Information about children reported to have ever been diagnosed with four different neurodevelopmental disorders: attention-deficit/hyperactivity disorder (ADHD), learning disabilities, autism, and intellectual disability.
Esbensen, Anna J; Schwichtenberg, Amy J
Individuals with intellectual and developmental disabilities (IDD) experience sleep problems at higher rates than the general population. Although individuals with IDD are a heterogeneous group, several sleep problems cluster within genetic syndromes or disorders. This review summarizes the prevalence of sleep problems experienced by individuals with Angelman syndrome, Cornelia de Lange syndrome, Cri du Chat syndrome, Down syndrome, fragile X syndrome, Prader-Willi syndrome, Smith-Magenis syndrome, Williams syndrome, autism spectrum disorder, and idiopathic IDD. Factors associated with sleep problems and the evidence for sleep treatments are reviewed for each neurodevelopmental disorder. Sleep research advancements in neurodevelopmental disorders are reviewed, including the need for consistency in defining and measuring sleep problems, considerations for research design and reporting of results, and considerations when evaluating sleep treatments. PMID:28503406
Di Pietro, Nina C; Whiteley, Louise Emma; Mizgalewicz, Ania
The Internet is a major source of health-related information for parents of sick children despite concerns surrounding quality. For neurodevelopmental disorders, the websites of advocacy groups are a largely unexamined source of information. We evaluated treatment information posted on nine highly......-trafficked advocacy websites for autism, cerebral palsy, and fetal alcohol spectrum disorder. We found that the majority of claims about treatment safety and efficacy were unsubstantiated. Instead, a range of rhetorical strategies were used to imply scientific support. When peer-reviewed publications were cited, 20...... % were incorrect or irrelevant. We call for new partnerships between advocacy and experts in developmental disorders to ensure better accuracy and higher transparency about how treatment information is selected and evidenced on advocacy websites....
Ehninger, Dan; Li, Weidong; Fox, Kevin; Stryker, Michael P; Silva, Alcino J
.... Surprisingly, a number of recent animal model studies of neurodevelopmental disorders demonstrate that reversing the underlying molecular deficits can result in substantial improvements in function...
Reijnders, Margot R F; Leventer, Richard J; Lee, Boo Hon; Baralle, Diana; Selber, Paulo; Paciorkowski, Alex R; Hunt, David
Clinical characteristics. PURA-related neurodevelopmental disorders include PURA syndrome, caused by a heterozygous pathogenic sequence variant in PURA, and 5q31.3 deletion syndrome, caused by a genomic 5q31.3 deletion encompassing all or part of PURA. PURA-related neurodevelopmental disorders are characterized by moderate to severe neurodevelopmental delay with absence of speech in most and lack of independent ambulation in many. Early-onset problems can include hypotonia, hypothermia, hyper...
Berry-Kravis, Elizabeth M; Lindemann, Lothar; Jønch, Aia E
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 gene...
There is a close relationship between sleep and childhood neurodevelopmental/neurodegenerative disorders. Understanding the sleep issues may provide greater insight into pathophysiology and treatment of these disorders. Copyright © 2015 Elsevier Inc. All rights reserved.
Mariën, Peter; Vidts, Annelies; Van Hecke, Wim; De Surgeloose, Didier; De Belder, Frank; Parizel, Paul M; Engelborghs, Sebastiaan; De Deyn, Peter P; Verhoeven, Jo
This paper reports the longitudinal clinical, neurocognitive, and neuroradiological findings in an adolescent patient with nonprogressive motor and cognitive disturbances consistent with a diagnosis of developmental coordination disorder (DCD). In addition to prototypical DCD, the development of mastication was severely impaired, while no evidence of swallowing apraxia, dysphagia, sensorimotor disturbances, abnormal tone, or impaired general cognition was found. He suffered from bronchopulmonary dysplasia and was ventilated as a newborn for 1.5 months. At the age of 3 months, a ventriculoperitoneal shunt was surgically installed because of obstructive hydrocephalus secondary to perinatal intraventricular bleeding. At the age of 5 years, the patient's attempts to masticate were characterized by rough, effortful, and laborious biting movements confined to the vertical plane. Solid food particles had a tendency to get struck in his mouth and there was constant spillage. As a substitute for mastication, he moved the unground food with his fingers in a lateral direction to the mandibular and maxillary vestibule to externally manipulate and squeeze the food between cheek and teeth with the palm of his hand. Once the food was sufficiently soft, the bolus was correctly transported by the tongue in posterior direction and normal deglutition took place. Repeat magnetic resonance imaging (MRI) during follow-up disclosed mild structural abnormalities as the sequelae of the perinatal intraventricular bleeding, but this could not explain impaired mastication behavior. Quantified Tc-99m-ethylcysteinate dimer single-photon emission computed tomography (Tc-99m-ECD SPECT), however, revealed decreased perfusion in the left cerebellar hemisphere, as well as in both inferior lateral frontal regions, both motor cortices, and the right anterior and lateral temporal areas. Anatomoclinical findings in this patient with DCD not only indicate that the functional integrity of the
Wetmore, Daniel Z; Garner, Craig C
A growing and interdisciplinary translational neuroscience research effort for neurodevelopmental disorders (NDDs) is investigating the mechanisms of dysfunction and testing effective treatment strategies in animal models and, when possible, in the clinic. NDDs with a genetic basis have received particular attention. Transgenic animals that mimic genetic insults responsible for disease in man have provided insight about mechanisms of dysfunction, and, surprisingly, have shown that cognitive deficits can be addressed in adult animals. This review will present recent translational research based on animal models of genetic NDDs, as well as pharmacotherapeutic strategies under development to address deficits of brain function for Down syndrome, fragile X syndrome, Rett syndrome, neurofibromatosis-1, tuberous sclerosis, and autism. Although these disorders vary in underlying causes and clinical presentation, common pathways and mechanisms for dysfunction have been observed. These include abnormal gene dosage, imbalance among neurotransmitter systems, and deficits in the development, maintenance and plasticity of neuronal circuits. NDDs affect multiple brain systems and behaviors that may be amenable to drug therapies that target distinct deficits. A primary goal of translational research is to replace symptomatic and supportive drug therapies with pharmacotherapies based on a principled understanding of the causes of dysfunction. Based on this principle, several recently developed therapeutic strategies offer clear promise for clinical development in man.
