corrective exercises by Bobath method. Considering the universality, accessibility of data and informative test quality it became possible to assess the stages of psychomotor development and mental qualities forming with the true definition of real psychophysical children age with movement disorders 3-4 years.   Key words: Bobath method, Munich diagnosis, psychomotor development, preschool children, motor disorders.

  3. The Depression Inventory Development Workgroup: A Collaborative, Empirically Driven Initiative to Develop a New Assessment Tool for Major Depressive Disorder.

    Science.gov (United States)

    Vaccarino, Anthony L; Evans, Kenneth R; Kalali, Amir H; Kennedy, Sidney H; Engelhardt, Nina; Frey, Benicio N; Greist, John H; Kobak, Kenneth A; Lam, Raymond W; MacQueen, Glenda; Milev, Roumen; Placenza, Franca M; Ravindran, Arun V; Sheehan, David V; Sills, Terrence; Williams, Janet B W

    2016-01-01

    The Depression Inventory Development project is an initiative of the International Society for CNS Drug Development whose goal is to develop a comprehensive and psychometrically sound measurement tool to be utilized as a primary endpoint in clinical trials for major depressive disorder. Using an iterative process between field testing and psychometric analysis and drawing upon expertise of international researchers in depression, the Depression Inventory Development team has established an empirically driven and collaborative protocol for the creation of items to assess symptoms in major depressive disorder. Depression-relevant symptom clusters were identified based on expert clinical and patient input. In addition, as an aid for symptom identification and item construction, the psychometric properties of existing clinical scales (assessing depression and related indications) were evaluated using blinded datasets from pharmaceutical antidepressant drug trials. A series of field tests in patients with major depressive disorder provided the team with data to inform the iterative process of scale development. We report here an overview of the Depression Inventory Development initiative, including results of the third iteration of items assessing symptoms related to anhedonia, cognition, fatigue, general malaise, motivation, anxiety, negative thinking, pain and appetite. The strategies adopted from the Depression Inventory Development program, as an empirically driven and collaborative process for scale development, have provided the foundation to develop and validate measurement tools in other therapeutic areas as well.

  4. Does the risk of developing dementia increase with the number of episodes in patients with depressive disorder and in patients with bipolar disorder?

    Science.gov (United States)

    Kessing, L V; Andersen, P K

    2004-12-01

    Several findings suggest that some patients with depressive or bipolar disorder may be at increased risk of developing dementia. The present study aimed to investigate whether the risk of developing dementia increases with the number of affective episodes in patients with depressive disorder and in patients with bipolar disorder. This was a case register study including all hospital admissions with primary affective disorder in Denmark during 1970-99. The effect of the number of prior episodes leading to admission on the rate of readmission with a diagnosis of dementia following the first discharge after 1985 was estimated. A total of 18,726 patients with depressive disorder and 4248 patients with bipolar disorder were included in the study. The rate of a diagnosis of dementia on readmission was significantly related to the number of prior affective episodes leading to admission. On average, the rate of dementia tended to increase 13% with every episode leading to admission for patients with depressive disorder and 6% with every episode leading to admission for patients with bipolar disorder, when adjusted for differences in age and sex. On average, the risk of dementia seems to increase with the number of episodes in depressive and bipolar affective disorders.

  5. Pharmacological treatment of severe psychiatric disorders in the developing world : lessons from India.

    Science.gov (United States)

    Patel, Vikram; Andrade, Chittaranjan

    2003-01-01

    Severe psychiatric disorders (schizophrenia, bipolar disorder and major depressive disorder) cause much morbidity and disability in developing countries. Most of the evidence on the efficacy and effectiveness of drug treatments for these disorders is based on trials conducted in Western countries. Cultural, biological and health system factors may profoundly influence the applicability of such evidence in developing countries. Attitudes towards, and concepts about, psychiatric disorders vary across cultures, and these may influence the acceptability of drug treatments. Genetic and environmental factors may lead to variations in the pharmacodynamics and pharmacokinetics of psychotropic drugs across ethnic groups. This may explain why lower doses of psychotropic drugs tend to be used for non-Caucasian patients. There is a dearth of mental health professionals and care facilities in developing countries, especially in rural areas. Epidemiological studies show that, despite this lack of services, the outcome of schizophrenia is favourable in developing countries. This suggests that cultural, genetic or environmental factors may play as much of a role in influencing outcome as access to antipsychotic treatment. Regional drug policies may influence the availability and cost of psychotropic drugs. In particular, the Indian experience, where drugs are manufactured by several local pharmaceutical firms, thus bringing their cost down, may represent a unique deregulated drug industry. However, the impending impact of the Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement, with the strict enforcement of patent laws, will almost certainly lead to a rise in drug costs in the coming years. This may influence the choice and cost effectiveness of various drugs. The implications of these cross-cultural variations for policy and practice are the need to ensure a reliable supply of affordable psychotropic drugs in developing countries, trained healthcare

  6. Psychomotor development in infants with Prader-Willi syndrome and associations with sleep-related breathing disorders.

    NARCIS (Netherlands)

    Festen, D.A.M.; Wevers, M.; Weerd, A.W. de; Bossche, R.A. van den; Duivenvoorden, H.J.; Otten, B.J.; Wit, J.M.; Hokken-Koelega, A.C.S.

    2007-01-01

    Prader-Willi syndrome (PWS) is a neurogenetic disorder with hypotonia, psychomotor delay, obesity, short stature, and sleep-related breathing disorders. The aim of this study was to evaluate the association between psychomotor development and sleep-related breathing disorders in PWS infants. Bayley

  7. Prenatal testosterone and theory of mind development: Findings from disorders of sex development.

    Science.gov (United States)

    Khorashad, Behzad S; Khazai, Behnaz; Roshan, Ghasem M; Hiradfar, Mehran; Afkhamizadeh, Mozhgan; van de Grift, Tim C

    2018-03-01

    Women on average perform better than men on the "Reading the Mind in the Eyes" test (RMET) which is a measure of Theory of Mind (ToM). The aim of this study was to assess whether these sex differences are influenced by differences in prenatal testosterone levels through a study on individuals with Disorders of Sex Development and matched controls. ToM performance was examined using the RMET in female-assigned-at-birth individuals with increased prenatal testosterone exposure (Congenital Adrenal Hyperplasia (CAH) and 5-alpha Reductase type-2 Deficiency (5α-RD-2)), female-assigned-at-birth individuals with testosterone insensitivity (Complete Androgen Insensitivity Syndrome (CAIS)), and their age-matched unaffected male and female relatives. A total number of 158 individuals participated in the study; 19 with 5α-RD-2, 17 with CAH, 18 women with CAIS, 52 matched unaffected men and 52 matched unaffected women. All subgroups were around 20 years of age. Women with CAH scored significantly lower on RMET than control women and CAIS individuals. CAIS individuals scored significantly higher than control men and participants with 5α-RD. Statistically, CAIS individuals' performance on RMET was similar to control women's, women with CAH did not differ significantly from control men and 5α-RD-2 individuals scored significantly lower than control men. These results, which are in line with previous theories, illustrate that performance on the RMET, as an index of ToM, may be influenced by variations in prenatal androgens levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Can sociocultural and historical mechanisms influence the development of borderline personality disorder?

    Science.gov (United States)

    Paris, Joel; Lis, Eric

    2013-02-01

    Borderline personality disorder (BPD) is a common and severe clinical problem. While cross-cultural research suggests that this condition can be identified in different societies, indirect evidence suggests that BPD and some of its associated symptoms (suicidality and self-harm) have a higher prevalence in developed countries. If so, sociocultural and historical mechanisms may have influenced the development of the disorder. While the vulnerabilities underlying BPD are broad and nonspecific, specific symptoms can be shaped by culture. The mechanisms involve the influence of a "symptom bank," as well as the role of social contagion. These trends may be related to a decrease in social cohesion and social capital in modern societies.

  9. Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia.

    Science.gov (United States)

    Nakagawa, Yutaka; Chiba, Kenji

    2016-09-01

    Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  10. Synthetic cannabinoid: prevalence, mechanisms of addiction development, mental disorders associated with the use of synthetic cannabinoid

    Directory of Open Access Journals (Sweden)

    Antsyborov A.V.

    2017-04-01

    Full Text Available according to the authors among the new psychoactive substances, the number of which is growing every year, despite the measures aimed at the obstacles to their dissemination there discovered the most frequent violations of psychotic conditions associated with use of synthetic cannabinoid in clinical practice. On the black market, they are distributed through online shops, under the guise of herbal mixtures for Smoking. When ingested, this group of drugs at the peak of intoxication raises a number of mental (different according to the depth of impaired consciousness, auditory and visual hallucinations, panic attacks, acute psychotic paranoid disorders, catatonic stupor, polar affective disorders, acute polythematic delusional symptoms and somatic disorders (disorders of heart rhythm and conduction, acute ischemic disorders, hypertension, depression of respiratory activity, violation of thermoregulation, development of acute renal failure, vomiting, expressed cephalgia, clinic of hypokalemia. In the reviewed literature and authors own observations there have been discovered some cases of mental addiction development to synthetic cannabinoids. The analysis of new literature data and own clinical observations helped the authors to compare the psychotropic effects caused by this group of drugs, relative to other known surfactants. The toxic effects of CSC on the body greatly exceeds the use of plant cannabinoids, and it has almost the same effects as the synthetic cathinone’s. The speed of formation of psychological dependence is lower compared to synthetic cathinone. Developing current strategies for diagnosis, treatment, and rehabilitation of patients who use synthetic cannabinoids remains an important task for practical healthcare.

  11. Heterogeneity in development of adolescent anxiety disorder symptoms in an 8-year longitudinal community study

    NARCIS (Netherlands)

    Nelemans, S.A.; Hale, W.W.; Branje, S.J.T.; Raaijmakers, Q.A.W.; Frijns, T.; van Lier, P.A.C.; Meeus, W.H.J.

    2014-01-01

    In this study, we prospectively examined developmental trajectories of five anxiety disorder symptom dimensions (generalized anxiety disorder, panic disorder, school anxiety, separation anxiety disorder, and social anxiety disorder) from early to late adolescence in a community sample of 239

  12. [Development of sexuality and motivational aspects of sexual behavior in men with obsessive-compulsive disorders].

    Science.gov (United States)

    2014-09-01

    Sexual behavior and formation of sexuality in men with obsessive-compulsive disorder is one of the pressing issues in contemporary medicine. Obsessive-compulsive disorder is characterized by the development of intrusive thoughts, memories, movements and actions, as well as a variety of pathological fears (phobias). Increase in the number of patients with this pathology in modern clinical practice of neurotic disorders, the young age of the patients and as a result violation of interpersonal, communicational and sexual nature is quite apparent. The study involved 35 men aged 23 to 47 years with clinical signs of OCD. We determined the severity of obsessive-compulsive symptoms using the Yale-Brown scale. We established the presence of a mild degree of disorder in 34,3% of cases; in 48,6% of cases disorder of moderate severity was diagnosed; remaining 17.1% were assessed subclinical condition of OCD at the applicable scale. The system of motivational maintenance of sexual behavior in men with obsessive-compulsive disorders is investigated. Motives of sexual behavior of the investigated men with the pathology are determined. The presented research in men with OCD have established multidimensionality and complexity of motivational ensuring of sexual behavior.

  13. Development of a voice disorder work productivity inventory utilizing cognitive interviewing technique.

    Science.gov (United States)

    Giliberto, John Paul; Zhu, Qiubei; Meyer, Tanya K

    2016-12-01

    Voice disorders have been shown to impair workplace productivity primarily by reduced efficiency while at work (presenteeism) versus increased days missed (absenteeism). Work productivity measures such as the Work Productivity and Activity Impairment (WPAI) Questionnaire or the World Health Organization Health - Work Performance Questionnaire (HPQ) can be customized to a specific disease but do not fully capture impaired work productivity associated with voice disorders. The purpose of this study was to develop a novel questionnaire to evaluate work productivity in patients with voice disorders. Descriptive. At a tertiary medical center, patients with gainful employment and with chronic voice disorders were given the WPAI, HPQ, and 20 voice-related statements (VRS-20). Cognitive interviews were conducted and recorded with all patients. Ten patients (7 females, 3 males) completed the questionnaires and subsequent cognitive interviews. One patient had spasmodic dysphonia, 6 had benign vocal fold lesions, and 3 had vocal fold motion disorders. The median VHI-10 was 18 (9-40). Themes that emerged during interviews include: avoiding oral communication/telephone, use of voice associated with strain/fatigue, frustration and stress at work, and workplace integrity. Conclusions : In cognitive interviews, participants felt the VRS-20 captured the impact of their voice disorder at work better than the WPAI and HPQ. Participants also felt some statements were more important than others. 5.

  14. Neutral endopeptidase up-regulation in isolated human umbilical artery: involvement in desensitization of bradykinin-induced vasoconstrictor effects.

    Science.gov (United States)

    Pelorosso, Facundo Germán; Halperin, Ana Verónica; Palma, Alejandro Martín; Nowak, Wanda; Errasti, Andrea Emilse; Rothlin, Rodolfo Pedro

    2007-02-01

    Previous reports show that bradykinin B(2) receptors mediate contractile responses induced by bradykinin (BK) in human umbilical artery (HUA). However, although it has been reported that BK-induced responses can desensitize in several inflammatory models, the effects of prolonged in vitro incubation on BK-induced vasoconstriction in HUA have not been studied. In isolated HUA rings, BK-induced responses after a 5-h in vitro incubation showed a marked desensitization compared with responses at 2 h. Inhibition of either angiotensin-converting enzyme (ACE) or neutral endopeptidase (NEP), both BK-inactivating enzymes, failed to modify responses to BK at 2 h. After 5 h, ACE inhibition produced only a slight potentiation of BK-induced responses. In contrast, BK-induced vasoconstriction at 5 h was markedly potentiated by NEP inhibition. Moreover, NEP activity, measured by hydrolysis of its synthetic substrate (Z-Ala-Ala-Leu-p-nitroanilide), showed a 2.4-fold increase in 5-h incubated versus 2-h incubated tissues, which was completely reversed by cycloheximide (CHX) treatment. Furthermore, CHX significantly potentiated BK-induced responses, suggesting that NEP-mediated kininase activity increase at 5 h depends on de novo protein synthesis. In addition, under NEP inhibition, CHX treatment failed to produce an additional potentiation of BK-induced vasoconstriction. Still, NEP up-regulation was confirmed by Western blot, showing a 2.1-fold increase in immunoreactive NEP in 5-h incubated versus 2-h incubated HUA. In summary, the present study provides strong pharmacological evidence that NEP is up-regulated and plays a key role in desensitization of BK-induced vasoconstriction after prolonged in vitro incubation in HUA. Our results provide new insights into the possible mechanisms involved in BK-induced response desensitization during sustained inflammatory conditions.

  15. The mecillinam resistome reveals a role for peptidoglycan endopeptidases in stimulating cell wall synthesis in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Ghee Chuan Lai

    2017-07-01

    Full Text Available Bacterial cells are typically surrounded by an net-like macromolecule called the cell wall constructed from the heteropolymer peptidoglycan (PG. Biogenesis of this matrix is the target of penicillin and related beta-lactams. These drugs inhibit the transpeptidase activity of PG synthases called penicillin-binding proteins (PBPs, preventing the crosslinking of nascent wall material into the existing network. The beta-lactam mecillinam specifically targets the PBP2 enzyme in the cell elongation machinery of Escherichia coli. Low-throughput selections for mecillinam resistance have historically been useful in defining mechanisms involved in cell wall biogenesis and the killing activity of beta-lactam antibiotics. Here, we used transposon-sequencing (Tn-Seq as a high-throughput method to identify nearly all mecillinam resistance loci in the E. coli genome, providing a comprehensive resource for uncovering new mechanisms underlying PG assembly and drug resistance. Induction of the stringent response or the Rcs envelope stress response has been previously implicated in mecillinam resistance. We therefore also performed the Tn-Seq analysis in mutants defective for these responses in addition to wild-type cells. Thus, the utility of the dataset was greatly enhanced by determining the stress response dependence of each resistance locus in the resistome. Reasoning that stress response-independent resistance loci are those most likely to identify direct modulators of cell wall biogenesis, we focused our downstream analysis on this subset of the resistome. Characterization of one of these alleles led to the surprising discovery that the overproduction of endopeptidase enzymes that cleave crosslinks in the cell wall promotes mecillinam resistance by stimulating PG synthesis by a subset of PBPs. Our analysis of this activation mechanism suggests that, contrary to the prevailing view in the field, PG synthases and PG cleaving enzymes need not function in multi

  16. The mecillinam resistome reveals a role for peptidoglycan endopeptidases in stimulating cell wall synthesis in Escherichia coli.

    Science.gov (United States)

    Lai, Ghee Chuan; Cho, Hongbaek; Bernhardt, Thomas G

    2017-07-01

    Bacterial cells are typically surrounded by an net-like macromolecule called the cell wall constructed from the heteropolymer peptidoglycan (PG). Biogenesis of this matrix is the target of penicillin and related beta-lactams. These drugs inhibit the transpeptidase activity of PG synthases called penicillin-binding proteins (PBPs), preventing the crosslinking of nascent wall material into the existing network. The beta-lactam mecillinam specifically targets the PBP2 enzyme in the cell elongation machinery of Escherichia coli. Low-throughput selections for mecillinam resistance have historically been useful in defining mechanisms involved in cell wall biogenesis and the killing activity of beta-lactam antibiotics. Here, we used transposon-sequencing (Tn-Seq) as a high-throughput method to identify nearly all mecillinam resistance loci in the E. coli genome, providing a comprehensive resource for uncovering new mechanisms underlying PG assembly and drug resistance. Induction of the stringent response or the Rcs envelope stress response has been previously implicated in mecillinam resistance. We therefore also performed the Tn-Seq analysis in mutants defective for these responses in addition to wild-type cells. Thus, the utility of the dataset was greatly enhanced by determining the stress response dependence of each resistance locus in the resistome. Reasoning that stress response-independent resistance loci are those most likely to identify direct modulators of cell wall biogenesis, we focused our downstream analysis on this subset of the resistome. Characterization of one of these alleles led to the surprising discovery that the overproduction of endopeptidase enzymes that cleave crosslinks in the cell wall promotes mecillinam resistance by stimulating PG synthesis by a subset of PBPs. Our analysis of this activation mechanism suggests that, contrary to the prevailing view in the field, PG synthases and PG cleaving enzymes need not function in multi-enzyme complexes

  17. Development and validation of the Accommodation and Enabling Scale for Eating Disorders (AESED for caregivers in eating disorders

    Directory of Open Access Journals (Sweden)

    Treasure Janet

    2009-09-01

    Full Text Available Abstract Background Families of people with eating disorders are often caught up in rule bound eating and safety behaviours that characterise the illness. The main aim of this study was to develop a valid and specific scale to measure family accommodation in the context of having a relative with an eating disorder. Methods A new scale, the Accommodation and Enabling Scale for Eating Disorders (AESED, was jointly generated by professionals and expert carers through qualitative analysis. In the first stage, this instrument was given to 201 family members of relatives diagnosed with an eating disorder, with additional self-report measures including the Experience of Caregiving Inventory (ECI, the Hospital Anxiety and Depression Scale (HADS and the Family Questionnaire (FQ. In the second stage, the sensitivity of the AESED to change was tested in a pre-and-post design study with a new sample of 116 caregivers, using a DVDs-distance skills training for caregivers. Results A 33 item instrument was derived consisting of five factors: Avoidance and Modifying Routine, Reassurance Seeking, Meal Ritual, Control of Family and Turning a Blind Eye, which together explained 60.1% of the variance. This scale had good psychometric properties in terms of Cronbach's alpha which ranged from 0.77 to 0.92. Regarding the convergent validity, most of the AESED subscales was moderately supported by correlations with anxiety (HADS; r = 0.24 to 0.48 and depression levels (HADS; r = 0.17 to 0.47, negative caregiving (ECI; r = 0.18 to 0.45, and expressed emotion levels (FQ; r = 0.17 to 0.51. Pre-post intervention assessments showed that the overall AESED scale (d = 0.38 and the avoidance and modifying routine (d = 0.52, meal ritual (d = 0.27 and control of the family (d = 0.49 subscales were sensitive to change. Conclusion Internal consistency was good and initial validity of the scale was adequate, it was able to discriminate differences between clinical variables, however

  18. Does the risk of developing dementia increase with the number of episodes in patients with depressive disorder and in patients with bipolar disorder?

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Andersen, Per Kragh

    2004-01-01

    OBJECTIVE: Several findings suggest that some patients with depressive or bipolar disorder may be at increased risk of developing dementia. The present study aimed to investigate whether the risk of developing dementia increases with the number of affective episodes in patients with depressive...... following the first discharge after 1985 was estimated. A total of 18,726 patients with depressive disorder and 4248 patients with bipolar disorder were included in the study. RESULTS: The rate of a diagnosis of dementia on readmission was significantly related to the number of prior affective episodes...... leading to admission. On average, the rate of dementia tended to increase 13% with every episode leading to admission for patients with depressive disorder and 6% with every episode leading to admission for patients with bipolar disorder, when adjusted for differences in age and sex. CONCLUSION...

  19. Visual and Proprioceptive Cue Weighting in Children with Developmental Coordination Disorder, Autism Spectrum Disorder and Typical Development

    Directory of Open Access Journals (Sweden)

    L Miller

    2013-10-01

    Full Text Available Accurate movement of the body and the perception of the body's position in space usually rely on both visual and proprioceptive cues. These cues are weighted differently depending on task, visual conditions and neurological factors. Children with Developmental Coordination Disorder (DCD and often also children with Autism Spectrum Disorder (ASD have movement deficits, and there is evidence that cue weightings may differ between these groups. It is often reported that ASD is linked to an increased reliance on proprioceptive information at the expense of visual information (Haswell et al, 2009; Gepner et al, 1995. The inverse appears to be true for DCD (Wann et al, 1998; Biancotto et al, 2011. I will report experiments comparing, for the first time, relative weightings of visual and proprioceptive information in children aged 8-14 with ASD, DCD and typical development. Children completed the Movement Assessment Battery for Children (MABC-II to assess motor ability and a visual-proprioceptive matching task to assess relative cue weighting. Results from the movement battery provided evidence for movement deficits in ASD similar to those in DCD. Cue weightings in the matching task did not differentiate the clinical groups, however those children with ASD with relatively spared movement skills tended to weight visual cues less heavily than those with DCD-like movement deficits. These findings will be discussed with reference to previous DSM-IV diagnostic criteria and also relevant revisions in the DSM-V.

  20. 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 ...

  1. Congenital malformations of the supratentorial brain. Pt. 1. Disorders of cortical development

    International Nuclear Information System (INIS)

    Ertl-Wagner, B.; Rummeny, C.; Reiser, M.F.

    2003-01-01

    Disorders of supratentorial cortical development are usually divided into disorders of neuronal proliferation, neuronal migration and cortical organization. Based upon molecular biologic discoveries, a modified classification has recently been proposed. The category of malformations of abnormal neuronal and glial proliferation and apoptosis now includes microlissencephalies, megalencephalies, hemimegalencephalies and cortical dysplasias with balloon cells. Malformations due to abnormal neuronal migration now subsume the lissencephaly spectrum including the subcortical band heterotopias, the cobblestone complex and the group of heterotopias. Malformations due to abnormal cortical organization include the spectrum of polymicrogyria and schizencephaly as well as cortical dysplasias without balloon cells. High-resolution magnetic resonance imaging (MRI) has led to an increasing awareness of these malformations. This article aims to illustrate the classification, MRI presentation and relevant clinical features of the most commonly encountered disorders of cortical development. (orig.) [de

  2. Development of a smartphone application for eating disorder self-monitoring.

    Science.gov (United States)

    Tregarthen, Jenna P; Lock, James; Darcy, Alison M

    2015-11-01

    This case report aims to (1) describe the development and refinement of a smartphone application for eating disorder self-monitoring; (2) characterize its users in terms of demographic and clinical characteristics; and (3) explore its feasibility and utilization as a self-monitoring tool. We developed a mobile phone application through which people with eating disorders can self-monitor meals, emotions, behaviors, and thoughts. The application also included positive reinforcement, coping skill suggestions, social support, and feedback components. The app was made available on two Internet app stores. Data include number of downloads and subsequent usage statistics, consumer ratings on app-stores are used as indicators of satisfaction, anonymous aggregate demographic data and Eating Disorder Examination Questionnaire scores from 57,940 individuals collected over a two-year period. The app demonstrated population-level utilization with over 100,000 users over a two-year period. Almost 50% percent of users stated that they are not currently receiving clinical treatment and 33% reported they had not told anyone about their eating disorder. A surprising number of people with severe problems are using the app. Smartphone apps have the capacity to reach and engage traditionally underserved individuals with eating disorders at a large scale. Additional work is indicated for the evaluation of the clinical effectiveness of applications for specific user groups and in clinical treatment contexts. © 2015 Wiley Periodicals, Inc.

  3. Development of cortical asymmetry in typically developing children and its disruption in attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Shaw, Philip; Lalonde, Francois; Lepage, Claude; Rabin, Cara; Eckstrand, Kristen; Sharp, Wendy; Greenstein, Deanna; Evans, Alan; Giedd, J N; Rapoport, Judith

    2009-08-01

    Just as typical development of anatomical asymmetries in the human brain has been linked with normal lateralization of motor and cognitive functions, disruption of asymmetry has been implicated in the pathogenesis of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD). No study has examined the development of cortical asymmetry using longitudinal neuroanatomical data. To delineate the development of cortical asymmetry in children with and without ADHD. Longitudinal study. Government Clinical Research Institute. A total of 218 children with ADHD and 358 typically developing children, from whom 1133 neuroanatomical magnetic resonance images were acquired prospectively. Cortical thickness was estimated at 40 962 homologous points in the left and right hemispheres, and the trajectory of change in asymmetry was defined using mixed-model regression. In right-handed typically developing individuals, a mean (SE) increase in the relative thickness of the right orbitofrontal and inferior frontal cortex with age of 0.011 (0.0018) mm per year (t(337) = 6.2, P left-hemispheric increase in the occipital cortical regions of 0.013 (0.0015) mm per year (t(337) = 8.1, P right-handed typically developing individuals was less extensive and was localized to different cortical regions. In ADHD, the posterior component of this evolving asymmetry was intact, but the prefrontal component was lost. These findings explain the way that, in typical development, the increased dimensions of the right frontal and left occipital cortical regions emerge in adulthood from the reversed pattern of childhood cortical asymmetries. Loss of the prefrontal component of this evolving asymmetry in ADHD is compatible with disruption of prefrontal function in the disorder and demonstrates the way that disruption of typical processes of asymmetry can inform our understanding of neurodevelopmental disorders.

  4. Temperament and Personality as Potential Factors in the Development and Treatment of Conduct Disorders.

    Science.gov (United States)

    Center, David; Kemp, Dawn

    2003-01-01

    This article examines the development of conduct disorder (CD) in children and adolescents using Hans Eysenck's biosocial theory of personality. Eysenck's antisocial behavior hypothesis is discussed and intervention suggestions based on this theory are presented. The interactions of temperament-based personality profiles with interventions for CD…

  5. Temperament as a Potential Factor in the Development and Treatment of Conduct Disorders.

    Science.gov (United States)

    Center, David; Kemp, Dawn

    This report examines the development of Conduct Disorder (CD) in children and adolescents from the perspective of Hans Eysenck's bio-social theory of personality. The theory views personality as a product of the interaction of temperament and socialization. Eysenck's three-factor model of personality is comprised of Extroversion (E), Neuroticism…

  6. Spontaneous Lexical Alignment in Children with an Autistic Spectrum Disorder and Their Typically Developing Peers

    Science.gov (United States)

    Branigan, Holly P.; Tosi, Alessia; Gillespie-Smith, Karri

    2016-01-01

    It is well established that adults converge on common referring expressions in dialogue, and that such lexical alignment is important for successful and rewarding communication. The authors show that children with an autistic spectrum disorder (ASD) and chronological- and verbal-age-matched typically developing (TD) children also show spontaneous…

  7. Role of childhood adversity in the development of medical co-morbidities associated with bipolar disorder

    NARCIS (Netherlands)

    Post, Robert M.; Altshuler, Lori L.; Leverich, Gabriele S.; Frye, Mark A.; Suppes, Trisha; McElroy, Susan L.; Keck, Paul E.; Nolen, Willem A.; Kupka, Ralph W.; Grunze, Heinz; Rowe, Mike

    Objective: A role for childhood adversity in the development of numerous medical conditions in adults has been described in the general population, but has not been examined in patients with bipolar disorder who have multiple medical comorbidities which contribute to their premature mortality.

  8. Using Self-Regulated Strategy Development for Written Expression with Students with Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    Reid, Robert; Hagaman, Jessica L.; Graham, Steve

    2014-01-01

    This review assessed the use of self-regulated strategy development (SRSD) for teaching written composition strategies to students with attention deficit hyperactivity disorders. We examined the participants and the settings in which SRSD has been used, the writing strategies tested, genres addressed, and the effects of SRSD on outcome measures.…

  9. Modulation of Attentional Blink with Emotional Faces in Typical Development and in Autism Spectrum Disorders

    Science.gov (United States)

    Yerys, Benjamin E.; Ruiz, Ericka; Strang, John; Sokoloff, Jennifer; Kenworthy, Lauren; Vaidya, Chandan J.

    2013-01-01

    Background: The attentional blink (AB) phenomenon was used to assess the effect of emotional information on early visual attention in typically developing (TD) children and children with autism spectrum disorders (ASD). The AB effect is the momentary perceptual unawareness that follows target identification in a rapid serial visual processing…

  10. Autism Spectrum Disorder Symptoms among Children Enrolled in the Study to Explore Early Development (SEED)

    Science.gov (United States)

    Wiggins, Lisa D.; Levy, Susan E.; Daniels, Julie; Schieve, Laura; Croen, Lisa A.; DiGuiseppi, Carolyn; Blaskey, Lisa; Giarelli, Ellen; Lee, Li-Ching; Pinto-Martin, Jennifer; Reynolds, Ann; Rice, Catherine; Rosenberg, Cordelia Robinson; Thompson, Patrick; Yeargin-Allsopp, Marshalyn; Young, Lisa; Schendel, Diana

    2015-01-01

    This study examined the phenotypic profiles of children aged 30-68 months in the Study to Explore Early Development (SEED). Children classified as autism spectrum disorder (ASD), developmental delay (DD) with ASD symptoms, DD without ASD symptoms, and population comparison (POP) differed significantly from each other on cognitive, adaptive,…

  11. Maternal Psychopathology and Infant Development at 18 Months: The Impact of Maternal Personality Disorder and Depression

    Science.gov (United States)

    Conroy, Susan; Pariante, Carmine M.; Marks, Maureen N.; Davies, Helen A.; Farrelly, Simone; Schacht, Robin; Moran, Paul

    2012-01-01

    Objective: No previous longitudinal study has examined the impact of comorbid maternal personality disorder (PD) and depression on child development. We set out to examine whether maternal PD and depression assessed at 2 months post partum would be independently associated with adverse developmental outcomes at 18 months of age. Method: Women were…

  12. Reading Skills of Students with Speech Sound Disorders at Three Stages of Literacy Development

    Science.gov (United States)

    Skebo, Crysten M.; Lewis, Barbara A.; Freebairn, Lisa A.; Tag, Jessica; Ciesla, Allison Avrich; Stein, Catherine M.

    2013-01-01

    Purpose: The relationship between phonological awareness, overall language, vocabulary, and nonlinguistic cognitive skills to decoding and reading comprehension was examined for students at 3 stages of literacy development (i.e., early elementary school, middle school, and high school). Students with histories of speech sound disorders (SSD) with…

  13. Mealtime Problems in Children with Autism Spectrum Disorder and Their Typically Developing Siblings: A Comparison Study

    Science.gov (United States)

    Nadon, Genevieve; Feldman, Debbie Ehrmann; Dunn, Winnie; Gisel, Erika

    2011-01-01

    Many children with autism spectrum disorders (ASD) have mealtime problems. Diagnosis and the social environment may influence eating behaviours. We examined whether children with ASD have more mealtime problems than their typically developing siblings, and whether age and sex are associated with mealtime problems. Forty-eight families participated…

  14. Comparison of Sedentary Behaviors between Children with Autism Spectrum Disorders and Typically Developing Children

    Science.gov (United States)

    Must, Aviva; Phillips, Sarah M.; Curtin, Carol; Anderson, Sarah E.; Maslin, Melissa; Lividini, Keith; Bandini, Linda G.

    2014-01-01

    Time spent in sedentary behavior is largely due to time spent engaged with electronic screen media. Little is known about the extent to which sedentary behaviors for children with autism spectrum disorder differ from typically developing children. We used parental report to assess and compare time spent in sedentary behaviors for 53 children with…

  15. Polysyllable Speech Accuracy and Predictors of Later Literacy Development in Preschool Children with Speech Sound Disorders

    Science.gov (United States)

    Masso, Sarah; Baker, Elise; McLeod, Sharynne; Wang, Cen

    2017-01-01

    Purpose: The aim of this study was to determine if polysyllable accuracy in preschoolers with speech sound disorders (SSD) was related to known predictors of later literacy development: phonological processing, receptive vocabulary, and print knowledge. Polysyllables--words of three or more syllables--are important to consider because unlike…

  16. The Effect of Cooperative Teaching on the Development of Reading Skills among Students with Reading Disorders

    Science.gov (United States)

    Ghanaat Pisheh, Etrat Alzahra; Sadeghpour, Narges; Nejatyjahromy, Yaser; Mir Nasab, Mir Mahmoud

    2017-01-01

    Cooperative teaching is the result of efforts made by two educators for teaching a heterogeneous group of students, especially one including those with specific needs, due to reading disorders for instance. The present study serves as an experimental investigation focusing on the effect of cooperative teaching on the development of reading skills…

  17. Is ADHD an early stage in the development of borderline personality disorder?

    Science.gov (United States)

    Storebø, Ole Jakob; Simonsen, Erik

    2014-07-01

    Several studies report associations between adults with borderline personality disorder (BPD) and a history of attention-deficit hyperactivity (ADHD) symptoms in childhood. To explore the association between BPD and a history of ADHD in childhood. A comprehensive search of EMBASE, PsychInfo and Medline and hand-searching yielded 238 "hits". Fifteen articles were found to have sufficient quality and relevance to be included in the final review. The data were considered in six possible explanatory psychopathological models of the association between ADHD and BPD. Most of the 15 articles showed a statistical association between ADHD and BPD. The data, most strongly provided a basis for the hypotheses that ADHD is either an early developmental stage of BPD, or that the two disorders share an environmental and genetic aetiology. Furthermore, one of the disorders seems to give a synergic effect, reinforce the other or complicate the disorders. In one prospective study, the risk factor for children with ADHD to develop BPD was as high as odds ratio 13.16. No studies have looked at treatment of ADHD as a mediator of the risk for BPD. Many studies pointed at shared aetiology or the risk for development of one disorder, when the other disorder is present. The data do not evaluate how treatment factors or other factors mediate the risk or how overlap of diagnostic criteria adds to the statistical association. More research is much needed, in particular studies looking at early intervention and which treatment of ADHD that might prevent later development of BPD.

  18. On the increased risk of developing late-onset epilepsy for patients with major affective disorder

    DEFF Research Database (Denmark)

    Nilsson, Flemming Mørkeberg; Kessing, Lars Vedel; Bolwig, Tom Gert

    2003-01-01

    for the control groups. However, the increased risk seemed to be due to the effect of comorbid alcohol or drug abuse and not to the effect of the affective illness itself. LIMITATIONS: The results only apply to hospitalised patients. Diagnoses are not validated for research purposes. CONCLUSION: Patients...... with a diagnosis of affective disorder have an increased risk of developing epilepsy in later life. In patients with affective disorder, comorbid alcoholism/drug abuse seriously increased the risk of a subsequent diagnosis of epilepsy....

  19. THE CORRELATION OF PARENTING STYLE WITH COGNITIVE DEVELOPMENT IN CHILDREN WITH ATTENTION DEFICIT HYPERACTIVITY DISORDER

    Directory of Open Access Journals (Sweden)

    Fitri Genisti

    2018-05-01

    Full Text Available Background: Child development is a very important phase, which children learn various skills as future generations in the future. Disorders that can impede child development process of Attention Deficit Hyperactivity Disorder (ADHD. Children with ADHD have problems with cognitive abilities, of which about 20-60% of them have learning disorders. The efforts to support cognitive development in ADHD children is to approach the child's environment through parenting parents. Objective: This study aimed to determine the correlation of parenting style with cognitive development in the children with ADHD in SLB Negeri 1 Denpasar. Methods: This study used correlational design with cross sectional approach. The sample size of 30 respondents were taken by purposive sampling technique. Data were collected using parenting style questionnaire (PSQ and the average value of odd semester report of 2016/2017 academic year. Results: The result of this research was found that most parents with democratic parenting type were 19 people (63.3%, authoritarian parenting type were 7 people (23.3% and permissive parenting were 4 people (13.3%. The result of contingency coefficient test with p-value = 0.039 (p <0.05 and correlation value of 0.501, which mean there was high correlation between parenting style with cognitive development in children with ADHD. Conclusion: It is suggested for parents with ADHD children to be able to provide good parenting for the child's development, especially for the child's cognitive development.

  20. The Eating Disorder Assessment for DSM-5 (EDA-5): Development and Validation of a Structured Interview for Feeding and Eating Disorders

    Science.gov (United States)

    Sysko, Robyn; Glasofer, Deborah R.; Hildebrandt, Tom; Klimek, Patrycja; Mitchell, James E.; Berg, Kelly C.; Peterson, Carol B.; Wonderlich, Stephen A.; Walsh, B. Timothy

    2016-01-01

    Objective Existing measures for DSM-IV eating disorder diagnoses have notable limitations, and there are important differences between DSM-IV and DSM-5 feeding and eating disorders. This study developed and validated a new semi-structured interview, the Eating Disorders Assessment for DSM-5 (EDA-5). Method Two studies evaluated the utility of the EDA-5. Study 1 compared the diagnostic validity of the EDA-5 to the Eating Disorder Examination (EDE) and evaluated the test-retest reliability of the new measure. Study 2 compared the diagnostic validity of an EDA-5 electronic application (“app”) to clinician interview and self-report assessments. Results In Study 1, the kappa for EDE and EDA-5 eating disorder diagnoses was 0.74 across all diagnoses (n= 64), with a range of κ=0.65 for Other Specified Feeding or Eating Disorder (OSFED)/Unspecified Feeding or Eating Disorder (USFED) to κ=0.90 for Binge Eating Disorder (BED). The EDA-5 test-retest kappa coefficient was 0.87 across diagnoses. For Study 2, clinical interview versus “app” conditions revealed a kappa of 0.83 for all eating disorder diagnoses (n=71). Across individual diagnostic categories, kappas ranged from 0.56 for OSFED/USFED to 0.94 for BN. Discussion High rates of agreement were found between diagnoses by EDA-5 and the EDE, and EDA-5 and clinical interviews. As this study supports the validity of the EDA-5 to generate DSM-5 eating disorders and the reliability of these diagnoses, the EDA-5 may be an option for the assessment of Anorexia Nervosa, Bulimia Nervosa, and BED. Additional research is needed to evaluate the utility of the EDA-5 in assessing DSM-5 feeding disorders. PMID:25639562

  1. Development and Psychometric Properties of the Standardized Assessment of Severity of Personality Disorder (SASPD).

    Science.gov (United States)

    Olajide, Kike; Munjiza, Jasna; Moran, Paul; O'Connell, Lesley; Newton-Howes, Giles; Bassett, Paul; Akintomide, Gbolagade; Ng, Nicola; Tyrer, Peter; Mulder, Roger; Crawford, Mike J

    2018-02-01

    Personality disorder (PD) is increasingly categorized according to its severity, but there is no simple way to screen for severity according to ICD-11 criteria. We set out to develop the Standardized Assessment of Severity of Personality Disorder (SASPD). A total of 110 patients completed the SASPD together with a clinical assessment of the severity of personality disorder. We examined the predictive ability of the SASPD using the area under the ROC curve (AUC). Two to four weeks later, 43 patients repeated the SASPD to examine reliability. The SASPD had good predictive ability for determining mild (AUC = 0.86) and moderate (AUC = 0.84) PD at cut points of 8 and 10, respectively. Test-retest reliability of the SASPD was high (intraclass correlation coefficient = 0.93, 95% CI [0.88, 0.96]). The SASPD thus provides a simple, brief, and reliable indicator of the presence of mild or moderate PD according to ICD-11 criteria.

  2. The Relationship between Autism Spectrum Disorder and Melatonin during Fetal Development

    Directory of Open Access Journals (Sweden)

    Yunho Jin

    2018-01-01

    Full Text Available The aim of this review is to clarify the interrelationship between melatonin and autism spectrum disorder (ASD during fetal development. ASD refers to a diverse range of neurodevelopmental disorders characterized by social deficits, impaired communication, and stereotyped or repetitive behaviors. Melatonin, which is secreted by the pineal gland, has well-established neuroprotective and circadian entraining effects. During pregnancy, the hormone crosses the placenta into the fetal circulation and transmits photoperiodic information to the fetus allowing the establishment of normal sleep patterns and circadian rhythms that are essential for normal neurodevelopment. Melatonin synthesis is frequently impaired in patients with ASD. The hormone reduces oxidative stress, which is harmful to the central nervous system. Therefore, the neuroprotective and circadian entraining roles of melatonin may reduce the risk of neurodevelopmental disorders such as ASD.

  3. Differences in adjustment by child developmental stage among caregivers of children with disorders of sex development

    Science.gov (United States)

    2011-01-01

    Background The current study sought to compare levels of overprotection and parenting stress reported by caregivers of children with disorders of sex development at four different developmental stages. Methods Caregivers (N = 59) of children with disorders of sex development were recruited from specialty clinics and were asked to complete the Parent Protection Scale and Parenting Stress Index/Short Form as measures of overprotective behaviors and parenting stress, respectively. Results Analyses of covariance (ANCOVAs) were conducted to examine differences between caregiver report of overprotection and parenting stress. Results revealed that caregivers of infants and toddlers exhibited more overprotective behaviors than caregivers of children in the other age groups. Further, caregivers of adolescents experienced significantly more parenting stress than caregivers of school-age children, and this effect was driven by personal distress and problematic parent-child interactions, rather than having a difficult child. Conclusions These results suggest that caregivers of children with disorders of sex development may have different psychosocial needs based upon their child's developmental stage and based upon the disorder-related challenges that are most salient at that developmental stage. PMID:22074416

  4. Differences in adjustment by child developmental stage among caregivers of children with disorders of sex development

    Directory of Open Access Journals (Sweden)

    Hullmann Stephanie E

    2011-11-01

    Full Text Available Abstract Background The current study sought to compare levels of overprotection and parenting stress reported by caregivers of children with disorders of sex development at four different developmental stages. Methods Caregivers (N = 59 of children with disorders of sex development were recruited from specialty clinics and were asked to complete the Parent Protection Scale and Parenting Stress Index/Short Form as measures of overprotective behaviors and parenting stress, respectively. Results Analyses of covariance (ANCOVAs were conducted to examine differences between caregiver report of overprotection and parenting stress. Results revealed that caregivers of infants and toddlers exhibited more overprotective behaviors than caregivers of children in the other age groups. Further, caregivers of adolescents experienced significantly more parenting stress than caregivers of school-age children, and this effect was driven by personal distress and problematic parent-child interactions, rather than having a difficult child. Conclusions These results suggest that caregivers of children with disorders of sex development may have different psychosocial needs based upon their child's developmental stage and based upon the disorder-related challenges that are most salient at that developmental stage.