Although antisocial personality disorder (APD) is one of the most researched personality disorders, it is still surprisingly resistant to treatment. This lack of clinical progress may be partly due to the failure to view APD as a neurodevelopmental disorder and to consider early interventions. After first defining what constitutes a neurodevelopmental disorder, this review evaluates the extent to which APD meets neurodevelopmental criteria, covering structural and functional brain imaging, neurocognition, genetics and epigenetics, neurochemistry, and early health risk factors. Prevention and intervention strategies for APD are then outlined, focusing on addressing early biological and health systems, followed by forensic and clinical implications. It is argued both that APD meets criteria for consideration as a neurodevelopmental disorder and that consideration should be given both to the possibility that early onset conduct disorder is neurodevelopmental in nature, and also to the inclusion of psychopathy as a specifier in future Diagnostic and Statistical Manual revisions of APD. Expected final online publication date for the Annual Review of Clinical Psychology Volume 14 is May 7, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
John R. Kelly
Full Text Available Humans evolved within a microbial ecosystem resulting in an interlinked physiology. The gut microbiota can signal to the brain via the immune system, the vagus nerve or other host-microbe interactions facilitated by gut hormones, regulation of tryptophan metabolism and microbial metabolites such as short chain fatty acids (SCFA, to influence brain development, function and behavior. Emerging evidence suggests that the gut microbiota may play a role in shaping cognitive networks encompassing emotional and social domains in neurodevelopmental disorders. Drawing upon pre-clinical and clinical evidence, we review the potential role of the gut microbiota in the origins and development of social and emotional domains related to Autism spectrum disorders (ASD and schizophrenia. Small preliminary clinical studies have demonstrated gut microbiota alterations in both ASD and schizophrenia compared to healthy controls. However, we await the further development of mechanistic insights, together with large scale longitudinal clinical trials, that encompass a systems level dimensional approach, to investigate whether promising pre-clinical and initial clinical findings lead to clinical relevance.
Kelly, John R.; Minuto, Chiara; Cryan, John F.; Clarke, Gerard; Dinan, Timothy G.
Humans evolved within a microbial ecosystem resulting in an interlinked physiology. The gut microbiota can signal to the brain via the immune system, the vagus nerve or other host-microbe interactions facilitated by gut hormones, regulation of tryptophan metabolism and microbial metabolites such as short chain fatty acids (SCFA), to influence brain development, function and behavior. Emerging evidence suggests that the gut microbiota may play a role in shaping cognitive networks encompassing emotional and social domains in neurodevelopmental disorders. Drawing upon pre-clinical and clinical evidence, we review the potential role of the gut microbiota in the origins and development of social and emotional domains related to Autism spectrum disorders (ASD) and schizophrenia. Small preliminary clinical studies have demonstrated gut microbiota alterations in both ASD and schizophrenia compared to healthy controls. However, we await the further development of mechanistic insights, together with large scale longitudinal clinical trials, that encompass a systems level dimensional approach, to investigate whether promising pre-clinical and initial clinical findings lead to clinical relevance. PMID:28966571
Decker, Scott L.
The role of school psychologists with training in neuropsychology is examined within the context of multitiered models of service delivery and educational reform policies. An expanded role is suggested that builds on expertise in the assessment of neurodevelopmental disorders and extends to broader tiers through consultation practice. Changes in…
Gatto, Cheryl L.; Broadie, Kendal
Heritable neurodevelopmental disorders are multifaceted disease conditions encompassing a wide range of symptoms including intellectual disability, cognitive dysfunction, autism and myriad other behavioral impairments. In cases where single, causative genetic defects have been identified, such as Angelman syndrome, Rett syndrome, Neurofibromatosis Type 1 and Fragile X syndrome, the classical Drosophila genetic system has provided fruitful disease models. Recent Drosophila studies have advance...
. Amongst DSM's most vocal 'insider' critics has been Thomas Insel, Director of the US National Institute of Mental Health. Insel has publicly criticised DSM's adherence to a symptom-based classification of mental disorder, and used the weight ...
Full Text Available GABAergic interneurons control neuronal excitability, integration, and plasticity. Further, they regulate the generation of temporal synchrony and oscillatory behavior among networks of pyramidal neurons. Such oscillations within and across neural systems are believed to serve various complex functions, such as perception, movement initiation, and memory. Alterations in the development of GABAergic circuits have been implicated in various brain diseases with neurodevelopmental origin. Here, we highlight recent studies suggesting a role for alterations of GABA transmission in the pathophysiology of two neurodevelopmental diseases, schizophrenia and autism. We further discuss how manipulations of GABA signaling may be used for novel therapeutic interventions.
Full Text Available Methylation of several lysine residues of histones is a crucial mechanism for relatively long-term regulation of genomic activity. Recent molecular biological studies have demonstrated that the function of histone methylation is more diverse and complex than previously thought. Moreover, studies using newly available genomics techniques, such as exome sequencing, have identified an increasing number of histone lysine methylation-related genes as intellectual disability-associated genes, which highlights the importance of accurate control of histone methylation during neurogenesis. However, given the functional diversity and complexity of histone methylation within the cell, the study of the molecular basis of histone methylation-related neurodevelopmental disorders is currently still in its infancy. Here, we review the latest studies that revealed the pathological implications of alterations in histone methylation status in the context of various neurodevelopmental disorders and propose possible therapeutic application of epigenetic compounds regulating histone methylation status for the treatment of these diseases.
Stoodley, Catherine J.
Cerebellar dysfunction is evident in several developmental disorders, including autism, attention deficit hyperactivity disorder (ADHD), and developmental dyslexia, and damage to the cerebellum early in development can have long-term effects on movement, cognition, and affective regulation. Early cerebellar damage is often associated with poorer outcomes than cerebellar damage in adulthood, suggesting that the cerebellum is particularly important during development. Differences in cerebellar development and/or early cerebellar damage could impact a wide range of behaviors via the closed-loop circuits connecting the cerebellum with multiple cerebral cortical regions. Based on these anatomical circuits, behavioral outcomes should depend on which cerebro-cerebellar circuits are affected. Here, we briefly review cerebellar structural and functional differences in autism, ADHD, and developmental dyslexia, and discuss clinical outcomes following pediatric cerebellar damage. These data confirm the prediction that abnormalities in different cerebellar subregions produce behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. These circuits might also be crucial to structural brain development, as peri-natal cerebellar lesions have been associated with impaired growth of the contralateral cerebral cortex. The specific contribution of the cerebellum to typical development may therefore involve the optimization of both the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains; when this process is disrupted, particularly in early development, there could be long-term alterations of these neural circuits, with significant impacts on behavior. PMID:26298473
Stoodley, Catherine J
Cerebellar dysfunction is evident in several developmental disorders, including autism, attention deficit-hyperactivity disorder (ADHD), and developmental dyslexia, and damage to the cerebellum early in development can have long-term effects on movement, cognition, and affective regulation. Early cerebellar damage is often associated with poorer outcomes than cerebellar damage in adulthood, suggesting that the cerebellum is particularly important during development. Differences in cerebellar development and/or early cerebellar damage could impact a wide range of behaviors via the closed-loop circuits connecting the cerebellum with multiple cerebral cortical regions. Based on these anatomical circuits, behavioral outcomes should depend on which cerebro-cerebellar circuits are affected. Here, we briefly review cerebellar structural and functional differences in autism, ADHD, and developmental dyslexia, and discuss clinical outcomes following pediatric cerebellar damage. These data confirm the prediction that abnormalities in different cerebellar subregions produce behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. These circuits might also be crucial to structural brain development, as peri-natal cerebellar lesions have been associated with impaired growth of the contralateral cerebral cortex. The specific contribution of the cerebellum to typical development may therefore involve the optimization of both the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains; when this process is disrupted, particularly in early development, there could be long-term alterations of these neural circuits, with significant impacts on behavior.
Gatto, Cheryl L; Broadie, Kendal
Heritable neurodevelopmental disorders are multifaceted disease conditions encompassing a wide range of symptoms including intellectual disability, cognitive dysfunction, autism and myriad other behavioral impairments. In cases where single, causative genetic defects have been identified, such as Angelman syndrome, Rett syndrome, Neurofibromatosis Type 1 and Fragile X syndrome, the classical Drosophila genetic system has provided fruitful disease models. Recent Drosophila studies have advanced our understanding of UBE3A, MECP2, NF1 and FMR1 function, respectively, in genetic, biochemical, anatomical, physiological and behavioral contexts. Investigations in Drosophila continue to provide the essential mechanistic understanding required to facilitate the conception of rational therapeutic treatments. Copyright © 2011 Elsevier Ltd. All rights reserved.
Bishop, Dorothy V M
There are substantial differences in the amount of research concerned with different disorders. This paper considers why. Bibliographic searches were conducted to identify publications (1985-2009) concerned with 35 neurodevelopmental disorders: Developmental dyslexia, Developmental dyscalculia, Developmental coordination disorder, Speech sound disorder, Specific language impairment, Attention deficit hyperactivity disorder, Autistic spectrum disorder, Tourette syndrome, Intellectual disability, Angelman syndrome, Cerebral palsy, Cornelia de Lange syndrome, Cri du chat syndrome, Down syndrome, Duchenne muscular dystrophy, Fetal alcohol syndrome, Fragile X syndrome, Galactosaemia, Klinefelter syndrome, Lesch-Nyhan syndrome, Lowe syndrome, Marfan syndrome, Neurofibromatosis type 1, Noonan syndrome, Phenylketonuria, Prader-Willi syndrome, Rett syndrome, Rubinstein-Taybi syndrome, Trisomy 18, Tuberous sclerosis, Turner syndrome, Velocardiofacial syndrome, Williams syndrome, XXX and XYY. A publication index reflecting N publications relative to prevalence was derived. The publication index was higher for rare than common conditions. However, this was partly explained by the tendency for rare disorders to be more severe. Although research activity is predictable from severity and prevalence, there are exceptions. Low rates of research, and relatively low levels of NIH funding, characterise conditions that are the domain of a single discipline with limited research resources. Growth in research is not explained by severity, and was exceptionally steep for autism and ADHD.