  5. DEVELOPMENT OF THE PARENT-CHILD PLAY SCALE FOR USE IN CHILDREN WITH FEEDING DISORDERS.

    Science.gov (United States)

    Chatoor, Irene; Hommel, Susanne; Sechi, Cristina; Lucarelli, Loredana

    2018-03-01

    The Parent-Child Play Scale was developed as a scale that complements the Parent-Child Feeding Scale, created by I. Chatoor et al. (1997), to evaluate mother-infant/toddler interactions in two different caregiving contexts of a young child's everyday life, specifically play and feeding. This Play Scale can be used with infants and toddlers ranging in age from 1 month to 3 years and provides reliable global ratings of mother-child interactions during 10 min of videotaped free-play in a laboratory setting. The scale consists of 32 mother and infant/toddler interactive behaviors which are rated by trained observers from videotaped observations. Four subscales are derived: Dyadic Reciprocity, Maternal Unresponsiveness to Infant's/Toddler's Cues, Dyadic Conflict, and Maternal Intrusiveness. Construct validity and interrater and test-retest reliability of the Play Scale have been demonstrated. This Play Scale discriminates between children with and without feeding disorders as well as between children with different subtypes of feeding disorders as defined by the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood, Revised (DC:0-3R) (Feeding Disorder of State Regulation, Feeding Disorder of Caregiver-Infant Reciprocity, and Infantile Anorexia). It can be used for research or clinical practice in the diagnosis and treatment of early feeding problems, to assess the pervasiveness of mother-infant/toddler difficulties and to monitor changes following therapy. © 2018 Michigan Association for Infant Mental Health.

  6. The role of the amygdala in naturalistic mentalising in typical development and in autism spectrum disorder.

    Science.gov (United States)

    Rosenblau, Gabriela; Kliemann, Dorit; Lemme, Benjamin; Walter, Henrik; Heekeren, Hauke R; Dziobek, Isabel

    2016-06-01

    The substantial discrepancy between mentalising in experimental settings v. real-life social interactions hinders the understanding of the neural basis of real-life social cognition and of social impairments in psychiatric disorders. To determine the neural mechanisms underlying naturalistic mentalising in individuals with and without autism spectrum disorder. We investigated mentalising with a new video-based functional magnetic resonance imaging task in 20 individuals with autism spectrum disorder and 22 matched healthy controls. Naturalistic mentalising implicated regions of the traditional mentalising network (medial prefrontal cortex, temporoparietal junction), and additionally the insula and amygdala. Moreover, amygdala activity predicted implicit mentalising performance on an independent behavioural task. Compared with controls, the autism spectrum disorder group did not show differences in neural activity within classical mentalising regions. They did, however, show reduced amygdala activity and a reduced correlation between amygdala activity and mentalising accuracy on the behavioural task, compared with controls. These findings highlight the crucial role of the amygdala in making accurate implicit mental state inferences in typical development and in the social cognitive impairments of individuals with autism spectrum disorder. © The Royal College of Psychiatrists 2016.

  7. Development of the uncinate fasciculus: Implications for theory and developmental disorders.

    Science.gov (United States)

    Olson, Ingrid R; Von Der Heide, Rebecca J; Alm, Kylie H; Vyas, Govinda

    2015-08-01

    The uncinate fasciculus (UF) is a long-range white matter tract that connects limbic regions in the temporal lobe to the frontal lobe. The UF is one of the latest developing tracts, and continues maturing into the third decade of life. As such, individual differences in the maturational profile of the UF may serve to explain differences in behavior. Indeed, atypical macrostructure and microstructure of the UF have been reported in numerous studies of individuals with developmental and psychiatric disorders such as social deprivation and maltreatment, autism spectrum disorders, conduct disorder, risk taking, and substance abuse. The present review evaluates what we currently know about the UF's developmental trajectory and reviews the literature relating UF abnormalities to specific disorders. Additionally, we take a dimensional approach and critically examine symptoms and behavioral impairments that have been demonstrated to cluster with UF aberrations, in an effort to relate these impairments to our speculations regarding the functionality of the UF. We suggest that developmental disorders with core problems relating to memory retrieval, reward and valuation computation, and impulsive decision making may be linked to aberrations in uncinate microstructure. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Development of the uncinate fasciculus: Implications for theory and developmental disorders

    Directory of Open Access Journals (Sweden)

    Ingrid R. Olson

    2015-08-01

    Full Text Available The uncinate fasciculus (UF is a long-range white matter tract that connects limbic regions in the temporal lobe to the frontal lobe. The UF is one of the latest developing tracts, and continues maturing into the third decade of life. As such, individual differences in the maturational profile of the UF may serve to explain differences in behavior. Indeed, atypical macrostructure and microstructure of the UF have been reported in numerous studies of individuals with developmental and psychiatric disorders such as social deprivation and maltreatment, autism spectrum disorders, conduct disorder, risk taking, and substance abuse. The present review evaluates what we currently know about the UF's developmental trajectory and reviews the literature relating UF abnormalities to specific disorders. Additionally, we take a dimensional approach and critically examine symptoms and behavioral impairments that have been demonstrated to cluster with UF aberrations, in an effort to relate these impairments to our speculations regarding the functionality of the UF. We suggest that developmental disorders with core problems relating to memory retrieval, reward and valuation computation, and impulsive decision making may be linked to aberrations in uncinate microstructure.

  9. INCLEN diagnostic tool for attention deficit hyperactivity disorder (INDT-ADHD): development and validation.

    Science.gov (United States)

    Mukherjee, Sharmila; Aneja, Satinder; Russell, Paul S S; Gulati, Sheffali; Deshmukh, Vaishali; Sagar, Rajesh; Silberberg, Donald; Bhutani, Vinod K; Pinto, Jennifer M; Durkin, Maureen; Pandey, Ravindra M; Nair, M K C; Arora, Narendra K

    2014-06-01

    To develop and validate INCLEN Diagnostic Tool for Attention Deficit Hyperactivity Disorder (INDT-ADHD). Diagnostic test evaluation by cross sectional design. Tertiary care pediatric centers. 156 children aged 65-117 months. After randomization, INDT-ADHD and Connors 3 Parent Rating Scale (C3PS) were administered, followed by an expert evaluation by DSM-IV-TR diagnostic criteria. Psychometric evaluation of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency. INDT-ADHD had 18 items that quantified symptoms and impairment. Attention deficit hyperactivity disorder was identified in 57, 87 and 116 children by expert evaluation, INDT-ADHD and C3PS, respectively. Psychometric parameters of INDT-ADHD for differentiating attention deficit hyperactivity disorder and normal children were: sensitivity 87.7%, specificity 97.2%, positive predictive value 98.0% and negative predictive value 83.3%, whereas for differentiating from other neuro-developmental disorders were 87.7%, 42.9%, 58.1% and 79.4%, respectively. Internal consistency was 0.91. INDT-ADHD has a 4-factor structure explaining 60.4% of the variance. Convergent validity with Conner's Parents Rating Scale was moderate (r =0.73, P= 0.001). INDT-ADHD is suitable for diagnosing attention deficit hyperactivity disorder in Indian children between the ages of 6 to 9 years.

  10. Parental Reports of Stigma Associated with Child’s Disorder of Sex Development

    OpenAIRE

    Rolston, Aimee M.; Gardner, Melissa; Vilain, Eric; Sandberg, David E.

    2015-01-01

    Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or anatomic sex development is atypical. DSD-associated stigma is purported to threaten positive psychosocial adaptation. Parental perceptions of DSD-related stigma were assessed in 154 parents of 107 children (newborn?17 years) questionnaire comprising two scales, child-focused and parent-focused, and three subscales, perceived stigmatization, future worries, and feelings about the child's condition. ...

  11. Decision aid prototype development for parents considering adenotonsillectomy for their children with sleep disordered breathing

    OpenAIRE

    Maguire, Erin; Hong, Paul; Ritchie, Krista; Meier, Jeremy; Archibald, Karen; Chorney, Jill

    2016-01-01

    Background To describe the process involved in developing a decision aid prototype for parents considering adenotonsillectomy for their children with sleep disordered breathing. Methods A paper-based decision aid prototype was developed using the framework proposed by the International Patient Decision Aids Standards Collaborative. The decision aid focused on two main treatment options: watchful waiting and adenotonsillectomy. Usability was assessed with parents of pediatric patients and prov...

  12. Gender Differences in Sleep During the Aftermath of Trauma and the Development of Posttraumatic Stress Disorder

    OpenAIRE

    Kobayashi, Ihori; Mellman, Thomas A.

    2012-01-01

    Women have a greater risk of developing posttraumatic stress disorder (PTSD) after exposure to trauma. Although sleep abnormalities have been implicated in the development of PTSD, gender differences in sleep soon after a traumatic event have not been investigated. This secondary analysis examined sleep characteristics using polysomnography in 13 female and 22 male trauma patients within a month of their traumatic injuries and assessed PTSD symptoms at 2-months post-injury. Results revealed m...

  13. Quasi-Drugs Developed in Japan for the Prevention or Treatment of Hyperpigmentary Disorders

    Directory of Open Access Journals (Sweden)

    Hideya Ando

    2010-06-01

    Full Text Available Excess production of melanin or its abnormal distribution, or both, can cause irregular hyperpigmentation of the skin, leading to melasma and age spots. To date, various quasi-drugs that prevent or improve hyperpigmentary disorders have been developed and officially approved by the Ministry of Health, Labor and Welfare of Japan. Many of these inhibit the activity of tyrosinase, an enzyme required for melanin synthesis, for example, by competitive or non-competitive inhibition of its catalytic activity, by inhibiting its maturation, or by accelerating its degradation. In this review, we categorize the quasi-drugs developed in Japan to prevent or treat hyperpigmentary disorders, or both, and discuss perspectives for future development.

  14. Endoplasmic reticulum KDEL-tailed cysteine endopeptidase 1 of Arabidopsis (AtCEP1 is involved in pathogen defense

    Directory of Open Access Journals (Sweden)

    Timo eHöwing

    2014-02-01

    Full Text Available Programmed cell death (PCD is a genetically determined process in all multicellular organisms. Plant PCD is effected by a unique group of papain-type cysteine endopeptidases (CysEP with a C-terminal KDEL endoplasmic reticulum (ER retention signal (KDEL CysEP. KDEL CysEPs can be stored as pro-enzymes in ER-derived endomembrane compartments and are released as mature CysEPs in the final stages of organelle disintegration. KDEL CysEPs accept a wide variety of amino acids at the active site, including the glycosylated hydroxyprolines of the extensins that form the basic scaffold of the cell wall. In Arabidopsis, three KDEL CysEPs (AtCEP1, AtCEP2, and AtCEP3 are expressed. Cell- and tissue-specific activities of these three genes suggest that KDEL CysEPs participate in the abscission of flower organs and in the collapse of tissues in the final stage of PCD as well as in developmental tissue remodelling.We observed that AtCEP1 is expressed in response to biotic stress stimuli in the leaf. atcep1 knockout mutants showed enhanced susceptibility to powdery mildew caused by the biotrophic ascomycete Erysiphe cruciferarum. A translational fusion protein of AtCEP1 with a three-fold hemaglutinin-tag and the green fluorescent protein under control of the endogenous AtCEP1 promoter (PCEP1::pre-pro-3xHA-EGFP-AtCEP1-KDEL rescued the pathogenesis phenotype demonstrating the function of AtCEP1 in restriction of powdery mildew. The spatiotemporal AtCEP1-reporter expression during fungal infection together with microscopic inspection of the interaction phenotype suggested a function of AtCEP1 in controlling late stages of compatible interaction including late epidermal cell death. Additionally, expression of stress response genes appeared to be deregulated in the interaction of atcep1 mutants and E. cruciferarum. Possible functions of AtCEP1 in restricting parasitic success of the obligate biotrophic powdery mildew fungus are discussed.

  15. Review disorders of sex development: The evolving role of genomics in diagnosis and gene discovery.

    Science.gov (United States)

    Croft, Brittany; Ayers, Katie; Sinclair, Andrew; Ohnesorg, Thomas

    2016-12-01

    Disorders of Sex Development (DSDs) are a major paediatric concern and are estimated to occur in around 1.7% of all live births (Fausto-Sterling, Sexing the Body: Gender Politics and the Construction of Sexuality, Basic Books, New York, 2000). They are often caused by the breakdown in the complex genetic mechanisms that underlie gonadal development and differentiation. Having a genetic diagnosis can be important for patients with a DSD: it can increase acceptance of a disorder often surrounded by stigma, alter clinical management and it can assist in reproductive planning. While Massively Parallel Sequencing (MPS) is advancing the genetic diagnosis of rare Mendelian disorders, it is not yet clear which MPS assay is best suited for the clinical diagnosis of DSD patients and to what extent other established methods are still relevant. To complicate matters, DSDs represent a wide spectrum of disorders caused by an array of different genetic changes, many of which are yet unknown. Here we discuss the different genetic lesions that are known to contribute to different DSDs, and review the utility of a range of MPS approaches for diagnosing DSD patients. Birth Defects Research (Part C) 108:337-350, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Are cognitive "insomnia" processes involved in the development and maintenance of delayed sleep wake phase disorder?

    Science.gov (United States)

    Richardson, Cele E; Gradisar, Michael; Barbero, Sebastian C

    2016-04-01

    Although individuals with delayed sleep wake phase disorder (DSWPD) and chronic insomnia disorder (CID) share many of the same phenomenological experiences, theories relating to the development and maintenance of these disorders are distinct in focus. Unlike CID, theory relating to DSWPD is primarily physiologically based and assumes almost no cognitive pathway. However, recent research findings suggest that individuals with DSWPD also display many of the sleep-disordered cognitive processes that were previously assumed to be unique to the insomnia experience. As such, this review aims to summarise current research findings to address the question "Could cognitive processes be involved in the development and maintenance of DSWPD?" In particular, the presence of cognitive and physiological pre-sleep arousal, sleep-related attentional bias, distorted perception of sleep and daytime functioning, dysfunctional beliefs and safety behaviours will be investigated. As this emerging area of research requires a stronger evidence base, we highlight suggestions for future investigation and provide preliminary practice points for clinicians assessing and treating "insomnia" in patients with DSWPD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. The impact of mental disorders on the development of nosological features of gelotophobia, gelotophilia and katagelasticism

    Directory of Open Access Journals (Sweden)

    O. M. Shportun

    2015-12-01

    Full Text Available Scientific psychological studies, which are provided in recent years, indicate lack of coverage of humour disorders as an emotion. Aim. In order to explore and discover the nosological features of gelotophobia, gelotophilia, katagelasticism, in 81 men and 50 women, 142 patients with mental disorders were included. Methods and results. Features of influence of diagnosis, gender, as well as symptoms of mental disorders on the development of gelotophobia, gelotophilia, katagelasticism were studied. The following methods were used: 1 a Russian-language version of the gelotophobia scale GELOPH-15; 2 Methodology of PhoPhiKat-45; 3 Gelotophobia scale GELOPH-15; 4 Picture Test Picture-GELOPH. The psychometric and factor analyses of data were also used. It was distinguished that the main factors in forming the main nosological features are: gender and diagnosis, that allow considering separately the impact of sexual differences and nosological specifics, as well as the impact of mental disorders symptoms on the development of gelotophobia, gelotophilia, katagelasticism. Conclusion. It indicates that the specificity of the manifestations of gelotophobia, gelotophilia, katagelasticism can be seen as indicators of the depth of the violation of human mental activity.

  18. Adolescent development and eating disorder related quality of life in Indian females.

    Science.gov (United States)

    Lal, M; Abraham, S

    2011-03-01

    To study the relationship of adolescent development and eating disorder related quality of life in Indian females. 461 female school students (aged 12-17 yrs) were recruited from middle to high socio-economic status (SES), English speaking schools in Delhi, India. Adolescent development was measured by Tanner stage and months since menarche. Subjects completed the Quality of Life for Eating Disorders questionnaire (QOL ED), which included six subscores. Correlation and partial correlation coefficient analysis to control for Body Mass Index (BMI) were performed. After controlling for BMI, all adolescent development measures were correlated with the psychological feelings (PSY) subscore. This subscore contained items relating to confusion, social unease, sadness, difficulty coping, desiring perfection and loss of control. Tanner breast stage was correlated with the eating behaviour (EB) subscore. During adolescent development, Indian girls became more aware of their psychological feelings and emotions. Only those reporting breast development were using behaviours to control their body, weight and shape. These behaviours are not associated with the presence of disordered eating thoughts, such as preoccupation with food, eating, body weight or shape.

  19. Implication of neuro-genesis during brain development in behavior disorders caused by depleted uranium

    International Nuclear Information System (INIS)

    Legrand, Marie

    2016-01-01

    Humans are continuously exposed to neurotoxic compounds in the environment. The developing brain is more susceptible to neurotoxic compounds and modifications in its growth could lead to disorders in adulthood. Uranium (U) is an environmental heavy metal and induces behavioral disorders as well as affects neurochemistry. The aim of my thesis was to investigate whether depleted uranium (DU) exposure affects neuro-genesis processes, which are implicated in brain development and in synaptic plasticity in adults. While DU increased cell proliferation in the hippocampal neuro-epithelium and decreased cell death at prenatal stages, DU lead to opposite effects in the dentate gyrus at postnatal stages. Moreover, DU had an inhibitory effect on the transition toward neuronal differentiation pathway during development. At adult stage, DU induced a decrease in neuronal differentiation but has no impact in cell proliferation. Finally, DU exposure during brain development caused depressive like behavior at late postnatal and adult stage, and decreased spatial memory at adult stage. Consequently, DU exposure during brain development caused modification in neuro-genesis processes associated to cognitive and emotional disorders at adult age. U could present a threat to human health, especially in pregnant women and children. (author)

  20. Study of child language development and disorders in Iran: A systematic review of the literature

    Directory of Open Access Journals (Sweden)

    Yalda Kazemi

    2015-01-01

    Full Text Available Child language development and disorder in Iran has been the focus for research by different professions, the most prominent ones among them being psychologists and speech therapists. Epidemiological studies indicate that between 8% and 12% of children show noticeable signs of language impairment in the preschool years; however, research on child language in Iran is not extensive compared to studies in English speaking countries, which are currently the basis of clinical decision-making in Iran. Consequently, there is no information about the prevalence of child language disorders in Iranian population. This review summarizes Iranian studies on child language development and disorder in the preschool years and aims to systematically find the most studied topics in the field of normal development, the assessment and diagnosis of language impairments as well as exploring the current gaps within the body of literature. Three main Iranian academic websites of indexed articles along with four other nonIranian databases were scrutinized for all relevant articles according to the inclusion criteria: Iranian studies within the field of Persian language development and disorders in preschool children published up to December 2013. They are classified according to the hierarchy of evidence and weighed against the criteria of critical appraisal of study types. As this is a type of nonintervention systematic review, the preferred reporting items for systematic reviews and meta-analyses is modified to be more compatible to the designs of eligible studies, including descriptive studies, test-developing and/or diagnostic studies. Several limitations made the process of searching and retrieving problematic; e.g., lack of unified keywords and incompatibility of Persian typing structure embedded in Iranian search engines. Overall, eligible studies met the criteria up to the third level of the hierarchy of evidence that shows the necessity of conducting studies

  1. Study of child language development and disorders in Iran: A systematic review of the literature.

    Science.gov (United States)

    Kazemi, Yalda; Stringer, Helen; Klee, Thomas

    2015-01-01

    Child language development and disorder in Iran has been the focus for research by different professions, the most prominent ones among them being psychologists and speech therapists. Epidemiological studies indicate that between 8% and 12% of children show noticeable signs of language impairment in the preschool years; however, research on child language in Iran is not extensive compared to studies in English speaking countries, which are currently the basis of clinical decision-making in Iran. Consequently, there is no information about the prevalence of child language disorders in Iranian population. This review summarizes Iranian studies on child language development and disorder in the preschool years and aims to systematically find the most studied topics in the field of normal development, the assessment and diagnosis of language impairments as well as exploring the current gaps within the body of literature. Three main Iranian academic websites of indexed articles along with four other nonIranian databases were scrutinized for all relevant articles according to the inclusion criteria: Iranian studies within the field of Persian language development and disorders in preschool children published up to December 2013. They are classified according to the hierarchy of evidence and weighed against the criteria of critical appraisal of study types. As this is a type of nonintervention systematic review, the preferred reporting items for systematic reviews and meta-analyses is modified to be more compatible to the designs of eligible studies, including descriptive studies, test-developing and/or diagnostic studies. Several limitations made the process of searching and retrieving problematic; e.g., lack of unified keywords and incompatibility of Persian typing structure embedded in Iranian search engines. Overall, eligible studies met the criteria up to the third level of the hierarchy of evidence that shows the necessity of conducting studies with higher levels of

  2. Environmental factors influence language development in children with autism spectrum disorders.

    Directory of Open Access Journals (Sweden)

    Marine Grandgeorge

    Full Text Available BACKGROUND: While it is clearly admitted that normal behavioural development is determined by the interplay of genetic and environmental influences, this is much less the case for psychiatric disorders for which more emphasis has been given in the past decades on biological determinism. Thus, previous studies have shown that Autistic Spectrum Disorders (ASD were not affected by parental style. However, animal research suggests that different behavioural traits can be differentially affected by genetic/environmental factors. METHODOLOGY/ PRINCIPAL FINDINGS: In the present study we hypothesized that amongst the ASD, language disorders may be more sensitive to social factors as language is a social act that develops under social influences. Using the Autism Diagnostic Interview-Revised, we compared the early characteristics of sensori-motor and language development in a large sample of children with ASD (n = 162 with parents belonging to different levels of education. The results showed that children raised by parents with a high level of education displayed earlier language development. Moreover, they showed earlier first words and phrases if their mother was at a high level of education, which reveals an additional gender effect. CONCLUSIONS/SIGNIFICANCE: To our knowledge this study may trigger important new lines of thought and research, help equilibrate social and purely biological perspectives regarding ASD and bring new hopes for environmentally based therapies.

  3. Profile Language Development in students with and without Attenion Deficit Hyperactivity Disorder

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    Hamid َAli-Zadeh

    2010-07-01

    Full Text Available Objective: The present study was designed to investigate language development in children with and without attention deficit hyperactivity disorder (ADHD. Materials & Methods: In this comparative and case–control research, 30 children with attention deficit hyperactivity disorder and 30 healthy matched children were selected simply and conveniently from the elementary first grade students of Qazvin city. Data collection tools included: test of language development– primary: 3th edition (TOLD-P:3, Connors’ rating scale – teachers form, and Raven color matrices. Data were analyzed by repeated measure analysis of variance. Results: There was significant difference in profile of language development between ADHD children and healthy children (P<0.001, but there were no significant differences between boys and girls in both case group (P=0.254 and control group (P=1.00. The results of multivariate analysis showed that the ADHD children were significantly lower in some aspects of language development skills including picture vocabulary, relative vocabulary, oral vocabulary, grammatical understanding, grammatical completion, word discrimination, listening, organizing, speaking, semantics and syntax. No significant difference was found in sentence imitation, phonemic analysis and word articulation. Conclusion: The attention deficit hyperactivity disorder children have some problems in many but not all aspects of language development.

  4. Development and Validation of the Somatic Symptom Disorder-B Criteria Scale (SSD-12).

    Science.gov (United States)

    Toussaint, Anne; Murray, Alexandra M; Voigt, Katharina; Herzog, Annabel; Gierk, Benjamin; Kroenke, Kurt; Rief, Winfried; Henningsen, Peter; Löwe, Bernd

    2016-01-01

    To develop and validate a new self-report questionnaire for the assessment of the psychological features of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition somatic symptom disorder. The Somatic Symptom Disorder-B Criteria Scale (SSD-12) was developed in several steps from an initial pool of 98 items. The SSD-12 is composed of 12 items; each of the three psychological subcriteria is measured by four items. In a cross-sectional study, the SSD-12 was administered to 698 patients (65.8% female, mean [standard deviation] age = 38.79 [14.15] years) from a psychosomatic outpatient clinic. Item and scale characteristics as well as measures of reliability and validity were determined. The SSD-12 has good item characteristics and excellent reliability (Cronbach α = .95). Confirmatory factor analyses suggested that a three-factorial structure that reflects the three psychological criteria interpreted as cognitive, affective, and behavioral aspects (n = 663, Comparative Fit Index > 0.99, Tucker-Lewis Index > 0.99, Root Mean Square Error of Approximation = 0.06, 90% confidence interval = 0.01-0.08). SSD-12 total sum score was significantly associated with somatic symptom burden (r = 0.47, p psychological symptom burden reported higher general physical and mental health impairment and significantly higher health care use. The SSD-12 is the first self-report questionnaire that operationalizes the new psychological characteristics of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition somatic symptom disorder. Initial assessment indicates that the SSD-12 has sufficient reliability and validity to warrant further testing in both research and clinical settings.

  5. Treatment of both native and deamidated gluten peptides with an endo-peptidase from Aspergillus niger prevents stimulation of gut-derived gluten-reactive T cells from either children or adults with celiac disease

    DEFF Research Database (Denmark)

    Toft-Hansen, Henrik; Rasmussen, Karina Søndergård; Nielsen, Anne Staal

    2014-01-01

    the proliferative response by a gluten-specific CD4+ T cell clone and seven gluten-reactive T cell lines to protease-digested gluten peptides. A proline-specific endo-peptidase from Aspergillus niger (AnP2), was particularly efficient at diminishing proliferation after stimulation with cleaved antigen, and could...

  6. Depressive disorders development in connection with gut microflora and dietary factors

    Directory of Open Access Journals (Sweden)

    Shuldyakov А.А.

    2016-06-01

    Full Text Available The morbidity of depressive disorders and their role in the formation of different human pathologies emphasize the actuality of searching for new approaches in the prophylaxis and treatment of depressions. The modification of gut microbiota may be a perspective direction of clinical investigation. Development in this area is based on the review of trials which confirm the significance of gut microflora composition in regulation of mental functions in particular mood and behavior as well as the role of diet in the development of depressions. The hypothesis of the role of gut microbiota in the development of depressive conditions was discussed.

  7. Video modeling for the development of personal hygiene skills in youth with autism spectrum disorder.

    Science.gov (United States)

    Piccin, S; Crippa, A; Nobile, M; Hardan, A Y; Brambilla, P

    2018-04-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder mainly characterised by deficits in social communication as well as by narrow patterns of behaviour and interests (American Psychiatric Association, 2013), often accompanied by language, intellectual and sensory impairments. The severity of these impairments may lead to deficits in the development of daily living activities such as simple meal preparation and feeding, community skills (e.g. buying groceries), personal care (e.g. dressing) and personal hygiene skills (bathing, toileting, hand washing, teeth brushing) needed for independence. Among others, the lack of independence in personal hygiene skills increases the burden of the caregiver and makes children with ASD more dependent (Flynn & Healy, 2012). Therefore, it is important to develop tools for helping individuals with ASD in increasing their ability to perform these basic life activities which will lead to savings that can be invested in other critical areas of needs.

  8. Dietary adequacy of Egyptian children with autism spectrum disorder compared to healthy developing children.

    Science.gov (United States)

    Meguid, Nagwa A; Anwar, Mona; Bjørklund, Geir; Hashish, Adel; Chirumbolo, Salvatore; Hemimi, Maha; Sultan, Eman

    2017-04-01

    Although the etiology and pathology of autism spectrum disorder (ASD) is still poorly understood, a number of environmental, anthropological, neurobiological and genetic factors have been related to the pathophysiology of ASD, even the impact of oxidative stress response related to the environment and nutrition intake. Usual recommended dietary habits are based on the combination of behavioral and dietary or nutraceutical interventions together with pharmacotherapy. Investigations about a reliable relationship between diet and ASD are still lacking. The present study aimed at comparing dietary regimens and habits of normally developing apparently healthy children, without diagnosed ASD, with a pediatric population of individuals affected by autistic disorder. Assessments of nutritional and anthropometric data, in addition to biochemical evaluation for nutrient deficiencies, were performed. A total of 80 children with autistic disorder and 80 healthy, normally developing pediatric individuals were enrolled in the study. Parents were asked to complete the standardized questionnaire regarding the different types of food and the proportion of a serving for their children. Biochemical analysis of micro- and macronutrients were also done. Plotting on the Egyptian sex-specific anthropometric growth (auximetric) chart, absolute weights as well as weight-related for age classes, were significantly higher in cases than healthy controls. No differences between groups were observed in regard to total kilocalories (kcal), carbohydrates, and fat intake. A total of 23.8% of children with autistic disorder vs. 11.3% in the healthy control group had a nutrient intake with features below the Recommended Dietary Allowance (RDA) of protein. Children with autistic disorder showed low dietary intake of some micronutrients; calcium (Ca), magnesium (Mg), iron (Fe), selenium (Se) and sodium (Na), also they had significantly high intake of potassium (K) and vitamin C compared to healthy

  9. Program for suicidal prevention, mental disorder treatment, and mental health development for resident doctors

    Directory of Open Access Journals (Sweden)

    José Luis Jiménez López

    2017-01-01

    Full Text Available High demand of care and the academic burden of courses of specialization in medicine affect the mental health of medical residents with events ranging from simple emotional discomfort to development of affective disorders in susceptible individuals. The suicide of physicians has produced programs for their attention in some countries. We present the first mental health clinic for residents of a high specialty hospital in Mexico, focused on the prevention of suicide and depression, treatment of mental disorders and mental health promotion. Unlike the reports of other countries, we get participation of more than 95%, we provide appropriate treatment and follow-up to residents with mental disorder, and there has not been a consummate suicide. We assume that the use of different strategies (scrutiny, adapting models of prevention of suicide as a peer and gatekeeper training, informative sessions of mental health promotion and stigma, interventions targeted at individuals and groups with conflicts has been useful against barriers that do not allow doctors to identify the risk of suicide warning signs, seek help for mental disorder, and seek to improve their mental health.

  10. Borderline personality pathology in young people at ultra high risk of developing a psychotic disorder.

    Science.gov (United States)

    Ryan, Jaymee; Graham, Anne; Nelson, Barnaby; Yung, Alison

    2017-06-01

    The association between borderline personality disorder and the ultra high risk (UHR) for psychosis state is unclear. The following study aimed to investigate the type of attenuated psychotic symptoms and prevalence of borderline personality pathology in a sample of UHR young people. Additionally, the study aimed to explore whether borderline personality pathology influenced the transition rate to psychosis. Medical records from Orygen Youth Health between 2007 and 2009 were examined. There were 180 patients who met UHR criteria and were included for analysis. Most patients were females (62.8%) and age ranged from 15 to 24 years. A quarter (25.2%) of UHR patients endorsed items consistent with borderline personality pathology. UHR patients with borderline personality pathology experienced a range of attenuated psychotic symptoms and could not be statistically differentiated from UHR patients with less significant or without borderline personality pathology. Borderline personality pathology did not increase or decrease the risk of developing a psychotic disorder. The absence of depression was the only predictor of psychosis. Many UHR patients present with concurrent borderline personality features. The psychotic experiences reported by UHR patients with borderline personality features were not limited to paranoid ideation, supporting the idea that borderline personality disorder may include a wider range of psychotic symptoms than previously thought. It is further possible that the psychotic symptoms experienced in this group could also be indicative of an emerging psychotic disorder. © 2015 Wiley Publishing Asia Pty Ltd.

  11. Study of child language development and disorders in Iran: A systematic review of the literature

    OpenAIRE

    Yalda Kazemi; Helen Stringer; Thomas Klee

    2015-01-01

    Child language development and disorder in Iran has been the focus for research by different professions, the most prominent ones among them being psychologists and speech therapists. Epidemiological studies indicate that between 8% and 12% of children show noticeable signs of language impairment in the preschool years; however, research on child language in Iran is not extensive compared to studies in English speaking countries, which are currently the basis of clinical decision-making in Ir...

  12. Aetiological bases of 46,XY disorders of sex development in the Hong Kong Chinese population.

    Science.gov (United States)

    Chan, Angel O K; But, W M; Lee, C Y; Lam, Y Y; Ng, K L; Loung, P Y; Lam, Aimen; Cheng, C W; Shek, C C; Wong, W S; Wong, K F; Wong, M Y; Tse, W Y

    2015-12-01

    Disorders of sex development are due to congenital defects in chromosomal, gonadal, or anatomical sex development. The objective of this study was to determine the aetiology of this group of disorders in the Hong Kong Chinese population. Five public hospitals in Hong Kong. Patients with 46,XY disorders of sex development under the care of paediatric endocrinologists between July 2009 and June 2011. Measurement of serum gonadotropins, adrenal and testicular hormones, and urinary steroid profiling. Mutational analysis of genes involved in sexual differentiation by direct DNA sequencing and multiplex ligation-dependent probe amplification. Overall, 64 patients were recruited for the study. Their age at presentation ranged from birth to 17 years. The majority presented with ambiguous external genitalia including micropenis and severe hypospadias. A few presented with delayed puberty and primary amenorrhea. Baseline and post-human chorionic gonadotropin-stimulated testosterone and dihydrotestosterone levels were not discriminatory in patients with or without AR gene mutations. Of the patients, 22 had a confirmed genetic disease, with 11 having 5α-reductase 2 deficiency, seven with androgen insensitivity syndrome, one each with cholesterol side-chain cleavage enzyme deficiency, Frasier syndrome, NR5A1-related sex reversal, and persistent Müllerian duct syndrome. Our findings suggest that 5α-reductase 2 deficiency and androgen insensitivity syndrome are possibly the two most common causes of 46,XY disorders of sex development in the Hong Kong Chinese population. Since hormonal findings can be unreliable, mutational analysis of the SRD5A2 and AR genes should be considered the first-line tests for these patients.

  13. Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders

    OpenAIRE

    Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; Maeyer, J H; Stanghellini, V

    2012-01-01

    Summary Background The nonselective 5-HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) an...

  14. Interpersonal Stress Regulation and the Development of Anxiety Disorders: An Attachment-Based Developmental Framework

    Science.gov (United States)

    Nolte, Tobias; Guiney, Jo; Fonagy, Peter; Mayes, Linda C.; Luyten, Patrick

    2011-01-01

    Anxiety disorders represent a common but often debilitating form of psychopathology in both children and adults. While there is a growing understanding of the etiology and maintenance of these disorders across various research domains, only recently have integrative accounts been proposed. While classical attachment history has been a traditional core construct in psychological models of anxiety, contemporary attachment theory has the potential to integrate neurobiological and behavioral findings within a multidisciplinary developmental framework. The current paper proposes a modern attachment theory-based developmental model grounded in relevant literature from multiple disciplines including social neuroscience, genetics, neuroendocrinology, and the study of family factors involved in the development of anxiety disorders. Recent accounts of stress regulation have highlighted the interplay between stress, anxiety, and activation of the attachment system. This interplay directly affects the development of social–cognitive and mentalizing capacities that are acquired in the interpersonal context of early attachment relationships. Early attachment experiences are conceptualized as the key organizer of a complex interplay between genetic, environmental, and epigenetic contributions to the development of anxiety disorders – a multifactorial etiology resulting from dysfunctional co-regulation of fear and stress states. These risk-conferring processes are characterized by hyperactivation strategies in the face of anxiety. The cumulative allostatic load and subsequent “wear and tear” effects associated with hyperactivation strategies converge on the neural pathways of anxiety and stress. Attachment experiences further influence the development of anxiety as potential moderators of risk factors, differentially impacting on genetic vulnerability and relevant neurobiological pathways. Implications for further research and potential treatments are outlined. PMID

  15. Interpersonal stress regulation and the development of anxiety disorders: an attachment-based developmental framework

    Directory of Open Access Journals (Sweden)

    Tobias eNolte

    2011-09-01

    Full Text Available Anxiety disorders represent a common but often debilitating form of psychopathology in both children and adults. While there is a growing understanding of the aetiology and maintainance of these disorders across various research domains, only recently have integrative accounts been proposed. While classical attachment history has been a traditional core construct in psychological models of anxiety, contemporary attachment theory has the potential to integrate neurobiological and behavioral findings within a multidisciplinary developmental framework.The current paper proposes a modern attachment theory-based developmental model grounded in relevant literature from multiple disciplines including social neuroscience, genetics, neuroendocrinology, and the study of family factors involved in the development of anxiety disorders. Recent accounts of stress regulation have highlighted the interplay between stress, anxiety and activation of the attachment system. This interplay directly affects the development of social cognitive and mentalizing capacities that are acquired in the interpersonal context of early attachment relationships. Early attachment experiences are conceptualised as the key organiser of a complex interplay between genetic, environmental and epigentic contributions to the development of anxiety disorders – a multifactorial aetiology resulting from dysfunctional co-regulation of fear and stress states. These risk-conferring processes are characterised by hyperactivation strategies in the face of anxiety.In the model, the cumulative allostatic load and subsequent wear and tear effects associated with hyperactivation strategies converge on the neural pathways of anxiety and stress. Attachment experiences further influence the development of anxiety as potential moderators of risk factors, differentially impacting on genetic vulnerability and relevant neurobiological pathways. Implications for further research and potential treatments

  16. Development and validation of the Eating Disorder Diagnostic Scale: a brief self-report measure of anorexia, bulimia, and binge-eating disorder.

    Science.gov (United States)

    Stice, E; Telch, C F; Rizvi, S L

    2000-06-01

    This article describes the development and validation of a brief self-report scale for diagnosing anorexia nervosa, bulimia nervosa, and binge-eating disorder. Study 1 used a panel of eating-disorder experts and provided evidence for the content validity of this scale. Study 2 used data from female participants with and without eating disorders (N = 367) and suggested that the diagnoses from this scale possessed temporal reliability (mean kappa = .80) and criterion validity (with interview diagnoses; mean kappa = .83). In support of convergent validity, individuals with eating disorders identified by this scale showed elevations on validated measures of eating disturbances. The overall symptom composite also showed test-retest reliability (r = .87), internal consistency (mean alpha = .89), and convergent validity with extant eating-pathology scales. Results implied that this scale was reliable and valid in this investigation and that it may be useful for clinical and research applications.

  17. An Emerging Natural History in the Development, Mechanisms and Worldwide Prevalence of Major Mental Disorders.

    Science.gov (United States)

    Pediaditakis, Nicholas

    2016-01-01

    Conciliating recent findings from molecular genetics, evolutionary biology, and clinical observations together point to new understandings regarding the mechanism, development and the persistent worldwide prevalence of major mental disorders (MMDs), which should be considered the result of an evolutionary downside trade off. Temperamental/trait variability, by facilitating choices for individual and group responses, confers robustness flexibility and resilience crucial to success of our species. Extreme temperamental variants, originating evolutionarily from the asocial aspect of human nature, also constitute the premorbid personality of the disorders. The latter create vulnerable individuals out of whom some will develop MMDs but at much higher rate to that of the general population. Significantly, similar temperamental "lopsidedness" enables many of these vulnerable individuals, if intelligent, tenacious, and curious, to be creative and contribute to our survival while some may also develop MMDs. All have a common neural-developmental origin and share characteristics in their clinical expression and pharmacological responses also expressed as mixed syndromes or alternating ones over time. Over-pruning of synaptic neurons may be considered the trigger of such occurrences or conversely, the failure to prevent them in spite of it. The symptoms of the major mental disorders are made up of antithetical substitutes as an expression of a disturbed over-all synchronizing property of brain function for all higher faculties previously unconsidered in their modeling. The concomitant presence of psychosis is a generic common occurrence.

  18. 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.

  19. 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

  20. 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.

  1. Higher risk of developing major depression and bipolar disorder in later life among adolescents with asthma: a nationwide prospective study.

    Science.gov (United States)

    Chen, Mu-Hong; Su, Tung-Ping; Chen, Ying-Sheue; Hsu, Ju-Wei; Huang, Kai-Lin; Chang, Wen-Han; Chen, Tzeng-Ji; Bai, Ya-Mei

    2014-02-01

    Previous studies have suggested an immunological dysfunction in mood disorders, but rarely have investigated the temporal association between allergic diseases and mood disorders. Using the Taiwan National Health Insurance Research Database, we attempted to investigate the association between asthma in early adolescence and the risk of unipolar depression and bipolar disorder in later life. In all, 1453 adolescents with asthma aged between 10 and 15 years and 5812 age-/gender-matched controls were selected in 1998-2000. Subjects with unipolar depression and bipolar disorder that occurred up to the end of follow-up (December 31 2010) were identified. Adolescents with asthma had a higher incidence of major depression (2.8% vs. 1.1%, p bipolar disorder (1.0% vs. 0.3%, p adolescence was associated with an increased risk of developing major depression (hazard ratio [HR]: 1.81, 95% confidence interval [CI]: 1.14-2.89), any depressive disorder (HR: 1.74, 95% CI: 1.27-2.37), and bipolar disorder (HR: 2.27, 95% CI: 1.01-5.07), after adjusting for demographic data and comorbid allergic diseases. Adolescents with asthma had an elevated risk of developing mood disorders in later life. Further studies would be required to investigate the underlying mechanisms for this comorbid association and elucidate whether prompt intervention for asthma would decrease the risk of developing mood disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Supporting Intrapersonal Development in Substance Use Disorder Programs: A Conceptual Framework for Client Assessment.

    Science.gov (United States)

    Turpin, Aaron; Shier, Micheal L

    2017-01-01

    Improvements to intrapersonal development of clients involved with substance use disorder treatment programs has widely been recognized as contributing to the intended goal of reducing substance misuse behaviors. This study sought to identify a broad framework of primary outcomes related to the intrapersonal development of clients in treatment for substance misuse. Using qualitative research methods, individual interviews were conducted with program participants (n = 41) at three treatment programs to identify the ways in which respondents experienced intrapersonal development through participation in treatment. The findings support the development of a conceptual model that captures the importance and manifestation of achieving improvements in the following outcomes: self-awareness, coping ability, self-worth, outlook, and self-determination. The findings provide a conceptual framework for client assessment that captures a broad range of the important intrapersonal development factors utilized as indicators for client development and recovery that should be measured in tandem during assessment.

  3. Does stress mediate the development of substance use disorders among youth transitioning to young adulthood?

    Science.gov (United States)

    Cornelius, Jack; Kirisci, Levent; Reynolds, Maureen; Tarter, Ralph

    2014-05-01

    Stress is a well-documented factor in the development of addiction. However, no longitudinal studies to date have assessed the role of stress in mediating the development of substance use disorders (SUD). Our previous results have demonstrated that a measure called Transmissible Liability Index (TLI) assessed during pre-adolescent years serves as a significant predictor of risk for substance use disorder among young adults. However, it remains unclear whether life stress mediates the relationship between TLI and SUD, or whether stress predicts SUD. We conducted a longitudinal study involving 191 male subjects to assess whether life stress mediates the relationship between TLI as assessed at age 10-12 and subsequent development of SUD at age 22, after controlling for other relevant factors. Logistic regression demonstrated that the development of SUD at age 22 was associated with stress at age 19. A path analysis demonstrated that stress at age 19 significantly predicted SUD at age 22. However, stress did not mediate the relationship between the TLI assessed at age 10-12 and SUD in young adulthood. These findings confirm that stress plays a role in the development of SUD, but also shows that stress does not mediate the development of SUD. Further studies are warranted to clarify the role of stress in the etiology of SUD.

  4. Quality of life in 70 women with disorders of sex development

    DEFF Research Database (Denmark)

    Johannsen, Trine H.; Ripa, Caroline P.L.; Mortensen, Erik L.

    2006-01-01

    OBJECTIVE: The aim of this study was to assess the quality of life and psychosocial well-being in women with disorders of sex development (DSD). DESIGN: An open case-control study. METHODS: Social and psychiatric information was collected via a structured interview from 70 Danish women diagnosed ...... and more affective distress were observed especially in CAH patients and virilized 46,XX and 46,XY females. This may be caused by trauma from distressing diagnostic procedures, the chronic illnesses per se, and psychosocial consequences of the disorders.......OBJECTIVE: The aim of this study was to assess the quality of life and psychosocial well-being in women with disorders of sex development (DSD). DESIGN: An open case-control study. METHODS: Social and psychiatric information was collected via a structured interview from 70 Danish women diagnosed...... with DSD, 70 controls matched on sex, age, and school education, and six women with isolated genital malformations. Quality of life and mental distress were assessed by 'Quality of Life-Assessment of Growth Hormone Deficiency in Adults' (QoL-AGHDA) and three symptom scales from the 'Hopkins Symptom...

  5. Results from a pediatric surgical centre justify early intervention in disorders of sex development.

    Science.gov (United States)

    Crawford, Jennifer M; Warne, Garry; Grover, Sonia; Southwell, Bridget R; Hutson, John M

    2009-02-01

    Controversy persists surrounding early management of disorders of sex development. We assessed genital appearance, gender identity, and quality of life in prepubertal children who have had early surgical intervention. Children treated for disorders of sex development who were 5 to 10 years of age were eligible (n = 54). Children were scored (modified Creighton scale) for anatomical and cosmetic outcome, and both patients and parents completed PedsQL quality-of-life and gender identity questionnaires, with ethics approval. Of 54 patients, 41 presented for review. Treatment began at 13.2 (1.8-250.1) months (median; range) and were reviewed at 7.5 +/- 2.1 (mean +/- SD) years of age. Nineteen were raised as girls and 22 as boys. Girls had good (85%) or satisfactory (15%) anatomical/cosmetic outcome, whereas 52% boys had good, 38% satisfactory, and 10% poor cosmetic outcomes. On gender identity questionnaire, boys scored 3.9 +/- 0.4 (mean +/- SD) and girls 3.6 +/- 0.5; 1 of 19 boys and 3 of 19 girls had lower scores, suggesting risk of gender identity disorder. Quality-of-life scores were 80+ for physical and 65 to 80 for psychosocial scores. Early intervention is generally associated with positive outcomes for patients and parents. Girls had better anatomical outcomes than boys, and gender dysphoria risks were low in both sexes.

  6. Gender identity and gender role orientation in female assigned patients with disorders of sex development.

    Science.gov (United States)

    Mattila, Aino K; Fagerholm, Riitta; Santtila, Pekka; Miettinen, Päivi J; Taskinen, Seppo

    2012-11-01

    Gender identity and gender role orientation were assessed in 24 female assigned patients with disorders of sex development. A total of 16 patients were prenatally exposed to androgens, of whom 15 had congenital adrenal hyperplasia and 1 was virilized due to maternal tumor. Eight patients had 46,XY karyotype, of whom 5 had partial and 3 had complete androgen insensitivity syndrome. Gender identity was measured by the 27-item Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults with 167 female medical students as controls, and gender role was assessed by the femininity and masculinity subscales of the 30-item Bem Sex Role Inventory with 104 female and 64 male medical students as controls. No patient reached the cutoff for gender identity disorder on the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults. However, patients with 46,XY karyotype demonstrated a somewhat more conflicted gender identity, although the overall differences were relatively small. As to gender role orientation, patients with complete androgen insensitivity syndrome had high scores on the femininity and masculinity scales of the Bem Sex Role Inventory, which made them the most androgynous group. Our findings, although clinically not clear cut, suggest that patients with disorders of sex development are a heterogeneous group regarding gender identity and gender role outcomes, and that this issue should be discussed with the family when treatment plans are made. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  7. Determinants of the development of post-traumatic stress disorder, in the general population.

    Science.gov (United States)

    Perrin, Marc; Vandeleur, Caroline L; Castelao, Enrique; Rothen, Stéphane; Glaus, Jennifer; Vollenweider, Peter; Preisig, Martin

    2014-03-01

    To assess (1) the lifetime prevalence of exposure both to trauma and post-traumatic stress disorder (PTSD); (2) the risk of PTSD by type of trauma; and (3) the determinants of the development of PTSD in the community. The Diagnostic Interview for Genetic Studies was administered to a random sample of an urban area (N = 3,691). (1) The lifetime prevalence estimates of exposure to trauma and PTSD were 21.0 and 5.0%; respectively, with a twice as high prevalence of PTSD in women compared to men despite a similar likelihood of exposure in the two sexes; (2) Sexual abuse was the trauma involving the highest risk of PTSD; (3) The risk of PTSD was most strongly associated with sexual abuse followed by preexisting bipolar disorder, alcohol dependence, antisocial personality, childhood separation anxiety disorder, being victim of crime, witnessing violence, Neuroticism and Problem-focused coping strategies. After adjustment for these characteristics, female sex was no longer found to be significantly associated with the risk of PTSD. The risk for the development of PTSD after exposure to traumatic events is associated with several factors including the type of exposure, preexisting psychopathology, personality features and coping strategies which independently contribute to the vulnerability to PTSD.

  8. 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

  9. Anxiety Disorders in Typically Developing Youth: Autism Spectrum Symptoms as a Predictor of Cognitive-Behavioral Treatment

    Science.gov (United States)

    Puleo, Connor M.; Kendall, Philip C.

    2011-01-01

    Symptoms of autism spectrum disorder (ASD) were assessed (Social Responsiveness Scale-Parent (SRS-P); coded in-session behavior) in typically-developing, anxiety-disordered children (N = 50) treated with cognitive-behavioral therapy (CBT). "Study 1": children with moderate autistic symptomology (per SRS-P) were significantly more likely to improve…

  10. The Efficiency of Peer Teaching of Developing Non Verbal Communication to Children with Autism Spectrum Disorder (ASD)

    Science.gov (United States)

    Alshurman, Wael; Alsreaa, Ihsani

    2015-01-01

    This study aimed at identifying the efficiency of peer teaching of developing non-verbal communication to children with autism spectrum disorder (ASD). The study was carried out on a sample of (10) children with autism spectrum disorder (ASD), diagnosed according to basics and criteria adopted at Al-taif qualification center at (2013) in The…

  11. Development of an IOS App Using Situated Learning, Communities of Practice, and Augmented Reality for Autism Spectrum Disorder

    Science.gov (United States)

    Clarkson, Jessica

    2014-01-01

    This paper presents the development process and framework used to construct a transportation app that uses situated learning, augmented reality, and communities of practice. Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause social impairments as well as the limit the potential for the individual to achieve independence…

  12. Two males with SRY-positive 46,XX testicular disorder of sex development.

    Science.gov (United States)

    Gunes, Sezgin; Asci, Ramazan; Okten, Gülsen; Atac, Fatih; Onat, Onur E; Ogur, Gonul; Aydin, Oguz; Ozcelik, Tayfun; Bagci, Hasan

    2013-02-01

    The 46,XX testicular disorder of sex development (46,XX testicular DSD) is a rare phenotype associated with disorder of the sex chromosomes. We describe the clinical, molecular, and cytogenetic findings of a 16- and a 30-year-old male patient with sex-determining region Y (SRY)-positive 46,XX testicular DSD. Chromosomal analysis revealed 46,XX karyotype. Fluorescence in situ hybridization (FISH) showed the SRY region translocated to the short arm of the X chromosome. The presence of the SRY gene was also confirmed by polymerase chain reaction (PCR). The X chromosome inactivation (XCI) assay showed that both patients have a random pattern of X chromosome inactivation. This report compares the symptoms and features of the SRY-positive 46,XX testicular DSD patients.

  13. Increased Risk of Developing Affective Disorder in Patients with Hypothyroidism: A Register-Based Study

    DEFF Research Database (Denmark)

    Thomsen, Anders F.; Kvist, Tine Kajsa; Andersen, Per Kragh

    2005-01-01

    BACKGROUND: Links between thyroid function and depression have been noted in many contexts. We assessed whether hospitalization with hypothyroidism was a risk factor for developing affective disorder. METHODS: We conducted a prospective cohort study using historical data from Danish registers....... The observational period was 1977-1999. Three study cohorts were identified: all patients with a first hospital admittance with the resulting index discharge diagnoses hypothyroidism, osteoarthritis, or nontoxic goiter. A later hospitalization with a resulting discharge diagnosis of affective disorder was used...... as event of interest, and rates of readmission were estimated and compared using competing risk models in survival analyses. FINDINGS: We identified 165,307 patients discharged with an index diagnosis. In the observational period, 1041 events occurred. An index diagnosis of hypothyroidism was associated...

  14. Language development in rural and urban Russian-speaking children with and without developmental language disorder.

    Science.gov (United States)

    Kornilov, Sergey A; Lebedeva, Tatiana V; Zhukova, Marina A; Prikhoda, Natalia A; Korotaeva, Irina V; Koposov, Roman A; Hart, Lesley; Reich, Jodi; Grigorenko, Elena L

    2016-02-01

    Using a newly developed Assessment of the Development of Russian Language (ORRIA), we investigated differences in language development between rural vs. urban Russian-speaking children (n = 100 with a mean age of 6.75) subdivided into groups with and without developmental language disorders. Using classical test theory and item response theory approaches, we found that while ORRIA displayed overall satisfactory psychometric properties, several of its items showed differential item functioning favoring rural children, and several others favoring urban children. After the removal of these items, rural children significantly underperformed on ORRIA compared to urban children. The urbanization factor did not significantly interact with language group. We discuss the latter finding in the context of the multiple additive risk factors for language development and emphasize the need for future studies of the mechanisms that underlie these influences and the implications of these findings for our understanding of the etiological architecture of children's language development.

  15. Language development in rural and urban Russian-speaking children with and without developmental language disorder

    Science.gov (United States)

    Kornilov, Sergey A.; Lebedeva, Tatiana V.; Zhukova, Marina A.; Prikhoda, Natalia A.; Korotaeva, Irina V.; Koposov, Roman A.; Hart, Lesley; Reich, Jodi; Grigorenko, Elena L.

    2015-01-01

    Using a newly developed Assessment of the Development of Russian Language (ORRIA), we investigated differences in language development between rural vs. urban Russian-speaking children (n = 100 with a mean age of 6.75) subdivided into groups with and without developmental language disorders. Using classical test theory and item response theory approaches, we found that while ORRIA displayed overall satisfactory psychometric properties, several of its items showed differential item functioning favoring rural children, and several others favoring urban children. After the removal of these items, rural children significantly underperformed on ORRIA compared to urban children. The urbanization factor did not significantly interact with language group. We discuss the latter finding in the context of the multiple additive risk factors for language development and emphasize the need for future studies of the mechanisms that underlie these influences and the implications of these findings for our understanding of the etiological architecture of children's language development. PMID:27346924

  16. Causal effects on child language development: A review of studies in communication sciences and disorders.

    Science.gov (United States)

    Rogers, Clare R; Nulty, Karissa L; Betancourt, Mariana Aparicio; DeThorne, Laura S

    2015-01-01

    We reviewed recent studies published across key journals within the field of communication sciences and disorders (CSD) to survey what causal influences on child language development were being considered. Specifically, we reviewed a total of 2921 abstracts published within the following journals between 2003 and 2013: Language, Speech, and Hearing Services in Schools (LSHSS); American Journal of Speech-Language Pathology (AJSLP); Journal of Speech, Language, and Hearing Research (JSLHR); Journal of Communication Disorders (JCD); and the International Journal of Language and Communication Disorders (IJLCD). Of the 346 eligible articles that addressed causal factors on child language development across the five journals, 11% were categorized as Genetic (37/346), 83% (287/346) were categorized as Environmental, and 6% (22/346) were categorized as Mixed. The bulk of studies addressing environmental influences focused on therapist intervention (154/296=52%), family/caregiver linguistic input (65/296=22%), or family/caregiver qualities (39/296=13%). A more in-depth review of all eligible studies published in 2013 (n=34) revealed that family/caregiver qualities served as the most commonly controlled environmental factor (e.g., SES) and only 3 studies explicitly noted the possibility of gene-environment interplay. This review highlighted the need to expand the research base for the field of CSD to include a broader range of environmental influences on child language development (e.g., diet, toxin exposure, stress) and to consider more directly the complex and dynamic interplay between genetic and environmental effects. Readers will be able to highlight causal factors on child language development that have been studied over the past decade in CSD and recognize additional influences worthy of consideration. In addition, readers will become familiar with basic tenets of developmental systems theory, including the complex interplay between genetic and environmental factors

  17. Sex determination and disorders of sex development according to the revised nomenclature and classification in 46,XX individuals.

    Science.gov (United States)

    Kousta, Eleni; Papathanasiou, Asteroula; Skordis, Nicos

    2010-01-01

    There have been considerable advances concerning understanding of the early and later stages of ovarian development; a number of genes have been implicated and their mutations have been associated with developmental abnormalities. The most important genes controlling the initial phase of gonadal development, identical in females and males, are Wilms' tumor suppressor 1 (WT1) and steroidogenic factor 1 (SF1). Four genes are likely to be involved in the subsequent stages of ovarian development (WNT4, DAX1, FOXL2 and RSPO1), but none is yet proven to be the ovarian determining factor. Changes in nomenclature and classification were recently proposed in order to incorporate genetic advances and substitute gender-based diagnostic labels in terminology. The term "disorders of sex development" (DSD) is proposed to substitute the previous term "intersex disorders". Three main categories have been used to describe DSD in the 46,XX individual: 1) disorders of gonadal (ovarian) development: ovotesticular DSD, previously named true hermaphroditism, testicular DSD, previously named XX males, and gonadal dysgenesis; 2) disorders related to androgen excess (congenital adrenal hyperplasia, aromatase deficiency and P450 oxidoreductase deficiency); and 3) other rare disorders. In this mini-review, recent advances concerning development of the genital system in 46,XX individuals and related abnormalities are discussed. Basic embryology of the ovary and molecular pathways determining ovarian development are reviewed, focusing on mutations disrupting normal ovarian development. Disorders of sex development according to the revised nomenclature and classification in 46,XX individuals are summarized, including genetic progress in the field.

  18. Development of an integrated model of personality, personality disorders and severe axis I disorders, with special reference to major affective disorders.

    Science.gov (United States)

    von Zerssen, Detlev

    2002-04-01

    A unidimensional model of the relationships between normal temperament, psychopathic variants of it and the two main forms of so-called endogenous psychoses (major affective disorders and schizophrenia) was derived from Kretschmer's constitutional typology. It was, however, not confirmed by means of a biometric approach nor was Kretschmer's broad concept of cyclothymia as a correlate of physical stoutness on the one hand and major affective disorders on the other supported by empirical data. Yet the concept of the 'melancholic type' of personality of patients with severe unipolar major depression (melancholia) which resembles descriptions by psychoanalysts could be corroborated. This was also true for the 'manic type' of personality as a (premorbid) correlate of predominantly manic forms of a bipolar I disorder. As predicted from a spectrum concept of major affective disorders, the ratio of traits of either type co-varied with the ratio of the depressive and the manic components in the long-term course of such a disorder. The two types of premorbid personality and a rare variant of the 'manic type', named 'relaxed, easy-going type', were conceived as 'affective types' dominating in major affective disorders. They are opposed to three 'neurotoid types' prevailing in so-called neurotic disorders as well as in schizophrenic psychoses. The similarity among the types can be visualized as spatial relationships in a circular, i.e. a two-dimensional, model (circumplex). Personality disorders as maladapted extreme variants of personality are, by definition, located outside the circle, mainly along its 'neurotoid' side. However, due to their transitional nature, axis I disorders cannot be represented adequately within the plane which represents (adapted as well as maladapted) forms of habitual behaviour (personality types and disorders, respectively). To integrate them into the spatial model of similarity interrelations, a dimension of actual psychopathology has to be added

  19. "Tension" in South Asian women: developing a measure of common mental disorder using participatory methods.

    Science.gov (United States)

    Karasz, Alison; Patel, Viraj; Kabita, Mahbhooba; Shimu, Parvin

    2013-01-01

    Although common mental disorder (CMD) is highly prevalent among South Asian immigrant women, they rarely seek mental treatment. This may be owing in part to the lack of conceptual synchrony between medical models of mental disorder and the social models of distress common in South Asian communities. Furthermore, common mental health screening and diagnostic measures may not adequately capture distress in this group. Community-based participatory research (CBPR) is ideally suited to help address measurement issues in CMD as well as to develop culturally appropriate treatment models. To use participatory methods to identify an appropriate, culturally specific mental health syndrome and develop an instrument to measure this syndrome. We formed a partnership between researchers, clinicians, and community members. The partnership selected a culturally specific model of emotional distress/illness, "tension," as a focus for further study. Partners developed a scale to measure Tension and tested the new scale on 162 Bangladeshi immigrant women living in the Bronx. The 24-item "Tension Scale" had high internal consistency (α = 0.83). On bivariate analysis, the scale significantly correlated in the expected direction with depressed as measured by the Patient Health Questionnaire (PHQ-2), age, education, self-rated health, having seen a physician in the past year, and other variables. Using participatory techniques, we created a new measure designed to assess CMD in an isolated immigrant group. The new measure shows excellent psychometric properties and will be helpful in the implementation of a community-based, culturally synchronous intervention for depression. We describe a useful strategy for the rapid development and field testing of culturally appropriate measures of mental distress and disorder.

  20. Development and validation of a screening instrument for bipolar spectrum disorder: The Mood Disorder Questionnaire Thai version

    Directory of Open Access Journals (Sweden)

    Waleeprakhon P

    2014-08-01

    Full Text Available Punjaporn Waleeprakhon,1 Pichai Ittasakul,1 Manote Lotrakul,1 Pattarabhorn Wisajun,1 Sudawan Jullagate,1 Terence A Ketter2 1Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA Background: The Mood Disorder Questionnaire (MDQ has been translated to many languages and has been used in many countries as a screening instrument for bipolar disorder. The main objective of this study was to evaluate validity of the Thai version of the MDQ as a screening instrument for bipolar disorder in a psychiatric outpatient sample, and to determine its optimum question #1 item threshold value for bipolar disorder.Methods: The English language Mood Disorder Questionnaire (MDQ was translated into Thai. The process involved back-translation, cross-cultural adaptation, field testing of the prefinal version, as well as final adjustments. Two hundred and fifty major depressive disorder outpatients were further assessed by the Thai version of the MDQ and the Thai version of the Mini International Neuropsychiatric Interview (MINI. During the assessment, reliability and validity analyses, and receiver operating characteristic curve (ROC analysis were performed.Results: The Thai version of the MDQ screening had adequate internal consistency (Cronbach’s alpha =0.791, omega total =0.68, and omega hierarchical =0.69. The optimal question #1 item threshold value was at least five positive items, which yielded adequate sensitivity (76.5%, specificity (72.7%, positive predictive value (74.3%, and negative predictive value (75.0%. The ROC area under the curve (AUC for this study was 0.82 (95% confidence interval: 0.70 to 0.90.Conclusion: The Thai version of the MDQ had some useful psychometric properties for screening for bipolar disorder in a mood disorder clinic setting, with a recommended question #1 item

  1. Variation in bull beef quality due to ultimate muscle pH is correlated to endopeptidase and small heat shock protein levels.

    Science.gov (United States)

    Pulford, D J; Dobbie, P; Fraga Vazquez, S; Fraser-Smith, E; Frost, D A; Morris, C A

    2009-09-01

    This study set out to determine if ultimate pH (pH(u)) affected the performance of intracellular small heat shock protein and endopeptidase dynamics in muscle during beef ageing. Longissimus dorsi muscles from 39 Angus or Limousin×Angus bulls were examined to see if pH(u) achieved at 22h post mortem (rigor) affected tenderness and water holding capacity of beef. Samples were segregated into three pH(u) groups termed high (pH>6.3), intermediate (5.7pHpHpH(u) beef. More than 30% of bull beef did not achieve acceptable tenderness at 8 days post mortem with this ageing regime. No significant differences in calpain or cathepsin enzyme levels due to meat pH were observed until after 22h post mortem, but low pH(u) beef had elevated caspase 3/7 activity soon after slaughter. At 22h post mortem, greater levels of μ-calpain enzyme were found in the high and intermediate pH(u) beef and cathepsin B levels were superior in the low pH(u) beef after 2 days post mortem. Different rates of desmin and troponin T protein degradation were also observed in aged bull beef. Both proteins were degraded within 6h post mortem for high pH(u) beef, but took >3 days post mortem for intermediate pH(u) beef. High levels of alpha β-crystallin (aβC) at 22h post mortem coincided with delayed muscle protein degradation for low pH(u) beef. Our results support the hypothesis that aβC shields myofibrils and buffers against endopeptidase degradation of beef structure during ageing.

  2. Traditional games in interpersonal relationships development in students with behavioral disorders

    Directory of Open Access Journals (Sweden)

    Lauriesky Hernández-Oruña

    2014-04-01

    Full Text Available The educational alternative proposed is aimed at promoting the development of interpersonal relationships of students with behavioral disorders. The study stand fom different theoretical approaches that have allowed psychological and pedagogical support of the actions developed, highlighting the importance of traditional games in the integral formation of the students. For the altrnative design it was started with a diagnosis in which identified problems that these are in this particular subject using different research methods. The results allowed the development of alternative that is suggested, thus responding to the problem identified. This work is based on Cuban traditional games that favor the development of appropriate interpersonal relationships with emphasis on the interaction among the pupils in Special School Hermanos Saiz from Pinar del Rio municipality.

  3. The psychological development of panic disorder: implications for neurobiology and treatment.

    Science.gov (United States)

    Cosci, Fiammetta

    2012-06-01

    The aim of this study was to survey the available literature on psychological development of panic disorder with or without agoraphobia [PD(A)] and its relationship with the neurobiology and the treatment of panic. Both a computerized (PubMed) and a manual search of the literature were performed. Only English papers published in peer-reviewed journals and referring to PD(A) as defined by the diagnostic classifications of the American Psychiatric Association or of the World Health Organization were included. A staging model of panic exists and is applicable in clinical practice. In a substantial proportion of patients with PD(A), a prodromal phase and, despite successful treatment, residual symptoms can be identified. Both prodromes and residual symptoms allow the monitoring of disorder evolution during recovery via the rollback phenomenon. The different stages of the disorder, as well as the steps of the rollback, have a correspondence in the neurobiology and in the treatment of panic. However, the treatment implications of the longitudinal model of PD(A) are not endorsed, and adequate interventions of enduring effects are missing.

  4. The potential impact of cannabis legalization on the development of cannabis use disorders.

    Science.gov (United States)

    Budney, Alan J; Borodovsky, Jacob T

    2017-11-01

    Specific provisions of legal cannabis legislation and regulation could influence cannabis initiation, frequency and quantity of use, and progression to cannabis use disorder. This brief essay highlights scientifically based principles and risk factors that underlie substance use and addiction that can be leveraged to inform policies that might mitigate the development and consequences of cannabis use disorder. Specifically, pharmacologic, access/availability, and environmental factors are discussed in relation to their influence on substance use disorders to illustrate how regulatory provisions can differentially affect these factors and risk for addiction. Relevant knowledge from research and experience with alcohol and tobacco regulation are also considered. Research designed to inform regulatory policy and to evaluate the impact of cannabis legislation on cannabis use and problems is progressing. However, definitive findings will come slowly, and more concerted efforts and resources are needed to expedite this process. In the meantime, policymakers should take advantage of the large body of scientific literature on substance use to foster empirically-guided, common sense approaches to cannabis policy that focus on prevention of addiction. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Mediating and Moderating Role of Depression, Conduct Disorder or Attention-Deficit/Hyperactivity Disorder in Developing Adolescent Substance Use Disorders: A Population-Based Study.

    Directory of Open Access Journals (Sweden)

    Kouichi Yoshimasu

    Full Text Available To evaluate the mediating/moderating effects of common internalizing /externalizing disorders on the association between ADHD and adolescent substance use disorders (SUD in a population-based birth cohort.Among 5718 children in the birth cohort, 343 ADHD incident cases and 712 matched controls were identified. Psychiatric diagnoses prior to age 19 were classified into DSM-IV categories. The association between ADHD and SUD was summarized (hazard ratios (HR, 95% CI. The effect of depression, CD/ODD, anxiety was evaluated separately.Assessment of the joint effects of ADHD and each psychiatric disorder did not support a moderating effect of these disorders on SUD on additive scale. However, the association between ADHD and SUD was partially explained by a mediating role of these psychiatric disorders.For clinicians our results emphasize that depression (or CD/ODD confers greater risk for SUD than ADHD alone. Early detection/treatment of SUD among adolescents with depression (or CD/ODD is crucial regardless of ADHD.

  6. Mediating and Moderating Role of Depression, Conduct Disorder or Attention-Deficit/Hyperactivity Disorder in Developing Adolescent Substance Use Disorders: A Population-Based Study.

    Science.gov (United States)

    Yoshimasu, Kouichi; Barbaresi, William J; Colligan, Robert C; Voigt, Robert G; Weaver, Amy L; Katusic, Slavica K

    2016-01-01

    To evaluate the mediating/moderating effects of common internalizing /externalizing disorders on the association between ADHD and adolescent substance use disorders (SUD) in a population-based birth cohort. Among 5718 children in the birth cohort, 343 ADHD incident cases and 712 matched controls were identified. Psychiatric diagnoses prior to age 19 were classified into DSM-IV categories. The association between ADHD and SUD was summarized (hazard ratios (HR), 95% CI). The effect of depression, CD/ODD, anxiety was evaluated separately. Assessment of the joint effects of ADHD and each psychiatric disorder did not support a moderating effect of these disorders on SUD on additive scale. However, the association between ADHD and SUD was partially explained by a mediating role of these psychiatric disorders. For clinicians our results emphasize that depression (or CD/ODD) confers greater risk for SUD than ADHD alone. Early detection/treatment of SUD among adolescents with depression (or CD/ODD) is crucial regardless of ADHD.

  7. The role of cytokines in development of hematological and immune disorders at radiation therapy for uterine body cancer

    International Nuclear Information System (INIS)

    Sorochan, P.P.; Prokhach, N.E.; Gromakova, Yi.A.; Krugova, Yi.M.; Sukhyin, V.S.

    2013-01-01

    The changes in hematological and immune parameters in patients with uterine body cancer were analyzed by the stages of the combined treatment. The rol of cytokines in the development of hematologic and immune disorders was assessed

  8. [Correction of psychophysical development of preschool children 3-4 year old with movement disorders by means of Bobath therapy

    OpenAIRE

    Bukhovets, B.O.

    2016-01-01

    This study deals with the definition of efficiency application means Bobath therapy as main correction psychophysical development method of preschool age 3 -4 years children, who have movement disorders.

  9. Extreme weather events in developing countries and related injuries and mental health disorders - a systematic review

    Directory of Open Access Journals (Sweden)

    Elisabeth Rataj

    2016-09-01

    Full Text Available Abstract Background Due to climate change, extreme weather events have an incremental impact on human health. Injuries and mental health disorders are a particular burden of disease, which is broadly investigated in high income countries. Most distressed populations are, however, those in developing countries. Therefore, this study investigates mental and physical health impacts arising from extreme weather events in these populations. Method Post-traumatic Stress Disorder (PTSD, injury [primary outcomes], anxiety and depressive disorders [secondary outcomes], caused by weather extremes were systematically analyzed in people of developing countries. A systematic review of observational studies was conducted searching six databases, complemented by hand search, and utilizing two search engines. Review processing was done independently by two reviewers. Prevalence rates were analyzed in a pre/post design; an additional semi-structured search was conducted, to provide reference data for studies not incorporating reference values. Results All 17 identified studies (70,842 individuals indicate a disease increase, compared to the reference data. Increase ranges from 0.7–52.6 % for PTSD, and from 0.3–37.3 % for injury. No studies on droughts and heatwaves were identified. All studies were conducted in South America and Asia. Conclusion There is an increased burden of psychological diseases and injury. This finding needs to be incorporated into activities of prevention, preparedness and general health care of those developing countries increasingly experiencing extreme weather events. There is also a gap in research in Africa (in quantity and quality of studies in this field and a predominant heterogeneity of health assessment tools. PROSPERO registration no.: CRD42014009109

  10. Annual Research Review: Infant Development, Autism, and ADHD--Early Pathways to Emerging Disorders

    Science.gov (United States)

    Johnson, Mark H.; Gliga, Teodora; Jones, Emily; Charman, Tony

    2015-01-01

    Background: Autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) are two of the most common neurodevelopmental disorders, with a high degree of co-occurrence. Methods: Prospective longitudinal studies of infants who later meet criteria for ASD or ADHD offer the opportunity to determine whether the two disorders share…

  11. Autistic disorder : Current psychopharmacological treatments and areas of interest for future developments

    NARCIS (Netherlands)

    Nikolov, R; Jonker, Jacob Jan; Scahill, L

    Autistic disorder and the group of related conditions defined as pervasive developmental disorders are chronic neurodevelopmental disorders starting in early childhood and affecting a significant number of children and families. Although the causes and much of the pathophysiology of the disorder

  12. Development of cortical thickness and surface area in autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Vincent T. Mensen

    2017-01-01

    Full Text Available Autism spectrum disorder (ASD is a neurodevelopmental disorder often associated with changes in cortical volume. The constituents of cortical volume – cortical thickness and surface area – have separable developmental trajectories and are related to different neurobiological processes. However, little is known about the developmental trajectories of cortical thickness and surface area in ASD. In this magnetic resonance imaging (MRI study, we used an accelerated longitudinal design to investigate the cortical development in 90 individuals with ASD and 90 typically developing controls, aged 9 to 20 years. We quantified cortical measures using the FreeSurfer software package, and then used linear mixed model analyses to estimate the developmental trajectories for each cortical measure. Our primary finding was that the development of surface area follows a linear trajectory in ASD that differs from typically developing controls. In typical development, we found a decline in cortical surface area between the ages of 9 and 20 that was absent in ASD. We found this pattern in all regions where developmental trajectories for surface area differed between groups. When we applied a more stringent correction that takes the interdependency of measures into account, this effect on cortical surface area retained significance for left banks of superior temporal sulcus, postcentral area, and right supramarginal area. These areas have previously been implicated in ASD and are involved in the interpretation and processing of audiovisual social stimuli and distinction between self and others. Although some differences in cortical volume and thickness were found, none survived the more stringent correction for multiple testing. This study underscores the importance of distinguishing between cortical surface area and thickness in investigating cortical development, and suggests the development of cortical surface area is of importance to ASD.

  13. Overwork-related disorders in Japan: recent trends and development of a national policy to promote preventive measures.

    Science.gov (United States)

    Yamauchi, Takashi; Yoshikawa, Toru; Takamoto, Masahiro; Sasaki, Takeshi; Matsumoto, Shun; Kayashima, Kotaro; Takeshima, Tadashi; Takahashi, Masaya

    2017-06-08

    Overwork-related disorders, such as cerebrovascular/cardiovascular diseases (CCVD) and mental disorders due to overwork, are a major occupational and public health issue worldwide, particularly in East Asian countries. This report discusses the recent trend of overwork-related disorders in Japan from the perspective of workers' compensated occupational diseases, as well as the development of a national policy for preventive measures against overwork-related disorders in Japan. Recently, the number of claimed and compensated cases of occupational mental disorders has increased substantially, particularly among young workers, as compared to those of occupational CCVD. In response to these situations and action from society, the Japanese Government passed the "Act on Promotion of Preventive Measures against Karoshi and Other Overwork-Related Health Disorders" in June 2014 to develop a national initiative towards the prevention of overwork-related disorders. Changes in the trend of overwork-related disorders in Japan under a legal foundation and an initiative by the central government should be closely monitored so that other countries can benefit from the experiences.

  14. [Development of vibration-induced intrahepatic cholestasis in pilots and new ways of correcting these disorders].

    Science.gov (United States)

    Preobrazhenskiĭ, V N; Vasilenko, V V; Taianovskiĭ, V Iu

    1999-01-01

    Data of analysis of the role of vibration in the development of hepatobiliary pathology in helicopter pilots are reported. Vibration was found to drastically deteriorate colloid-osmotic qualities of the bile and increase the lithogenesis risk. Exposure to vibration over 10 and more years of the flying career may instigate cholelithiasis. Dynamic USI with functional testing for early diagnostics and correction with ursodeoxycholic acid (ursosan) of disorders in the colloid-osmotic properties of the bile and can be proposed as one of the methods to prevent cholelithiasis.

  15. [Role of the family in the development of borderline personality disorder].

    Science.gov (United States)

    Gagnon, P

    1993-11-01

    The role of family in the development of borderline personality disorder is examined with an emphasis on dimensions of family functioning. A synthesis of theoretical concepts implicating such factors, derived mostly from psychoanalysis, is proposed with an emphasis on separation-individuation, early frustrations, regression to recognition memory, oscillations in attachment and social influences. Empirical studies are reviewed. Affective neglect and parental overprotection are often cited, although dysfunctional behaviour control may have a regulatory effect on these factors and a crucial impact on psychic reality of the patient recalling his childhood.

  16. Developing a User-Centred Planning Tool for Young Adults with Development Disorders: A Research-Based Teaching Project.

    Science.gov (United States)

    Ribu, Kirsten; Patel, Tulpesh

    2016-01-01

    People with development disorders, for instance autism, need structured plans to help create predictability in their daily lives. Digital plans can facilitate enhanced independency, learning, and quality of life, but existing apps are largely general purpose and lack the flexibility required by this specific but heterogeneous user group. Universal design is both a goal and a process and should be based on a holistic approach and user-centered design, interacting with the users in all stages of the development process. At Oslo and Akershus University College (HiOA) we conducted a research-based teaching project in co-operation with the Department of Neuro-habilitation at Oslo University Hospital (OUS) with two employees acting as project managers and students as developers. Three groups of Computer Science bachelor students developed digital prototypes for a planning tool for young adults with pervasive development disorders, who live either with their families or in supervised residences, and do not receive extensive public services. The students conducted the initial planning phase of the software development process, focusing on prototyping the system requirements, whilst a professional software company programmed the end solution. The goal of the project was to develop flexible and adaptive user-oriented and user-specific app solutions for tablets that can aid this diverse user group in structuring daily life, whereby, for example, photos of objects and places known to the individual user replace general pictures or drawings, and checklists can be elaborate or sparse as necessary. The three student groups worked independently of each other and created interactive working prototypes based on tests, observations and short interviews with end users (both administrators and residents) and regular user feedback from the project managers. Three very different solutions were developed that were of high enough quality that an external software company were able to

  17. Amygdalar, hippocampal, and thalamic volumes in youth at high risk for development of bipolar disorder.

    Science.gov (United States)

    Karchemskiy, Asya; Garrett, Amy; Howe, Meghan; Adleman, Nancy; Simeonova, Diana I; Alegria, Dylan; Reiss, Allan; Chang, Kiki

    2011-12-30

    Children of parents with bipolar disorder (BD), especially those with attention deficit hyperactivity disorder (ADHD) and symptoms of depression or mania, are at significantly high risk for developing BD. As we have previously shown amygdalar reductions in pediatric BD, the current study examined amygdalar volumes in offspring of parents (BD offspring) who have not yet developed a full manic episode. Youth participating in the study included 22 BD offspring and 22 healthy controls of comparable age, gender, handedness, and IQ. Subjects had no history of a manic episode, but met criteria for ADHD and moderate mood symptoms. MRI was performed on a 3T GE scanner, using a 3D volumetric spoiled gradient echo series. Amygdalae were manually traced using BrainImage Java software on positionally normalized brain stacks. Bipolar offspring had similar amygdalar volumes compared to the control group. Exploratory analyses yielded no differences in hippocampal or thalamic volumes. Bipolar offspring do not show decreased amygdalar volume, possibly because these abnormalities occur after more prolonged illness rather than as a preexisting risk factor. Longitudinal studies are needed to determine whether amygdalar volumes change during and after the development of BD. 2011 Elsevier Ireland Ltd. All rights reserved.

  18. The development of an attachment-based treatment program for borderline personality disorder.

    Science.gov (United States)

    Bateman, Anthony W; Fonagy, Peter

    2003-01-01

    The treatment of borderline personality disorder (BPD) remains controversial. The authors have developed an evidence-based treatment program rooted in attachment theory that integrates research on constitutional factors with environmental influences. BPD is conceived of as a disorder in the self-structure brought about through environmentally induced distortion of psychological functioning, which decouples key mental processes necessary for interpersonal and social function. The primary mental function involved is mentalization, which is enfeebled by an absence of contingent and marked mirroring during development. Treatment strategies target mentalization in order to foster the development of stable internal representations, to aid the formation of a coherent sense of self, and to enable to borderline patient to form more secure relationships in which motivations of self and other are better understood. Destabilization of the self leads to emotional volatility, so treatment also needs to focus on identification and appropriate expression of affect. This article describes some of the techniques used to enhance mentalization within the context of group and individual psychotherapy. Targeting of current symptomatology and behavior is insufficient. Therapists need to retain their own ability to mentalize, maintain mental closeness, focus on current mental states, and avoid excessive use of conflict interpretation and metaphor while paying careful attention to the use of transference and countertransference.

  19. Inflammation reduces physiological tissue tolerance in the development of work-related musculoskeletal disorders.

    Science.gov (United States)

    Barr, Ann E; Barbe, Mary F

    2004-02-01

    Work-related musculoskeletal disorders (MSDs) cause substantial worker discomfort, disability and loss of productivity. Due to the difficulty in analyzing the tissues of patients in the early stages of work-related MSD, there is controversy concerning the pathomechanisms of the development of these disorders. The pathophysiology of work-related MSD can be studied more easily in animal models. The purpose of this review is to relate theories of the development of tissue injury due to repeated motion to findings of recent investigations in animals that address the role of the inflammatory response in propagating tissue injury and contributing to chronic or recurring tissue injury. These tissue effects are related to behavioral indicators of discomfort and movement dysfunction with the aim of clarifying key time points for specific intervention approaches. The results from animal models of MSD are discussed in the light of findings in patients, whose tissues are examined at a much later phase of MSD development. Finally, a conceptual model of the potentially negative impact of inflammation on tissue tolerance is proposed along with suggestions for future research directions.

  20. Negative emotional reactivity as a marker of vulnerability in the development of borderline personality disorder symptoms.

    Science.gov (United States)

    Stepp, Stephanie D; Scott, Lori N; Jones, Neil P; Whalen, Diana J; Hipwell, Alison E

    2016-02-01

    Negative emotionality is a distinguishing feature of borderline personality disorder (BPD). However, this person-level characteristic has not been examined as a marker of vulnerability in the development of this disorder. The current study utilized a multimethod approach to examine the interplay between negative emotional reactivity and cumulative exposure to family adversity on the development of BPD symptoms across 3 years (ages 16-18) in a diverse, at-risk sample of adolescent girls (N = 113). A latent variable of negative emotional reactivity was created from multiple assessments at age 16: self-report, emotion ratings to stressors from ecological assessments across 1 week, and observer-rated negative affectivity during a mother-daughter conflict discussion task. Exposure to family adversity was measured cumulatively between ages 5 and 16 from annual assessments of family poverty, single parent household, and difficult life circumstances. The results from latent growth curve models demonstrated a significant interaction between negative emotional reactivity and family adversity, such that exposure to adversity strengthened the association between negative emotional reactivity and BPD symptoms. In addition, family adversity predicted increasing BPD symptoms during late adolescence. These findings highlight negative emotional reactivity as a marker of vulnerability that ultimately increases risk for the development of BPD symptoms.

  1. Negative emotional reactivity as a marker of vulnerability in the development of borderline personality disorder symptoms

    Science.gov (United States)

    Stepp, Stephanie D.; Scott, Lori N.; Jones, Neil P.; Whalen, Diana J.; Hipwell, Alison E.

    2015-01-01

    Negative emotionality is a distinguishing feature of borderline personality disorder (BPD). However, this person-level characteristic has not been examined as a marker of vulnerability in the development of this disorder. The current study utilized a multi-method approach to examine the interplay between negative emotional reactivity and cumulative exposure to family adversity on the development of BPD symptoms across three years (ages 16–18) in a diverse, at-risk sample of adolescent girls (N=113). A latent variable of negative emotional reactivity was created from multiple assessments at age 16: (1) self-report, (2) emotion ratings to stressors from ecological assessments across one week, and (3) observer-rated negative affectivity during a mother-daughter conflict discussion task. Exposure to family adversity was measured cumulatively between ages 5 and 16 from annual assessments of family poverty, single parent household, and difficult life circumstances. Results from latent growth curve models demonstrated a significant interaction between negative emotional reactivity and family adversity, such that exposure to adversity strengthened the association between negative emotional reactivity and BPD symptoms. Additionally, family adversity predicted increasing BPD symptoms during late adolescence. These findings highlight negative emotional reactivity as a marker of vulnerability that ultimately increases risk for the development of BPD symptoms. PMID:25925083

  2. Heterogeneity in development of aspects of working memory predicts longitudinal attention deficit hyperactivity disorder symptom change.