Dorothy V M Bishop
Full Text Available There are substantial differences in the amount of research concerned with different disorders. This paper considers why.Bibliographic searches were conducted to identify publications (1985-2009 concerned with 35 neurodevelopmental disorders: Developmental dyslexia, Developmental dyscalculia, Developmental coordination disorder, Speech sound disorder, Specific language impairment, Attention deficit hyperactivity disorder, Autistic spectrum disorder, Tourette syndrome, Intellectual disability, Angelman syndrome, Cerebral palsy, Cornelia de Lange syndrome, Cri du chat syndrome, Down syndrome, Duchenne muscular dystrophy, Fetal alcohol syndrome, Fragile X syndrome, Galactosaemia, Klinefelter syndrome, Lesch-Nyhan syndrome, Lowe syndrome, Marfan syndrome, Neurofibromatosis type 1, Noonan syndrome, Phenylketonuria, Prader-Willi syndrome, Rett syndrome, Rubinstein-Taybi syndrome, Trisomy 18, Tuberous sclerosis, Turner syndrome, Velocardiofacial syndrome, Williams syndrome, XXX and XYY. A publication index reflecting N publications relative to prevalence was derived.The publication index was higher for rare than common conditions. However, this was partly explained by the tendency for rare disorders to be more severe.Although research activity is predictable from severity and prevalence, there are exceptions. Low rates of research, and relatively low levels of NIH funding, characterise conditions that are the domain of a single discipline with limited research resources. Growth in research is not explained by severity, and was exceptionally steep for autism and ADHD.
Full Text Available Complex Neurodevelopmental disorders NDDs exhibit complex etiological and genetic features and the mutations have a fundamental role in this complexity including common polymorphisms and rare variations in a single gene or cluster of genes. The analysis of complex NDDs have shown that the genetics has the major role in causation of such complex diseases. Interestingly both mutations and polymorphisms are involved occurring in a single gene or clusters of genes. Likewise a single gene variation may also be involved in multiple neurological disorders making the diagnosis of neurological diseases more difficult. Many candidate genes and chromosomal regions have been identified that are widely involved in neurological symptoms which necessitates the genotypic approach for describing the phenotype.
Livingston, Lucy Anne; Happé, Francesca
Within research into neurodevelopmental disorders, little is known about the mechanisms underpinning changes in symptom severity across development. When the behavioural presentation of a condition improves/symptoms lessen, this may be because core underlying atypicalities in cognition/neural function have ameliorated. An alternative possibility is 'compensation'; that the behavioural presentation appears improved, despite persisting deficits at cognitive and/or neurobiological levels. There is, however, currently no agreed technical definition of compensation or its behavioural, cognitive and neural characteristics. Furthermore, its workings in neurodevelopmental disorders have not been studied directly. Here, we review current evidence for compensation in neurodevelopmental disorders, using Autism Spectrum Disorder as an example, in order to move towards a better conceptualisation of the construct. We propose a transdiagnostic framework, where compensation represents the processes responsible for an observed mismatch between behaviour and underlying cognition in a neurodevelopmental disorder, at any point in development. Further, we explore potential cognitive and neural mechanisms driving compensation and discuss the broader relevance of the concept within research and clinical settings. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Engbers, Hannelie M; Berger, Ruud; van Hasselt, Peter; de Koning, Tom; de Sain-van der Velden, Monique G M; Kroes, Hester Y; Visser, Gepke
The timing and yield of metabolic studies for patients with neurodevelopmental disorders is a matter of continuing debate. We determined the yield of additional or repeated metabolic studies in patients with neurodevelopmental disorders. Patients referred to a tertiary diagnostic center for patients
De Theije, Caroline G M; Bavelaar, Bas M.; Lopes da Silva, Sofia; Korte, Sijmen Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D.
Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders which occur in childhood and may persist into adulthood. Although the etiology of these disorders is largely unknown, genetic and environmental factors are thought to play a role in
Arnsten, Amy F. T.; Rubia, Katya
Objective: This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Method: Studies of animals,…
Heussler, Helen S
Sleep disorders in individuals with developmental difficulties continue to be a significant challenge for families, carers, and therapists with a major impact on individuals and carers alike. This review is designed to update the reader on recent developments in this area. A systematic search identified a variety of studies illustrating advances in the regulation of circadian rhythm and sleep disturbance in neurodevelopmental disorders. Specific advances are likely to lead in some disorders to targeted therapies. There is strong evidence that behavioural and sleep hygiene measures should be first line therapy; however, studies are still limited in this area. Nonpharmacological measures such as exercise, sensory interventions, and behavioural are reported. Behavioural regulation and sleep hygiene demonstrate the best evidence for improved sleep parameters in individuals with neurodisability. Although the mainstay of management of children with sleep problems and neurodevelopmental disability is similar to that of typically developing children, there is emerging evidence of behavioural strategies being successful in large-scale trials and the promise of more targeted therapies for more specific resistant disorders.
Nguyen Quoc Vuong Tran
Full Text Available The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD and attention deficit hyperactivity disorder (ADHD, calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates, persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment.
Hellmuth, S G; Pedersen, L H; Miltoft, C B
OBJECTIVE: To investigate the association between fetal nuchal translucency (NT) thickness and neurodevelopmental disorders in euploid children. METHODS: This study included 222 505 euploid children who had undergone routine first-trimester screening during fetal life. Children were divided...... spectrum disorders (ASD), cerebral palsy, epilepsy and febrile seizures was obtained from national patient registries. RESULTS: There was no excess risk of neurodevelopmental disorders among euploid children with first-trimester NT 95(th) -99(th) percentile. For children with NT > 99(th) percentile...... in the risk of cerebral palsy (OR, 1.91 (95% CI, 0.61-5.95), 0.47%), epilepsy (OR, 1.51 (95% CI, 0.63-3.66), 0.78%) or febrile seizures (OR, 0.72 (95% CI, 0.44-1.16), 2.65%). CONCLUSIONS: In a large unselected cohort of euploid children, there was no increased risk of neurodevelopmental disorders among those...
Vogel, Alecia C; Gutmann, David H; Morris, Stephanie M
Over the past several decades, neurofibromatosis type 1 (NF1) has become increasingly recognized as a neurodevelopmental disorder conferring increased risk for several important neurodevelopmental problems. In this review, we summarize the specific neurodevelopmental problems encountered in the context of NF1. These include impairments in general cognitive function, deficits in specific cognitive domains such as executive function and visuospatial processing and risk for specific learning disorders, impairments in attention and social skills and the overlap with attention-deficit-hyperactivity disorder and autism spectrum disorder, and the risk of developing other psychiatric conditions including anxiety and depression. Early recognition of these developmental impairments is important for the effective treatment of children with NF1, and further characterization is essential to improve our understanding of how mutations in the NF1 gene create the diversity of clinical neuropsychiatric symptomatology observed in this at-risk population. © 2017 Mac Keith Press.
Mouga, Susana; Café, Cátia; Almeida, Joana; Marques, Carla; Duque, Frederico; Oliveira, Guiomar
The influence of specific autism spectrum disorder (ASD) deficits in Intelligence Quotients (IQ), Indexes and subtests from the Wechsler Intelligence Scale for Children-III was investigated in 445 school-aged children: ASD (N = 224) and other neurodevelopmental disorders (N = 221), matched by Full-Scale IQ and chronological age. ASD have lower…
Mouga, Susana; Almeida, Joana; Café, Cátia; Duque, Frederico; Oliveira, Guiomar
We investigated the influence of specific autism spectrum disorder (ASD) deficits in learning adaptive behaviour, besides intelligence quotient (IQ). Participated 217 school-aged: ASD (N = 115), and other neurodevelopmental disorders (OND) groups (N = 102) matched by Full-Scale IQ. We compared standard scores of Vineland Adaptive Behaviour Scale…
Ullman, Michael T; Pullman, Mariel Y
Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional in these disorders, and because it can learn and retain numerous types of information, functions, and tasks, this system should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications. Copyright © 2015 Elsevier Ltd. All rights reserved.
de Theije, Caroline G M; Bavelaar, Bas M; Lopes da Silva, Sofia; Korte, Sijmen Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D
Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders which occur in childhood and may persist into adulthood. Although the etiology of these disorders is largely unknown, genetic and environmental factors are thought to play a role in the development of ASD and ADHD. Allergic immune reactions, in prenatal and postnatal phases, are examples of these environmental factors, and adverse reactions to foods are reported in these children. In this review, we address the clinical and preclinical findings of (food) allergy in ASD and ADHD and suggest possible underlying mechanisms. Furthermore, opportunities for nutritional interventions in neurodevelopmental disorders are provided. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Prenatal infection is an environmental risk factor for various brain disorders with neurodevelopmental components, including autism spectrum disorder and schizophrenia. Modeling this association in animals shows that maternal immune activation negatively affects fetal brain development and leads to the emergence of behavioral disturbances later in life. Recent discoveries in these preclinical models suggest that epigenetic modifications may be a critical molecular mechanism by which prenatal immune activation can mediate changes in brain development and functions, even across generations. This review discusses the potential epigenetic mechanisms underlying the effects of prenatal infections, thereby highlighting how infection-mediated epigenetic reprogramming may contribute to the transgenerational transmission of pathological traits. The identification of epigenetic and transgenerational mechanisms in infection-mediated neurodevelopmental disorders appears relevant to brain disorders independently of existing diagnostic classifications and may help identifying complex patterns of transgenerational disease transmission beyond genetic inheritance. The consideration of ancestral infectious histories may be of great clinical interest and may be pivotal for developing new preventive treatment strategies against infection-mediated neurodevelopmental disorders.
Full Text Available A dysfunction of cortical and limbic GABAergic circuits has been postulated to contribute to multiple neurodevelopmental disorders in humans, including schizophrenia, autism, and epilepsy. In the current paper, I summarize the characteristics that underlie the great diversity of cortical GABAergic interneurons and explore how the multiple roles of these cells in developing and mature circuits might contribute to the aforementioned disorders. Furthermore, I review the tightly controlled genetic cascades that determine the fate of cortical interneurons and summarize how the dysfunction of genes important for the generation, specification, maturation, and function of cortical interneurons might contribute to these disorders.
Kubota, Takeo; Takae, Hirasawa; Miyake, Kunio
The number of children with mild neurodevelopmental disorders, such as autism, has been recently increasing in advanced countries. This increase is probably caused by environmental factors rather than genetic factors, because it is unlikely that genetic mutation rates suddenly increased within a short period. Epigenetics is a mechanism that regulates gene expression, depending not on the underlying DNA sequence but on the chemical modifications of DNA and histone proteins. Because mental stre...
Dykens, Elisabeth M
Developmental disabilities are increasingly recognized, and remarkable progress is being made on the genetic and neurobiological underpinnings of many disorders. Yet, only a tiny percentage of the disability literature addresses families of children with disabilities. A review of recently published family studies reveals salient trends and gaps. Consistent with previous work, high levels of parent stress, illness, anxiety, and depression are apparent. Studies in the USA focused on parents of children with autism; in contrast, studies on parents of children with intellectual disabilities were almost always conduced abroad. Compared to other disabilities, families of children with psychiatric disorders and genetic syndromes are understudied. The majority of family studies are descriptive, with very few trials or interventions aimed at reducing parental stress. Of these, mindfulness practices and a peer-mentor model of treatment delivery hold much promise for effective stress reduction. Psychoeducational programs and respite care are differentially beneficial. A new era of family intervention research is in order. This work can take advantage of many advances in telemedicine, peer-mentor models, smart technology, and biomarkers as indices of change. Benefit could also stem from group interventions with parents who share similar concerns, regardless of their child's diagnostic label.