    Science.gov (United States)

    Karalunas, Sarah L; Gustafsson, Hanna C; Dieckmann, Nathan F; Tipsord, Jessica; Mitchell, Suzanne H; Nigg, Joel T

    2017-08-01

    The role of cognitive mechanisms in the clinical course of neurodevelopmental disorders is poorly understood. Attention Deficit Hyperactivity Disorder (ADHD) is emblematic in that numerous alterations in cognitive development are apparent, yet how they relate to changes in symptom expression with age is unclear. To resolve the role of cognitive mechanisms in ADHD, a developmental perspective that takes into account expected within-group heterogeneity is needed. The current study uses an accelerated longitudinal design and latent trajectory growth mixture models in a sample of children ages 7-13 years carefully characterized as with (n = 437) and without (n = 297) ADHD to (a) identify heterogeneous developmental trajectories for response inhibition, visual spatial working memory maintenance, and delayed reward discounting and (b) to assess the relationships between these cognitive trajectories and ADHD symptom change. Best-fitting models indicated multiple trajectory classes in both the ADHD and typically developing samples, as well as distinct relationships between each cognitive process and ADHD symptom change. Developmental change in response inhibition and delayed reward discounting were unrelated to ADHD symptom change, while individual differences in the rate of visual spatial working memory maintenance improvement predicted symptom remission in ADHD. Characterizing heterogeneity in cognitive development will be crucial for clarifying mechanisms of symptom persistence and recovery. Results here suggest working memory maintenance may be uniquely related to ADHD symptom improvement. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  3. The Risk of Offspring Developing Substance Use Disorders when Exposed to One versus Two Parent(s) with Alcohol Use Disorder

    DEFF Research Database (Denmark)

    Mellentin, Angelina Isabella; Brink, Maria; Andersen, Lene

    2016-01-01

    with AUD was linked to a 2.29-fold increased risk (95% CI, 1.64 – 3.20). No significant differences were found in relation to either parental or offspring gender. Conclusions: Exposure to parental AUD is linked to an increased risk of offspring developing SUD. This risk is additive for offspring exposed......Aim: Few population-based, family studies have examined associations between exposure to one vs. two parent(s) with alcohol use disorder (AUD) and the risk of offspring developing substance use disorder (SUD). Moreover, these studies have focused solely on the development of AUD, and not SUD......, in offspring. The purpose of this study was to investigate whether exposure to one vs. two parent(s) with AUD increases the risk of offspring developing SUD. Methods: A population-based, cohort study was conducted in which offspring born in Denmark between 1983 and 1989 were followed through national...

  4. Cephalic Disorders

    Science.gov (United States)

    ... destructive lesions, but are sometimes the result of abnormal development. The disorder can occur before or after birth. Porencephaly most ... decade of life. SCHIZENCEPHALY is a rare developmental disorder characterized by abnormal slits, or clefts, in the cerebral hemispheres. Schizencephaly ...

  5. Developing and Testing Twelve-Step Facilitation for Adolescents with Substance Use Disorder: Manual Development and Preliminary Outcomes

    Directory of Open Access Journals (Sweden)

    John F. Kelly

    2016-01-01

    Full Text Available Adolescent substance use disorder treatment programs are often based on the 12-step philosophy of Alcoholics Anonymous and/or link adolescents to these free resources. Despite this, no studies have developed and rigorously tested a twelve-step facilitation (TSF intervention for young people, leaving a significant evidence gap. This study describes the first systematic development of an outpatient adolescent TSF treatment. An integrated twelve-step facilitation (iTSF treatment incorporated TSF, motivational enhancement therapy, and cognitive behavioral therapy elements and was developed in an iterative manner with weekly feedback provided by 36 adolescents ( M age 17 years [SD = 1.4]; 52.8% white with DSM-IV substance use disorder recruited from the community. Assessments were conducted at baseline and at three and six months. Participants completed 6 of 10 sessions on average (8 participants completed all 10. Notable treatment developments were the inclusion of “in-services” led by Marijuana Anonymous members, including parents in a portion of individual sessions to provide a rationale for TSF, and use of a Socratic therapeutic interaction style. Acceptability and feasibility of the treatment were excellent (treatment satisfaction was 4.29 [SD = 0.59] out of 5. In keeping with TSF theory, the intervention substantially increased 12-step participation, and greater participation related to greater abstinence. iTSF is a replicable manualized treatment that can be implemented and tested in outpatient settings. Given the widespread compatibility of iTSF with the current adolescent treatment, if found efficacious, iTSF could be relatively easily adopted, implemented, and sustained and could provide an evidence-based option that could undergird current practice.

  6. Mechanisms of developing post-traumatic stress disorder: new targets for drug development and other potential interventions.

    Science.gov (United States)

    Wimalawansa, Sunil J

    2014-01-01

    The post-traumatic stress disorder (PTSD) is defined as a severe anxiety disorder that develops after exposure to an event with actual, threatened, or perceived death or serious injury, or a threat to the physical integrity of oneself or others that results in significant psychological trauma. Moreover, the ability of people to handle acute severe stress experiences varies among individuals. Depending on the underlying personality and resiliency, therefore, PTSD can occur in individuals exposed to exceedingly stressful incidences or those who have encountered seemingly less overwhelming stressors. In addition to severe stressful exposure, multiple other factors including genetic susceptibility; past experiences; cultural, spiritual, and personal beliefs; bullying and harassments; and lack of support at the workplace, social, and home environement may contribute to the development of PTSD. Author investigated multiple potential mechanisms for the development and sustenance of PTSD based on the recent literature and his own experiences and insight. Based on this search, author indicates that among other pathological and biochemical abnormalities, hormonal aberrations are most likely key mechanisms initiating and the maintenance of the PTSD. These pathophysiological neuro-hormonal changes instigate maladaptive learning processes caused by sustained high levels of anxiety and fear, through a hypo-responsive hypothalamic-pituitary axis and hyper-responsive catecholamine system (persistently elevated blood norepinephrine levels and lower than appropriate glucocorticoid levels). In addition to having inappropriately low serum cortisol levels and high epinephrine and norepinephrine levels, patients with PTSD also have mitochondrial dysfunctions and other hormonal abnormalities. Based on these data, author concluded that these pathological, biochemical and sustained neurohormonal abnormalities are likely to influence the structural brain changes, particularly in the

  7. The Development of Coordinated Communication in Infants at Heightened Risk for Autism Spectrum Disorder

    Science.gov (United States)

    Parladé, Meaghan V.; Iverson, Jana M.

    2015-01-01

    This study evaluated the extent to which developmental change in coordination of social communication in early infancy differentiates children eventually diagnosed with ASD from those not likely to develop the disorder. A prospective longitudinal design was used to compare 9 infants at heightened risk for ASD (HR) later diagnosed with ASD, to 13 HR infants with language delay, 28 HR infants with no diagnosis, and 30 low risk infants. Hierarchical Linear Modeling (HLM) analyses revealed that ASD infants exhibited significantly slower growth in coordinations overall and in gestures coordinated with vocalizations, even relative to HR infants with language delay. Disruption in the development of gesture-vocalization coordinations may result in negative cascading effects that negatively impact later social and linguistic development. PMID:25689930

  8. Verbal Problem-Solving Difficulties in Autism Spectrum Disorders and Atypical Language Development

    Science.gov (United States)

    Alderson-Day, Ben

    2018-01-01

    Children with autism spectrum disorders (ASDs) adopt less efficient strategies than typically developing (TD) peers on the Twenty Questions Task (TQT), a measure of verbal problem-solving skills. Although problems with the TQT are typically associated with executive dysfunction, they have also been reported in children who are deaf, suggesting a role for atypical language development. To test the contribution of language history to ASD problem solving, TQT performance was compared in children with high-functioning autism (HFA), children with Asperger syndrome (AS) and TD children. The HFA group used significantly less efficient strategies than both AS and TD children. No group differences were evident on tests of question understanding, planning or verbal fluency. Potential explanations for differences in verbal problem-solving skill are discussed with reference to the development of inner speech and use of visual strategies in ASD. PMID:25346354

  9. Review of foreign approaches to development of communication in children with autistic spectrum disorders

    Directory of Open Access Journals (Sweden)

    Soldatenkova E.N.

    2015-03-01

    Full Text Available The article presents a generalized overview of international approaches to the evaluation and formation of communication in children with autism spectrum disor ders (ASD. Described radicals communication disorders in children with ASD. Analyzed foreign approaches (Communication system for the exchange of images (PECS Lori Frost and Andrew Bondy; options piktogramme6ideogrammic communication (bliss6symbolism, Loeb system, a system of sign language; Program in Applied verbal behavior; a Method of facilitating communication (FC and others used for the development of communication in children with ASD and donditions underlying these approaches. Examined differences in focus for the development of communication in children with ASD in domestic and foreign schools. The main conditions for the development of communication in children with ASD described in the framework of cultural historical psychology and activity approach, ensuring the inclusion of children with ASD in education.

  10. Psychological aspects of the treatment of patients with disorders of sex development.

    Science.gov (United States)

    Sandberg, David E; Gardner, Melissa; Cohen-Kettenis, Peggy T

    2012-10-01

    Research on the psychological development of persons with Disorders of Sex Development (DSD) has focused on understanding the influence of atypical sex hormone exposure during steroid-sensitive periods of prenatal brain development on the process of psychosexual differentiation (i.e., gender identity, gender role, and sexual orientation). In contrast, analysis of clinical management strategies has focused on gender assignment and the desirability and timing of genital surgery. This review focuses on the psychological issues that confront clinicians managing the care of persons born with DSD and their families. Particular attention is paid to processes and factors that potentially mediate or moderate psychosocial and psychosexual outcomes within and across developmental stages. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  11. Psychological Aspects of the Treatment of Patients with Disorders of Sex Development

    Science.gov (United States)

    Sandberg, David E.; Gardner, Melissa; Cohen-Kettenis, Peggy T.

    2013-01-01

    Research on the psychological development of persons with Disorders of Sex Development (DSD) has focused on understanding the influence of atypical sex hormone exposure during steroid-sensitive periods of prenatal brain development on the process of psychosexual differentiation (i.e., gender identity, gender role, and sexual orientation). In contrast, analysis of clinical management strategies has focused on gender assignment and the desirability and timing of genital surgery. This review focuses on the psychological issues that confront clinicians managing the care of persons born with DSD and their families. Particular attention is paid to processes and factors that potentially mediate or moderate psychosocial and psychosexual outcomes within and across developmental stages. PMID:23044882

  12. Verbal problem-solving difficulties in autism spectrum disorders and atypical language development.

    Science.gov (United States)

    Alderson-Day, Ben

    2014-12-01

    Children with autism spectrum disorders (ASDs) adopt less efficient strategies than typically developing (TD) peers on the Twenty Questions Task (TQT), a measure of verbal problem-solving skills. Although problems with the TQT are typically associated with executive dysfunction, they have also been reported in children who are deaf, suggesting a role for atypical language development. To test the contribution of language history to ASD problem solving, TQT performance was compared in children with high-functioning autism (HFA), children with Asperger syndrome (AS) and TD children. The HFA group used significantly less efficient strategies than both AS and TD children. No group differences were evident on tests of question understanding, planning or verbal fluency. Potential explanations for differences in verbal problem-solving skill are discussed with reference to the development of inner speech and use of visual strategies in ASD. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.

  13. Trait Impulsivity and Anhedonia: Two Gateways for the Development of Impulse Control Disorders in Parkinson's Disease?

    Science.gov (United States)

    Houeto, Jean-Luc; Magnard, Robin; Dalley, Jeffrey W; Belin, David; Carnicella, Sebastien

    2016-01-01

    Apathy and impulsivity are two major comorbid syndromes of Parkinson's disease (PD) that may represent two extremes of a behavioral spectrum modulated by dopamine-dependent processes. PD is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta to which are attributed the cardinal motor symptoms of the disorder. Dopamine replacement therapy (DRT), used widely to treat these motor symptoms, is often associated with deficits in hedonic processing and motivation, including apathy and depression, as well as impulse control disorders (ICDs). ICDs comprise pathological gambling, hypersexuality, compulsive shopping, binge eating, compulsive overuse of dopaminergic medication, and punding. More frequently observed in males with early onset PD, ICDs are associated not only with comorbid affective symptoms, such as depression and anxiety, but also with behavioral traits, such as novelty seeking and impulsivity, as well as with personal or familial history of alcohol use. This constellation of associated risk factors highlights the importance of inter-individual differences in the vulnerability to develop comorbid psychiatric disorders in PD patients. Additionally, withdrawal from DRT in patients with ICDs frequently unmasks a severe apathetic state, suggesting that apathy and ICDs may be caused by overlapping neurobiological mechanisms within the cortico-striato-thalamo-cortical networks. We suggest that altered hedonic and impulse control processes represent distinct prodromal substrates for the development of these psychiatric symptoms, the etiopathogenic mechanisms of which remain unknown. Specifically, we argue that deficits in hedonic and motivational states and impulse control are mediated by overlapping, yet dissociable, neural mechanisms that differentially interact with DRT to promote the emergence of ICDs in vulnerable individuals. Thus, we provide a novel heuristic framework for basic and clinical research to better

  14. Oppositionality and socioemotional competence: interacting risk factors in the development of childhood conduct disorder symptoms.

    Science.gov (United States)

    Mandy, William; Skuse, David; Steer, Colin; St Pourcain, Beate; Oliver, Bonamy R

    2013-07-01

    Oppositional behavior in childhood is a probabilistic risk factor for the subsequent development of more serious conduct problems characteristic of conduct disorder (CD). The capacity to understand the subjective states of others (socioemotional competence) helps regulate antisocial behavior in typical development. We hypothesized that socioemotional competence moderates the developmental relationship between oppositionality and CD symptoms, such that oppositional defiant disorder (ODD) symptoms pose the greatest risk for subsequent CD symptoms in children with poor socioemotional competence. Parent-report data were collected for 6,218 children at 7 and 10 years of age. Bootstrap multiple regression predicting CD symptoms at age 10 was used to test for an interaction between socioemotional competence and ODD symptoms, while also accounting for direct effects and controlling for sex, maternal education, attention-deficit/hyperactivity disorder symptoms, and CD symptoms at 7 years. We further tested whether the interaction applied to both males and females, and to both aggressive and rule-breaking CD symptoms. A significant interaction was found between ODD and socioemotional competence: the association between oppositionality at 7 years and CD traits at 10 years was strongest for children with poor socioemotional capacities. As predicted, this moderation effect was significant in a model predicting aggression, but it was not significant for rule-breaking CD symptoms. Socioemotional competence moderates the developmental relationship between mid-childhood oppositionality and more serious conduct problems in later childhood. A capacity to understand the subjective states of others may buffer the risk posed by oppositionality for later CD symptoms, including aggression. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. National survey and community advisory board development for a bipolar disorder biobank.

    Science.gov (United States)

    Frye, Mark A; Doederlein, Allen; Koenig, Barbara; McElroy, Susan L; Nassan, Malik; Seymour, Lisa R; Biernacka, Joanna M; Daniels, Allen S

    2015-09-01

    The aim of the present study was to engage a national advocacy group and local stakeholders for guidance in developing a bipolar disorder biobank through a web-based survey and a community advisory board. The Depression and Bipolar Support Alliance and the Mayo Clinic Bipolar Biobank conducted a national web-based survey inquiring about interest in participating in a biobank (i.e., giving DNA and clinical information). A community advisory board was convened to guide establishment of the biobank and identify key deliverables from the research project and for the community. Among 385 survey respondents, funding source (87%), professional opinion (76%), mental health consumer opinion (79%), and return of research results (91%) were believed to be important for considering study participation. Significantly more patients were willing to participate in a biobank managed by a university or clinic (78.2%) than one managed by government (63.4%) or industry (58.2%; both p bipolar disorder developing in a child of an affected parent and which medications to avoid. The advisory board endorsed the use of a comprehension questionnaire to evaluate participants' understanding of the study (e.g., longevity of DNA specimens, right to remove samples, accessing medical records) as a means to strengthen the informed consent process. These national survey and community advisory data support the merit of establishing a biobank to enable studies of disease risk, provided that health records and research results are adequately protected. The goals of earlier diagnosis and individualized treatment of bipolar disorder were endorsed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Internet-Related Disorders: Development of the Short Compulsive Internet Use Scale.

    Science.gov (United States)

    Besser, Bettina; Rumpf, Hans-Jürgen; Bischof, Anja; Meerkerk, Gert-Jan; Higuchi, Susumu; Bischof, Gallus

    2017-11-01

    The addiction treatment system only reaches a small number of individuals suffering from Internet-related disorders. Therefore, it is important to improve case detection for preventive measures and brief interventions. Existing screening instruments are often time-consuming and rarely validated using clinical criteria. The aim of this study is to develop an optimized short screening for problematic Internet use and Internet addiction (IA). A regression analysis was conducted in random subsamples of a merged sample (N = 3,040; N = 1,209) to examine the item performance of the Compulsive Internet Use Scale (CIUS). Based on the results, a short version of the CIUS was developed and compared with the original CIUS. A fully structured diagnostic interview, covering the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for the Internet gaming disorder with a broader focus on all Internet activities, was conducted. A five-item version of the short screening performed best across the samples. Comparing the area under the curve (AUC) of the receiver operating characteristic between the Short CIUS and the original test revealed no significant difference (AUC = 0.968; 0.977). A cutoff point of 7 turned out to perform best for case detection and yielded a sensitivity of 0.95 and a specificity of 0.87, Cronbach's alpha was 0.77. The analysis showed that the performance of the Short CIUS is just as good in detecting problematical Internet use and IA as the performance of the original CIUS. The Short CIUS provides an economical and valid instrument for the assessment of problematic Internet use and IA.

  17. Autism spectrum disorder in adults: diagnosis, management, and health services development

    Science.gov (United States)

    Murphy, Clodagh M; Wilson, C Ellie; Robertson, Dene M; Ecker, Christine; Daly, Eileen M; Hammond, Neil; Galanopoulos, Anastasios; Dud, Iulia; Murphy, Declan G; McAlonan, Grainne M

    2016-01-01

    Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by pervasive difficulties since early childhood across reciprocal social communication and restricted, repetitive interests and behaviors. Although early ASD research focused primarily on children, there is increasing recognition that ASD is a lifelong neurodevelopmental disorder. However, although health and education services for children with ASD are relatively well established, service provision for adults with ASD is in its infancy. There is a lack of health services research for adults with ASD, including identification of comorbid health difficulties, rigorous treatment trials (pharmacological and psychological), development of new pharmacotherapies, investigation of transition and aging across the lifespan, and consideration of sex differences and the views of people with ASD. This article reviews available evidence regarding the etiology, legislation, diagnosis, management, and service provision for adults with ASD and considers what is needed to support adults with ASD as they age. We conclude that health services research for adults with ASD is urgently warranted. In particular, research is required to better understand the needs of adults with ASD, including health, aging, service development, transition, treatment options across the lifespan, sex, and the views of people with ASD. Additionally, the outcomes of recent international legislative efforts to raise awareness of ASD and service provision for adults with ASD are to be determined. Future research is required to identify high-quality, evidence-based, and cost-effective models of care. Furthermore, future health services research is also required at the beginning and end of adulthood, including improved transition from youth to adult health care and increased understanding of aging and health in older adults with ASD. PMID:27462160

  18. Stressful life events during pregnancy as risk factors for developing autistic disorder in children

    Directory of Open Access Journals (Sweden)

    Salman Abdi

    2016-12-01

    Full Text Available Introduction: This study aimed to examine the role of prenatal stressful events in mothers of children and adolescents with autistic disorder (AD. Methods: This case-control study was conducted in 2014. A total number of 115 children and adolescents with AD were selected by convenience method from the autism rehabilitation centers in Tabriz, Iran. Moreover, 112 typically developing (TD children and adolescents were selected from public schools using a random clustering method. Two groups were matched in terms of mother's and child's age and mother's educational level. The Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS semi-structured diagnostic interview was used to evaluate the presence of psychiatric disorders. The diagnosis of AD was made based on the DSM-IV criteria during separate diagnostic interviews by two child and adolescent psychiatrists. The life stressful events’ inventory was used to assess the presence of stressful events during pregnancy. Results: According to Fisher's exact test, the frequency of stressful life events including failure to achieve life goals, high debt, frequent marital conflict, conflict with spouse's family, changes in sleeping habits, and sexual difficulties in the mothers of AD children during pregnancy was significantly higher than the mothers of TD children. Also, mothers of AD children reported significantly higher frequency for the positive stressful life events including the major job progress, starting or finishing education, change of education, location, and summer vacation during pregnancy. Conclusion: Some stressful life events in mothers during pregnancy may be considered as risk factors for developing AD in their children. Further researches are needed to establish the results of this study.

  19. Trait impulsivity and anhedonia: two gateways for the development of impulse control disorders in Parkinson's disease?

    Directory of Open Access Journals (Sweden)

    Jean-Luc eHoueto

    2016-05-01

    Full Text Available Apathy and impulsivity are two major comorbid syndromes of Parkinson’s disease (PD that may represent two extremes of a behavioral spectrum modulated by dopamine-dependent processes. PD is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta to which are attributed the cardinal motor symptoms of the disorder. Dopamine replacement therapy (DRT, used widely to treat these motor symptoms, is often associated with deficits in hedonic processing and motivation, including apathy and depression, as well as impulse control disorders (ICDs. ICDs comprise pathological gambling, hypersexuality, compulsive shopping, binge eating, compulsive overuse of dopaminergic medication, and punding. More frequently observed in males with early onset PD, ICDs are associated not only with co-morbid affective symptoms such as depression and anxiety, but also with behavioral traits such as novelty seeking and impulsivity, as well as with personal or familial history of alcohol use. This constellation of associated risk factors highlights the importance of inter-individual differences in the vulnerability to develop comorbid psychiatric disorders in PD patients. Additionally, withdrawal from DRT in patients with ICDs frequently unmasks a severe apathetic state, suggesting that apathy and ICDs may be caused by overlapping neurobiological mechanisms within the cortico-striato-thalamo-cortical networks. We suggest that altered hedonic and impulse control processes represent distinct prodromal substrates for the development of these psychiatric symptoms, the etiopathogenic mechanisms of which remain unknown. Specifically, we argue that deficits in hedonic and motivational states and impulse control are mediated by overlapping, yet dissociable, neural mechanisms that differentially interact with DRT to promote the emergence of ICDs in vulnerable individuals. We thus provide a novel heuristic framework for basic and clinical

  20. Development of a Family-School Intervention for Young Children With Attention Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Mautone, Jennifer A; Marshall, Stephen A; Sharman, Jaclyn; Eiraldi, Ricardo B; Jawad, Abbas F; Power, Thomas J

    2012-01-01

    Although numerous studies have evaluated the effectiveness of multi-modal psychosocial interventions for children with attention deficit hyperactivity disorder, these programs are limited in that there has not beeti an explicit focus on the connection between fatnily and school. This study was designed to develop and pilot test a family-school ititervention, Family-School Success-Early Elementary (FSS-EE), for kindergarten and first-grade studetits with attention deficit hyperactivity disorder. Key components of FSS-EE were family-school behavioral consultatioti, daily report cards, and strategies to improve parent-child relationships atid family involvement in educatioti. FSS-EE was developed using a multistep iterative process. The piloted version consisted of 12 weekly sessions including 6 group meetings, 4 individualized family sessions, and 2 school-based consultations. Families participating in the study were given the choice of placing their childreti on medication; 25% of children were on medication at the time of random assignmetit. Childreti ( n = 61) were randomly assigned to FSS-EE or a comparison group controlling for nonspecific treatment effects. Outcomes were assessed at post interventioti and 2-month follow-up. Study findings indicated that FSS-EE was feasible to implement and acceptable to paretits atid teachers. In addition, the findings provided preliminary evidence that FSS-EE is effective in improving parenting practices, child behavior at school, and the student-teacher relationship.

  1. 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.

  2. Development of allosteric modulators of GPCRs for treatment of CNS disorders.

    Science.gov (United States)

    Nickols, Hilary Highfield; Conn, P Jeffrey

    2014-01-01

    The discovery of allosteric modulators of G protein-coupled receptors (GPCRs) provides a promising new strategy with potential for developing novel treatments for a variety of central nervous system (CNS) disorders. Traditional drug discovery efforts targeting GPCRs have focused on developing ligands for orthosteric sites which bind endogenous ligands. Allosteric modulators target a site separate from the orthosteric site to modulate receptor function. These allosteric agents can either potentiate (positive allosteric modulator, PAM) or inhibit (negative allosteric modulator, NAM) the receptor response and often provide much greater subtype selectivity than orthosteric ligands for the same receptors. Experimental evidence has revealed more nuanced pharmacological modes of action of allosteric modulators, with some PAMs showing allosteric agonism in combination with positive allosteric modulation in response to endogenous ligand (ago-potentiators) as well as "bitopic" ligands that interact with both the allosteric and orthosteric sites. Drugs targeting the allosteric site allow for increased drug selectivity and potentially decreased adverse side effects. Promising evidence has demonstrated potential utility of a number of allosteric modulators of GPCRs in multiple CNS disorders, including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, as well as psychiatric or neurobehavioral diseases such as anxiety, schizophrenia, and addiction. © 2013.

  3. Current State and Model for Development of Technology-Based Care for Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    Riley, Steven J.; Calub, Catrina A.; Schweitzer, Julie B.

    2016-01-01

    Abstract Introduction: Care (i.e., evaluation and intervention) delivered through technology is used in many areas of mental health services, including for persons with attention deficit hyperactivity disorder (ADHD). Technology can facilitate care for individuals with ADHD, their parents, and their care providers. The adoption of technological tools for ADHD care requires evidence-based studies to support the transition from development to integration into use in the home, school, or work for persons with the disorder. The initial phase, which is development of technological tools, has begun in earnest; however, the evidence base for many of these tools is lacking. In some instances, the uptake of a piece of technology into home use or clinical practice may be further along than the research to support its use. Methods: In this study, we review the current evidence regarding technology for ADHD and also propose a model to evaluate the support for other tools that have yet to be tested. Results: We propose using the Research Domain Criteria as a framework for evaluating the tools' relationships to dimensions related to ADHD. Conclusion: This article concludes with recommendations for testing new tools that may have promise in improving the evaluation or treatment of persons with ADHD. PMID:26985703

  4. Development of Communication in Children with Autism Spectrum Disorders in the United States and Russia

    Directory of Open Access Journals (Sweden)

    Esterbrook R.L.,

    2016-10-01

    Full Text Available The article presents an analysis of theoretical principles and methodological approaches within the framework of research schools both in the United States and Russia; these schools provide the basis for the development of effective learning and communication skills for children with Autism Spectrum Disorders (ASD. The authors consider the indicators for communication disorders in children with ASD, as well as the main strategies for overcoming them in the context of utilizing verbal behavior analysis (B.F. Skinner, M.L. Sundberg, J.W. Partington, and M.L. Barbera - USA, the tradition of cultural-historical psychology (L.S. Vygotsky, D.B. Elkonin, B.D. Elkonin - Russia, reflective-activity approach (A.N. Leontiev, V.K. Zaretsky – Russia, the theory of systemic dynamic localization of higher mental functions(A.R. Luria – Russia, and method of ”replacing ontogenesis” (B.A. Arkhipov, A.V. Semenovich Russia. Despite the differences in methodologies used by American and Russian scholars, the most important idea is that the researchers and practitioners of both schools have common goal: to concentrate their efforts on developing social interaction skills in children with ASD, which helps them to better adjust in their lives and function in the social environment

  5. The Role of Vaspin in the Development of Metabolic and Glucose Tolerance Disorders and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Rumyana Dimova

    2015-01-01

    Full Text Available In recent years, most research efforts have been focused on studying insulin-sensitizing adipokines. One of the most recently discovered adipokines is vaspin, a visceral adipose tissue-derived serine protease inhibitor. Vaspin levels have been found significantly increased in mice with obesity and insulin resistance. It has been assumed that vaspin serves as an insulin sensitizer with anti-inflammatory effects and might act as a compensatory mechanism in response to decreased insulin sensitivity. Most studies in humans have shown a positive correlation between vaspin gene expression and serum levels, and metabolic syndrome parameters. Vaspin gene expression is influenced by age and gender, and the administration of insulin sensitizers enhances it in mice, whereas the use of metformin decreases serum vaspin levels in humans, probably due to different regulatory mechanisms. Presumably vaspin plays local and endocrine role in the development of initial and advanced atherosclerosis in obese subjects and might be used as a predictor of coronary and cerebrovascular disease. It is believed that vaspin could be regarded as a new link between obesity and related metabolic disorders, including glucose intolerance. The entire understanding of vaspin intimate mechanism of action might enable the development of novel etiology-based treatment strategies, targeting metabolic and glucose tolerance disorders.

  6. Melatonin in Pregnancy: Effects on Brain Development and CNS Programming Disorders.

    Science.gov (United States)

    Sagrillo-Fagundes, Lucas; Assunção Salustiano, Eugênia Maria; Yen, Philippe Wong; Soliman, Ahmed; Vaillancourt, Cathy

    2016-01-01

    Melatonin is an important neuroprotective factor and its receptors are expressed in the fetal brain. During normal pregnancy, maternal melatonin level increases progressively until term and is highly transferred to the fetus, with an important role in brain formation and differentiation. Maternal melatonin provides the first circadian signal to the fetus. This indolamine is also produced de novo and plays a protective role in the human placenta. In pregnancy disorders, both maternal and placental melatonin levels are decreased. Alteration in maternal melatonin level has been associated with disrupted brain programming with long-term effects. Melatonin has strong antioxidant protective effects directly and indirectly via the activation of its receptors. The fetal brain is highly susceptible to oxygenation variation and oxidative stress that can lead to neuronal development disruption. Based on that, several approaches have been tested as a treatment in case of pregnancy disorders and melatonin, through its neuroprotective effect, has been recently accepted against fetal brain injury. This review provides an overview about the protective effects of melatonin during pregnancy and on fetal brain development.

  7. [Child and adolescent development: common mental disorders according to age and gender].

    Science.gov (United States)

    Navarro-Pardo, Esperanza; Meléndez Moral, Juan Carlos; Sales Galán, Alicia; Sancerni Beitia, M Dolores

    2012-01-01

    Despite the increase in the incidence and prevalence rates of children and adolescents' mental disorders, there are few works performed with large and representative samples of children and adolescents with psychopathological symptoms. The present work analyses 588 participants referred by first care pediatricians to a specialized unit for children and adolescents' mental health. As a result of the study, a statistically significant relation was found between age and diagnosis: a larger incidence of behavioral disorders, communication disorders, elimination disorders, pervasive developmental disorders, impulse-control disorders from 0 to 5 years; behavioral disorders and attention deficit hyperactivity disorder (ADHD) were more common from 6 to 11 years, behavioral and anxiety disorders were more likely at 12 to 15 years; and, lastly, behavioral disorders were more prevalent from 16 to 18 years. With respect to gender, there was a significant relationship with diagnosis: boys had more behavioral disorders, whereas girl had more anxiety disorders. To conclude, a relationship between mental disorders and developmental achievements could be indicated in the younger group. Additionally, externalizing disorders in boys and internalizing ones n girls were more prevalent across all ages.

  8. Development of a Chinese medicine pattern severity index for understanding eating disorders.

    Science.gov (United States)

    Fogarty, Sarah; Harris, David; Zaslawski, Chris; McAinch, Andrew J; Stojanovska, Lily

    2012-06-01

    Eating disorders commonly affect young girls and women. Four eating disorders are analyzed in this study: anorexia nervosa (AN), bulimia nervosa (BN), eating disorders not otherwise specified (EDNOS), and binge eating disorder (BED). Eating disorders are a modern concept and as such there is no critically appraised research on how Traditional Chinese Medicine (TCM) conceptualizes of or treats eating disorders. The purpose of this study is to identify and quantify the TCM patterns relevant to eating disorders based on a systematic evaluation of the results of a self-reported questionnaire. One hundred and ninety-six (196) female participants (142 with a self-reported eating disorder and 54 with no eating disorder) completed an online survey, designed to collect data on their current general health and, where relevant, their eating disorder. The Berle methodology was used to identify TCM patterns involved in eating disorders to tabulate and score the number of signs and symptoms experienced by the participants. For many of the TCM patterns, statistically significant differences were found between presentation severity across the four eating disorders. For the first time, there is evidence-based research to classify the TCM patterns involved in AN, BN, EDNOS, and BED. Evidence is given to support the anecdotal theories of TCM patterns involved in eating disorder presentation. These results have relevance on how eating disorders are treated and viewed by TCM practitioners.

  9. [Early development of language in small children with autism spectrum disorder using alternative systems].

    Science.gov (United States)

    Fortea-Sevilla, M Sol; Escandell-Bermúdez, M Olga; Castro-Sánchez, José Juan; Martos-Pérez, Juan

    2015-02-25

    The latest research findings show the importance of early intervention in children with autism spectrum disorder (ASD) in all areas of development, including language. The use of augmentative and alternative communication systems (AACS) favors linguistic and communicative development. To show the effectiveness of AACS to develop oral language in non-verbal toddlers diagnosed with ASD. Thirty children (25 males and 5 females) diagnosed with ASD when they were between 18 and 30 months of age, through the instruments ADOS and ADIR. None of them displayed oral language development at the time of assessment. An intervention program in the area of language was designed based on the use of total communication by the therapist and training the child in the Picture Exchange Communication System (PECS). One year later, the formal aspects of language were assessed with the PLON-R because oral language had been developed. All the children had developed oral language to some extent over a one-year period. Early intervention and the use of AACS with visual props favor the development of oral language in children with ASD in the first years of life.

  10. A longitudinal study on gross motor development in children with learning disorders.

    Science.gov (United States)

    Westendorp, Marieke; Hartman, Esther; Houwen, Suzanne; Huijgen, Barbara C H; Smith, Joanne; Visscher, Chris

    2014-02-01

    This longitudinal study examined the development of gross motor skills, and sex-differences therein, in 7- to 11-years-old children with learning disorders (LD) and compared the results with typically developing children to determine the performance level of children with LD. In children with LD (n=56; 39 boys, 17 girls), gross motor skills were assessed with the Test of Gross Motor Development-2 and measured annually during a 3-year period. Motor scores of 253 typically developing children (125 boys, 112 girls) were collected for references values. The multilevel analyses showed that the ball skills of children with LD improved with age (p50). Boys had higher ball skill scores than girls (p=.002) and these differences were constant over time. Typically developing children outperformed the children with LD on the locomotor skills and ball skills at all ages, except the locomotor skills at age 7. Children with LD develop their ball skills later in the primary school-period compared to typically developing peers. However, 11 year-old children with LD had a lag in locomotor skills and ball skills of at least four and three years, respectively, compared to their peers. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Psychomotor development in infants with Prader-Willi syndrome and associations with sleep-related breathing disorders.

    Science.gov (United States)

    Festen, Dederieke A M; Wevers, Maaike; de Weerd, Al W; van den Bossche, Renilde A S; Duivenvoorden, Hugo J; Otten, Barto J; Wit, Jan Maarten; Hokken-Koelega, Anita C S

    2007-08-01

    Prader-Willi syndrome (PWS) is a neurogenetic disorder with hypotonia, psychomotor delay, obesity, short stature, and sleep-related breathing disorders. The aim of this study was to evaluate the association between psychomotor development and sleep-related breathing disorders in PWS infants. Bayley Scales of Infant Development were performed in 22 PWS infants, with a median (interquartile range, IQR) age of 1.8 (1.1-3.4) y, and a body mass index SD score (BMISDS) of -0.5 (-1.3 to 1.6). We evaluated psychomotor development in relation to results of polysomnography. Median (IQR) mental and motor development was 73.1% (64.3-79.6%) and 55.2% (46.5-63.1%) of normal children, respectively. All infants had sleep-related breathing disorders, mostly of central origin. The apnea hypopnea index was not associated with psychomotor development. Only four infants had obstructive sleep apnea syndrome (OSAS). They had a significantly delayed mental development of 65.5% (60.0-70.3%) of normal. They had a median BMISDS of 1.4 (0.1-1.6), which tended to be higher than in those without OSAS. Our data indicate that psychomotor development in PWS infants is not related to central sleep-related breathing disorders, but infants with OSAS have more severely delayed mental development, suggesting that PWS infants should be screened for OSAS.

  12. Development and disease in a dish: the epigenetics of neurodevelopmental disorders.

    Science.gov (United States)

    Lewis, Emily Ma; Kroll, Kristen L

    2018-02-01

    Human neurodevelopmental disorders (NDDs) involve mutations in hundreds of individual genes, with over-representation in genes encoding proteins that alter chromatin structure to modulate gene expression. Here, we highlight efforts to model these NDDs through in vitro differentiation of patient-specific induced pluripotent stem cells into neurons. We discuss how epigenetic regulation controls normal cortical development, how mutations in several classes of epigenetic regulators contribute to NDDs, and approaches for modeling cortical development and function using both directed differentiation and formation of cerebral organoids. We explore successful applications of these models to study both syndromic and nonsyndromic NDDs and to define convergent mechanisms, addressing both the potential and challenges of using this approach to define cellular and molecular mechanisms that underlie NDDs.

  13. Parenting Children with Disorders of Sex Development (DSD): A Developmental Perspective Beyond Gender.

    Science.gov (United States)

    Wisniewski, A B; Sandberg, D E

    2015-05-01

    Advances in therapeutics for specific conditions have contributed to a categorical psychological approach to chronic diseases that affect children. Consensus statements and clinical guidelines recognize stress associated with disorders of sex development (DSD) for patients and their caregivers - yet much remains to be learned concerning the social adjustment, mental health, and quality of life of affected children and their families. We present preliminary data on the psychosocial comorbidities of caregivers of children with DSD, including stigma, isolation, stress, anxiety, and depressive symptomatology. Evidence is offered in support of individualized psychological approaches for families according to such variables as: 1) gender of the caregiver, 2) gender of the affected child and 3) presence of genital ambiguity at birth. Development of feasible, targeted interventions to ameliorate psychosocial comorbidities among caregivers is needed to optimize social adjustment, mental health, and health-related quality of life (HRQoL) for children with DSD. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Gender identity outcomes in children with disorders/differences of sex development: Predictive factors.

    Science.gov (United States)

    Bakula, Dana M; Mullins, Alexandria J; Sharkey, Christina M; Wolfe-Christensen, Cortney; Mullins, Larry L; Wisniewski, Amy B

    2017-06-01

    Disorders/differences of sex development (DSD) comprise multiple congenital conditions in which chromosomal, gonadal, and/or anatomical sex are discordant. The prediction of future gender identity (i.e., self-identifying as male, female, or other) in children with DSD can be imprecise, and current knowledge about the development of gender identity in people with, and without DSD, is limited. However, sex of rearing is the strongest predictor of gender identity for the majority of individuals with various DSD conditions. When making decisions regarding sex of rearing biological factors (e.g., possession of a Y chromosome, degree and duration of pre- and postnatal androgen exposure, phenotypic presentation of the external genitalia, and fertility potential), social and cultural factors, as well as quality of life should be considered. Information on gender identity outcomes across a range of DSD diagnoses is presented to aid in sex of rearing assignment. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Development of a College Transition and Support Program for Students with Autism Spectrum Disorder.

    Science.gov (United States)

    White, Susan W; Elias, Rebecca; Capriola-Hall, Nicole N; Smith, Isaac C; Conner, Caitlin M; Asselin, Susan B; Howlin, Patricia; Getzel, Elizabeth E; Mazefsky, Carla A

    2017-10-01

    Empirically based, consumer-informed programming to support students with Autism Spectrum Disorder (ASD) transitioning to college is needed. Informed by theory and research, the Stepped Transition in Education Program for Students with ASD (STEPS) was developed to address this need. The first level (Step 1) supports high school students and the second level (Step 2) is for postsecondary students with ASD. Herein, we review the extant research on transition supports for emerging adults with ASD and describe the development of STEPS, including its theoretical basis and how it was informed by consumer input. The impact of STEPS on promotion of successful transition into college and positive outcomes for students during higher education is currently being evaluated in a randomized controlled trial.

  16. Developing a classification system of social communication functioning of preschool children with autism spectrum disorder.

    Science.gov (United States)

    Di Rezze, Briano; Rosenbaum, Peter; Zwaigenbaum, Lonnie; Hidecker, Mary Jo Cooley; Stratford, Paul; Cousins, Martha; Camden, Chantal; Law, Mary

    2016-09-01

    Impairments in social communication are the hallmark of autism spectrum disorder (ASD). Operationalizing 'severity' in ASD has been challenging; thus, stratifying by functioning has not been possible. The purpose of this study is to describe the development of the Autism Classification System of Functioning: Social Communication (ACSF:SC) and to evaluate its consistency within and between parent and professional ratings. (1) ACSF:SC development based on focus groups and surveys involving parents, educators, and clinicians familiar with preschoolers with ASD; and (2) evaluation of the intra- and interrater agreement of the ACSF:SC using weighted kappa (кw ). Seventy-six participants were involved in the development process. Core characteristics of social communication were ascertained: communicative intent; communicative skills and reciprocity; and impact of environment. Five ACSF:SC levels were created and content-validated across participants. Best capacity and typical performance agreement ratings varied as follows: intrarater agreement on 41 children was кw =0.61 to 0.69 for parents, and кw =0.71 to 0.95 for professionals; interrater agreement between professionals was кw =0.47 to 0.61, and between parents and professionals was кw =0.33 to 0.53. Perspectives from parents and professionals informed ACSF:SC development, providing common descriptions of the levels of everyday communicative abilities of children with ASD to complement the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Rater agreement demonstrates that the ACSF:SC can be used with acceptable consistency compared with other functional classification systems. © 2016 Mac Keith Press.

  17. Does MRI add to ultrasound in the assessment of disorders of sex development?

    Energy Technology Data Exchange (ETDEWEB)

    Mansour, S.M., E-mail: sahar_mnsr@yahoo.com [Radiology Department (Women' s imaging unit), Faculty of Medicine, Cairo University,Egypt (Egypt); Hamed, S.T., E-mail: sohathamed@yahoo.com [Radiology Department (Women' s imaging unit), Faculty of Medicine, Cairo University,Egypt (Egypt); Adel, L., E-mail: lamiaadel73@yahoo.com [Radiology Department (Women' s imaging unit), Faculty of Medicine, Cairo University,Egypt (Egypt); Kamal, R.M., E-mail: rashaakamal@hotmail.com [Radiology Department (Women' s imaging unit), Faculty of Medicine, Cairo University,Egypt (Egypt); Ahmed, D.M., E-mail: sahar_mnsr@yahoo.com [National Research Center, Cairo (Egypt)

    2012-09-15

    Objective: The objective of the study was to evaluate the need of magnetic resonance imaging and using different approaches (transabdominal, endoluminal and transperineal) in the proper assessment of disorders of sex development regarding gonadal detection and gender differentiation. Subjects and methods: Twenty five patients with abnormalities of sex disorders were included. They were classified into two groups according to the time of clinical presentation: Group 1 (early onset) included eight cases. Their age ranged from one month to 12 years (mean age = 3.0). They presented with overt genital ambiguity of clitoral hypertrophy in a phenotypic female, non palpable testes or micropenis in a phenotypic male. Group 2 (late onset) included 17 cases. Their age ranged from 16 to 33 years (mean age 18.1). This group presented by distressing puberty symptoms of primary amenorrhea in a female phenotype or undescended testis and behaving as a male. Cases were subjected to Ultrasound and MR imaging examinations. Imaging results were correlated results of chromosomal and hormonal assays as well as laparoscopy findings. Results: The study included: 10/25 cases (40%) of female pseudo-hermaphroditism, 13/25 cases (52%) of male pseudo-hermaphroditism, one case (4%) of true hermaphroditism and one case (4%) of pure gonadal dysgenesis. The accuracy of multi approach ultrasound was 89.8% compared to 85.7% in MR imaging. Conclusion: Ultrasound should be considered the initial screening modality in the assessment of developmental sex disorders. MRI examination could be reserved for gonad identification when ultrasound examination fails to do so and for corrective surgery guidance.

  18. Does MRI add to ultrasound in the assessment of disorders of sex development?

    International Nuclear Information System (INIS)

    Mansour, S.M.; Hamed, S.T.; Adel, L.; Kamal, R.M.; Ahmed, D.M.

    2012-01-01

    Objective: The objective of the study was to evaluate the need of magnetic resonance imaging and using different approaches (transabdominal, endoluminal and transperineal) in the proper assessment of disorders of sex development regarding gonadal detection and gender differentiation. Subjects and methods: Twenty five patients with abnormalities of sex disorders were included. They were classified into two groups according to the time of clinical presentation: Group 1 (early onset) included eight cases. Their age ranged from one month to 12 years (mean age = 3.0). They presented with overt genital ambiguity of clitoral hypertrophy in a phenotypic female, non palpable testes or micropenis in a phenotypic male. Group 2 (late onset) included 17 cases. Their age ranged from 16 to 33 years (mean age 18.1). This group presented by distressing puberty symptoms of primary amenorrhea in a female phenotype or undescended testis and behaving as a male. Cases were subjected to Ultrasound and MR imaging examinations. Imaging results were correlated results of chromosomal and hormonal assays as well as laparoscopy findings. Results: The study included: 10/25 cases (40%) of female pseudo-hermaphroditism, 13/25 cases (52%) of male pseudo-hermaphroditism, one case (4%) of true hermaphroditism and one case (4%) of pure gonadal dysgenesis. The accuracy of multi approach ultrasound was 89.8% compared to 85.7% in MR imaging. Conclusion: Ultrasound should be considered the initial screening modality in the assessment of developmental sex disorders. MRI examination could be reserved for gonad identification when ultrasound examination fails to do so and for corrective surgery guidance

  19. The development and psychometric evaluation of the Internet Disorder Scale (IDS-15).

    Science.gov (United States)

    Pontes, Halley M; Griffiths, Mark D

    2017-01-01

    Previously published research suggests that improvement in the assessment of Internet addiction (IA) is paramount in advancing the field. However, little has been done to address inconsistencies in the assessment of IA using a more updated framework. The aim of the present study was to develop a new instrument to assess IA based on a modification of the nine Internet Gaming Disorder (IGD) criteria as suggested by the American Psychiatric Association in the latest (fifth) edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and to provide a taxonomy of the potential risk of IA risk among participants. A heterogeneous sample of Internet users (n=1105) was recruited online (61.3% males, mean age 33years). Construct validity of the new instrument - Internet Disorder Scale (IDS-15) - was assessed by means of factorial, convergent, and discriminant validity. Criterion-related validity and reliability were also investigated. Additionally, latent profile analysis (LPA) was carried out to differentiate and characterize Internet users based on their potential IA risk. The construct and criterion-related validity of the IDS-15 were both warranted. The IDS-15 proved to be a valid and reliable tool. Using the LPA, participants were classed as "low addiction risk" (n=183, 18.2%), "medium addiction risk" (n=456, 41.1%), and "high addiction risk" (n=455, 40.77%). Furthermore, key differences emerged among these classes in terms of age, relationship status, cigarette consumption, weekly Internet usage, age of Internet use initiation, and IDS-15 total scores. The present findings support the viability of using adapted IGD criteria as a framework to assess IA. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Risk of developing major depression and bipolar disorder among adolescents with atopic diseases: A nationwide longitudinal study in Taiwan.

    Science.gov (United States)

    Wei, Han-Ting; Lan, Wen-Hsuan; Hsu, Ju-Wei; Huang, Kai-Lin; Su, Tung-Ping; Li, Cheng-Ta; Lin, Wei-Chen; Chen, Tzeng-Ji; Bai, Ya-Mei; Chen, Mu-Hong

    2016-10-01

    Previous studies have found an increased prevalence of atopic diseases among patients with major depression and bipolar disorder. But the temporal association between atopic diseases in adolescence and the subsequent risk of developing mood disorders has been rarely investigated. Using the Taiwan National Health Insurance Research Databases, 5075 adolescents with atopic diseases (atopic cohort) and 44,729 without (non-atopic cohort) aged between 10 and 17 in 2000 were enrolled into our study and followed to the end of 2010. Subjects who developed major depression or bipolar disorder during the follow-up were identified. The atopic cohort had an increased risk of developing major depression (HR: 2.45, 95% CI: 1.93~3.11) and bipolar disorder (HR: 2.51, 95% CI: 1.71~3.67) compared to the non-atopic cohort, with a dose-dependent relationship between having a greater number of atopic comorbidities and a greater likelihood of major depression (1 atopic disease: HR: 1.80, 95% CI: 1.29~2.50; 2 atopic comorbidities: HR: 2.42, 95% CI: 1.93~3.04;≥3 atopic comorbidities: HR: 3.79, 95% CI: 3.05~4.72) and bipolar disorder (HR: 1.40, 95% CI: 0.57~3.44; HR: 2.81, 95% CI: 1.68~4.68; HR: 3.02, 95% CI: 1.69~5.38). Having atopic diseases in adolescence increased the risk of developing major depression and bipolar disorder in later life. Further studies may be required to clarify the underlying mechanism between atopy and mood disorders, and to investigate whether prompt intervention may decrease the risk of subsequent mood disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Development and evaluation of a digistory about autistic spectrum disorder - a pilot study.

    Science.gov (United States)

    Codd, Anthony; Burford, Bryan; Petruso, Gabriella; Davidson, Neil; Vance, Gillian

    2018-05-28

    Digital storytelling ('digistories') offers a way of sharing the personal impact of a condition, if students have limited direct contact. Autistic spectrum disorder (ASD) exemplifies a common condition, where there is need to improve practise in primary care. Hence, we chose this condition to develop and evaluate a digistory. We considered stigmatising attitudes to ASD and wider educational effects. In the digistory, a mother of a boy with severe ASD describes her autobiographical experiences, illustrated by customised cartoons. Participants completed, pre-post, a validated attitude questionnaire and word association exercise. Views on educational value were gathered through free text and focus group. Questionnaire scores indicated positive attitudes, with no significant change. In contrast, content analysis of word association responses showed prevalent negative associations. Thematic analysis identified increased empathy of students with the family, enabled by the resource design. The digistory helped students challenge stereotypes associated with the condition and encouraged greater confidence to engage in future clinical encounters. The digistory is an accessible and authentic patient analogue that gives additional insight into living with autistic spectrum disorder, with potential benefits for patient-centred learning.

  2. New Developments in Cognitive-Behavioral Therapy for Social Anxiety Disorder.

    Science.gov (United States)

    Stangier, Ulrich

    2016-03-01

    Social anxiety disorder (SAD) is a highly prevalent and chronic disorder that causes considerable psychosocial impairment. This article reviews recent changes in the definition of SAD in DSM-5 and summarizes the current evidence for effective cognitive-behavioral treatments in adults, children, and adolescents. Current data suggests that cognitive-behavioral therapy (CBT) is efficacious in the treatment of this condition. Among different CBT approaches, individual cognitive therapy may be associated with the largest effect sizes. In this review, interventions targeting dysfunctional cognitive processes that contribute to the effective treatment of SAD are discussed. Some recent findings from neuroimaging research and studies on the augmentation of CBT using neuroenhancers indicate that changes in emotion regulation as well as fear extinction are important psychological mediators of positive outcome. Furthermore, internet-delivered CBT is a promising field of technological innovation that may improve access to effective treatments. Despite the availability of effective treatments, treatment-resistant SAD remains a common problem in clinical practice that requires more research efforts. Finally, potential areas for further development of CBT as well as its dissemination in health care are summarized.

  3. Children with autism spectrum disorders who do not develop phrase speech in the preschool years.

    Science.gov (United States)

    Norrelgen, Fritjof; Fernell, Elisabeth; Eriksson, Mats; Hedvall, Åsa; Persson, Clara; Sjölin, Maria; Gillberg, Christopher; Kjellmer, Liselotte

    2015-11-01

    There is uncertainty about the proportion of children with autism spectrum disorders who do not develop phrase speech during the preschool years. The main purpose of this study was to examine this ratio in a population-based community sample of children. The cohort consisted of 165 children (141 boys, 24 girls) with autism spectrum disorders aged 4-6 years followed longitudinally over 2 years during which time they had received intervention at a specialized autism center. In this study, data collected at the 2-year follow-up were used. Three categories of expressive language were defined: nonverbal, minimally verbal, and phrase speech. Data from the Vineland Adaptive Behavior Scales-II were used to classify expressive language. A secondary objective of the study was to analyze factors that might be linked to verbal ability, namely, child age, cognitive level, autism subtype and severity of core autism symptoms, developmental regression, epilepsy or other medical conditions, and intensity of intervention. The proportion of children who met the criteria for nonverbal, minimally verbal, and phrase speech were 15%, 10%, and 75%, respectively. The single most important factor linked to expressive language was the child's cognitive level, and all children classified as being nonverbal or minimally verbal had intellectual disability. © The Author(s) 2014.

  4. Neurophysiological basis of rapid eye movement sleep behavior disorder: informing future drug development

    Directory of Open Access Journals (Sweden)

    Jennum P

    2016-04-01

    Full Text Available Poul Jennum, Julie AE Christensen, Marielle Zoetmulder Department of Clinical Neurophysiology, Faculty of Health Sciences, Danish Center for Sleep Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Abstract: Rapid eye movement (REM sleep behavior disorder (RBD is a parasomnia characterized by a history of recurrent nocturnal dream enactment behavior and loss of skeletal muscle atonia and increased phasic muscle activity during REM sleep: REM sleep without atonia. RBD and associated comorbidities have recently been identified as one of the most specific and potentially sensitive risk factors for later development of any of the alpha-synucleinopathies: Parkinson’s disease, dementia with Lewy bodies, and other atypical parkinsonian syndromes. Several other sleep-related abnormalities have recently been identified in patients with RBD/Parkinson’s disease who experience abnormalities in sleep electroencephalographic frequencies, sleep–wake transitions, wake and sleep stability, occurrence and morphology of sleep spindles, and electrooculography measures. These findings suggest a gradual involvement of the brainstem and other structures, which is in line with the gradual involvement known in these disorders. We propose that these findings may help identify biomarkers of individuals at high risk of subsequent conversion to parkinsonism. Keywords: motor control, brain stem, hypothalamus, hypocretin

  5. Neurophysiological basis of rapid eye movement sleep behavior disorder: informing future drug development

    Science.gov (United States)

    Jennum, Poul; Christensen, Julie AE; Zoetmulder, Marielle

    2016-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by a history of recurrent nocturnal dream enactment behavior and loss of skeletal muscle atonia and increased phasic muscle activity during REM sleep: REM sleep without atonia. RBD and associated comorbidities have recently been identified as one of the most specific and potentially sensitive risk factors for later development of any of the alpha-synucleinopathies: Parkinson’s disease, dementia with Lewy bodies, and other atypical parkinsonian syndromes. Several other sleep-related abnormalities have recently been identified in patients with RBD/Parkinson’s disease who experience abnormalities in sleep electroencephalographic frequencies, sleep–wake transitions, wake and sleep stability, occurrence and morphology of sleep spindles, and electrooculography measures. These findings suggest a gradual involvement of the brainstem and other structures, which is in line with the gradual involvement known in these disorders. We propose that these findings may help identify biomarkers of individuals at high risk of subsequent conversion to parkinsonism. PMID:27186147

  6. Duplication of SOX9 associated with 46,XX ovotesticular disorder of sex development.

    Science.gov (United States)

    López-Hernández, Berenice; Méndez, Juan Pablo; Coral-Vázquez, Ramón Mauricio; Benítez-Granados, Jesús; Zenteno, Juan Carlos; Villegas-Ruiz, Vanessa; Calzada-León, Raúl; Soderlund, Daniela; Canto, Patricia

    2018-04-04

    The purpose of the present study was to investigate whether ten unrelated SRY-negative individuals with this sex differentiation disorder presented a double dose of SOX9 as the cause of their disease. Ten unrelated SRY-negative 46,XX ovotesticular disorder of sexual development (DSD) subjects were molecularly studied. Multiplex-ligation dependent probe amplification (MLPA) and quantitative real-time PCR analysis (qRT-PCR) for SOX9 were performed. The MLPA analysis demonstrated that one patient presented a heterozygous duplication of the entire SOX9 coding region (above 1.3 value of peak ratio), as well as at least a ~ 483 kb upstream duplication. Moreover, no duplication of other SOX9 probes was observed corresponding to the region between -1007 and -1500 kb upstream. A qRT-PCR analysis showed a duplication of at least -581 kb upstream and ~1.63 kb of the coding region that encompasses exon 3. The limits of the duplication were mapped approximately from ~71539762 to 72122741 of Chr17. No molecular abnormalities were found in the remaining nine patients. This study is thought to be the first report regarding a duplication of SOX9 that is associated with the presence of 46,XX ovotesticular DSD, encompassing at least -581 kb upstream, and the almost entire coding region of the gene. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  7. The Spectrum of Ovotesticular Disorders of Sex Development in South Africa: A Single-Centre Experience.

    Science.gov (United States)

    Ganie, Yasmeen; Aldous, Colleen; Balakrishna, Yusentha; Wiersma, Rinus

    2017-01-01

    To describe the clinical characteristics, biochemistry, histopathology, and long-term outcomes in subjects with ovotesticular (OT) disorder of sex development (DSD). This is a retrospective subset analysis of 64 cases of histologically confirmed OT DSD. All subjects were South African; 97% (n = 62) were African and 92% (n = 59) were of Zulu ethnicity. The most common karyotype was 46,XX (88%; n = 56), followed by 46,XY (8%), 46,XY/45,X (3%), and 46,XX/46,XY (1%). The median age at presentation was 7 months (0.5 months to 5.1 years). Sixty-one of the subjects (95%) presented with DSD. The ovotestis was the most frequent gonad (56%), followed by the ovary (23%) and the testis (16%). Testes were more commonly located on the right and ovaries on the left (p gender was the predominant sex of rearing in two-thirds of the subjects. Gender dysphoria was noted in 8 subjects (11%) at a median of 6.4 (4.3-9.3) years. Long-term follow-up (n = 14) revealed spontaneous puberty in 5 subjects, gender dysphoria in 2 subjects, and neuropsychiatric disorders in 4 subjects. OT DSD is an important differential diagnosis in Black South Africans with 46,XX DSD. © 2017 S. Karger AG, Basel.

  8. The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders.

    Science.gov (United States)

    Law, Kelsey B; Bronte-Tinkew, Dana; Di Pietro, Erminia; Snowden, Ann; Jones, Richard O; Moser, Ann; Brumell, John H; Braverman, Nancy; Kim, Peter K

    2017-05-04

    Peroxisome biogenesis disorders (PBDs) are metabolic disorders caused by the loss of peroxisomes. The majority of PBDs result from mutation in one of 3 genes that encode for the peroxisomal AAA ATPase complex (AAA-complex) required for cycling PEX5 for peroxisomal matrix protein import. Mutations in these genes are thought to result in a defect in peroxisome assembly by preventing the import of matrix proteins. However, we show here that loss of the AAA-complex does not prevent matrix protein import, but instead causes an upregulation of peroxisome degradation by macroautophagy, or pexophagy. The loss of AAA-complex function in cells results in the accumulation of ubiquitinated PEX5 on the peroxisomal membrane that signals pexophagy. Inhibiting autophagy by genetic or pharmacological approaches rescues peroxisome number, protein import and function. Our findings suggest that the peroxisomal AAA-complex is required for peroxisome quality control, whereas its absence results in the selective degradation of the peroxisome. Thus the loss of peroxisomes in PBD patients with mutations in their peroxisomal AAA-complex is a result of increased pexophagy. Our study also provides a framework for the development of novel therapeutic treatments for PBDs.

  9. Comparing Service Use and Costs among Adolescents with Autism Spectrum Disorders, Special Needs and Typical Development

    Science.gov (United States)

    Barrett, Barbara; Mosweu, Iris; Jones, Catherine R. G.; Charman, Tony; Baird, Gillian; Simonoff, Emily; Pickles, Andrew; Happé, Francesca; Byford, Sarah

    2015-01-01

    Autism spectrum disorder is a complex condition that requires specialised care. Knowledge of the costs of autism spectrum disorder, especially in comparison with other conditions, may be useful to galvanise policymakers and leverage investment in education and intervention to mitigate aspects of autism spectrum disorder that negatively impact…

  10. The influence of genes and environment on the development of bipolar disorder : A twin study

    NARCIS (Netherlands)

    Vonk, Ronald

    2016-01-01

    Bipolar disorder (or manic-depressive disorder) is a severe mood disorder in which episodes of (hypo) mania (e.g. elevated mood en hyperactivity) and depression (e.g. decreased mood and reduced activity) alternate with periods of normal mood and functioning. Genetic factors as well as environmental

  11. Development and Psychometric Evaluation of a Clinical Global Impression for Schizoaffective Disorder Scale

    OpenAIRE

    Allen, Michael H; Daniel, David G; Revicki, Dennis A; Canuso, Carla M; Turkoz, Ibrahim; Fu, Dong-Jing; Alphs, Larry; Ishak, K. Jack; Bartko, John J; Lindenmayer, Jean-Pierre

    2012-01-01

    Objective: The Clinical Global Impression for Schizoaffective Disorder scale is a new rating scale adapted from the Clinical Global Impression scale for use in patients with schizoaffective disorder. The psychometric characteristics of the Clinical Global Impression for Schizoaffective Disorder are described.

  12. The development of psychotic disorders in adolescence: a potential role for hormones.

    Science.gov (United States)

    Trotman, Hanan D; Holtzman, Carrie W; Ryan, Arthur T; Shapiro, Daniel I; MacDonald, Allison N; Goulding, Sandra M; Brasfield, Joy L; Walker, Elaine F

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". The notion that adolescence is characterized by dramatic changes in behavior, and often by emotional upheaval, is widespread and longstanding in popular western culture. In recent decades, this notion has gained increasing support from empirical research showing that the peri- and post-pubertal developmental stages are associated with a significant rise in the rate of psychiatric symptoms and syndromes. As a result, interest in adolescent development has burgeoned among researchers focused on the origins of schizophrenia and other psychotic disorders. Two factors have fueled this trend: 1) increasing evidence from longitudinal research that adolescence is the modal period for the emergence of "prodromal" manifestations, or precursors of psychotic symptoms, and 2) the rapidly accumulating scientific findings on brain structural and functional changes occurring during adolescence and young adulthood. Further, gonadal and adrenal hormones are beginning to play a more prominent role in conceptualizations of adolescent brain development, as well as in the origins of psychiatric symptoms during this period (Walker and Bollini, 2002; Walker et al., 2008). In this paper, we begin by providing an overview of the nature and course of psychotic disorders during adolescence/young adulthood. We then turn to the role of hormones in modulating normal brain development, and the potential role they might play in the abnormal brain changes that characterize youth at clinical high-risk (CHR) for psychosis. The activational and organizational effects of hormones are explored, with a focus on how hormone-induced changes might be linked with neuropathological processes in the emergence of psychosis. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Profile of children diagnosed with autistic spectrum disorder managed at a tertiary child development unit.

    Science.gov (United States)

    Lian, Wee Bin; Ho, Selina Kah Ying

    2012-12-01

    There has been a rising trend in childhood developmental and behavioural disorders (CDABD). This study reports the profile of children with autistic spectrum disorders (ASD) initially referred for evaluation of CDABD. The CDABD database prospectively collected data of all consenting children referred in 2003 to the then Child Development Unit at KK Women's and Children's Hospital. All received medical consultation, followed by further assessments and intervention. Patients were tracked for one year. Among 542 referred children, 32% (n = 170) received a diagnosis of ASD one year after the first consultation. Most were male, with a male to female ratio of 4.5:1. The median age at the first consultation was 41 (19,109) months. The main presenting concern was a delay in the development of speech and language skills in 78% of the children. A significant number had behavioural (63%) and social interaction (34%) issues. Criteria for the diagnosis of ASD according to the Diagnostic Statistical Manual IV-Revised were fulfilled in almost 90%. With the remaining refusing or deferring evaluation, only 74% received a psychological assessment. ASD was assessed to be severe or moderate in 86% of the children. Three-quarters remained on follow-up one year after the first consultation. The majority were referred for either centre- or school-based intervention programmes, with 70% assessed to have improved at the one-year mark. This is the first presentation of local data that aids programme planning and resource allocation. Children with ASD have varied outcomes. It is important to identify and intervene early in order to optimise development and functionality.

  14. Developing biomarkers in mood disorders research through the use of rapid-acting antidepressants.

    Science.gov (United States)

    Niciu, Mark J; Mathews, Daniel C; Nugent, Allison C; Ionescu, Dawn F; Furey, Maura L; Richards, Erica M; Machado-Vieira, Rodrigo; Zarate, Carlos A

    2014-04-01

    An impediment to progress in mood disorders research is the lack of analytically valid and qualified diagnostic and treatment biomarkers. Consistent with the National Institute of Mental Health (NIMH)'s Research Domain Criteria (RDoC) initiative, the lack of diagnostic biomarkers has precluded us from moving away from a purely subjective (symptom-based) toward a more objective diagnostic system. In addition, treatment response biomarkers in mood disorders would facilitate drug development and move beyond trial-and-error toward more personalized treatments. As such, biomarkers identified early in the pathophysiological process are proximal biomarkers (target engagement), while those occurring later in the disease process are distal (disease pathway components). One strategy to achieve this goal in biomarker development is to increase efforts at the initial phases of biomarker development (i.e. exploration and validation) at single sites with the capability of integrating multimodal approaches across a biological systems level. Subsequently, resultant putative biomarkers could then undergo characterization and surrogacy as these latter phases require multisite collaborative efforts. We have used multimodal approaches - genetics, proteomics/metabolomics, peripheral measures, multimodal neuroimaging, neuropsychopharmacological challenge paradigms and clinical predictors - to explore potential predictor and mediator/moderator biomarkers of the rapid-acting antidepressants ketamine and scopolamine. These exploratory biomarkers may then be used for a priori stratification in larger multisite controlled studies during the validation and characterization phases with the ultimate goal of surrogacy. In sum, the combination of target engagement and well-qualified disease-related measures are crucial to improve our pathophysiological understanding, personalize treatment selection, and expand our armamentarium of novel therapeutics. © 2013 Wiley Periodicals, Inc.

  15. Pathophysiologic aspects of the development of cognitive disorders in chronic heart failure in elderly patients

    Directory of Open Access Journals (Sweden)

    M A Pokachalova

    2018-04-01

    Full Text Available The present literature review presents current views on pathophysiologic aspects of the formation and progression of cognitive disorders in chronic heart failure in elderly patients. Advanced age itself is an important predictor of the development of cardiovascular, neurodegenerative and other diseases. Involutive changes of cardiovascular system are known to potentiate the development of chronic heart failure. Heart failure in older people usually develops gradually. Formation of the cognitive deficit in heart disease is associated with chronic cerebral ischemia as well as a cascade of neurochemical processes occurring in the brain, eventually forming a vicious circle. Often the symptoms of cerebral ischemia due to reduced stroke volume occur much earlier than congestion signs in other organs and systems. Chronic cerebral ischemia that occurs due to violation of cerebral hemodynamics, is associated with both extracerebral and intracerebral causes, which in turn contributes to the development of chronic brain hypoxia and aggravation of cognitive dysfunction. Thus, the features of the development and course of disease in people of older age groups indicate that in geriatric practice existing diagnostic schemes are not always applicable. When observing patients of elderly and senile age with chronic heart failure, during the assessment of their condition and running diagnostic tests, special attention should be payed to the earliest detection of cognitive dysfunction signs in order to correct the patient's treatment and improve quality of life.

  16. Autism spectrum disorder in adults: diagnosis, management, and health services development

    Directory of Open Access Journals (Sweden)

    Murphy CM

    2016-07-01

    Full Text Available Clodagh M Murphy,1,2 C Ellie Wilson,1–3 Dene M Robertson,1,2 Christine Ecker,1,4 Eileen M Daly,1,2 Neil Hammond,1,2 Anastasios Galanopoulos,1,2 Iulia Dud,1,2 Declan G Murphy,1,2 Grainne M McAlonan1,2 1Sackler Institute for Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Sciences, King’s College London, Institute of Psychiatry, Psychology & Neuroscience, 2Behavioural and Developmental Psychiatry Clinical Academic Group, Behavioural Genetics Clinic, National Adult Autism Service, South London and Maudsley Foundation NHS Trust, London, UK; 3Individual Differences, Language and Cognition Lab, Department of Developmental and Educational Psychology, University of Seville, Spain; 4Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital, Goethe-University, Frankfurt am Main, Germany Abstract: Autism spectrum disorder (ASD is a common neurodevelopmental disorder characterized by pervasive difficulties since early childhood across reciprocal social communication and restricted, repetitive interests and behaviors. Although early ASD research focused primarily on children, there is increasing recognition that ASD is a lifelong neurodevelopmental disorder. However, although health and education services for children with ASD are relatively well established, service provision for adults with ASD is in its infancy. There is a lack of health services research for adults with ASD, including identification of comorbid health difficulties, rigorous treatment trials (pharmacological and psychological, development of new pharmacotherapies, investigation of transition and aging across the lifespan, and consideration of sex differences and the views of people with ASD. This article reviews available evidence regarding the etiology, legislation, diagnosis, management, and service provision for adults with ASD and considers what is needed to support adults with ASD as they age. We conclude

  17. Maternal depression and anxiety disorders (MDAD and child development: A Manitoba population-based study.

    Directory of Open Access Journals (Sweden)

    Brenda Comaskey

    Full Text Available To examine the association between maternal depression and anxiety disorders (MDAD and child development assessed during the kindergarten year.Administrative data from several health and social databases in Manitoba, Canada, were used to study 18,331 mother-child pairs. MDAD over the period from one year prior to the child's birth to the kindergarten year was defined using physician diagnoses and filled prescriptions. Child development was assessed during the kindergarten year using the Early Development Instrument (EDI which measures vulnerability across five domains of development. Structural equation modeling was used to examine associations between timing, recurrence and severity of MDAD and child outcomes. Health at Birth (preterm, low birth weight, neonatal intensive care stay and long birth hospitalization, Family Context (teen mother, lone parent, socio-economic status (SES, child age and child sex were covariates.MDAD had a modest negative association with child EDI scores across all models tested, particularly for social, emotional and physical development. Prenatal MDAD had a stronger negative association with outcomes than other time periods; however, recurrent MDAD had a stronger negative association with outcomes than any specific time period or MDAD severity. The influence of MDAD was mediated by Family Context, which had a strong, negative association with outcomes, particularly language and cognitive development.The number of time periods a child was exposed to MDAD in early childhood was more negatively associated with five areas of child development than timing or severity. Prenatal exposure may be more sensitive to MDAD than other time periods. The familial context (teen mother, lone parenthood and low SES had a stronger influence on child outcomes than MDAD. Findings can be used to inform interventions which address maternal mental health from the prenatal period onward, and to support disadvantaged families to encourage

  18. Longitudinal development of thalamic and internal capsule microstructure in autism spectrum disorder.

    Science.gov (United States)

    McLaughlin, Kristine; Travers, Brittany G; Dadalko, Olga I; Dean, Douglas C; Tromp, Do; Adluru, Nagesh; Destiche, Daniel; Freeman, Abigail; Prigge, Molly D; Froehlich, Alyson; Duffield, Tyler C; Zielinski, Brandon A; Bigler, Erin D; Lange, Nicholas; Anderson, Jeff S; Alexander, Andrew L; Lainhart, Janet E

    2018-03-01

    The thalamus is a key sensorimotor relay area that is implicated in autism spectrum disorder (ASD). However, it is unknown how the thalamus and white-matter structures that contain thalamo-cortical fiber connections (e.g., the internal capsule) develop from childhood into adulthood and whether this microstructure relates to basic motor challenges in ASD. We used diffusion weighted imaging in a cohort-sequential design to assess longitudinal development of the thalamus, and posterior- and anterior-limbs of the internal capsule (PLIC and ALIC, respectively) in 89 males with ASD and 56 males with typical development (3-41 years; all verbal). Our results showed that the group with ASD exhibited different developmental trajectories of microstructure in all regions, demonstrating childhood group differences that appeared to approach and, in some cases, surpass the typically developing group in adolescence and adulthood. The PLIC (but not ALIC nor thalamus) mediated the relation between age and finger-tapping speed in both groups. Yet, the gap in finger-tapping speed appeared to widen at the same time that the between-group gap in the PLIC appeared to narrow. Overall, these results suggest that childhood group differences in microstructure of the thalamus and PLIC become less robust in adolescence and adulthood. Further, finger-tapping speed appears to be mediated by the PLIC in both groups, but group differences in motor speed that widen during adolescence and adulthood suggest that factors beyond the microstructure of the thalamus and internal capsule may contribute to atypical motor profiles in ASD. Autism Res 2018, 11: 450-462. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Microstructure of the thalamus, a key sensory and motor brain area, appears to develop differently in individuals with autism spectrum disorder (ASD). Microstructure is important because it informs us of the density and organization of different brain tissues. During

  19. Recent developments in the treatment of anxiety disorders in children and adolescents.

    Science.gov (United States)

    Creswell, Cathy; Waite, Polly

    2016-08-01

    Anxiety disorders are among the most common emotional difficulties experienced by children and young people. They cause significant disturbance to the lives of young people and their families and present a risk for lifelong psychological disturbance. Effective psychological (ie, cognitive-behaviour therapy (CBT)) and pharmacological interventions (eg, selective serotonin reuptake inhibitors (SSRIs)) have been established. However, the risk of adverse effects and unknown long-term effects of using SSRIs has led to recommendations that CBT is delivered as a first-line intervention. Recent innovations have included the development of low-intensity CBT programmes, delivered briefly via parents or online. These hold promise to increase access to psychological therapies for children and young people with these common and severe difficulties. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  20. Morbidity, mortality, and socioeconomics in females with 46,XY disorders of sex development: a nationwide study

    DEFF Research Database (Denmark)

    Berglund, Agnethe; Johannsen, Trine H; Stochholm, Kirstine

    2018-01-01

    Context: Little is known about long-term health outcomes in phenotypic females with 46,XY disorders of sex development (XY females) and the socioeconomic profile is not described in detail. Objective: To describe morbidity, mortality and socioeconomic status in XY females in a comparison...... the general population. Interventions: None. Main outcome measures: combined mortality and morbidity as well as chapter-specific morbidity. Medicinal use and socioeconomic profile, including education, cohabitation and retirement. Results: Compared to female controls overall morbidity was increased in XY...... closely related to the DSD condition. Judged on educational level and income XY females perform well on the labor market. However, DSD seems to impact on the prospects of family life.​....

  1. Incidence, prevalence, diagnostic delay, and clinical presentation of female 46,XY disorders of sex development

    DEFF Research Database (Denmark)

    Berglund, Agnethe; Johannsen, Trine H; Krag, Kirstine Stochholm

    2016-01-01

    CONTEXT: The prevalence of phenotypic females with a 46,XY karyotype is low, thus current knowledge about age and clinical presentation at diagnosis is sparse even for the most frequent conditions, androgen insensitivity syndrome (AIS), and gonadal dysgenesis. OBJECTIVE: To estimate incidence......, prevalence, age at diagnosis, and clinical presentation at diagnosis in 46,XY females. DESIGN AND SETTING: A nationwide study covering all known females with a 46,XY karyotype in Denmark since 1960. The diagnosis of 46,XY disorder of sex development (DSD) was determined by medical record evaluation, data.......0-13.5; range, 0-34 y) in AIS and 17.0 years (95% confidence interval, 15.5-19.0; range, 0-28 y) in gonadal dysgenesis (P = .001). Clinical presentation was dependent on cause of DSD. CONCLUSIONS: The first estimate on prevalence of 46,XY females is 6.4 per 100 000 live born females. The presentation of AIS...

  2. Development and Evaluation of a Smartphone-Based Measure of Social Rhythms for Bipolar Disorder.

    Science.gov (United States)

    Matthews, Mark; Abdullah, Saeed; Murnane, Elizabeth; Voida, Stephen; Choudhury, Tanzeem; Gay, Geri; Frank, Ellen

    2016-08-01

    Dynamic psychological processes are most often assessed using self-report instruments. This places a constraint on how often and for how long data can be collected due to the burden placed on human participants. Smartphones are ubiquitous and highly personal devices, equipped with sensors that offer an opportunity to measure and understand psychological processes in real-world contexts over the long term. In this article, we present a novel smartphone approach to address the limitations of self-report in bipolar disorder where mood and activity are key constructs. We describe the development of MoodRhythm, a smartphone application that incorporates existing self-report elements from interpersonal and social rhythm therapy, a clinically validated treatment, and combines them with novel inputs from smartphone sensors. We reflect on lessons learned in transitioning from an existing self-report instrument to one that involves smartphone sensors and discuss the potential impact of these changes on the future of psychological assessment.

  3. How parents introduce new words to young children: The influence of development and developmental disorders.

    Science.gov (United States)

    Adamson, Lauren B; Bakeman, Roger; Brandon, Benjamin

    2015-05-01

    This study documents how parents weave new words into on-going interactions with children who are just beginning to speak. Dyads with typically developing toddlers and with young children with autism spectrum disorder and Down syndrome (n=56, 23, and 29) were observed using a Communication Play Protocol during which parents could use novel words to refer to novel objects. Parents readily introduced both labels and sound words even when their child did not respond expressively or produce the words. Results highlight both how parents act in ways that may facilitate their child's appreciation of the relation between a new word and its referent and how they subtly adjust their actions to suit their child's level of word learning and specific learning challenges. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Patient-identified events implicated in the development of body dysmorphic disorder.

    Science.gov (United States)

    Weingarden, Hilary; Curley, Erin E; Renshaw, Keith D; Wilhelm, Sabine

    2017-06-01

    Little is known about the causes of body dysmorphic disorder (BDD), but researchers have proposed a diathesis-stress model. This study uses a patient-centered approach to identify stressful events to which patients attribute the development of their BDD symptoms. An Internet-recruited sample of 165 adults with BDD participated. A large minority of participants attributed the development of their BDD to a triggering event. Bullying experiences were the most commonly described type of event. Additionally, most events were interpersonal and occurred during grade school or middle school. There were no differences in severity of psychosocial outcomes between participants who did or did not attribute their BDD to a specific triggering event. However, participants who specifically attributed their BDD development to a bullying experience had poorer psychosocial outcomes (i.e., perceived social support, depression severity, functional impairment, quality of life) compared to those who attributed their BDD development to another type of triggering event. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Connectivity dynamics in typical development and its relationship to autistic traits and autism spectrum disorder.

    Science.gov (United States)

    Rashid, Barnaly; Blanken, Laura M E; Muetzel, Ryan L; Miller, Robyn; Damaraju, Eswar; Arbabshirani, Mohammad R; Erhardt, Erik B; Verhulst, Frank C; van der Lugt, Aad; Jaddoe, Vincent W V; Tiemeier, Henning; White, Tonya; Calhoun, Vince

    2018-03-30

    Recent advances in neuroimaging techniques have provided significant insights into developmental trajectories of human brain function. Characterizations of typical neurodevelopment provide a framework for understanding altered neurodevelopment, including differences in brain function related to developmental disorders and psychopathology. Historically, most functional connectivity studies of typical and atypical development operate under the assumption that connectivity remains static over time. We hypothesized that relaxing stationarity assumptions would reveal novel features of both typical brain development related to children on the autism spectrum. We employed a "chronnectomic" (recurring, time-varying patterns of connectivity) approach to evaluate transient states of connectivity using resting-state functional MRI in a population-based sample of 774 6- to 10-year-old children. Dynamic connectivity was evaluated using a sliding-window approach, and revealed four transient states. Internetwork connectivity increased with age in modularized dynamic states, illustrating an important pattern of connectivity in the developing brain. Furthermore, we demonstrated that higher levels of autistic traits and ASD diagnosis were associated with longer dwell times in a globally disconnected state. These results provide a roadmap to the chronnectomic organization of the developing brain and suggest that characteristics of functional brain connectivity are related to children on the autism spectrum. © 2018 Wiley Periodicals, Inc.

  6. Intellectual Development in Autism Spectrum Disorders: New Insights from Longitudinal Studies

    Directory of Open Access Journals (Sweden)

    Giacomo eVivanti

    2013-07-01

    Full Text Available The presence/absence of Intellectual Disability (ID is considered to be the most critical factor affecting outcomes in individuals with Autism Spectrum Disorders (ASD. However, the question of the specific nature of ID in ASD has received little attention, with the current view being that ID is a co-morbid condition (i.e., one that is unrelated in etiology and causality from the ASD itself. Recent advances in developmental neuroscience, highlighting the importance of early exposure to social experiences for cognitive development, support an alternative view; that ID in ASD might emerge as a consequence of severe social-communication deficits on the experience-dependent mechanisms underlying neurocognitive development. We tested this prediction in two independent samples of young children with ASD (Ns=23 and 60, finding that children with greater ASD severity at an initial assessment were more likely to present with poorer cognitive outcomes at a later assessment, irrespective of initial cognitive level. These results suggest that ASD symptom severity contributes to the extent to which the environmental input required to support ‘typical’ brain development can be processed by the individual, so that the risk of developing ID increases as the number and severity of ASD social-communicative impairments increase.

  7. Neurodevelopmental Versus Neurodegenerative Model of Schizophrenia and Bipolar Disorder: Comparison with Physiological Brain Development and Aging.

    Science.gov (United States)

    Buoli, Massimiliano; Serati, Marta; Caldiroli, Alice; Cremaschi, Laura; Altamura, Alfredo Carlo

    2017-03-01

    Available data support a contribution of both neurodevelopmental and neurodegenerative factors in the etiology of schizophrenia (SCH) and bipolar disorder (BD). Of note, one of the most important issue of the current psychiatric research is to identify the specific factors that contribute to impaired brain development and neurodegeneration in SCH and BD, and especially how these factors alter normal brain development and physiological aging process. Our hypothesis is that only specific damages, taking place in precise brain development stages, are associated with future SCH /BD onset and that neurodegeneration consists of an acceleration of brain aging after SCH /BD onset. In support of our hypothesis, the results of the present narrative mini-review shows as neurodevelopmental damages generally contribute to neuropsychiatric syndromes (e.g. hypothyroidism or treponema pallidum), but only some of them are specifically associated with adult SCH and BD (e.g. toxoplasma or substance abuse), particularly if they happen in specific stages of brain development. On the other hand, cognitive impairment and brain changes, associated with long duration of SCH /BD, look like what happens during aging: memory, executive domains and prefrontal cortex are implicated both in aging and in SCH /BD progression. Future research will explore possible validity of this etiological model for SCH and BD.

  8. Gender role behavior in children with XY karyotype and disorders of sex development.

    Science.gov (United States)

    Jürgensen, Martina; Hiort, Olaf; Holterhus, Paul-Martin; Thyen, Ute

    2007-03-01

    Children exhibit gender-typical preferences in play, toys, activities and interests, and playmates. Several studies suggest that high concentrations of pre- and postnatal androgens contribute to male-typical behavior development, whereas female-typical behavior develops in the absence of high androgens levels. This study aims to explore the consequences of hypoandrogenization on gender-typical behavior in children who have an XY karyotype and disorder of sex development (DSD). Participants included 33 children (ages 2-12 years) with an XY karyotype and DSD; 21 reared as girls and 12 reared as boys. Children's preferred activities and interests and playmate preferences were assessed with parent report questionnaires, a structured free-play task, and choice of a toy to keep as a gift. Participant's responses were compared to those of children recruited in a pre-school and elementary school survey (N=166). In this study, the degree of hypoandrogenization as indicated by genital stage and diagnosis showed a significant relationship to nearly all of the gender-related behaviors assessed, supporting the hypothesis that masculinization of gender role behavior is a function of prenatal androgen exposure. Despite the fact that children with partial androgen effects reared as girls showed increased "boyish" behaviors, they did not show increased signs of gender identity confusion or instability on a group level. We conclude that androgen exposure plays a decisive role in the development of gender-typical behavior in children with XY karyotype and DSD conditions.

  9. Analysis of the peptidoglycan hydrolase complement of Lactobacillus casei and characterization of the major γ-D-glutamyl-L-lysyl-endopeptidase.