Crawley, Jacqueline N
Autism is a neurodevelopmental disorder whose diagnosis is based on three behavioral criteria: unusual reciprocal social interactions, deficits in communication, and stereotyped repetitive behaviors with restricted interests. A large number of de novo single gene mutations and chromosomal deletions are associated with autism spectrum disorders. Based on the strong genetic evidence, mice with targeted mutations in homologous genes have been generated as translational research tools. Mouse models of autism have revealed behavioral and biological outcomes of mutations in risk genes. The field is now poised to employ the most robust phenotypes in the most replicable mouse models for preclinical screening of novel therapeutics.
Ikumi Hori; Takanobu Otomo; Mitsuko Nakashima; Fuyuki Miya; Yutaka Negishi; Hideaki Shiraishi; Yutaka Nonoda; Shinichi Magara; Jun Tohyama; Nobuhiko Okamoto; Takeshi Kumagai; Konomi Shimoda; Yoshiya Yukitake; Daigo Kajikawa; Tomohiro Morio; Ayako Hattori; Motoo Nakagawa; Naoki Ando; Ichizo Nishino; Mitsuhiro Kato; Tatsuhiko Tsunoda; Hirotomo Saitsu; Yonehiro Kanemura; Mami Yamasaki; Kenjiro Kosaki; Naomichi Matsumoto; Tamotsu Yoshimori; Shinji Saitoh
Vici syndrome (VICIS) is a rare, autosomal recessive neurodevelopmental disorder with multisystem involvement characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency...
Jawaid, A.; Riby, D. M.; Owens, J.; White, S. W.; Tarar, T.; Schulz, P. E.
In some neuro-developmental disorders, the combined effect of intellectual disability and atypicalities of social cognition may put individuals at increased vulnerability in their social environment. The neuro-developmental disorders Williams syndrome, characterised by "hypersociability", and autism spectrum disorders, characterised by "social…
Full Text Available The number of children with mild neurodevelopmental disorders, such as autism, has been recently increasing in advanced countries. This increase is probably caused by environmental factors rather than genetic factors, because it is unlikely that genetic mutation rates suddenly increased within a short period. Epigenetics is a mechanism that regulates gene expression, depending not on the underlying DNA sequence but on the chemical modifications of DNA and histone proteins. Because mental stress can alter the epigenetic status in neuronal cells, environmental factors may alter brain function through epigenetic changes. However, one advantage of epigenetic changes is their reversibility. Therefore, diseases due to abnormal epigenetic regulation are theoretically treatable. In fact, several drugs for treating mental diseases are known to have restoring effects on aberrant epigenetic statuses, and a novel therapeutic strategy targeting gene has been developed. In this review, we discuss epigenetic mechanisms of congenital and acquired neurodevelopmental disorders, drugs with epigenetic effects, novel therapeutic strategies for epigenetic diseases, and future perspectives in epigenetic medicine.
Zinkstok, J.; Buitelaar, J.
BACKGROUND: The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) was published in May, 2013. AIM: To review the changes in the diagnostic criteria for autism spectrum disorder (ASD) and ADHD in DSM-5, compared to DSM-IV. METHOD: The diagnostic criteria for ASD and ADHD
Bruining, Hilgo; Passtoors, Laurien; Goriounova, Natalia; Jansen, Floor; Hakvoort, Britt; de Jonge, Maretha; Poil, Simon-Shlomo
The diuretic agent bumetanide has recently been put forward as a novel, promising treatment of behavioral symptoms in autism spectrum disorder (ASD) and related conditions. Bumetanide can decrease neuronal chloride concentrations and may thereby reinstate γ-aminobutyric acid (GABA)-ergic inhibition in patients with neurodevelopmental disorders. However, strategies to select appropriate candidates for bumetanide treatment are lacking. We hypothesized that a paradoxical response to GABA-enforcing agents such as benzodiazepines may predict the efficacy of bumetanide treatment in neurodevelopmental disorders. We describe a case of a 10-year-old girl with ASD, epilepsy, cortical dysplasia, and a 15q11.2 duplication who had exhibited marked behavioral arousal after previous treatment with clobazam, a benzodiazepine. We hypothesized that this response indicated the presence of depolarizing excitatory GABA and started bumetanide treatment with monitoring of behavior, cognition, and EEG. The treatment resulted in a marked clinical improvement in sensory behaviors, rigidity, and memory performance, which was substantiated by questionnaires and cognitive assessments. At baseline, the girl's EEG showed a depression in absolute α power, an electrographic sign previously related to ASD, which was normalized with bumetanide treatment. The effects of bumetanide on cognition and EEG seemed to mirror the "nonparadoxical" responses to benzodiazepines in healthy subjects. In addition, temporal lobe epilepsy and cortical dysplasia have both been linked to disturbed chloride homeostasis and seem to support our assumption that the observed paradoxical response was due to GABA-mediated excitation. This case highlights that a paradoxical behavioral response to GABA-enforcing drugs may constitute a framework for targeted treatment with bumetanide. Copyright © 2015 by the American Academy of Pediatrics.
Alberto J Lopez
Full Text Available It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, schizophrenia, and Autism Spectrum Disorder. Together, these human developmental and intellectual disability disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.
Homberg, J.R.; Kyzar, E.J.; Nguyen, M; Norton, W.H.; Pittman, J.; Poudel, M.K.; Gaikwad, S.; Nakamura, S.; Koshiba, M.; Yamanouchi, H.; Scattoni, M.L.; Ullman, J.F.; Diamond, D.M.; Kaluyeva, A.A.; Parker, M.O.; Klimenko, V.M.; Apryatin, S.A.; Brown, R.E.; Song, C.; Gainetdinov, R.R.; Gottesman, II; Kalueff, A.V.