    Science.gov (United States)

    Regulski, Krzysztof; Courtin, Pascal; Meyrand, Mickael; Claes, Ingmar J J; Lebeer, Sarah; Vanderleyden, Jos; Hols, Pascal; Guillot, Alain; Chapot-Chartier, Marie-Pierre

    2012-01-01

    Peptidoglycan (PG) is the major component of Gram positive bacteria cell wall and is essential for bacterial integrity and shape. Bacteria synthesize PG hydrolases (PGHs) which are able to cleave bonds in their own PG and play major roles in PG remodelling required for bacterial growth and division. Our aim was to identify the main PGHs in Lactobacillus casei BL23, a lactic acid bacterium with probiotic properties.The PGH complement was first identified in silico by amino acid sequence similarity searches of the BL23 genome sequence. Thirteen PGHs were detected with different predicted hydrolytic specificities. Transcription of the genes was confirmed by RT-PCR. A proteomic analysis combining the use of SDS-PAGE and LC-MS/MS revealed the main seven PGHs synthesized during growth of L. casei BL23. Among these PGHs, LCABL_02770 (renamed Lc-p75) was identified as the major one. This protein is the homolog of p75 (Msp1) major secreted protein of Lactobacillus rhamnosus GG, which was shown to promote survival and growth of intestinal epithelial cells. We identified its hydrolytic specificity on PG and showed that it is a γ-D-glutamyl-L-lysyl-endopeptidase. It has a marked specificity towards PG tetrapeptide chains versus tripeptide chains and for oligomers rather than monomers. Immunofluorescence experiments demonstrated that Lc-p75 localizes at cell septa in agreement with its role in daughter cell separation. It is also secreted under an active form as detected in zymogram. Comparison of the muropeptide profiles of wild type and Lc-p75-negative mutant revealed a decrease of the amount of disaccharide-dipeptide in the mutant PG in agreement with Lc-p75 activity. As a conclusion, Lc-p75 is the major L. casei BL23 PGH with endopeptidase specificity and a key role in daughter cell separation. Further studies will aim at investigating the role of Lc-p75 in the anti-inflammatory potential of L. casei BL23.

  10. Analysis of the peptidoglycan hydrolase complement of Lactobacillus casei and characterization of the major γ-D-glutamyl-L-lysyl-endopeptidase.

    Directory of Open Access Journals (Sweden)

    Krzysztof Regulski

    Full Text Available Peptidoglycan (PG is the major component of Gram positive bacteria cell wall and is essential for bacterial integrity and shape. Bacteria synthesize PG hydrolases (PGHs which are able to cleave bonds in their own PG and play major roles in PG remodelling required for bacterial growth and division. Our aim was to identify the main PGHs in Lactobacillus casei BL23, a lactic acid bacterium with probiotic properties.The PGH complement was first identified in silico by amino acid sequence similarity searches of the BL23 genome sequence. Thirteen PGHs were detected with different predicted hydrolytic specificities. Transcription of the genes was confirmed by RT-PCR. A proteomic analysis combining the use of SDS-PAGE and LC-MS/MS revealed the main seven PGHs synthesized during growth of L. casei BL23. Among these PGHs, LCABL_02770 (renamed Lc-p75 was identified as the major one. This protein is the homolog of p75 (Msp1 major secreted protein of Lactobacillus rhamnosus GG, which was shown to promote survival and growth of intestinal epithelial cells. We identified its hydrolytic specificity on PG and showed that it is a γ-D-glutamyl-L-lysyl-endopeptidase. It has a marked specificity towards PG tetrapeptide chains versus tripeptide chains and for oligomers rather than monomers. Immunofluorescence experiments demonstrated that Lc-p75 localizes at cell septa in agreement with its role in daughter cell separation. It is also secreted under an active form as detected in zymogram. Comparison of the muropeptide profiles of wild type and Lc-p75-negative mutant revealed a decrease of the amount of disaccharide-dipeptide in the mutant PG in agreement with Lc-p75 activity. As a conclusion, Lc-p75 is the major L. casei BL23 PGH with endopeptidase specificity and a key role in daughter cell separation. Further studies will aim at investigating the role of Lc-p75 in the anti-inflammatory potential of L. casei BL23.

  11. THE ROLE OF IMMUNOLOGICAL DISORDERS IN THE DEVELOPMENT OF ATOPIC DERMATITIS

    Directory of Open Access Journals (Sweden)

    E. E. Zhiltsova

    2018-01-01

    Full Text Available The basis for the development of atopic dermatitis (AtD is a complex interaction between genetic disorders, environmental factors, lack of the skin barrier and immunological disorders. In view of the importance of immunological disorders in the etiopathogenesis of atopic dermatitis, the study of these parameters in patients with AtD is a necessary aspect to assess the severity of the course, prognosis of complications and recurrence.Purpose. Comprehensive assessment of clinical and immunological parameters in adolescents with atopic dermatitis.Materials and methods. The study included examination of 28 patients with atopic dermatitis aged from 12 to 16 years, with disease duration from 10 to 15 years, which included analysis of complaints and anamnesis data, evaluation of disease severity on the SCORAD scale, General clinical and immunological studies. The peculiarities of cellular and humoral immunity in the relapse stage were determined. The main indicators of phagocytic activity of blood neutrophils were also investigated.Results. In the analysis of anamnestic data of patients, a history of diseases associated with atopia in 16 (57.1% of 28 adolescents (AtD, bronchial asthma in relatives of the first and second line of kinship was revealed. When assessing the disease severity on a scale of SCORAD, prevailed patients with moderate to severe atopic dermatitis over — 19 (67,9% patients, the average score of the assessment of the severity of AtD amounted to 29.3 ± 1,25. The conducted immunological examination with assessment of cellular and humoral immunity showed significant changes in immunological reactivity in patients with AtD. On the part of the cellular immunity level it is necessary to note a clear decrease in CD3+ and CD8+, as well as an increase in the subpopulation of T-lymphocytes — CD4+ and b-lymphocytes — CD20+ in most patients compared to normal indicators characteristic of this age group. Compared to healthy adolescents

  12. Surgery in disorders of sex development (DSD) with a gender issue: If (why), when, and how?

    Science.gov (United States)

    Mouriquand, Pierre D E; Gorduza, Daniela Brindusa; Gay, Claire-Lise; Meyer-Bahlburg, Heino F L; Baker, Linda; Baskin, Laurence S; Bouvattier, Claire; Braga, Luis H; Caldamone, Anthony C; Duranteau, Lise; El Ghoneimi, Alaa; Hensle, Terry W; Hoebeke, Piet; Kaefer, Martin; Kalfa, Nicolas; Kolon, Thomas F; Manzoni, Gianantonio; Mure, Pierre-Yves; Nordenskjöld, Agneta; Pippi Salle, J L; Poppas, Dix Phillip; Ransley, Philip G; Rink, Richard C; Rodrigo, Romao; Sann, Léon; Schober, Justine; Sibai, Hisham; Wisniewski, Amy; Wolffenbuttel, Katja P; Lee, Peter

    2016-06-01

    Ten years after the consensus meeting on disorders of sex development (DSD), genital surgery continues to raise questions and criticisms concerning its indications, its technical aspects, timing and evaluation. This standpoint details each distinct situation and its possible management in 5 main groups of DSD patients with atypical genitalia: the 46,XX DSD group (congenital adrenal hyperplasia); the heterogeneous 46,XY DSD group (gonadal dysgenesis, disorders of steroidogenesis, target tissues impairments …); gonosomic mosaicisms (45,X/46,XY patients); ovo-testicular DSD; and "non-hormonal/non chromosomal" DSD. Questions are summarized for each DSD group with the support of literature and the feed-back of several world experts. Given the complexity and heterogeneity of presentation there is no consensus regarding the indications, the timing, the procedure nor the evaluation of outcome of DSD surgery. There are, however, some issues on which most experts would agree: 1) The need for identifying centres of expertise with a multidisciplinary approach; 2) A conservative management of the gonads in complete androgen insensitivity syndrome at least until puberty although some studies expressed concerns about the heightened tumour risk in this group; 3) To avoid vaginal dilatation in children after surgical reconstruction; 4) To keep asymptomatic mullerian remnants during childhood; 5) To remove confirmed streak gonads when Y material is present; 6) It is likely that 46,XY cloacal exstrophy, aphallia and severe micropenis would do best raised as male although this is based on limited outcome data. There is general acknowledgement among experts that timing, the choice of the individual and irreversibility of surgical procedures are sources of concerns. There is, however, little evidence provided regarding the impact of non-treated DSD during childhood for the individual development, the parents, society and the risk of stigmatization. The low level of evidence should

  13. The role of alexithymia in the development of functional motor symptoms (conversion disorder).

    Science.gov (United States)

    Demartini, Benedetta; Petrochilos, Panayiota; Ricciardi, Lucia; Price, Gary; Edwards, Mark J; Joyce, Eileen

    2014-10-01

    The mechanisms leading to the development of functional motor symptoms (FMS) are of pathophysiological and clinical relevance, yet are poorly understood. The aim of the present study was to evaluate whether impaired emotional processing at the cognitive level (alexithymia) is present in patients affected by FMS. We conducted a cross-sectional study in a population of patients with FMS and in two control groups (patients with organic movement disorders (OMD) and healthy volunteers). 55 patients with FMS, 33 patients affected by OMD and 34 healthy volunteers were recruited. The assessment included the 20-item Toronto Alexithymia Scale (TAS-20), the Montgomery-Asberg Depression Rating Scale, the Reading the Mind in the Eyes' Test and the Structured Clinical Interview for Personality Disorders. Alexithymia was present in 34.5% of patients with FMS, 9.1% with OMD and 5.9% of the healthy volunteers, which was significantly higher in the FMS group (χ(2) (2)=14.129, pOCPD) in the FMS group (χ(2) (2)=16.217, pOCPD also reached threshold criteria for alexithymia. Because alexithymia is a mental state denoting the inability to identify emotions at a cognitive level, one hypothesis is that some patients misattribute autonomic symptoms of anxiety, for example, tremor, paraesthesiae, paralysis, to that of a physical illness. Further work is required to understand the contribution of OCPD to the development of FMS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. Development of TRPN dendrimer-modified disordered mesoporous silica for CO{sub 2} capture

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xiaoyun; Zhang, Sisi; Qin, Hongyan; Wu, Wei, E-mail: wuweiupc@upc.edu.cn

    2014-08-15

    Highlights: • A novel series of TRPN dendrimers are synthesized. • Structurally disordered mesoporous silica was used to develop the CO{sub 2} adsorbent. • The CO{sub 2} adsorption capacity is relatively high. • The sorbent exhibits a high stability after 12 cycling runs. • The sorbent achieves complete desorption at low temperature (60 °C). - Abstract: A novel series of tri(3-aminopropyl) amine (TRPN) dendrimers were synthesized and impregnated on structurally disordered mesoporous silica (DMS) to generate CO{sub 2} adsorbents (TS). The physicochemical and adsorption properties of the adsorbents before and after dendrimer modification were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and N{sub 2} adsorption–desorption (N{sub 2}-BET) techniques. CO{sub 2} adsorption–desorption tests indicated that the sorbent demonstrates high CO{sub 2} adsorption capacity (138.1 mg g{sup −1} for G1 sample TS-G1-3CN-50 and 91.7 mg g{sup −1} for G2 sample TS-G2-6CN-50), and can completely desorb CO{sub 2} under vacuum at 60 °C. Its CO{sub 2} adsorption capacity at 25 °C increases with the amine loading, achieving the highest adsorption capacity (140.6 mg g{sup −1} for TS-G1-3CN) at 60%. The developed TS materials exhibited excellent cycling stability. After 12 consecutive adsorption–desorption runs, TS-G1-3CN-50 shows an adsorption capacity of 136.0 mg g{sup −1}, retaining 98.5% of its original value.

  15. Abnormal development of monoaminergic neurons is implicated in mood fluctuations and bipolar disorder.

    Science.gov (United States)

    Jukic, Marin M; Carrillo-Roa, Tania; Bar, Michal; Becker, Gal; Jovanovic, Vukasin M; Zega, Ksenija; Binder, Elisabeth B; Brodski, Claude

    2015-03-01

    Subtle mood fluctuations are normal emotional experiences, whereas drastic mood swings can be a manifestation of bipolar disorder (BPD). Despite their importance for normal and pathological behavior, the mechanisms underlying endogenous mood instability are largely unknown. During embryogenesis, the transcription factor Otx2 orchestrates the genetic networks directing the specification of dopaminergic (DA) and serotonergic (5-HT) neurons. Here we behaviorally phenotyped mouse mutants overexpressing Otx2 in the hindbrain, resulting in an increased number of DA neurons and a decreased number of 5-HT neurons in both developing and mature animals. Over the course of 1 month, control animals exhibited stable locomotor activity in their home cages, whereas mutants showed extended periods of elevated or decreased activity relative to their individual average. Additional behavioral paradigms, testing for manic- and depressive-like behavior, demonstrated that mutants showed an increase in intra-individual fluctuations in locomotor activity, habituation, risk-taking behavioral parameters, social interaction, and hedonic-like behavior. Olanzapine, lithium, and carbamazepine ameliorated the behavioral alterations of the mutants, as did the mixed serotonin receptor agonist quipazine and the specific 5-HT2C receptor agonist CP-809101. Testing the relevance of the genetic networks specifying monoaminergic neurons for BPD in humans, we applied an interval-based enrichment analysis tool for genome-wide association studies. We observed that the genes specifying DA and 5-HT neurons exhibit a significant level of aggregated association with BPD but not with schizophrenia or major depressive disorder. The results of our translational study suggest that aberrant development of monoaminergic neurons leads to mood fluctuations and may be associated with BPD.

  16. Treatment Development and Feasibility Study of Family-Focused Treatment for Adolescents with Bipolar Disorder and Comorbid Substance Use Disorders

    Science.gov (United States)

    Goldstein, Benjamin I.; Goldstein, Tina R.; Collinger, Katelyn A.; Axelson, David A.; Bukstein, Oscar G.; Birmaher, Boris; Miklowitz, David J.

    2014-01-01

    Background Comorbid substance use disorders (SUD) are associated with increased illness severity and functional impairment among adolescents with bipolar disorder (BD). Previous psychosocial treatment studies have excluded adolescents with both BD and SUD. Studies suggest that integrated interventions are optimal for adults with BD and SUD. Methods We modified family-focused treatment for adolescents with BD (FFT-A) in order to explicitly target comorbid SUD (FFT-SUD). Ten adolescents with BD who had both SUD and an exacerbation of manic, depressed, or mixed symptoms within the last 3 months were enrolled. FFT-SUD was offered as an adjunct to pharmacotherapy, with a target of 21 sessions over 12 months of treatment. The FFT-SUD manual was iteratively modified to integrate a concurrent focus on SUD. Results Six subjects completed a mid-treatment 6-month assessment (after a mean of 16 sessions was completed). Of the 10 subjects, 3 dropped out early ( after ≤ 1 session); in the case of each of these subjects, the participating parent had active SUD. No other subjects in the study had a parent with active SUD. Preliminary findings suggested significant reductions in manic symptoms and depressive symptoms and improved global functioning. Reduction in cannabis use was modest and did not reach significance. Limitations Limitations included a small sample, open treatment, concurrent medications, and no control group. Conclusions These preliminary findings suggest that FFT-SUD is a feasible intervention, particularly for youth without parental SUD. FFT-SUD may be effective in treating mood symptoms, particularly depression, despite modest reductions in substance use. Integrating motivation enhancing strategies may augment the effect of this intervention on substance use. Additional strategies, such as targeting parental substance use, may prevent early attrition. PMID:24847999

  17. Language Development in Children with Language Disorders: An Introduction to Skinner's Verbal Behavior and the Techniques for Initial Language Acquisition

    Science.gov (United States)

    Casey, Laura Baylot; Bicard, David F.

    2009-01-01

    Language development in typically developing children has a very predictable pattern beginning with crying, cooing, babbling, and gestures along with the recognition of spoken words, comprehension of spoken words, and then one word utterances. This predictable pattern breaks down for children with language disorders. This article will discuss…

  18. Associations between Language Development and Skin Conductance Responses to Faces and Eye Gaze in Children with Autism Spectrum Disorder

    Science.gov (United States)

    Stagg, Steven D.; Davis, Robert; Heaton, Pamela

    2013-01-01

    Attention to social stimuli is associated with language development, and arousal is associated with the increased viewing of stimuli. We investigated whether skin conductance responses (SCRs) are associated with language development in autism spectrum disorder (ASD): a population that shows abnormalities in both attention to others and language…

  19. Mealtime Behaviors of Preschool Children: Comparison of Children with Autism Spectrum Disorder and Children with Typical Development

    Science.gov (United States)

    Provost, Beth; Crowe, Terry K.; Osbourn, Patricia L.; McClain, Catherine; Skipper, Betty J.

    2010-01-01

    This study identified mealtime behaviors of young children (3-6 years old) with autism spectrum disorder (ASD) and compared these behaviors to children with typical development matched for age, gender, and ethnicity. The parents of children with ASD (n = 24) and children with typical development (n = 24) completed a mealtime survey to assess early…

  20. Evaluation of a Web-Based Professional Development Program (Project ACE) for Teachers of Children with Autism Spectrum Disorders

    Science.gov (United States)

    Rakap, Salih; Jones, Hazel A.; Emery, Alice Kaye

    2015-01-01

    This article describes the development, implementation, and second-year evaluation of Project Autism Competencies for Endorsement (ACE), a web-based professional development (PD) program that is designed to train teachers currently working in the field to meet the unique and diverse needs of children with autism spectrum disorders (ASDs). A…

  1. Recognition of Emotion from Facial Expressions with Direct or Averted Eye Gaze and Varying Expression Intensities in Children with Autism Disorder and Typically Developing Children

    Directory of Open Access Journals (Sweden)

    Dina Tell

    2014-01-01

    Full Text Available Eye gaze direction and expression intensity effects on emotion recognition in children with autism disorder and typically developing children were investigated. Children with autism disorder and typically developing children identified happy and angry expressions equally well. Children with autism disorder, however, were less accurate in identifying fear expressions across intensities and eye gaze directions. Children with autism disorder rated expressions with direct eyes, and 50% expressions, as more intense than typically developing children. A trend was also found for sad expressions, as children with autism disorder were less accurate in recognizing sadness at 100% intensity with direct eyes than typically developing children. Although the present research showed that children with autism disorder are sensitive to eye gaze direction, impairments in the recognition of fear, and possibly sadness, exist. Furthermore, children with autism disorder and typically developing children perceive the intensity of emotional expressions differently.

  2. Legal substance use and the development of a DSM-IV cannabis use disorder during adolescence: the TRAILS study.

    Science.gov (United States)

    Prince van Leeuwen, Andrea; Creemers, Hanneke E; Verhulst, Frank C; Vollebergh, Wilma A M; Ormel, Johan; van Oort, Floor; Huizink, Anja C

    2014-02-01

    To examine whether early onset of tobacco or alcohol use, and continued use of tobacco or alcohol in early adolescence, are related to a higher likelihood of developing a cannabis use disorder during adolescence. Data were used from four consecutive assessment waves of the TRacking Adolescents' Individual Lives Survey (TRAILS), a general Dutch population study. TRAILS is an ongoing longitudinal study that will follow the same group of adolescents from the ages of 10 to 24 years. The sample consisted of 1108 (58% female) adolescents (mean ages at the four assessment waves are 11.09, 13.56, 16.27 and 19.05 years, respectively) Cannabis use disorders were assessed using the Composite International Diagnostic Interview 3.0 (CIDI). Adolescent tobacco and alcohol use were assessed using self-report questionnaires. Early-onset tobacco use [odds ratio (OR) = 1.82, confidence interval (CI) = 1.05-3.14, P  0.05), was associated with a higher likelihood of developing a cannabis use disorder. Similarly, adolescents who reported continued use of tobacco (OR = 2.47, CI = 1.02-5.98, P  0.05), were more likely to develop a cannabis use disorder. Early-onset and continued tobacco use appear to predict the development of a cannabis use disorder in adolescence, whereas early onset and continued alcohol use do not. © 2013 Society for the Study of Addiction.

  3. Development of schizotypal symptoms following psychiatric disorders in childhood or adolescence.

    Science.gov (United States)

    Fagel, Selene S A A; Swaab, Hanna; De Sonneville, Leo M J; Van Rijn, Sophie; Pieterse, Jolijn K; Scheepers, Floor; Van Engeland, Herman

    2013-11-01

    It was examined how juvenile psychiatric disorders and adult schizotypal symptoms are associated. 731 patients of the Department of Child and Adolescent Psychiatry of the University Medical Centre Utrecht, the Netherlands, with mean age of 12.1 years (SD = 4.0) were reassessed at the mean age of 27.9 years (SD = 5.7) for adult schizotypal symptoms using the Schizotypal Personality Questionnaire-Revised (Vollema, Schizophr Bull 26(3):565-575, 2000). Differences between 13 juvenile DSM categories and normal controls (n = 80) on adult schizotypal total and factor scores were analyzed, using (M)ANCOVA. Pervasive developmental disorders (PDD), attention deficit hyperactivity disorders (ADHD), deferred diagnosis, sexual and gender identity disorders and depressive disorders had higher SPQ total scores when compared to normal controls (p gender identity disorders, depressive disorders, disruptive disorders, and the category of 'Other conditions that may be a focus of clinical attention' (p < 0.001). No differences with normal controls were found for adult positive schizotypal symptoms (p < 0.110). The current findings are suggestive of the idea that psychiatric disorders in childhood or adolescence are a more general expression of a liability to schizophrenia spectrum pathology in future life. In addition, specific patterns of adult schizotypal symptomatology are associated with different types of juvenile psychiatric disorder.

  4. Differential brain development with low and high IQ in attention-deficit/hyperactivity disorder.

    Directory of Open Access Journals (Sweden)

    Patrick de Zeeuw

    Full Text Available Attention-Deficit/Hyperactivity Disorder (ADHD and intelligence (IQ are both heritable phenotypes. Overlapping genetic effects have been suggested to influence both, with neuroimaging work suggesting similar overlap in terms of morphometric properties of the brain. Together, this evidence suggests that the brain changes characteristic of ADHD may vary as a function of IQ. This study investigated this hypothesis in a sample of 108 children with ADHD and 106 typically developing controls, who participated in a cross-sectional anatomical MRI study. A subgroup of 64 children also participated in a diffusion tensor imaging scan. Brain volumes, local cortical thickness and average cerebral white matter microstructure were analyzed in relation to diagnostic group and IQ. Dimensional analyses investigated possible group differences in the relationship between anatomical measures and IQ. Second, the groups were split into above and below median IQ subgroups to investigate possible differences in the trajectories of cortical development. Dimensionally, cerebral gray matter volume and cerebral white matter microstructure were positively associated with IQ for controls, but not for ADHD. In the analyses of the below and above median IQ subgroups, we found no differences from controls in cerebral gray matter volume in ADHD with below-median IQ, but a delay of cortical development in a number of regions, including prefrontal areas. Conversely, in ADHD with above-median IQ, there were significant reductions from controls in cerebral gray matter volume, but no local differences in the trajectories of cortical development.In conclusion, the basic relationship between IQ and neuroanatomy appears to be altered in ADHD. Our results suggest that there may be multiple brain phenotypes associated with ADHD, where ADHD combined with above median IQ is characterized by small, more global reductions in brain volume that are stable over development, whereas ADHD with

  5. Differential Brain Development with Low and High IQ in Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    de Zeeuw, Patrick; Schnack, Hugo G.; van Belle, Janna; Weusten, Juliette; van Dijk, Sarai; Langen, Marieke; Brouwer, Rachel M.; van Engeland, Herman; Durston, Sarah

    2012-01-01

    Attention-Deficit/Hyperactivity Disorder (ADHD) and intelligence (IQ) are both heritable phenotypes. Overlapping genetic effects have been suggested to influence both, with neuroimaging work suggesting similar overlap in terms of morphometric properties of the brain. Together, this evidence suggests that the brain changes characteristic of ADHD may vary as a function of IQ. This study investigated this hypothesis in a sample of 108 children with ADHD and 106 typically developing controls, who participated in a cross-sectional anatomical MRI study. A subgroup of 64 children also participated in a diffusion tensor imaging scan. Brain volumes, local cortical thickness and average cerebral white matter microstructure were analyzed in relation to diagnostic group and IQ. Dimensional analyses investigated possible group differences in the relationship between anatomical measures and IQ. Second, the groups were split into above and below median IQ subgroups to investigate possible differences in the trajectories of cortical development. Dimensionally, cerebral gray matter volume and cerebral white matter microstructure were positively associated with IQ for controls, but not for ADHD. In the analyses of the below and above median IQ subgroups, we found no differences from controls in cerebral gray matter volume in ADHD with below-median IQ, but a delay of cortical development in a number of regions, including prefrontal areas. Conversely, in ADHD with above-median IQ, there were significant reductions from controls in cerebral gray matter volume, but no local differences in the trajectories of cortical development. In conclusion, the basic relationship between IQ and neuroanatomy appears to be altered in ADHD. Our results suggest that there may be multiple brain phenotypes associated with ADHD, where ADHD combined with above median IQ is characterized by small, more global reductions in brain volume that are stable over development, whereas ADHD with below median IQ is

  6. A research framework for the development and implementation of interventions preventing work-related musculoskeletal disorders.

    Science.gov (United States)

    van der Beek, Allard J; Dennerlein, Jack T; Huysmans, Maaike A; Mathiassen, Svend Erik; Burdorf, Alex; van Mechelen, Willem; van Dieën, Jaap H; Frings-Dresen, Monique Hw; Holtermann, Andreas; Janwantanakul, Prawit; van der Molen, Henk F; Rempel, David; Straker, Leon; Walker-Bone, Karen; Coenen, Pieter

    2017-11-01

    Objectives Work-related musculoskeletal disorders (MSD) are highly prevalent and put a large burden on (working) society. Primary prevention of work-related MSD focuses often on physical risk factors (such as manual lifting and awkward postures) but has not been too successful in reducing the MSD burden. This may partly be caused by insufficient knowledge of etiological mechanisms and/or a lack of adequately feasible interventions (theory failure and program failure, respectively), possibly due to limited integration of research disciplines. A research framework could link research disciplines thereby strengthening the development and implementation of preventive interventions. Our objective was to define and describe such a framework for multi-disciplinary research on work-related MSD prevention. Methods We described a framework for MSD prevention research, partly based on frameworks from other research fields (ie, sports injury prevention and public health). Results The framework is composed of a repeated sequence of six steps comprising the assessment of (i) incidence and severity of MSD, (ii) risk factors for MSD, and (iii) underlying mechanisms; and the (iv) development, (v) evaluation, and (vi) implementation of preventive intervention(s). Conclusions In the present framework for optimal work-related MSD prevention, research disciplines are linked. This framework can thereby help to improve theories and strengthen the development and implementation of prevention strategies for work-related MSD.

  7. A Korean boy with 46,XX testicular disorder of sex development caused by SOX9 duplication.

    Science.gov (United States)

    Lee, Gyung Min; Ko, Jung Min; Shin, Choong Ho; Yang, Sei Won

    2014-06-01

    The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male syndrome, is a rare form of DSD and clinical phenotype shows complete sex reversal from female to male. The sex-determining region Y (SRY) gene can be identified in most 46,XX testicular DSD patients; however, approximately 20% of patients with 46,XX testicular DSD are SRY-negative. The SRY-box 9 (SOX9) gene has several important functions during testis development and differentiation in males, and overexpression of SOX9 leads to the male development of 46,XX gonads in the absence of SRY. In addition, SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans. Here, we report a 4.2-year-old SRY-negative 46,XX boy with complete sex reversal caused by SOX9 duplication for the first time in Korea. He showed normal external and internal male genitalia except for small testes. Fluorescence in situ hybridization and polymerase chain reaction (PCR) analyses failed to detect the presence of SRY, and SOX9 intragenic mutation was not identified by direct sequencing analysis. Therefore, we performed real-time PCR analyses with specific primer pairs, and duplication of the SOX9 gene was revealed. Although SRY-negative 46,XX testicular DSD is a rare condition, an effort to make an accurate diagnosis is important for the provision of proper genetic counseling and for guiding patients in their long-term management.

  8. Latest developments in post-traumatic stress disorder: diagnosis and treatment.

    Science.gov (United States)

    Greenberg, Neil; Brooks, Samantha; Dunn, Rebecca

    2015-06-01

    Most people will experience a traumatic event during their lives. However, not all will develop Post-Traumatic Stress Disorder (PTSD). There have been recent changes in diagnostic criteria for PTSD and there are a number of treatment options available. This review is based on published literature in the field of PTSD, its management and the recently published DSM-V. The most influential risk factors relate to the post-incident environment rather than pre-incident or the incident itself. There are two established and effective psychological therapies; trauma-focussed cognitive behavioural therapy and eye movement desensitization and reprocessing. It is unclear what actually constitutes a traumatic event. Psychological debriefing or counselling interventions, shortly after trauma-exposure are found to be ineffective and may cause harm. Medication, whilst common practice, is not recommended as first line management. Future psychotherapies for PTSD may be just as effective if delivered in carefully considered group settings or through remote means. Research into the most effective ways to prevent individuals at risk of developing PTSD is still at an early stage and development of effective early interventions could substantially reduce the morbidity associated with PTSD. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Development and Initial Validation of a Parent Report Measure of the Behavioral Development of Infants at Risk for Autism Spectrum Disorders

    Science.gov (United States)

    Feldman, Maurice A.; Ward, Rebecca A.; Savona, Danielle; Regehr, Kaleigh; Parker, Kevin; Hudson, Melissa; Penning, Henderika; Holden, Jeanette J. A.

    2012-01-01

    We developed and evaluated a new parent report instrument--Parent Observation of Early Markers Scale (POEMS)--to monitor the behavioral development of infants at risk for autism spectrum disorder (ASD) because they have older affected siblings. Parents of 108 at-risk infants (74 males, 34 females) completed the POEMS from child age 1-24 months.…

  10. Development of the Parent Form of the Preschool Children's Communication Skills Scale and Comparison of the Communication Skills of Children with Normal Development and with Autism Spectrum Disorder

    Science.gov (United States)

    Aydin, Aydan

    2016-01-01

    This study aims at developing an assessment scale for identifying preschool children's communication skills, at distinguishing children with communication deficiencies and at comparing the communication skills of children with normal development (ND) and those with autism spectrum disorder (ASD). Participants were 427 children of up to 6 years of…

  11. Familial forms of disorders of sex development may be common if infertility is considered a comorbidity.

    Science.gov (United States)

    Brauner, Raja; Picard-Dieval, Flavia; Lottmann, Henri; Rouget, Sébastien; Bignon-Topalovic, Joelle; Bashamboo, Anu; McElreavey, Ken

    2016-11-29

    Families with 46,XY Disorders of Sex Development (DSD) have been reported, but they are considered to be exceptionally rare, with the exception of the familial forms of disorders affecting androgen synthesis or action. The families of some patients with anorchia may include individuals with 46,XY gonadal dysgenesis. We therefore analysed a large series of patients with 46,XY DSD or anorchia for the occurrence in their family of one of these phenotypes and/or ovarian insufficiency and/or infertility and/or cryptorchidism. A retrospective study chart review was performed for 114 patients with 46,XY DSD and 26 patients with 46,XY bilateral anorchia examined at a single institution over a 33 year period. Of the 140 patients, 25 probands with DSD belonged to 21 families and 7 with anorchia belonged to 7 families. Familial forms represent 22% (25/114) of the 46,XY DSD and 27% (7/26) of the anorchia cases. No case had disorders affecting androgen synthesis or action or 5 α-reductase deficiency. The presenting symptom was genital ambiguity (n = 12), hypospadias (n = 11) or discordance between 46,XY karyotyping performed in utero to exclude trisomy and female external genitalia (n = 2) or anorchia (n = 7). Other familial affected individuals presented with DSD and/or premature menopause (4 families) or male infertility (4 families) and/or cryptorchidism. In four families mutations were identified in the genes SRY, NR5A1, GATA4 and FOG2/ZFPM2. Surgery discovered dysgerminoma or gonadoblastoma in two cases with gonadal dysgenesis. This study reveals a surprisingly high frequency of familial forms of 46,XY DSD and anorchia when premature menopause or male factor infertility are included. It also demonstrates the variability of the expression of the phenotype within the families. It highlights the need to the physician to take a full family history including fertility status. This could be important to identify familial cases, understand modes of transmission

  12. The Nursing Diagnosis Development of Unemployment Disorder: Content Validation With Nursing Experts.

    Science.gov (United States)

    Bocchino, Anna; Medialdea, María Jesús; Lepiani, Isabel; Mejías, Concepción; Dueñas, María

    2017-10-01

    This study aimed to validate the definition and define the characteristics and related factors of unemployment disorder, a proposed nursing diagnosis. Using Fehring's diagnostic content validity model, Spanish experts were asked to assess the adequacy of the label, defining the characteristics and other related factors. The content validity index was 0.8690. A total of 16 defining characteristics reached major criteria (>0.80). The present study supports the proposed development of a nursing diagnosis for the human response to unemployment. The results suggest that the inclusion of the "unemployment disorder" diagnostic NANDA-I taxonomy would allow nursing professionals to identify the disorder and its causes and manifestations, and therefore provide the information needed for planning more relevant interventions and results. Validación de la definición, características definitorias y factores relacionados de trastorno por desempleo, una propuesta de diagnóstico enfermero. METODOLOGÍA: Usando el modelo de validación de contenido de Fehring, se consensuó mediante expertos españoles la denominación de la etiqueta, las características definitorias y otros factores relacionados. El índice de validez de contenido global fue 0.8690. Un total de 16 características definitorias alcanzaron carácter crítico (>0.80). CONCLUSIÓN: El presente estudio apoya la propuesta de elaborar un diagnóstico de enfermería para la respuesta humana al desempleo. IMPLICACIONES PRÁCTICAS: Los resultados obtenidos sugieren que la inclusión en la taxonomía NANDA-I del diagnóstico "trastorno por desempleo" permitiría a los profesionales de enfermería identificar el problema, sus causas y manifestaciones, y por lo tanto ofrecerían la información necesaria para planificar las intervenciones y resultados más pertinentes. © 2016 NANDA International, Inc.

  13. Health status in 1040 adults with disorders of sex development (DSD: a European multicenter study

    Directory of Open Access Journals (Sweden)

    Henrik Falhammar

    2018-03-01

    Full Text Available Objective: The knowledge about health status in adults with disorder of sex development (DSD is scarce. Design and methods: A cross-sectional observational study in 14 European tertiary centers recruited 1040 participants (717 females, 311 males, 12 others with DSD. Mean age was 32.4 ± 13.6 year (range 16–75. The cohort was divided into: Turner (n = 301, Klinefelter (n = 224, XY-DSD (n = 222, XX-DSD (excluding congenital adrenal hyperplasia (CAH and 46,XX males (n = 21, 46,XX-CAH (n = 226 and 45,X/46,XY (n = 45. Perceived and objective health statuses were measured and compared to European control data. Results: In DSD, fair to very good general health was reported by 91.4% and only 8.6% reported (very bad general health (controls 94.0% and 6.0%, P < 0.0001. Longstanding health issues other than DSD and feeling limited in daily life were reported in 51.0% and 38.6%, respectively (controls 24.5% and 13.8%, P < 0.0001 both. Any disorder except DSD was present in 84.3% (controls 24.6%, P < 0.0001. Males reported worse health than females. In the subgroup analysis, Klinefelter and 46, XX-DSD patients reported bad general health in 15.7% and 16.7%, respectively (Turner 3.2% and CAH 7.4%. Comorbidities were prevalent in all DSD subgroups but Klinefelter and Turner were most affected. Early diagnosis of DSD and a healthy lifestyle were associated with less comorbidities. Conclusions: Overall, general health appeared to be good but a number of medical problems were reported, especially in Klinefelter and Turner. Early diagnosis of DSD and a healthy lifestyle seemed to be important. Lifelong follow-up at specialized centers is necessary.

  14. Testicular dysgenesis syndrome and the development and occurrence of male reproductive disorders

    International Nuclear Information System (INIS)

    Virtanen, H.E.; Rajpert-De Meyts, E.; Main, K.M.; Skakkebaek, N.E.; Toppari, J.

    2005-01-01

    Patients with 45,X0/46XY karyotype often present with intersex phenotype and testicular dysgenesis. These patients may also have undescended testes (cryptorchidism), hypospadias and their spermatogenesis is severely disrupted. They have a high risk for testicular cancer. These patients have the most severe form of testicular dysgenesis syndrome (TDS). We have hypothesized that testicular cancer, cryptorchidism, hypospadias and poor spermatogenesis are all signs of a developmental disturbance that was named as testicular dysgenesis syndrome. The hypothesis is based on clinical and epidemiological findings and on biological and experimental evidence. Signs of TDS share several risk factors, such as small birth weight (particularly being small for gestational age), and they are risk factors for each other. All of them have background in fetal development. They show strong epidemiological links so that countries with high incidence of testicular cancer, such as Denmark, tend to also have high prevalence rates of cryptorchidism and hypospadias and poor semen quality. Vice versa, in countries with good male reproductive health, e.g., in Finland, all these aspects are better than in Denmark. Although genetic abnormalities can cause these disorders, in the majority of cases, the reasons remain unclear. Adverse trends in the incidence of male reproductive disorders suggest that environmental and life style factors contribute to the problem. Endocrine disrupters are considered as prime candidates for environmental influence. Fetal exposure to high doses of dibutyl phthalate was shown to cause a TDS-like phenotype in the rats. Studies are underway to assess whether there is any exposure-outcome relation with selected chemicals (persistent organic pollutants, pesticides, phthalates) and cryptorchidism

  15. Predictors of posttraumatic stress in parents of children diagnosed with a disorder of sex development.

    Science.gov (United States)

    Pasterski, Vickie; Mastroyannopoulou, Kiki; Wright, Deborah; Zucker, Kenneth J; Hughes, Ieuan A

    2014-02-01

    The aims of the current study were twofold: (1) to assess the prevalence/severity of posttraumatic stress symptoms (PTSS) as well as cognitive and emotional responses in parents whose children were diagnosed with a disorder of sex development (DSD); and (2) to assess factors which contributed to PTSS. We hypothesized that parents would show elevated levels of PTSS and that negative cognitive and/or emotional responses would be predictive. Participants were parents of children diagnosed with a DSD. Thirty-six mothers and 11 fathers completed a measure of posttraumatic stress and reported difficulties in the domains of cognition (e.g., confusion) and emotion (e.g., grief). Using multiple regression, we determined factors contributing to parental PTSS. Reported PTSS was high: 31 % of mothers and 18 % of fathers met the threshold for caseness for Posttraumatic Stress Disorder. Regression included: child sex, parent sex, child age at diagnosis, years since diagnosis, genital ambiguity, father occupation, cognitive confusion, and emotional distress. Only cognitive confusion contributed significantly to variance in PTSS. Parents of children with DSD may experience the diagnosis as traumatic, evidenced by high rates of PTSS in the current report. Assessment of reactions to their children's diagnoses revealed that cognitive confusion, and not emotional distress, predicted PTSS. In this case, direct cognitive interventions may be applicable. Though psychological support is widely recommended, no detailed intervention has been offered. Our findings suggest that we may directly apply models successful in other areas of pediatrics, such as pediatric oncology. Future studies may assess the usefulness of such an intervention.

  16. Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

    Science.gov (United States)

    Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; De Maeyer, J H; Stanghellini, V

    2012-04-01

    The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility. © 2012 Blackwell Publishing Ltd.

  17. Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders

    Science.gov (United States)

    Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; Maeyer, J H; Stanghellini, V

    2012-01-01

    Summary Background The nonselective 5-HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006–2008 and DDW 2008–2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Results Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT4 agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT4 agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT1 receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT4 agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT4 agonists with no hERG or 5-HT1 affinity (renzapride, clebopride, mosapride). Conclusions 5-HT4 agonists for GI disorders differ in chemical structure and selectivity for 5-HT4 receptors. Selectivity for 5-HT4 over non-5-HT4 receptors may influence the agent's safety and overall risk–benefit profile. Based on available evidence, highly selective 5-HT4 agonists may offer improved safety to treat patients with impaired GI motility. PMID:22356640

  18. Predictors of sense of coherence in typically developing adolescent siblings of individuals with autism spectrum disorder.

    Science.gov (United States)

    Smith, L O; Elder, J H; Storch, E A; Rowe, M A

    2015-01-01

    Children with autism spectrum disorder (ASD) may be a stressor for family members yet there is little published research on the impact of having a child with ASD on their typically developing (TD) adolescent siblings. According to Antonovsky's salutogenic model, a strong sense of coherence leads to the view that the stressor is a manageable challenge rather than a burden and promotes healthier adaptation. This study examines the relationship between stress, TD sibling resources and the sense of coherence in TD siblings. This quantitative mail-based study uses a survey methodology, analysing the responses of TD adolescent siblings (n = 96) of individuals with autism, Asperger's syndrome, or pervasive developmental disorder - not otherwise specified to several rating scales. Adolescent siblings, ages 11 to 18 years, completed the Adolescent Coping Orientation for Problem Experience (ACOPE), Network of Relationship Inventory - Social Provision Version (NRI-SPV), Youth Self Report (YSR), and Sense of Coherence (SOC) instruments; parents completed the Child Autism Rating Scale - 2nd Edition (CARS-2). The salutogenesis model was used to guide and inform this research. Findings suggested the following: (a) the stress of ASD severity and resource of adjustment are related in TD adolescent siblings; (b) TD sibling adjustment has a strong relationship with sense of coherence levels; and (c) a greater number of positive coping strategies buffer TD sibling coherence levels when ASD severity scores are high. ASD severity and TD adolescent sibling resources influence sense of coherence in adolescent TD siblings of individuals with ASD. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

  19. The role of positive and negative childhood events in the risk of developing personality disorders

    OpenAIRE

    Chua, M

    2015-01-01

    Existing research has predominantly focused on a limited range of childhood events and personality disorders, such as childhood maltreatment and borderline personality disorder. Moreover, researchers rarely account for multiple risk factors within the same study, despite the reality that childhood events do not occur in isolation. Therefore, the current research aims to contribute to the knowledge on childhood events and personality disorder symptoms by investigating a wider range of risk and...

  20. Early gross motor skills predict the subsequent development of language in children with autism spectrum disorder.

    Science.gov (United States)

    Bedford, Rachael; Pickles, Andrew; Lord, Catherine

    2016-09-01

    Motor milestones such as the onset of walking are important developmental markers, not only for later motor skills but also for more widespread social-cognitive development. The aim of the current study was to test whether gross motor abilities, specifically the onset of walking, predicted the subsequent rate of language development in a large cohort of children with autism spectrum disorder (ASD). We ran growth curve models for expressive and receptive language measured at 2, 3, 5 and 9 years in 209 autistic children. Measures of gross motor, visual reception and autism symptoms were collected at the 2 year visit. In Model 1, walking onset was included as a predictor of the slope of language development. Model 2 included a measure of non-verbal IQ and autism symptom severity as covariates. The final model, Model 3, additionally covaried for gross motor ability. In the first model, parent-reported age of walking onset significantly predicted the subsequent rate of language development although the relationship became non-significant when gross motor skill, non-verbal ability and autism severity scores were included (Models 2 & 3). Gross motor score, however, did remain a significant predictor of both expressive and receptive language development. Taken together, the model results provide some evidence that early motor abilities in young children with ASD can have longitudinal cross-domain influences, potentially contributing, in part, to the linguistic difficulties that characterise ASD. Autism Res 2016, 9: 993-1001. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.