Neurodevelopmental disorders (NDDs) are highly prevalent and severely debilitating brain illnesses caused by aberrant brain growth and development. Resulting in cognitive, social, motor, language and affective disabilities, common NDDs include autism spectrum disorder (ASD), intellectual disability,
Wentz, Elisabet; Björk, Anna; Dahlgren, Jovanna
To investigate prevalence of neurodevelopmental disorders in children with obesity and to compare body mass index (BMI) and metabolic profile in the children. Seventy-six children (37 girls, 39 boys) were consecutively recruited from a university outpatient clinic specialized in severe obesity. Neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental coordination disorder (DCD) were assessed using interviews and questionnaires. Neurodevelopmental diagnoses were collected retrospectively in medical records. BMI ranged between 1.9 and 5.9 SDS and age between 5.1 and 16.5 years. In 13.2% and 18.4% ASD and ADHD was assigned, respectively. In addition, 25% screened positive for DCD, 31.6% had at least one neurodevelopmental disorder, and 18.4% had a parent who screened positive for adult ADHD. Girls with ASD/ADHD had higher BMI SDS than girls without neurodevelopmental disorder (P = 0.006). One third of children with obesity referred to specialist centers have a neurodevelopmental disorder including deviant motor skills, and these problems may deteriorate weight status. One fifth of the parents exhibit ADHD symptomatology which could partly explain the poor adherence by some families in obesity units. Future obesity therapy could benefit from incorporating a neurodevelopmental treatment approach. © 2016 The Obesity Society.
Evers, Christina; Staufner, Christian; Granzow, Martin; Paramasivam, Nagarajan; Hinderhofer, Katrin; Kaufmann, Lilian; Fischer, Christine; Thiel, Christian; Opladen, Thomas; Kotzaeridou, Urania; Wiemann, Stefan; Schlesner, Matthias; Eils, Roland; Kölker, Stefan; Bartram, Claus R; Hoffmann, Georg F; Moog, Ute
Whole exome sequencing (WES) is well established in research and is now being introduced into clinically indicated diagnostics (so-called clinical exomes). We evaluated the diagnostic yield and clinical implications of WES in 72 patients from 60 families with undiagnosed neurodevelopmental disorders (NDD), neurometabolic disorders, and dystonias. Pathogenic or likely pathogenic variants leading to a molecular diagnosis could be identified in 21 of the 60 families (overall 35%, in 36% of patients with NDD, in 43% of patients with neurometabolic disorders, in 25% of patients with dystonias). In one family two coexisting autosomal recessive diseases caused by homozygous pathogenic variants in two different genes were diagnosed. In another family, a homozygous frameshift variant in STRADA was found to cause a severe NDD with early onset epilepsy, brain anomalies, hypotonia, heart defect, nephrocalcinosis, macrocephaly and distinctive facies so far designated as PMSE (polyhydramnios, megalencephaly, symptomatic epilepsy) syndrome. In 7 of the 21 families with a molecular diagnosis the pathogenic variants were only identified by clinical follow-up, manual reevaluation of the literature, a change of filter setting, and/or reconsideration of inheritance pattern. Most importantly, clinical implications included management changes in 8 cases and impact on family planning in 20 families with a molecular diagnosis. This study shows that reevaluation and follow-up can improve the diagnostic rate and that WES results have important implications on medical management and family planning. Furthermore, we could confirm STRADA as a gene associated with syndromic ID but find it questionable if the current designation as PMSE depicts the most important clinical features. Copyright © 2017 Elsevier Inc. All rights reserved.
Rubab G. Arim
Full Text Available The purpose of this study was to compare rates of participation for children (4–9 years of age with neurodevelopmental disorders (NDDs with and without externalizing behavior problems (EBPs with children without disability and to examine mediators of the relation between disability and physical activity participation. Data for this study were drawn from Cycle 7 (2006-07 of the Canadian National Longitudinal Survey of Children and Youth (NLSCY. The frequency of children’s participation in organized sports or physical activities varied depending on the child’s health condition with children with NDDs and both NDDs and EBPs participating least in organized sports or physical activities followed by children with EBPs only. In contrast, there were no statistically significant differences by health group for children’s participation in unorganized sports or physical activities. These differences remained even after controlling for the effects of other child and family sociodemographic characteristics, except for children with EBPs only. These findings highlight the importance of considering children’s primary and other existing health conditions as well as family sociodemographic characteristics in order to better understand the factors that influence participation in organized physical activities for children with disabilities.
Parker, Whitney E.; Orlova, Ksenia A.; Parker, William H.; Birnbaum, Jacqueline F.; Krymskaya, Vera P.; Goncharov, Dmitry A.; Baybis, Marianna; Helfferich, Jelte; Okochi, Kei; Strauss, Kevin A.; Crino, Peter B.
A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological
Conclusion: These findings stress that it is essential to accurately identify motor coordination impairments and the interventions that would consider motor coordination problems related to cognitive abilities and academic achievement in Japanese children with neurodevelopmental disorders.