  1. [Mass media influence and risk of developing eating disorders in female students from Lima, Peru].

    Science.gov (United States)

    Lazo Montoya, Yessenia; Quenaya, Alejandra; Mayta-Tristán, Percy

    2015-12-01

    Eating disorders (EDs) are a public health problem, and their relationship to mass media is still controversial. To assess whether there is an association between models of body image shown in mass media and the risk of developing EDs among female adolescent students from Lima, Peru. Cross-sectional study conducted in three schools located in the district of La Victoria, Lima, Peru. The risk of developing EDs was measured using the Eating Attitudes Test-26 (EAT-26), while mass media influence was measured using the Sociocultural Attitudes Towards Appearance Questionnaire-3 (SATAQ-3), which was categorized into tertiles both in the overall score and its subscales (information, pressure, general internalization, and athletic internalization). Adjusted prevalence ratios (aPR) for EDs were estimated. Four hundred and eighty-three students were included, their median age was 14 ? 3 years old. A risk of developing an ED was observed in 13.9% of them. Students who are more influenced by mass media (upper tertile of the SATAQ-3) have a higher probability of having a risk of developing an ED (aPR: 4.24; 95% confidence interval |-CI-|: 2.10-8.56), as well as those who have a greater access to information (PR: 1.89; 95% CI: 1.09-3.25), suffer more pressure (PR: 4.97; 95% CI: 2.31-10.69), show a greater general internalization (PR: 5.00; 95% CI: 2.39-10.43), and show a greater level of athletic internalization (PR: 4.35; 95% CI: 2.19-8-66). The greater the influence of mass media, the greater the probability of having a risk of developing an ED among female students from Lima, Peru.

  2. Development and validation of a prediction algorithm for the onset of common mental disorders in a working population.

    Science.gov (United States)

    Fernandez, Ana; Salvador-Carulla, Luis; Choi, Isabella; Calvo, Rafael; Harvey, Samuel B; Glozier, Nicholas

    2018-01-01

    Common mental disorders are the most common reason for long-term sickness absence in most developed countries. Prediction algorithms for the onset of common mental disorders may help target indicated work-based prevention interventions. We aimed to develop and validate a risk algorithm to predict the onset of common mental disorders at 12 months in a working population. We conducted a secondary analysis of the Household, Income and Labour Dynamics in Australia Survey, a longitudinal, nationally representative household panel in Australia. Data from the 6189 working participants who did not meet the criteria for a common mental disorders at baseline were non-randomly split into training and validation databases, based on state of residence. Common mental disorders were assessed with the mental component score of 36-Item Short Form Health Survey questionnaire (score ⩽45). Risk algorithms were constructed following recommendations made by the Transparent Reporting of a multivariable prediction model for Prevention Or Diagnosis statement. Different risk factors were identified among women and men for the final risk algorithms. In the training data, the model for women had a C-index of 0.73 and effect size (Hedges' g) of 0.91. In men, the C-index was 0.76 and the effect size was 1.06. In the validation data, the C-index was 0.66 for women and 0.73 for men, with positive predictive values of 0.28 and 0.26, respectively Conclusion: It is possible to develop an algorithm with good discrimination for the onset identifying overall and modifiable risks of common mental disorders among working men. Such models have the potential to change the way that prevention of common mental disorders at the workplace is conducted, but different models may be required for women.

  3. Ex vivo effects of an Oenothera paradoxa extract on the reactive oxygen species generation and neutral endopeptidase activity in neutrophils from patients after acute myocardial infarction.

    Science.gov (United States)

    Kiss, Anna K; Kapłon-Cieślicka, Agnieszka; Filipiak, Krzysztof J; Opolski, Grzegorz; Naruszewicz, Marek

    2012-04-01

    Oxidative stress induced by reactive oxygen species (ROS) is considered to play an important part in the aetiology of coronary heart disease. Apart from ROS, neutrophils are a source of neutral endopeptidase (NEP) that inactivates protective natriuretic peptides. The aim of the present study was to evaluate the in vitro ROS generation and inhibition of NEP activity in neutrophils obtained from healthy volunteers and from patients after acute myocardial infarction (AMI) by an aqueous extract of Oenothera paradoxa. Neutrophils isolated from AMI patients showed two-fold higher ROS generation compared with cells from healthy donors, especially in the lucigenin-enhanced luminescence model, which suggests intensive O₂⁻ generation. The addition of O. paradoxa extract at concentrations of 0.2, 2 and 20 µg/mL resulted in a significant reduction in ROS generation. The extracellular NEP activity was higher in patients after AMI compared with healthy individuals (15.0 ± 0.9 versus 10.3 ± 0.5 nmol AMC/10(6) cells/60 min; p = 0.001). The addition of O. paradoxa extract at concentrations of 20, 50 and 100 µg/mL resulted in a significant reduction in NEP activity in both groups. O. paradoxa extract appears to be an interesting candidate for supplementation in the prevention of cardiovascular diseases. Copyright © 2011 John Wiley & Sons, Ltd.

  4. Multifunctional amaranth cystatin inhibits endogenous and digestive insect cysteine endopeptidases: A potential tool to prevent proteolysis and for the control of insect pests.

    Science.gov (United States)

    Valdés-Rodríguez, Silvia; Galván-Ramírez, Juan Pablo; Guerrero-Rangel, Armando; Cedro-Tanda, Alberto

    2015-01-01

    In a previous study, the amaranth cystatin was characterized. This cystatin is believed to provide protection from abiotic stress because its transcription is induced in response to heat, drought, and salinity. It has also been shown that recombinant amaranth cystatin inhibits bromelain, ficin, and cysteine endopeptidases from fungal sources and also inhibits the growth of phytopathogenic fungi. In the present study, evidence is presented regarding the potential function of amaranth cystatin as a regulator of endogenous proteinases and insect digestive proteinases. During amaranth germination and seedling growth, different proteolytic profiles were observed at different pH levels in gelatin-containing SDS-PAGE. Most of the proteolytic enzymes detected at pH 4.5 were mainly inhibited by trans-epoxysuccinyl-leucyl amido(4-guanidino)butane (E-64) and the purified recombinant amaranth cystatin. Furthermore, the recombinant amaranth cystatin was active against insect proteinases. In particular, the E-64-sensitive proteolytic digestive enzymes from Callosobruchus maculatus, Zabrotes subfasciatus, and Acanthoscelides obtectus were inhibited by the amaranth cystatin. Taken together, these results suggest multiple roles for cystatin in amaranth, specifically during germination and seedling growth and in the protection of A. hypochondriacus against insect predation. Amaranth cystatin represents a promising tool for diverse applications in the control of insect pest and for preventing undesirable proteolytic activity. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

  5. Psychosexual development in adolescents and adults with disorders of sex development--results from the German Clinical Evaluation Study.

    Science.gov (United States)

    Jürgensen, Martina; Kleinemeier, Eva; Lux, Anke; Steensma, Thomas D; Cohen-Kettenis, Peggy T; Hiort, Olaf; Thyen, Ute; Köhler, Birgit

    2013-11-01

    Both biological and psychosocial factors influence psychosexual development. High levels of pre- and postnatal androgens lead to more male-typical behavior. So far, the influence of androgens on gender identity and sexual orientation is unclear. Disorders of sex development (DSDs) are heterogeneous genetic conditions with different levels of prenatal androgens resulting in variations of genital development. Through DSD, the role of the different factors, especially androgen exposure, on psychosexual development can be evaluated. The purpose of the study was to assess psychosexual development in adolescents and adults with different forms of DSD. For the examination of psychosexual development of 66 adolescents and 110 adults with DSD, the authors used the Utrecht Gender Dysphoria Scale for adolescents, the Questionnaire of Gender Identity for adults, and a condition-specific DSD study questionnaire. Individuals were analyzed in four subgroups reflecting the karyotype, absence/presence of androgen effects, and gender of rearing. Main outcome measures used were gender identity, friendships, love and sexual relationships, and sexual orientation in adolescents and adults with DSD. Individuals with DSD did not show increased gender dysphoria. However, partnership and sexuality were identified to be difficult areas of life. Both adolescents and adults with DSD reported fewer experiences regarding love or sexual relationships compared with unaffected individuals. Especially men with DSD and undervirilization and women with DSD and androgen effects less often had a love relationship. Adult women with DSD and androgen effects more frequently engaged in love and sexual relationships with individuals of the same gender compared with women without DSD. Individuals with DSD experience atypical hormonal influences (higher levels of androgens in girls/women and lower levels in androgens in boys/men); however, they did not show increased gender dysphoria in this study. However

  6. Designing affective video games to support the social-emotional development of teenagers with autism spectrum disorders.

    Science.gov (United States)

    Khandaker, Mitu

    2009-01-01

    Autism spectrum disorders (ASD) are a group of developmental neuropsychiatric disorders, comprised of three diagnostic entities - autistic disorder (AD), Asperger's disorder (AS), and Pervasive Developmental Disorder Not Otherwise Specified (including atypical autism) (PDD-NOS). A number of intervention techniques are currently used to reduce some of the associated challenges, with techniques ranging from behavioral therapy to dietary interventions and traditional counseling. This positional paper proposes the use of video games which leverage affective computing technologies as intervention in autism spectrum disorders in the context of the use of traditional play therapy with adolescents, who may feel uncomfortable engaging in traditional play with toys they may be too old for. It aims to explore the potential for greater 'social physics' made possible by affective computing technologies. This involves computationally 'recognizing' emotions in a user, often through the use of multimodal affective sensors, including facial expressions, postural shifts, and physiological signals such as heart rate, skin conductivity, and EEG signals. However, it is suggested that this should be augmented by researching the effect of social game design mechanisms on social-emotional development, particularly for those who experience difficulty with social interaction.

  7. The early development of infant siblings of children with autism spectrum disorder: Characteristics of sibling interactions

    Science.gov (United States)

    Warreyn, Petra; Van der Paelt, Sara; Demurie, Ellen; Roeyers, Herbert

    2018-01-01

    Although sibling interactions play an important role in children’s early development, they are rarely studied in very young children with an older brother or sister with autism spectrum disorder (ASD). This study used a naturalistic, observational method to compare interactions between 18-month-old infants and their older sibling with ASD (n = 22) with a control group of 18-month-old infants and their typically developing (TD) older sibling (n = 29). In addition, role (a)symmetry and the influence of gender were evaluated. Sibling interactions in ASD-dyads were characterized by higher levels of negativity. Although somewhat less pronounced in ASD-dyads, role asymmetry was present in both groups, with the older child taking the dominant position. Finally, siblings pairs with an older sister were characterized by more positive behaviours. Since differences in sibling interactions may alter the developmental trajectories of both siblings, these early relationships should be taken into account in future ASD research and interventions. PMID:29543814

  8. Maternal Perceptions of Mealtimes: Comparison of Children with Autism Spectrum Disorder and Children with Typical Development

    Directory of Open Access Journals (Sweden)

    Terry K. Crowe

    2017-03-01

    Full Text Available Background: This study examined mealtime techniques reported by mothers of preschool children with Autism Spectrum Disorder (ASD and mothers of children with typical development (TD. The mothers’ perceived levels of success and sources of information for mealtime techniques were also reported. Method: The participants were 24 mothers of children with ASD (ASD group and 24 mothers of children with typical development (TD group between 3 and 6 years of age. The Background Information Survey and the Mealtime Techniques Interview were administered. Results: The ASD group used significantly more techniques in categories of food appearances, restrictive diets, and vitamin/supplement therapy. The TD group used significantly more techniques in the categories of etiquette and negative consequences. Both groups rated techniques similarly with no significant difference between the perceived rate of success for each category. Finally, 91% of mealtime techniques for both groups were parent generated with few from professionals. Conclusion: The results showed that many of the mothers in both groups used similar mealtime techniques and most implemented techniques that were self-generated with generally moderate perception of success. Occupational therapists should collaboratively work with families to increase mealtime success by recommending interventions that are individualized and family centered.

  9. Children with disorders of sex development: A qualitative study of early parental experience

    Directory of Open Access Journals (Sweden)

    Crissman Halley P

    2011-10-01

    Full Text Available Abstract Background Clinical research on psychological aspects of disorders of sex development (DSD has focused on psychosexual differentiation with relatively little attention directed toward parents' experiences of early clinical management and their influence on patient and family psychosocial adaptation. Objectives To characterize parental experiences in the early clinical care of children born with DSD. Study Design Content analysis of interviews with parents (n = 41 of 28 children, newborn to 6 years, with DSD. Results Four major domains emerged as salient to parents: (1 the gender assignment process, (2 decisions regarding genital surgery, (3 disclosing information about their child's DSD, and (4 interacting with healthcare providers. Findings suggested discordance between scientific and parental understandings of the determinants of "sex" and "gender." Parents' expectations regarding the benefits of genital surgery appear largely met; however, parents still had concerns about their child's future physical, social and sexual development. Two areas experienced by many parents as particularly stressful were: (1 uncertainties regarding diagnosis and optimal management, and (2 conflicts between maintaining privacy versus disclosing the condition to access social support. Conclusions Parents' experiences and gaps in understanding can be used to inform the clinical care of patients with DSD and their families. Improving communication between parents and providers (and between parents and their support providers throughout the early clinical management process may be important in decreasing stress and improving outcomes for families of children with DSD.

  10. Visual Scan Paths and Recognition of Facial Identity in Autism Spectrum Disorder and Typical Development

    Science.gov (United States)

    Wilson, C. Ellie; Palermo, Romina; Brock, Jon

    2012-01-01

    Background Previous research suggests that many individuals with autism spectrum disorder (ASD) have impaired facial identity recognition, and also exhibit abnormal visual scanning of faces. Here, two hypotheses accounting for an association between these observations were tested: i) better facial identity recognition is associated with increased gaze time on the Eye region; ii) better facial identity recognition is associated with increased eye-movements around the face. Methodology and Principal Findings Eye-movements of 11 children with ASD and 11 age-matched typically developing (TD) controls were recorded whilst they viewed a series of faces, and then completed a two alternative forced-choice recognition memory test for the faces. Scores on the memory task were standardized according to age. In both groups, there was no evidence of an association between the proportion of time spent looking at the Eye region of faces and age-standardized recognition performance, thus the first hypothesis was rejected. However, the ‘Dynamic Scanning Index’ – which was incremented each time the participant saccaded into and out of one of the core-feature interest areas – was strongly associated with age-standardized face recognition scores in both groups, even after controlling for various other potential predictors of performance. Conclusions and Significance In support of the second hypothesis, results suggested that increased saccading between core-features was associated with more accurate face recognition ability, both in typical development and ASD. Causal directions of this relationship remain undetermined. PMID:22666378

  11. Parental Reports of Stigma Associated with Child’s Disorder of Sex Development

    Directory of Open Access Journals (Sweden)

    Aimee M. Rolston

    2015-01-01

    Full Text Available Disorders of sex development (DSD are congenital conditions in which chromosomal, gonadal, or anatomic sex development is atypical. DSD-associated stigma is purported to threaten positive psychosocial adaptation. Parental perceptions of DSD-related stigma were assessed in 154 parents of 107 children (newborn–17 years questionnaire comprising two scales, child-focused and parent-focused, and three subscales, perceived stigmatization, future worries, and feelings about the child’s condition. Medical chart excerpts identified diagnoses and clinical management details. Stigma scale scores were generally low. Parents of children with DSD reported less stigma than parents of children with epilepsy; however, a notable proportion rated individual items in the moderate to high range. Stigma was unrelated to child’s age or the number of DSD-related surgeries. Child-focused stigma scores exceeded parent-focused stigma and mothers reported more stigma than fathers, with a moderate level of agreement. Within 46,XY DSD, reported stigma was higher for children reared as girls. In conclusion, in this first quantitative study of ongoing experiences, DSD-related stigma in childhood and adolescence, while limited in the aggregate, is reported at moderate to high levels in specific areas. Because stigma threatens positive psychosocial adaptation, systematic screening for these concerns should be considered and, when reported, targeted for psychoeducational counseling.

  12. Health-related quality of life in children with disorders of sex development (DSD).

    Science.gov (United States)

    Jürgensen, Martina; Lux, Anke; Wien, Sebastian Benedikt; Kleinemeier, Eva; Hiort, Olaf; Thyen, Ute

    2014-07-01

    Disorders of sex development (DSD) are rare genetic conditions resulting in atypical development of the sex organs. While some evidence is available on psychosexual outcomes, much less is known about the quality of life in this population, especially in children. Health-related quality of life (HRQOL) is a widely accepted endpoint for assessment and evaluation of interventions and medical care. Within the German DSD Network study, 86 children aged 8-12 years with several subtypes of DSD were recruited from Germany, Austria and Switzerland. Demographic, medical and psychosocial variables were collected through interviews of the attending physicians, the children and the parents. HRQOL was the primary outcome. It was assessed by the KINDL-R Questionnaire [2001]. Psychosexual determinants included gender identity/gender dysphoria, gender role behaviour, the child's knowledge about the condition and number/timing of genital surgery. A significant reduction of HRQOL was reported in children's self-report (p self-esteem (p gender dysphoria reported lower HRQOL scores compared to the study group at large. Atypical gender role behaviour was not associated with HRQOL. Psychosocial support of children with DSD and their families appears to be necessary in at least some cases and must be accessible for all patients.

  13. Pupillary and affective responses to maternal feedback and the development of borderline personality disorder symptoms.

    Science.gov (United States)

    Scott, Lori N; Zalewski, Maureen; Beeney, Joseph E; Jones, Neil P; Stepp, Stephanie D

    2017-08-01

    Etiological models propose that a biological vulnerability to emotional reactivity plays an important role in the development of borderline personality disorder (BPD). However, the physiological and phenomenological components of emotional reactivity that predict the course of BPD symptoms in adolescence are poorly understood. This prospective study examines pupillary and affective responses to maternal feedback as predictors of BPD symptom development in adolescent girls over 18 months. Fifty-seven 16-year-old girls completed a laboratory task in which they heard recorded clips of their own mothers making critical or praising statements about them, as well as neutral statements that did not pertain to them. Changes in girls' pupil dilation and subjective affect were assessed throughout the task. The results demonstrated that greater pupillary response to maternal criticism predicted increases in BPD symptoms over time. In addition, greater pupillary and positive affective responses to maternal praise were associated with higher BPD symptoms at age 16 and faster decreases in BPD symptoms over time, but only among girls who heard clips that were rated by independent observers as less praising. The results suggest that emotional reactivity can serve as either a risk or a protective factor depending on context, with differential effects of reactivity to criticism versus praise.

  14. Development and Validation of Personality Disorder Spectra Scales for the MMPI-2-RF.

    Science.gov (United States)

    Sellbom, Martin; Waugh, Mark H; Hopwood, Christopher J

    2018-01-01

    The purpose of this study was to develop and validate a set of MMPI-2-RF (Ben-Porath & Tellegen, 2008/2011) personality disorder (PD) spectra scales. These scales could serve the purpose of assisting with DSM-5 PD diagnosis and help link categorical and dimensional conceptions of personality pathology within the MMPI-2-RF. We developed and provided initial validity results for scales corresponding to the 10 PD constructs listed in the DSM-5 using data from student, community, clinical, and correctional samples. Initial validation efforts indicated good support for criterion validity with an external PD measure as well as with dimensional personality traits included in the DSM-5 alternative model for PDs. Construct validity results using psychosocial history and therapists' ratings in a large clinical sample were generally supportive as well. Overall, these brief scales provide clinicians using MMPI-2-RF data with estimates of DSM-5 PD constructs that can support cross-model connections between categorical and dimensional assessment approaches.

  15. Abnormal Development of the Earliest Cortical Circuits in a Mouse Model of Autism Spectrum Disorder.

    Science.gov (United States)

    Nagode, Daniel A; Meng, Xiangying; Winkowski, Daniel E; Smith, Ed; Khan-Tareen, Hamza; Kareddy, Vishnupriya; Kao, Joseph P Y; Kanold, Patrick O

    2017-01-31

    Autism spectrum disorder (ASD) involves deficits in speech and sound processing. Cortical circuit changes during early development likely contribute to such deficits. Subplate neurons (SPNs) form the earliest cortical microcircuits and are required for normal development of thalamocortical and intracortical circuits. Prenatal valproic acid (VPA) increases ASD risk, especially when present during a critical time window coinciding with SPN genesis. Using optical circuit mapping in mouse auditory cortex, we find that VPA exposure on E12 altered the functional excitatory and inhibitory connectivity of SPNs. Circuit changes manifested as "patches" of mostly increased connection probability or strength in the first postnatal week and as general hyper-connectivity after P10, shortly after ear opening. These results suggest that prenatal VPA exposure severely affects the developmental trajectory of cortical circuits and that sensory-driven activity may exacerbate earlier, subtle connectivity deficits. Our findings identify the subplate as a possible common pathophysiological substrate of deficits in ASD. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. The Influence of Adipose Tissue on Brain Development, Cognition, and Risk of Neurodegenerative Disorders.

    Science.gov (United States)

    Letra, Liliana; Santana, Isabel

    2017-01-01

    The brain is a highly metabolic organ and thus especially vulnerable to changes in peripheral metabolism, including those induced by obesity-associated adipose tissue dysfunction. In this context, it is likely that the development and maturation of neurocognitive circuits may also be affected and modulated by metabolic environmental factors, beginning in utero. It is currently recognized that maternal obesity, either pre-gestational or gestational, negatively influences fetal brain development and elevates the risk of cognitive impairment and neuropsychiatric disorders in the offspring. During infancy and adolescence, obesity remains a limiting factor for healthy neurodevelopment, especially affecting executive functions but also attention, visuospatial ability, and motor skills. In middle age, obesity seems to induce an accelerated brain aging and thus may increase the risk of age-related neurodegenerative diseases such as Alzheimer's disease. In this chapter we review and discuss experimental and clinical evidence focusing on the influence of adipose tissue dysfunction on neurodevelopment and cognition across lifespan, as well as some possible mechanistic links, namely the role of the most well studied adipokines.

  17. Adaptive maternal immune deviations as a ground for autism spectrum disorders development in children.

    Science.gov (United States)

    Poletaev, Alexander B; Poletaeva, Alina A; Pukhalenko, Alexander I; Zamaleeva, Roza S; Cherepanova, Natalia A; Frizin, Dmitry V

    2014-01-01

    Autism is a vexed problem today. Overall, there is a high frequency of birth children (1:80 - 1:150) with late diagnosed autism spectrum disorders (ASD) and this trend is getting progressively stronger. The causes for the currently increased frequency of ASD and the pathogenesis of ASD are not fully understood yet. One of the most likely mechanisms inducing ASD may be a maternal immune imprinting. This phenomenon is based on transplacental translocation of maternal antibodies of IgG class and, as a consequence, on the epigenetic "tuning" of immune system of the fetus and child. This mechanism provides development of child's anti-infection resistance before meeting with microorganisms, but it can be also a cause of inborn pathology including the ASD appearance. The quantitative changes in maternal blood serum autoantibodies depend on a specific microbial population, or are induced by environmental chemical pollutants in association with some individual features of the maternal metabolism. These immune changes are adaptive in most cases for the maternal organism, but can be pathogenic for the fetus in some cases. We discuss in the present paper the possibilities to predict the risk from abnormal development of nervous system in fetus and early diagnosis of ASD in high-risk group of children.

  18. How Do Individuals Develop Alcohol Use Disorder After Bariatric Surgery? A Grounded Theory Exploration.

    Science.gov (United States)

    Yoder, Ruth; MacNeela, Padraig; Conway, Ronan; Heary, Caroline

    2018-03-01

    Bariatric surgery is the most effective treatment for severe obesity. However, following Roux-en-Y gastric bypass (RYGB) surgery, a small minority of patients develop new-onset alcohol use disorder (AUD), the aetiology of which is poorly understood. The aim is to construct a theory to explain the development of AUD among a sample of individuals who reported problematic drinking following RYGB. Semi-structured interviews were conducted with eight RYGB patients diagnosed with AUD attending a multi-disciplinary outpatient weight management service at a public hospital in the Republic of Ireland. A constructivist grounded theory methodology was used to analyse interview transcripts. Participants' main concern was identified as 'unresolved psychological issues' which were managed by 'external coping mechanisms', namely, 'eating to cope'. After RYGB, comfort eating was no longer possible to the same extent. Following a 'honeymoon period', participants' need for an external coping mechanism resurfaced. 'Filling the void' provides a framework to explain how participants managed the symptoms of their unresolved psychological issues through 'behavioural substitution', that is, drinking alcohol instead of eating. The theoretical framework of 'filling the void' adds to contemporary research that conceptualises AUD behavioural substitution as 'addiction transfer' by describing the process by which the phenomenon occurs as well as the characteristics of participants. The clinical implication of this research is to advocate for a reshaping of treatment of RYGB patients, with increased psychological input following surgery.

  19. Symmetry in Infancy: Analysis of Motor Development in Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Gianluca Esposito

    2009-12-01

    Full Text Available Motor asymmetry, defined as the lack of symmetry in movements or postures, is often observed briefly in many typically developing children. However, if such asymmetry persists, it may be a sign of neurological disease. Recent studies have suggested that motor asymmetries may be an early symptom of Autism Spectrum Disorders (ASD. ASD involve a range of social, cognitive, and behavioral problems, at different degrees of functioning, which are thought to be the final common pathway of multiple etiological mechanisms. Furthermore, early identification of ASD has been recognized as a critical aspect for treatment. Our study aims to analyze symmetry in the motor milestones of infants with ASD compared with typically developing infants (TD or infants with other developmental delay (DD during the first year of life. Our results highlight that there are different patterns of motor symmetry in the groups. In particular, infants with ASD scored significantly poorer (higher levels of asymmetry then the TD and DD infants. We also identified two subgroups of infants with ASD, one with a typical level and the other with a lower level of motor functioning. Implications of the study for diagnosis and treatment are described.

  20. Trauma memory characteristics and the development of acute stress disorder and post-traumatic stress disorder in youth.

    Science.gov (United States)

    McKinnon, A; Brewer, N; Meiser-Stedman, R; Nixon, R D V

    2017-03-01

    The present study addresses gaps in knowledge regarding the association between trauma memory processes and posttraumatic stress responses in youth. Our primary goal was to explore the relative contribution of perceptions of trauma memory quality versus narrative trauma memory characteristics to explain overall adjustment. Children (N = 67) were interviewed within four weeks (T1) of an injury leading to hospital treatment and then again eight weeks later (T2). In each interview, the child told a trauma narrative (which were later coded), and answered the Trauma Memory Quality Questionnaire (Meiser-Stedman, Smith, Yule, & Dalgleish, 2007a), a self-report measure indexing the sensory, fragmented, and disorganised characteristics of trauma memory. They then completed measures of Acute Stress Disorder (ASD) symptoms and associated psychopathology at T1 and measures of Posttraumatic Stress (PTS) symptoms and associated psychopathology at T2. Self-reported trauma memory characteristics predicted ASD symptoms cross-sectionally at T1 and PTS symptoms prospectively over time. At both time points, self-reported trauma memory characteristics accounted for all of the unique variance in symptoms initially explained by narrative characteristics. A reduction in self-report ratings, but not the hypothesised narrative features (e.g., disorganised or lexical elements of the narrative), significantly predicted a reduction in PTS symptoms over time. The small sample size and the absence of a within-subjects narrative control were the main limitations of the study. These findings underscore the importance of self-reported trauma memory characteristics to the aetiology of PTSD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Developing Social Interaction and Understanding in Individuals with Autism Spectrum Disorder: A Groupwork Intervention

    Science.gov (United States)

    MacKay, Tommy; Knott, Fiona; Dunlop, Aline-Wendy

    2007-01-01

    Background: Difficulties with social interaction and understanding lie at the heart of the communication disorder that characterises the autism spectrum. This study sought to improve social communication for individuals with autism spectrum disorder (ASD) by means of a groupwork intervention focusing on social and emotional perspective-taking,…

  2. The BASC-2 Profiles of Female Adolescents At-Risk of Developing an Eating Disorder

    Science.gov (United States)

    Stachowitz, Annie L.

    2012-01-01

    Eating disorders, disordered eating, and body dissatisfaction prevalence rates are on the rise among adolescent females. The present study sought to examine a commonly used social-emotional instrument, the Behavior Assessment System for Children-Second Edition, Self-Report of Personality (BASC-2, SRP), for the emergence of a common profile of…

  3. A brief web-based screening questionnaire for common mental disorders: Development and validation

    NARCIS (Netherlands)

    Donker, T.; van Straten, A.; Marks, I.M.; Cuijpers, P.

    2009-01-01

    Background: The advent of Internet-based self-help systems for common mental disorders has generated a need for quick ways to triage would-be users to systems appropriate for their disorders. This need can be met by using brief online screening questionnaires, which can also be quickly used to

  4. One Factor or Two Parallel Processes? Comorbidity and Development of Adolescent Anxiety and Depressive Disorder Symptoms

    Science.gov (United States)

    Hale, William W., III; Raaijmakers, Quinten A. W.; Muris, Peter; van Hoof, Anne; Meeus, Wim H. J.

    2009-01-01

    Background: This study investigates whether anxiety and depressive disorder symptoms of adolescents from the general community are best described by a model that assumes they are indicative of one general factor or by a model that assumes they are two distinct disorders with parallel growth processes. Additional analyses were conducted to explore…

  5. Development of Borderline Personality Disorder in Adolescence and Young Adulthood: Introduction to the Special Section

    Science.gov (United States)

    Stepp, Stephanie D.

    2012-01-01

    Recognizable symptoms and features of borderline personality disorder (BPD) appear during adolescence. However, there has been resistance to diagnose or research this disorder prior to adulthood because of clinical lore that BPD is a long-standing illness and that personality traits are not stable until adulthood. This has resulted in little…

  6. Cognitive Abuse within the Incestuous Family as a Factor in the Development of Dissociative Identity Disorder

    Science.gov (United States)

    Reed-Gavish, Maya

    2013-01-01

    The polarized nature of the ongoing controversies surrounding the genesis and validity of dissociative identity disorder pit advocates who see and work with dissociative identity disorder sufferers against skeptics who claim it to be an artificial iatrogenically produced phenomenon. This paper suggests that such a dichotomy is unwarranted and…

  7. Social Development in Individuals with High Functioning Autism and Asperger Disorder

    Science.gov (United States)

    Koegel, Robert L.

    2007-01-01

    Until recently, and even in many current research circles, social behavior in individuals with autism spectrum disorders (including those with high functioning autism or Asperger disorder) was considered to be unmodifiable. Mundy, Henderson, Inge, and Coman and McGee and Daly shed new light on this concept of intractability, suggesting that…

  8. A Prospective Study of Risk Factors for the Development of Depression and Disordered Eating in Adolescents

    Science.gov (United States)

    Ferreiro, Fatima; Seoane, Gloria; Senra, Carmen

    2011-01-01

    There is evidence that females display higher levels of depressive symptoms and disordered eating than males from adolescence onward. This study examined whether different risk factors and their interaction with sex (moderator effect) prospectively predicted depressive symptoms and disordered eating in adolescents. A total of 415 female…

  9. Alcohol Use Disorders and Depression: Protective Factors in the Development of Unique versus Comorbid Outcomes

    Science.gov (United States)

    Mason, W. Alex; Hawkins, J. David; Kosterman, Rick; Catalano, Richard F.

    2010-01-01

    This study examines protective factors for young adult alcohol use disorders, depression, and comorbid alcohol use disorders and depression. Participants were recruited from all fifth-grade students attending 18 Seattle elementary schools. Of the 1,053 students eligible, 808 (77%) agreed to participate. Youths were surveyed when they were 10 years…

  10. Development of the "Recovery from Eating Disorders for Life" Food Guide (REAL Food Guide) - a food pyramid for adults with an eating disorder.

    Science.gov (United States)

    Hart, Susan; Marnane, Claire; McMaster, Caitlin; Thomas, Angela

    2018-01-01

    There is limited evidence to inform nutrition and dietetic interventions for individuals with eating disorders even though it is recommended as an essential part of multidisciplinary management. There is minimal guidance, an absence of standardised nutrition educational material, and no research on how best to educate patients on healthy eating and how to achieve nutrition adequacy. Therefore the REAL Food Guide was developed. The REAL Food Guide is a pyramid with four layers and key nutrition messages beside each layer that was conceived to address gaps in nutrition education and intervention for individuals with eating disorders. Written and verbal consumer feedback was obtained from consumers receiving treatment regarding the acceptability and usefulness of the REAL Food Guide. A unique database was developed to reflect the types of foods and realistic portion sizes that patients are likely to select. This database was used for nutrition modelling to assess the nutrition adequacy of three meal patterns (meat containing, vegetarian and semi-vegan) for both weight maintenance and weight regain. Each meal pattern was compared to the Nutrient Reference Values for Australia and New Zealand. Nutritional analysis demonstrated nutritional adequacy of meal patterns for energy, macronutrients and most micronutrients when the recommended number of serves from the REAL Food Guide were assessed. All meal patterns were adequate in micronutrients except for the semi-vegan meal pattern that was inadequate in vitamin D. Feedback from individuals with eating disorders demonstrates the nutrition education tool was acceptable to them as they felt it was more helpful for their recovery than general nutrition guidelines. The REAL Food Guide is a comprehensive and user-friendly guide that clinicians can use to educate patients about components of a balanced and healthy diet. The guide can educate all eating disorder clinicians, including those who are new to the field, about the

  11. Compression of Cognitive Flexibility and Adjustment of Students with Developmental Coordination Disorder (DCD and Typically Developing Students

    Directory of Open Access Journals (Sweden)

    Hasan Sadeghi

    2012-10-01

    Full Text Available Objectives: The aim of this research is to compare cognitive flexibility and adjustment between two groups of students with Developmental Coordination Disorder (DCD and typically developing students. Methods: For this purpose, 50 students with DCD and 50 typically developing students were chosen among 12 primary schools. The Developmental Coordination Disorder Questionnaire (DCD-Q, Adjustment Inventory for School Students (AISS and Wisconsin Card Sorting Test (WCST were used to measure the research variables. Results: The results of the multivariate analysis of variance (MANOVA showed that the mean score of cognitive flexibility and emotional, educational and social adjustment is significantly higher in the students with developmental coordination disorder (P<0.001. The results of multivariate regression analysis also showed that a 25% variance percentage of cognitive flexibility and adjustment can explain the variance of developmental coordination disorder in people with such a disorder (P<0.001. Discussion: The result of the present study provides further evidence based on low cognitive flexibility and Adjustment in students with DCD.

  12. Multifinality in the Development of Personality Disorders: A Biology × Sex × Environment Interaction Model of Antisocial and Borderline Traits

    Science.gov (United States)

    Beauchaine, Theodore P.; Klein, Daniel N.; Crowell, Sheila E.; Derbidge, Christina; Gatzke-Kopp, Lisa

    2009-01-01

    Although antisocial personality disorder (ASPD) is more common among males and borderline personality disorder (BPD) is more common among females, some (e.g., Paris, 1997) have suggested that the two disorders reflect multifinal outcomes of a single etiology. This assertion is based on several overlapping symptoms and features, including trait impulsivity, emotional lability, high rates of depression and suicide, and a high likelihood of childhood abuse and/or neglect. Furthermore, rates of ASPD are elevated in the first degree relatives of those with BPD, and concurrent comorbidity rates for the two disorders are high. In this article, we present a common model of antisocial and borderline personality development. We begin by reviewing issues and problems with diagnosing and studying personality disorders in children and adolescents. Next, we discuss dopaminergic and serotonergic mechanisms of trait impulsivity as predisposing vulnerabilities to ASPD and BPD. Finally, we extend shared risk models for ASPD and BPD by specifying genetic loci that may confer differential vulnerability to impulsive aggression and mood dysregulation among males and impulsive self-injury and mood dysregulation among females. Although the precise mechanisms of these sex-moderated genetic vulnerabilities remain poorly understood, they appear to interact with environmental risk factors including adverse rearing environments to potentiate the development of ASPD and BPD. PMID:19583882

  13. Embryonic Testicular Regression Syndrome Presenting as Primary Amenorrhea: A Case Report and Review of Disorders of Sexual Development.

    Science.gov (United States)

    Hunter, J D; Pierce, S R; Calikoglu, A S; Howell, J O

    2016-08-01

    Sex development depends on the synchronous interaction of complicated genetic and hormonal events. Sex differentiation begins with sex determination, which is the assignment of the embryonic bipotential gonads as either testes or ovaries on the basis of transcriptional regulation. Hormonal regulation then directs the development of the male or female phenotype. Disruptions of this intricate cascade of events result in disorders of sexual development. A 16-year-old female adolescent presented with primary amenorrhea. Evaluation revealed female external genitalia, XY karyotype, absent gonadal tissue, and rudimentary Müllerian structures. On the basis of her constellation of findings, the most logical diagnosis was the rare embryonic testicular regression syndrome. A careful understanding of embryonic sexual development is critical to the evaluation of patients with disorders of sexual development. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  14. Classification of functioning and impairment: the development of ICF core sets for autism spectrum disorder.

    Science.gov (United States)

    Bölte, Sven; de Schipper, Elles; Robison, John E; Wong, Virginia C N; Selb, Melissa; Singhal, Nidhi; de Vries, Petrus J; Zwaigenbaum, Lonnie

    2014-02-01

    Given the variability seen in Autism Spectrum Disorder (ASD), accurate quantification of functioning is vital to studying outcome and quality of life in affected individuals. The International Classification of Functioning, Disability and Health (ICF) provides a comprehensive, universally accepted framework for the description of health-related functioning. ICF Core Sets are shortlists of ICF categories that are selected to capture those aspects of functioning that are most relevant when describing a person with a specific condition. In this paper, the authors preview the process for developing ICF Core Sets for ASD, a collaboration with the World Health Organization and the ICF Research Branch. The ICF Children and Youth version (ICF-CY) was derived from the ICF and designed to capture the specific situation of the developing child. As ASD affects individuals throughout the life span, and the ICF-CY includes all ICF categories, the ICF-CY will be used in this project ("ICF(-CY)" from now on). The ICF(-CY) categories to be included in the ICF Core Sets for ASD will be determined at an ICF Core Set Consensus Conference, where evidence from four preparatory studies (a systematic review, an expert survey, a patient and caregiver qualitative study, and a clinical cross-sectional study) will be integrated. Comprehensive and Brief ICF Core Sets for ASD will be developed with the goal of providing useful standards for research and clinical practice and generating a common language for functioning and impairment in ASD in different areas of life and across the life span. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

  15. Psychosocial well-being in Dutch adults with disorders of sex development.

    Science.gov (United States)

    de Neve-Enthoven, Nita G M; Callens, Nina; van Kuyk, Maaike; van Kuppenveld, Jet H; Drop, Stenvert L S; Cohen-Kettenis, Peggy T; Dessens, Arianne B

    2016-04-01

    Atypical sex development is associated with psychosocial vulnerability. We investigated psychosocial well-being in individuals with disorders of sex development (DSD) and hypothesized that psychosocial well-being was related to degree of genital atypicality at birth. 120 male (n=16) and female (n=104) persons with DSD, aged 14-60 years, participated in a follow-up audit on psychosocial well-being. They were stratified in: women with 1) 46,XY and female genitalia, 2) 46,XY or 46,XX and atypical genitalia, and 3) men with 46,XY and atypical genitalia. We used the Illness Cognition Questionnaire (ICQ), Checklist Individual Strength (CIS8R), TNO-AZL Quality of Life questionnaire (TAAQOL), Adult Self-Report (ASR), and the Rosenberg Self-Esteem Scale (RSES). Data were compared to reference groups. Participants generally were coping well with DSD (ICQ). Women with DSD reported elevated levels of fatigue (CIS8R) and slightly more attention and memory problems (TAAQOL, ASR). Women with atypical genitalia reported more emotional and behavioral problems. On the ASR Rule-breaking Behavior and Antisocial Personality scales, these women had similar scores as reference men. Women with DSD reported a higher self-esteem (RSES). No differences in psychosocial well-being were found between men with DSD and reference men. Individuals with DSD across all diagnostic groups generally reported a good psychosocial well-being. The results further suggest involvement of prenatal androgens in the development of personality traits related to assertiveness and egocentricity. We recommend that individuals with a DSD and their families are involved in decision-making processes and have access to multidisciplinary care. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. 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.

  17. Gender Issues and Related Social Stigma Affecting Patients with a Disorder of Sex Development in India.

    Science.gov (United States)

    Joseph, Angela Ann; Kulshreshtha, Bindu; Shabir, Iram; Marumudi, Eunice; George, Tony Sam; Sagar, Rajesh; Mehta, Manju; Ammini, Ariachery C

    2017-02-01

    Children with disorders of sex development (DSD) manifest at birth with malformed genitalia or later with atypical pubertal development. Those born with malformed genitalia are often diagnosed at birth. However, in resource-poor countries like India, where not all births are supervised by healthcare workers, some of these children remain undiagnosed until puberty or even later. The aim of this study was to assess the gender issues and psychosocial problems of children with DSD. Participants included 205 children with DSD (103 with 46,XX DSD and 102 with 46,XY DSD). Both the children with DSD and their parents underwent semistructured interviews by a clinical psychologist. The birth of a child with DSD was perceived as a major medical and social problem by parents from all socioeconomic strata. Mothers were distressed as many believed the DSD condition was transmitted through the mother. Children who were not diagnosed and treated during infancy or early childhood experienced considerable social discrimination not only from relatives and friends but also from medical and paramedical staff in hospitals. Several patients had been operated during infancy without an etiological diagnosis and without provision of adequate information to the parents. Some children had problems related to complications of surgery. Most teenage patients with 5α-reductase-2 deficiency reared as females presented with gender dysphoria, while children with androgen insensitivity (except for one) or with gonadal dysgenesis developed a gender identity concordant with their gender of rearing. Parents of children with DSD preferred a male gender assignment for their children (if that was possible) because of the social advantages of growing up male in a patriarchal society.

  18. Early social-communicative and cognitive development of younger siblings of children with autism spectrum disorders.

    Science.gov (United States)

    Stone, Wendy L; McMahon, Caitlin R; Yoder, Paul J; Walden, Tedra A

    2007-04-01

    To compare the early social-communicative development of younger siblings of children with autism spectrum disorders (ASDs) with that of younger siblings of children with typical development, using parental report and child-based measures. Group comparison. Vanderbilt University, between July 1, 2003, and July 31, 2006. Younger siblings of children with ASD (n = 64) and younger siblings of children with typical development (n = 42) between the ages of 12 and 23 months (mean, 16 months). Main Exposure Having a sibling with an ASD. Child-based measures included a cognitive assessment; an interactive screening tool assessing play, imitation, and communication; and a rating of autism symptoms. Parental report measures were an interview of social-communicative interactions and a questionnaire assessing language and communication skills. Younger siblings of children with ASD demonstrated weaker performance in nonverbal problem solving (mean difference [MD], 5.91; 95% confidence interval [CI], 2.48-9.34), directing attention (MD, 0.52; 95% CI, 0.07-0.97), understanding words (MD, 33.30; 95% CI, 3.11-63.48), understanding phrases (MD, 4.56; 95% CI, 1.85-7.27), gesture use (MD, 1.49; 95% CI, 0.51-2.47), and social-communicative interactions with parents (MD, 1.32; 95% CI, 0.27-2.37), and had increased autism symptoms (MD, 2.54; 95% CI, 1.05-4.03), relative to control siblings. A substantial minority of the ASD sibling group exhibited lower performance relative to controls. Significant correlations between child-based measures and parental reports assessing similar constructs were found (r = -0.74 to 0.53; P range, .000-.002). The weaker performance found for children in the ASD sibling group may represent early-emerging features of the broader autism phenotype, thus highlighting the importance of developmental surveillance for younger siblings.

  19. Germ cell tumors in patients with disorders of sex development: Risk factors, initial developmental stages and targets for early diagnosis

    NARCIS (Netherlands)

    M.B.C.M. Cools (Martine)

    2006-01-01

    textabstractThis thesis describes the origin, identification and correct diagnosis of the earliest stages of malignant germ cell tumors, i.e. intra tubular germ cell neoplasia unclassified (ITGNU) and gonadoblastoma, in patients with disorders of sex development. Special attention is given to the

  20. Development of the Observation Scale for Aggressive Behavior (OSAB) for Dutch forensic psychiatric inpatients with an antisocial personality disorder.

    NARCIS (Netherlands)

    Hornsveld, R.H.J.; Nijman, H.L.I.; Hollin, C.R.; Kraaimaat, F.W.

    2007-01-01

    The Observation Scale for Aggressive Behavior (OSAB) has been developed to evaluate inpatient treatment programs designed to reduce aggressive behavior in Dutch forensic psychiatric patients with an antisocial personality disorder, who are "placed at the disposal of the government". The scale should

  1. Smoking and the Developing Brain : Altered White Matter Microstructure in Attention-Deficit/Hyperactivity Disorder and Healthy Controls

    NARCIS (Netherlands)

    van Ewijk, Hanneke; Groenman, Annabeth P.; Zwiers, Marcel P.; Heslenfeld, Dirk J.; Faraone, Stephen V.; Hartman, Catharina A.; Luman, Marjolein; Greven, Corina U.; Hoekstra, Pieter J.; Franke, Barbara; Buitelaar, Jan; Oosterlaan, Jaap

    Brain white matter (WM) tracts, playing a vital role in the communication between brain regions, undergo important maturational changes during adolescence and young adulthood, a critical period for the development of nicotine dependence. Attention-deficit/hyperactivity disorder (ADHD) is associated

  2. 78 FR 19723 - Proposed Collection; 60-Day Comment Request; Evaluation of the Brain Disorders in the Developing...

    Science.gov (United States)

    2013-04-02

    ... contribute to the long-term goal of building sustainable research capacity in nervous system function and... Comment Request; Evaluation of the Brain Disorders in the Developing World Program of the John E. Fogarty.... Written comments and/or suggestions from the public and affected agencies are invited on one or more of...

  3. Gesture, Play, and Language Development of Spanish-Speaking Toddlers with Developmental Language Disorders: A Preliminary Study

    Science.gov (United States)

    Guiberson, Mark

    2016-01-01

    The purpose of this preliminary study was to (a) examine relationships between the symbolic and language skills of a mixed (developmental language disordered [DLD] and typical language [TL]) Spanish-speaking sample; (b) describe gesture, play, and language skills of DLD and TL groups; (c) compare the development between groups; and (d) explore…

  4. Altered Development of White Matter in Youth at High Familial Risk for Bipolar Disorder: A Diffusion Tensor Imaging Study

    Science.gov (United States)

    Versace, Amelia; Ladouceur, Cecile D.; Romero, Soledad; Birmaher, Boris; Axelson, David A.; Kupfer, David J.; Phillips, Mary L.

    2010-01-01

    Objective: To study white matter (WM) development in youth at high familial risk for bipolar disorder (BD). WM alterations are reported in youth and adults with BD. WM undergoes important maturational changes in adolescence. Age-related changes in WM microstructure using diffusion tensor imaging with tract-based spatial statistics in healthy…

  5. Variability in Classroom Social Communication: Performance of Children with Fetal Alcohol Spectrum Disorders and Typically Developing Peers

    Science.gov (United States)

    Kjellmer, Liselotte; Olswang, Lesley B.

    2013-01-01

    Purpose: In this study, the authors examined how variability in classroom social communication performance differed between children with fetal alcohol spectrum disorders (FASD) and pair-matched, typically developing peers. Method: Twelve pairs of children were observed in their classrooms, 40 min per day (20 min per child) for 4 days over a…

  6. Identification of ectopic ovotestis in a dog with XX ovotesticular, SRY-negative, disorder of sexual development.

    Science.gov (United States)

    Diel de Amorim, M; Lerer, A; Durzi, T; Foster, R A; Gartley, C J

    2018-06-01

    A 1-year-old, previously spayed phenotypic female Poodle/Soft-coated Wheaten Terrier (Whoodle) cross was presented for a suspected ovarian remnant. Serum luteinizing hormone (LH) concentration was below the detection limit (XX karyotype, thus confirming the diagnosis of ectopic ovotestis in a XX ovotesticular, SRY-negative, disorder of sexual development in a dog. © 2018 Blackwell Verlag GmbH.

  7. Theory of Mind and Executive Function in Preschoolers with Typical Development versus Intellectually Able Preschoolers with Autism Spectrum Disorder

    Science.gov (United States)

    Kimhi, Yael; Shoam-Kugelmas, Dana; Agam Ben-Artzi, Galit; Ben-Moshe, Inbal; Bauminger-Zviely, Nirit

    2014-01-01

    Children with autism spectrum disorder (ASD) have difficulties in theory of mind (ToM) and executive function (EF), which may be linked because one domain (EF) affects the other (ToM). Group differences (ASD vs. typical development) were examined in both cognitive domains, as well as EF's associations and regressions with ToM. Participants…

  8. Characterizing Early Psychosocial Functioning of Parents of Children with Moderate to Severe Genital Ambiguity due to Disorders of Sex Development.

    Science.gov (United States)

    Suorsa, Kristina I; Mullins, Alexandria J; Tackett, Alayna P; Reyes, Kristy J Scott; Austin, Paul; Baskin, Laurence; Bernabé, Kerlly; Cheng, Earl; Fried, Allyson; Frimberger, Dominic; Galan, Denise; Gonzalez, Lynette; Greenfield, Saul; Kropp, Bradley; Meyer, Sabrina; Meyer, Theresa; Nokoff, Natalie; Palmer, Blake; Poppas, Dix; Paradis, Alethea; Yerkes, Elizabeth; Wisniewski, Amy B; Mullins, Larry L

    2015-12-01

    We examined the psychosocial characteristics of parents of children with disorders of sex development at early presentation to a disorders of sex development clinic. Parental anxiety, depression, quality of life, illness uncertainty and posttraumatic stress symptoms were assessed. Additionally we evaluated the relationship of assigned child gender to parental outcomes. A total of 51 parents of children with ambiguous or atypical genitalia were recruited from 7 centers specializing in treatment of disorders of sex development. At initial assessment no child had undergone genitoplasty. Parents completed the Cosmetic Appearance Rating Scale, Beck Anxiety Inventory, Beck Depression Inventory, SF-36, Parent Perception of Uncertainty Scale and Impact of Event Scale-Revised. A large percentage of parents (54.5%) were dissatisfied with the genital appearance of their child, and a small but significant percentage reported symptoms of anxiety, depression, diminished quality of life, uncertainty and posttraumatic stress. Few gender differences emerged. Although many parents function well, a subset experience significant psychological distress around the time of diagnosis of a disorder of sex development in their child. Early screening to assess the need for psychosocial interventions is warranted. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  9. Incidence, prevalence, diagnostic delay, morbidity, mortality and socioeconomic status in males with 46,XX disorders of sex development

    DEFF Research Database (Denmark)

    Berglund, A.; Johannsen, T. H.; Stochholm, K.

    2017-01-01

    STUDY QUESTION What is the epidemiology and trajectory of health and socioeconomic status in males with 46,XX disorders of sex development (DSD)? SUMMARY ANSWER 46,XX DSD males had an increased overall morbidity compared to male background population controls, and the socioeconomic status was inf...

  10. Sex Differences in Children with Autism Spectrum Disorders Compared with Their Unaffected Siblings and Typically Developing Children

    Science.gov (United States)

    Park, Subin; Cho, Soo-Churl; Cho, In Hee; Kim, Boong-Nyun; Kim, Jae-Won; Shin, Min-Sup; Chung, Un-Sun; Park, Tae-Won; Son, Jung-Woo; Yoo, Hee Jeong

    2012-01-01

    This study examined the nature of cognitive and behavioral sex differences in children with autism spectrum disorders (ASDs) and two comparison groups: a group of typically developing (TD) children and a group of unaffected siblings of ASD children. Sex differences in core autistic symptoms, co-occurring behavioral symptoms, and cognitive styles…

  11. Delusional disorder in old age and the risk of developing dementia: a nationwide register-based study

    DEFF Research Database (Denmark)

    Kørner, Alex; Lopez, Ana G; Lauritzen, Lise

    2008-01-01

    OBJECTIVE: To examine whether very late first-contact delusional disorder carries a risk for later development of dementia. METHODS: By linkage of the psychiatric and the somatic nationwide registers of all out- and in-patients with hospital contact in Denmark, we included all 60+ patients with f...

  12. Development of motor imagery and anticipatory action planning in children with developmental coordination disorder: A longitudinal approach

    NARCIS (Netherlands)

    Adams, I.L.J.; Lust, J.M.; Wilson, P.H.; Steenbergen, B.

    2017-01-01

    Children with impaired motor coordination (or Development Coordination Disorder - DCD) have difficulty with the predictive control of movements, evidenced by cross-sectional studies that show impaired motor imagery and action planning abilities. What remains unclear is whether this deficit in

  13. The Investigation of Quality of Life in 87 Chinese Patients with Disorders of Sex Development

    Directory of Open Access Journals (Sweden)

    Chunqing Wang

    2015-01-01

    Full Text Available Objective. In the process of care for disorders of sex development (DSD, clinical decisions should focus on the long-term quality of life (QOL. We sought to investigate the QOL of patients with DSD in China. Design. Case-control study was carried out. Patients. 90 patients of DSD participated in the study. Finally, 87 patients were analyzed including Turner’s syndrome (23, Noonan syndrome (2, androgen insensitivity syndrome (22, testicular regression syndrome (2, congenital adrenal hyperplasia (16, and pure gonadal dysgenesis (22. Measurements. The WHOQOL-BREF questionnaire was chosen for the present investigation. Four domain scores were analyzed independently including physical, psychological, and social relationship and environmental domains. Results. The average age of the DSD group is 22.34 ± 4.97 years, and only 13.79% patients ever had sexual life. The scores of psychological and environmental domains were lower than that of the physical and social relationship domains, but the difference was not significant (P>0.05. Compared with the Chinese urban population, the QOL scores of DSD patients in China were not significantly lower. Conclusions. With proper treatment, including the follow-up and psychological support, the QOL of DSD patients cannot be significantly reduced. For DSD patients, more attention should be paid to the potential psychological and sexual problems.

  14. Epstein-Barr Virus-associated lymphoproliferative disorders: experimental and clinical developments

    Science.gov (United States)

    Geng, Lingyun; Wang, Xin

    2015-01-01

    Epstein-Barr Virus (EBV), the first human virus related to oncogenesis, was initially identified in a Burkitt lymphoma cell line in 1964. EBV infects over 90% of the world’s population. Most infected people maintain an asymptomatic but persistent EBV infection lifelong. However, in some individuals, EBV infection has been involved in the development of cancer and autoimmune disease. Nowadays, oncogenic potential of EBV has been intensively studied in a wide range of human neoplasms, including Hodgkin’s lymphoma (HL), non-Hodgkin’s lymphoma (NHL), nasopharyngeal carcinoma (NPC), gastric carcinoma (GC), etc. EBV encodes a series of viral protein and miRNAs, promoting its persistent infection and the transformation of EBV-infected cells. Although the exact role of EBV in the oncogenesis remains to be clarified, novel diagnostic and targeted therapeutic approaches are encouraging for the management of EBV-related malignancies. This review mainly focuses on the experimental and clinical advances of EBV-associated lymphoproliferative disorders. PMID:26628948

  15. Polysyllable Speech Accuracy and Predictors of Later Literacy Development in Preschool Children With Speech Sound Disorders.

    Science.gov (United States)

    Masso, Sarah; Baker, Elise; McLeod, Sharynne; Wang, Cen

    2017-07-12

    The aim of this study was to determine if polysyllable accuracy in preschoolers with speech sound disorders (SSD) was related to known predictors of later literacy development: phonological processing, receptive vocabulary, and print knowledge. Polysyllables-words of three or more syllables-are important to consider because unlike monosyllables, polysyllables have been associated with phonological processing and literacy difficulties in school-aged children. They therefore have the potential to help identify preschoolers most at risk of future literacy difficulties. Participants were 93 preschool children with SSD from the Sound Start Study. Participants completed the Polysyllable Preschool Test (Baker, 2013) as well as phonological processing, receptive vocabulary, and print knowledge tasks. Cluster analysis was completed, and 2 clusters were identified: low polysyllable accuracy and moderate polysyllable accuracy. The clusters were significantly different based on 2 measures of phonological awareness and measures of receptive vocabulary, rapid naming, and digit span. The clusters were not significantly different on sound matching accuracy or letter, sound, or print concept knowledge. The participants' poor performance on print knowledge tasks suggested that as a group, they were at risk of literacy difficulties but that there was a cluster of participants at greater risk-those with both low polysyllable accuracy and poor phonological processing.

  16. Imitation and communication skills development in children with pervasive developmental disorders

    Directory of Open Access Journals (Sweden)

    Andrea De Giacomo

    2009-06-01

    Full Text Available Andrea De Giacomo1, Claudia Portoghese1, Domenico Martinelli2, Isabella Fanizza1, Luciano L’Abate3, Lucia Margari11Child Neurological and Psychiatric Unit, Department of Neurological and Psychiatric sciences, University of Bari, Italy; 2Department of Biomedical science and Oncology, University of Bari, Italy; 3Department of Psychology, Georgia State University Abstract: This study evaluates the correlation between failure to develop spontaneous imitation and language skills in pervasive developmental disorders. Sixty-four children between the age of 3 and 8 years were assessed using the Autism Diagnostic Interview-Revised (ADI-R, the Childhood Autism Rating Scale (CARS, and the Autism Diagnostic Observation Schedule (ADOS, as well as direct observation of imitation. The sample was subdivided into a verbal and a nonverbal group. Analysis of mean scores on the CARS “imitation” items and of ADI-R “spontaneous imitation” and “pointing to express interest” revealed a statistically significant difference between verbal and nonverbal groups, with more severe impairment/higher scores in the nonverbal than the verbal group. These results suggest that nonverbal children have specifically impaired imitation and pointing skills.Keywords: autism, imitation, communication, language, pointing

  17. Risk Factors for Developing Work-Related Musculoskeletal Disorders during Dairy Farming

    Directory of Open Access Journals (Sweden)

    Sayed Mohammad Taghavi

    2017-01-01

    Full Text Available Background: Dairy farming work involves frequent use of poor postures. These postures may increase the risk of developing musculoskeletal disorders among dairy workers. Objective: To assess postural load during performance of various tasks related to dairy farming. Methods: This cross-sectional study was conducted on a dairy farm in Iran. In order to assess postural load, tasks related to dairy farming were divided into 3 categories: feeding, milking, and manure disposal. Each task was then divided into its constituent work subdivisions (tasks. Finally, the working posture for each work subdivision was evaluated using Rapid Entire Body Assessment (REBA. Results: Based on the results from the REBA score, the poorest risk scores (risk level 4 were associated with the following tasks: (1 manure disposal, (2 filling feed bags, and (3 pouring milk into a bucket. Other tasks such as filling corn containers, pouring corn into the milling machine, preparing the feed, pouring food into mangers, attaching the milking machine, and pouring milk from a bucket into a tank imposed high risk (risk level 3. The risk for the tasks of washing and disinfecting the udders were assessed as medium risks. Conclusion: The risk levels associated with most of the tasks on the studied farm were unacceptably high. Therefore, it is essential to implement ergonomic interventions to reduce risk levels of the tasks.

  18. Risk Factors for Developing Work-Related Musculoskeletal Disorders during Dairy Farming.

    Science.gov (United States)

    Taghavi, Sayed Mohammad; Mokarami, Hamidreza; Ahmadi, Omran; Stallones, Lorann; Abbaspour, Asghar; Marioryad, Hossein

    2017-01-01

    Dairy farming work involves frequent use of poor postures. These postures may increase the risk of developing musculoskeletal disorders among dairy workers. To assess postural load during performance of various tasks related to dairy farming. This cross-sectional study was conducted on a dairy farm in Iran. In order to assess postural load, tasks related to dairy farming were divided into 3 categories: feeding, milking, and manure disposal. Each task was then divided into its constituent work subdivisions (tasks). Finally, the working posture for each work subdivision was evaluated using Rapid Entire Body Assessment (REBA). Based on the results from the REBA score, the poorest risk scores (risk level 4) were associated with the following tasks: (1) manure disposal, (2) filling feed bags, and (3) pouring milk into a bucket. Other tasks such as filling corn containers, pouring corn into the milling machine, preparing the feed, pouring food into mangers, attaching the milking machine, and pouring milk from a bucket into a tank imposed high risk (risk level 3). The risk for the tasks of washing and disinfecting the udders were assessed as medium risks. The risk levels associated with most of the tasks on the studied farm were unacceptably high. Therefore, it is essential to implement ergonomic interventions to reduce risk levels of the tasks.

  19. Caregivers of children with a disorder of sex development: associations between parenting capacities and psychological distress.

    Science.gov (United States)

    Wolfe-Christensen, Cortney; Fedele, David A; Kirk, Katherine; Mullins, Larry L; Lakshmanan, Yegappan; Wisniewski, Amy B

    2014-06-01

    Caregivers of children with a disorder of sex development (DSD) are at increased risk for maladaptive parenting capacities, such as high levels of parental overprotection and perceived vulnerability of their child, in addition to parenting stress. The current study aims to examine whether there are relationships between these parenting capacities and psychological distress, including depressive and anxious symptoms. Participants included 134 caregivers of 90 children with a DSD. Caregivers completed measures of parental overprotection, perceived vulnerability, parenting stress, anxiety, and depression. Hierarchical regression analyses revealed that higher levels of parenting stress were related to more anxious and depressive symptoms in caregivers. Higher levels of perceived vulnerability were related to more anxious symptoms. Levels of parental overprotection were unrelated to anxious or depressive symptoms. There is a relationship between parenting capacities and mental health outcomes in caregivers of children with DSD, although the direction of this relationship is not clear. Given the strong relationships between parenting stress and anxious and depressive symptoms, targeting parenting stress and/or psychological distress in these caregivers could result in better functioning overall. Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  20. The first case of 38,XX (SRY-positive) disorder of sex development in a cat.

    Science.gov (United States)

    Szczerbal, Izabela; Stachowiak, Monika; Dzimira, Stanislaw; Sliwa, Krystyna; Switonski, Marek

    2015-01-01

    SRY-positive XX testicular disorder of sex development (DSD) caused by X;Y translocations was not yet reported in domestic animals. In humans it is rarely diagnosed and a majority of clinical features resemble those which are typical for Klinefelter syndrome (KS). Here we describe the first case of SRY-positive XX DSD in a tortoiseshell cat with a rudimentary penis and a lack of scrotum. Molecular analysis showed the presence of two Y-linked genes (SRY and ZFY) and a normal sequence of the SRY gene. Application of classical cytogenetic techniques revealed two X chromosomes (38,XX), but further FISH studies with the use of the whole X chromosome painting probe and BAC probes specific to the Yp chromosome facilitated identification of Xp;Yp translocation. The SRY gene was localised at a distal position of Xp. The karyotype of the studied case was described as: 38,XX.ish der(X)t(X;Y)(p22;p12)(SRY+). Moreover, the X inactivation status assessed by a sequential R-banding and FISH with the SRY-specific probe showed a random inactivation of the derivative X(SRY) chromosome. Our study showed that among DSD tortoiseshell cats, apart from XXY trisomy and XX/XY chimerism, also SRY-positive XX cases may occur. It is hypothesized that the extremely rare occurrence of this abnormality in domestic animals, when compared with humans, may be associated with a different organisation of the Yp arm in these species.

  1. Ovotesticular disorder of sexual development and a rare 46,XX/47,XXY karyotype.

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    Ozsu, Elif; Mutlu, Gul Yesiltepe; Cizmecioglu, Filiz M; Ekingen, Gülsen; Muezzinoglu, Bahar; Hatun, Sukru

    2013-01-01

    Ovotesticular disorder of sexual development (DSD) is characterized by the presence of both ovarian and testicular tissues in the same individual. The most common karyotype is 46,XX. Here, we report the case of a boy with a 46,XX/47,XXY karyotype diagnosed as ovotesticular DSD by gonadal biopsy. A 5-month-old boy presented with hypospadias, unilateral cryptorchidism, and a micropenis. Pelvic magnetic resonance imaging revealed a suspicious gonad tissue that is solid in structure in the right scrotum and a suspicious gonad that is cystic in structure in the left inguinal canal. He underwent a diagnostic laparoscopy. Cytogenetic analysis of peripheral blood revealed a 46,XX/47,XXY karyotype. Histopathologic examination of the left gonad showed ovarian tissue containing primordial follicles with ipsilateral undifferentiated tuba uterina. The right gonad showed immature testis tissue. He underwent left gonadectomy and hypospadias repair, and was raised as a male. Through this rare case, we highlight the importance of histological and cytogenetic investigation in DSD.

  2. Checklist for the Structural Description of the Deep Phenotype in Disorders of Sexual Development

    Directory of Open Access Journals (Sweden)

    L. Wünsch

    2012-01-01

    Full Text Available This paper addresses the question, how the variations of the deep phenotype in disorders of sex development (DSD are appropriately described. This is a relevant question, because extensive phenotypic variability occurs in gonads and sex ducts. With the advance of video endoscopy and laparoscopy, fresh insight in gonadal and sex duct anatomy is emerging. So far, an attempt to standardize the diagnostic approach and, in particular, how to document these findings has not been published. We propose a standardized examination schedule for these procedures. It consists of 5 pictures of relevant anatomic features. For laparoscopy, it includes two pictures each of gonads and sex ducts on either side and an image of the retrovesical space. For endoscopy, the examination of the ureteric orifices, the posterior urethra, and the urogenital sinus derivates is recommended. Adherence of a standardized schedule and image storing enhances patient autonomy, because they can carry their examination for a second opinion without need for repeated examination. Physicians and scientists create a structured image library that facilitates the comparison of clinical outcomes, research on genotype phenotype associations and may lead to better classifications.

  3. Islamic bioethical deliberation on the issue of newborns with disorders of sex development.

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    Mohamed, Mohd Salim; Noor, Siti Nurani Mohd

    2015-04-01

    This article presents the Islamic bioethical deliberation on the issue of sex assignment surgery (SAS) for infants with disorders of sex development (DSD) or intersexed as a case study. The main objective of this study is to present a different approach in assessing a biomedical issue within the medium of the Maqasid al-Shari'ah. Within the framework of the maqasidic scheme of benefits and harms, any practice where benefits are substantial is considered permissible, while those promoting harms are prohibited. The concept of Maqasid al-Shari'ah which is the mechanistic interpretation of Qur'an and Hadith presents the holistic attention of Islam on many life activities, including healthcare. Indeed, this concept encompasses many aspects of worldly life, both for the human individual and collectively for the whole society. In healthcare, the practice of SAS on DSD newborns has presented an assortment of implications on the future livelihood of the affected individual. The process of decision-making seems to be very multifaceted since every element such as the determination of the 'correct' sex and the urgency of early surgery must consider the benefits and harms, as well as the child's rights and best interest. The application of the concept of Maqasid al-Shari'ah, would convey a pragmatic approach that is often disregarded in Western medicine. This approach considers the right of the individual to live life optimally, individually and socially and practice his faith, precisely, in accordance with the assigned gender.

  4. Child maltreatment and trajectories of personality and behavioral functioning: implications for the development of personality disorder.

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    Kim, Jungmeen; Cicchetti, Dante; Rogosch, Fred A; Manly, Jody Todd

    2009-01-01

    This study investigated the longitudinal impact of maltreatment parameters on personality processes and maladjustment and prospective relationships between personality trajectory classes and subsequent maladjustment outcomes. The sample involved maltreated (n = 249) and nonmaltreated (n = 200) children followed longitudinally between ages 6 and 10. Growth mixture modeling indicated multifinality in personality development depending on the risk status (i.e., maltreated vs. nonmaltreated). Two trajectory classes of ego resiliency were identified for maltreated children: those who showed a declining trajectory exhibited greater maladjustment. In contrast, three trajectory classes of ego control were identified for nonmaltreated children; the subgroups showing increases in ego undercontrol or dramatic changes from high ego undercontrol to high ego overcontrol exhibited poor adjustment. Experiencing multiple maltreatment subtypes and physical/sexual abuse were related to higher levels of ego undercontrol and externalizing symptomatology, whereas early onset of maltreatment was associated with the low and decreasing trajectory of ego resiliency and higher levels of internalizing symptomatology. The findings suggest that ego resiliency and ego control, personality processes related to self-regulation, may be important factors in identifying distinct pathways to later personality disorders as well as pathways to resilient functioning.

  5. Dopamine and the development of executive dysfunction in autism spectrum disorders.

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    Kriete, Trenton; Noelle, David C

    2015-01-01

    Persons with autism regularly exhibit executive dysfunction (ED), including problems with deliberate goal-directed behavior, planning, and flexible responding in changing environments. Indeed, this array of deficits is sufficiently prominent to have prompted a theory that executive dysfunction is at the heart of these disorders. A more detailed examination of these behaviors reveals, however, that some aspects of executive function remain developmentaly appropriate. In particular, while people with autism often have difficulty with tasks requiring cognitive flexibility, their fundamental cognitive control capabilities, such as those involved in inhibiting an inappropriate but relatively automatic response, show no significant impairment on many tasks. In this article, an existing computational model of the prefrontal cortex and its role in executive control is shown to explain this dichotomous pattern of behavior by positing abnormalities in the dopamine-based modulation of frontal systems in individuals with autism. This model offers excellent qualitative and quantitative fits to performance on standard tests of cognitive control and cognitive flexibility in this clinical population. By simulating the development of the prefrontal cortex, the computational model also offers a potential explanation for an observed lack of executive dysfunction early in life.

  6. Dopamine and the development of executive dysfunction in autism spectrum disorders.

    Directory of Open Access Journals (Sweden)

    Trenton Kriete

    Full Text Available Persons with autism regularly exhibit executive dysfunction (ED, including problems with deliberate goal-directed behavior, planning, and flexible responding in changing environments. Indeed, this array of deficits is sufficiently prominent to have prompted a theory that executive dysfunction is at the heart of these disorders. A more detailed examination of these behaviors reveals, however, that some aspects of executive function remain developmentaly appropriate. In particular, while people with autism often have difficulty with tasks requiring cognitive flexibility, their fundamental cognitive control capabilities, such as those involved in inhibiting an inappropriate but relatively automatic response, show no significant impairment on many tasks. In this article, an existing computational model of the prefrontal cortex and its role in executive control is shown to explain this dichotomous pattern of behavior by positing abnormalities in the dopamine-based modulation of frontal systems in individuals with autism. This model offers excellent qualitative and quantitative fits to performance on standard tests of cognitive control and cognitive flexibility in this clinical population. By simulating the development of the prefrontal cortex, the computational model also offers a potential explanation for an observed lack of executive dysfunction early in life.

  7. Behavioural Problems in Children with 46XY Disorders of Sex Development

    Directory of Open Access Journals (Sweden)

    Nalini M. Selveindran

    2017-01-01

    Full Text Available The aim of this study is to determine the behavioural problems of children with 46XY disorders of sex development (DSD with genital ambiguity and to identify the risk factors that may influence behaviour. The 27 participants (aged 6–18 years consisted of 21 patients raised as boys and 6 patients raised as girls. Control data were obtained from a representative sibling of each patient who was matched for age and gender. The study tool used was the Child Behaviour Checklist (CBCL, which is a parent-administered questionnaire. The analysis of the behavioural scores revealed that the patient group had poorer scores in the total, externalizing, and internalizing realms. This group also had poorer scores in the anxious-depressed, social, and rule-breaking realms as compared to the control group. In addition, the XY-F group had higher scores (more pathological than the XY-M group, although the difference in the scores was not statistically significant. A comparison of the prevalence of patients with scores in the clinical range with that of the control group was not statistically significant. These findings support the current recommendations that psychological counselling should be an integral part of the professional support offered to patients with DSD.

  8. Reading Skills of Students With Speech Sound Disorders at Three Stages of Literacy Development

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    Skebo, Crysten M.; Lewis, Barbara A.; Freebairn, Lisa A.; Tag, Jessica; Ciesla, Allison Avrich; Stein, Catherine M.

    2015-01-01

    Purpose The relationship between phonological awareness, overall language, vocabulary, and nonlinguistic cognitive skills to decoding and reading comprehension was examined for students at 3 stages of literacy development (i.e., early elementary school, middle school, and high school). Students with histories of speech sound disorders (SSD) with and without language impairment (LI) were compared to students without histories of SSD or LI (typical language; TL). Method In a cross-sectional design, students ages 7;0 (years; months) to 17;9 completed tests that measured reading, language, and nonlinguistic cognitive skills. Results For the TL group, phonological awareness predicted decoding at early elementary school, and overall language predicted reading comprehension at early elementary school and both decoding and reading comprehension at middle school and high school. For the SSD-only group, vocabulary predicted both decoding and reading comprehension at early elementary school, and overall language predicted both decoding and reading comprehension at middle school and decoding at high school. For the SSD and LI group, overall language predicted decoding at all 3 literacy stages and reading comprehension at early elementary school and middle school, and vocabulary predicted reading comprehension at high school. Conclusion Although similar skills contribute to reading across the age span, the relative importance of these skills changes with children’s literacy stages. PMID:23833280

  9. Promoting Shared Decision Making in Disorders of Sex Development (DSD): Decision Aids and Support Tools.

    Science.gov (United States)

    Siminoff, L A; Sandberg, D E

    2015-05-01

    Specific complaints and grievances from adult patients with disorders of sex development (DSD), and their advocates center around the lack of information or misinformation they were given about their condition and feeling stigmatized and shamed by the secrecy surrounding their condition and its management. Many also attribute poor sexual function to damaging genital surgery and/or repeated, insensitive genital examinations. These reports suggest the need to reconsider the decision-making process for the treatment of children born with DSD. This paper proposes that shared decision making, an important concept in adult health care, be operationalized for the major decisions commonly encountered in DSD care and facilitated through the utilization of decision aids and support tools. This approach may help patients and their families make informed decisions that are better aligned with their personal values and goals. It may also lead to greater confidence in decision making with greater satisfaction and less regret. A brief review of the past and current approach to DSD decision making is provided, along with a review of shared decision making and decision aids and support tools. A case study explores the need and potential utility of this suggested new approach. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Regional variations in the management of testicular or ovotesticular disorders of sex development.

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    Josso, N; Audi, L; Shaw, G

    2011-01-01

    Disorders of sex development arise in parts of the world with different socio-economic and cultural characteristics. We wished to determine the regional variations in the management of these conditions. A questionnaire was e-mailed to the 650 members of the European Society for Paediatric Endocrinology (ESPE), an international society with a mainly European membership but which also includes professionals from other continents. Results were subjected to statistical analysis. A total of 62 answers were received, a satisfactory rate given that not all members are involved in this issue. Results show statistically significant regional differences for available diagnostic resources, age of the patient at gender assignment, parameters considered important for gender assignment, and timing of discussion of various issues with parents and patient. The regional variations exist not only between different continents, as already demonstrated by others, but also between Northern, Latin and Eastern European countries. This suggests that 'one-fits-all' guidelines for management are not appropriate. Copyright © 2011 S. Karger AG, Basel.

  11. Progress in bipolar disorder drug design toward the development of novel therapeutic targets: a clinician's perspective.

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    Fornaro, Michele; Kardash, Lubna; Novello, Stefano; Fusco, Andrea; Anastasia, Annalisa; De Berardis, Domenico; Perna, Giampaolo; Carta, Mauro Giovanni

    2018-03-01

    Bipolar disorder (BD) is a considerable burden to the affected individual. The need for novel drug targets and improved drug design (DD) in BD is therefore clear. Areas covered: The following article provides a brief, narrative, clinician-oriented overview of the most promising novel pharmacological targets for BD along with a concise overview regarding the general DD process and the unmet needs relevant to BD. Expert opinion: A number of novel potential drug targets have been investigated. With the notable exception of the kynurenine pathway, available evidence is too scarce to highlight a definitive roadmap for forthcoming DD in BD. BD itself may present with different facets, as it is a polymorphic clinical spectrum. Therefore, promoting clinical-case stratification should be based on precision medicine, rather than on novel biological targets. Furthermore, the full release of raw study data to the scientific community and the development of uniform clinical trial standards (including more realistic outcomes) should be promoted to facilitate the DD process in BD.

  12. Development and psychometric evaluation of a clinical global impression for schizoaffective disorder scale.

    Science.gov (United States)

    Allen, Michael H; Daniel, David G; Revicki, Dennis A; Canuso, Carla M; Turkoz, Ibrahim; Fu, Dong-Jing; Alphs, Larry; Ishak, K Jack; Bartko, John J; Lindenmayer, Jean-Pierre

    2012-01-01

    The Clinical Global Impression for Schizoaffective Disorder scale is a new rating scale adapted from the Clinical Global Impression scale for use in patients with schizoaffective disorder. The psychometric characteristics of the Clinical Global Impression for Schizoaffective Disorder are described. Content validity was assessed using an investigator questionnaire. Inter-rater reliability was determined with 12 sets of videotaped interviews rated independently by two trained individuals. Test-retest reliability was assessed using 30 randomly selected raters from clinical trials who evaluated the same videos on separate occasions two weeks apart. Convergent and divergent validity and effect size were evaluated by comparing scores between the Clinical Global Impression for Schizoaffective Disorder and the Positive and Negative Syndrome Scale, 21-item Hamilton Rating Scale for Depression, and Young Mania Rating Scale scales using pooled patient data from two clinical trials. Clinical Global Impression for Schizoaffective Disorder scores were then linked to corresponding Positive and Negative Syndrome Scale scores. Content validity was strong. Inter-rater agreement was good to excellent for most scales and subscales (intra-class correlation coefficient ≥ 0.50). Test-retest showed good reproducibility, with intraclass correlation coefficients ranging from 0.444 to 0.898. Spearman correlations between Clinical Global Impression for Schizoaffective Disorder domains and corresponding symptom scales were 0.60 or greater, and effect sizes for Clinical Global Impression for Schizoaffective Disorder overall and domain scores were similar to Positive and Negative Syndrome Scale Young Mania Rating Scale, and 21-item Hamilton Rating Scale for Depression scores. Raters anticipated that the scale might be less effective in distinguishing negative from depressive symptoms, and, in fact, the results here may reflect that clinical reality. Multiple lines of evidence support the

  13. Development of a Simple Tool for Identifying Alcohol Use Disorder in Female Korean Drinkers from Previous Questionnaires.

    Science.gov (United States)

    Seo, Yu Ri; Kim, Jong Sung; Kim, Sung Soo; Yoon, Seok Joon; Suh, Won Yoon; Youn, Kwangmi

    2016-01-01

    This study aimed to develop a simple tool for identifying alcohol use disorders in female Korean drinkers from previous questionnaires. This research was conducted on 400 women who consumed at least one alcoholic drink during the past month and visited the health promotion center at Chungnam National University Hospital between June 2013 to May 2014. Drinking habits and alcohol use disorders were assessed by structured interviews using the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnostic criteria. The subjects were also asked to answer the Alcohol Use Disorders Identification Test (AUDIT), AUDIT-Consumption, CAGE (Cut down, Annoyed, Guilty, Eye-opener), TWEAK (Tolerance, Worried, Eye-opener, Amnesia, Kut down), TACE (Tolerance, Annoyed, Cut down, Eye-opener), and NET (Normal drinker, Eye-opener, Tolerance) questionnaires. The area under receiver operating characteristic (AUROC) of each question of the questionnaires on alcohol use disorders was assessed. After combining two questions with the largest AUROC, it was compared to other previous questionnaires. Among the 400 subjects, 58 (14.5%) were identified as having an alcohol use disorder. Two questions with the largest AUROC were question no. 7 in AUDIT, "How often during the last year have you had a feeling of guilt or remorse after drinking?" and question no. 5 in AUDIT, "How often during the past year have you failed to do what was normally expected from you because of drinking?" with an AUROC (95% confidence interval [CI]) of 0.886 (0.850-0.915) and 0.862 (0.824-0.894), respectively. The AUROC (95% CI) of the combination of the two questions was 0.958 (0.934-0.976) with no significant difference as compared to the existing AUDIT with the largest AUROC. The above results suggest that the simple tool consisting of questions no. 5 and no. 7 in AUDIT is useful in identifying alcohol use disorders in Korean female drinkers.

  14. Neurobehavioural and cognitive development in infants born to mothers with eating disorders.

    Science.gov (United States)

    Barona, Manuela; Taborelli, Emma; Corfield, Freya; Pawlby, Susan; Easter, Abigail; Schmidt, Ulrike; Treasure, Janet; Micali, Nadia

    2017-08-01

    Although recent research has focused on the effects of maternal eating disorders (EDs) on children, little is known about the effect of maternal EDs on neurobiological outcomes in newborns and infants. This study is the first to investigate neurobehavioural regulation and cognitive development in newborns and infants of mothers with EDs. Women with an active and past ED and healthy controls were recruited to a prospective longitudinal study during their first trimester or second trimester of pregnancy. Newborns and infants of mothers with ED were compared with newborns and infants of healthy controls on (a) neurobehavioural dysregulation using the Brazelton Neonatal Behavioural Assessment Scale at 8 days postpartum (active ED, n = 15; past ED, n = 20; healthy controls, n = 28); and (b) cognitive development using the Bayley Scales of Infant and Toddler Development at 1-year postpartum (active ED, n = 18; past ED, n = 19; healthy controls, n = 28). In order to maintain the largest possible sample at each time point, sample size varied across time points. Newborns of mothers with an active ED had worse autonomic stability when compared with newborns of healthy controls [B = -0.34 (-1.81, -0.26)]. Infants of mothers with a past ED had poorer language [B = -0.33 (-13.6, -1.9)] and motor development [B = -0.32 (-18.4, -1.3)] compared with healthy controls. Children of mothers with ED display neurobehavioural dysregulation early after birth and poorer language and motor development at 1 year. These characteristics suggest evidence of early neurobiological markers in children at risk. Differential outcomes in children of women with active versus past ED suggest that active symptomatology during pregnancy might have an effect on physiological reactivity while cognitive characteristics might be more stable markers of risk for ED. © 2017 Association for Child and Adolescent Mental Health.

  15. Texas Medication Algorithm Project: development and feasibility testing of a treatment algorithm for patients with bipolar disorder.

    Science.gov (United States)

    Suppes, T; Swann, A C; Dennehy, E B; Habermacher, E D; Mason, M; Crismon, M L; Toprac, M G; Rush, A J; Shon, S P; Altshuler, K Z

    2001-06-01

    Use of treatment guidelines for treatment of major psychiatric illnesses has increased in recent years. The Texas Medication Algorithm Project (TMAP) was developed to study the feasibility and process of developing and implementing guidelines for bipolar disorder, major depressive disorder, and schizophrenia in the public mental health system of Texas. This article describes the consensus process used to develop the first set of TMAP algorithms for the Bipolar Disorder Module (Phase 1) and the trial testing the feasibility of their implementation in inpatient and outpatient psychiatric settings across Texas (Phase 2). The feasibility trial answered core questions regarding implementation of treatment guidelines for bipolar disorder. A total of 69 patients were treated with the original algorithms for bipolar disorder developed in Phase 1 of TMAP. Results support that physicians accepted the guidelines, followed recommendations to see patients at certain intervals, and utilized sequenced treatment steps differentially over the course of treatment. While improvements in clinical symptoms (24-item Brief Psychiatric Rating Scale) were observed over the course of enrollment in the trial, these conclusions are limited by the fact that physician volunteers were utilized for both treatment and ratings. and there was no control group. Results from Phases 1 and 2 indicate that it is possible to develop and implement a treatment guideline for patients with a history of mania in public mental health clinics in Texas. TMAP Phase 3, a recently completed larger and controlled trial assessing the clinical and economic impact of treatment guidelines and patient and family education in the public mental health system of Texas, improves upon this methodology.

  16. Body image and self-esteem in disorders of sex development: A European multicenter study.

    Science.gov (United States)

    van de Grift, Tim C; Cohen-Kettenis, Peggy T; de Vries, Annelou L C; Kreukels, Baudewijntje P C

    2018-04-01

    Disorders/differences of sex development (DSD) refer to congenital conditions with atypical sex development and are associated with psychosexual issues. The aim of this study was to assess body image and self-esteem across the DSD spectrum and to study the impact of diagnosis and mediating characteristics. Data collection was part of dsd-LIFE, a cross-sectional study conducted by 14 European expert clinics on wellbeing and health care evaluation of adults diagnosed with DSD. Main outcome measures in the present analyses were the Body Image Scale and Rosenberg Self-Esteem Scale. Additional data were obtained on treatments, openness, body embarrassment, sexual satisfaction, anxiety, and depression. The participating sample (n = 1,040) included 226 classified as Congenital Adrenal Hyperplasia, 225 as Klinefelter Syndrome, 322 as Turner Syndrome, and 267 as conditions with 46,XY karyotype. Many participants had received hormonal and surgical treatments. Participants scored lower on body image and self-esteem compared to control values, whereas each diagnosis showed different areas of concern. Limited openness, body embarrassment, and sexual issues were frequently reported. Overall body satisfaction was associated with BMI, hormone use, openness, body embarrassment, anxiety, and depression; genital satisfaction wi