Schubert, D; Martens, G J M; Kolk, S M
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. PMID:25450230
Harris, James C
Paul MacLean has investigated integrated brain functioning through selected brain lesions in animals that disturb circuits necessary for complex behaviors, such as social displays. MacLean is unique in his comparative neurobehavioral approach that emphasizes the evolutionary origins of parenting and social behaviors and the implications of brain changes in the evolution from reptiles (social displays) to mammals (nursing, audiovocal communication, play) to man (self-awareness, intentionality, social context) that link affect and cognition. Subjectively, how "looking with feeling toward others," the basic element in empathy, evolved has been a central concern of his. Neuroimaging studies of social cognition, mother-infant communication, moral behavior, forgiveness, and trust are consistent with particular brain systems being activated in cooperative social behaviors. The identification of mirror neurons is pertinent to MacLean's model of isopraxis and studies of thalamocortical resonances may be pertinent to his neurobehavioral models. Studies of behavioral phenotypes in human neurodevelopmental disorders are consistent with MacLean's model of brain circuits being linked to complex behaviors during development. In autistic disorder, the behavioral phenotype involves disrupted social communication, deviant imaginative play, and motor stereotypies. In Lesch-Nyhan syndrome (LNS), self-injury occurs in individuals with normal sensory systems intact who require and request physical restraint to prevent self-injury; they ask for assistance from others to prevent them from harming themselves. Autism involves the lack of subjective awareness of others intentions and LNS involves a failure in self-regulation and self-control of self-injurious behavior. MacLean's models laid the groundwork for studies focused on understanding brain functioning in these conditions.
Smith, Michael; Peacock, Georgina; Uyeki, Timothy M; Moore, Cynthia
Children with neurologic or neurodevelopmental disorders (NNDDs) are at increased risk of complications from influenza. Although the Advisory Committee on Immunization Practices (ACIP) has recognized NNDDs as high-risk conditions for influenza complications since 2005, little is known about influenza vaccination practices in this population. CDC collaborated with Family Voices, a national advocacy group for children with special healthcare needs, to recruit parents of children with chronic medical conditions. Parents were surveyed about their knowledge, attitudes, and practices surrounding influenza vaccination. The primary outcome of interest was parental report of vaccination, or intent to vaccinate, at the time of survey participation. CDC also collaborated with the American Academy of Pediatrics to recruit primary care and specialty physicians who provide care for high-risk children, specifically those with neurologic conditions. The primary outcome was physician recognition of ACIP high-risk influenza conditions. 2138 surveys were completed by parents of children with high-risk conditions, including 1143 with at least one NNDD. Overall, 50% of children with an NNDD were vaccinated, or their parents planned to have them vaccinated against influenza. Among all 2138 children, in multivariable analysis, the presence of a respiratory condition and prior seasonal influenza vaccination was significantly associated with receipt or planned current season influenza vaccination, but the presence of an NNDD was not. 412 pediatricians completed the provider survey. Cerebral palsy was recognized as a high-risk influenza condition by 74% of physician respondents, but epilepsy (51%) and intellectual disability (46%) were less commonly identified. Our estimates of influenza vaccination in children with NNDDs are comparable to published reports of vaccination in healthy children, which continue to be suboptimal. Education of parents of children with NNDDs and healthcare
O'Shea, K Sue; McInnis, Melvin G
Bipolar disorder (BP) is a chronic neuropsychiatric condition characterized by pathological fluctuations in mood from mania to depression. Adoption, twin and family studies have consistently identified a significant hereditary component to BP, yet there is no clear genetic event or consistent neuropathology. BP has been suggested to have a developmental origin, although this hypothesis has been difficult to test since there are no viable neurons or glial cells to analyze, and research has relied largely on postmortem brain, behavioral and imaging studies, or has examined proxy tissues including saliva, olfactory epithelium and blood cells. Neurodevelopmental factors, particularly pathways related to nervous system development, cell migration, extracellular matrix, H3K4 methylation, and calcium signaling have been identified in large gene expression and GWAS studies as altered in BP. Recent advances in stem cell biology, particularly the ability to reprogram adult somatic tissues to a pluripotent state, now make it possible to interrogate these pathways in viable cell models. A number of induced pluripotent stem cell (iPSC) lines from BP patient and healthy control (C) individuals have been derived in several laboratories, and their ability to form cortical neurons examined. Early studies suggest differences in activity, calcium signaling, blocks to neuronal differentiation, and changes in neuronal, and possibly glial, lineage specification. Initial observations suggest that differentiation of BP patient-derived neurons to dorsal telencephalic derivatives may be impaired, possibly due to alterations in WNT, Hedgehog or Nodal pathway signaling. These investigations strongly support a developmental contribution to BP and identify novel pathways, mechanisms and opportunities for improved treatments. Copyright © 2015 Elsevier Inc. All rights reserved.
Uljarević, Mirko; Katsos, Napoleon; Hudry, Kristelle; Gibson, Jenny L
Language and communication skills are essential aspects of child development, which are often disrupted in children with neurodevelopmental disorders. Cutting edge research in psycholinguistics suggests that multilingualism has potential to influence social, linguistic and cognitive development. Thus, multilingualism has implications for clinical assessment, diagnostic formulation, intervention and support offered to families. We present a systematic review and synthesis of the effects of multilingualism for children with neurodevelopmental disorders and discuss clinical implications. We conducted systematic searches for studies on multilingualism in neurodevelopmental disorders. Keywords for neurodevelopmental disorders were based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition categories as follows; Intellectual Disabilities, Communication Disorders, Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder, Specific Learning Disorder, Motor Disorders, Other Neurodevelopmental Disorders. We included only studies based on empirical research and published in peer-reviewed journals. Fifty studies met inclusion criteria. Thirty-eight studies explored multilingualism in Communication Disorders, 10 in ASD and two in Intellectual Disability. No studies on multilingualism in Specific Learning Disorder or Motor Disorders were identified. Studies which found a disadvantage for multilingual children with neurodevelopmental disorders were rare, and there appears little reason to assume that multilingualism has negative effects on various aspects of functioning across a range of conditions. In fact, when considering only those studies which have compared a multilingual group with developmental disorders to a monolingual group with similar disorders, the findings consistently show no adverse effects on language development or other aspects of functioning. In the case of ASD, a positive effect on communication and social functioning has
Gillberg, I Carina; Helles, Adam; Billstedt, Eva; Gillberg, Christopher
We examined comorbid psychiatric and neurodevelopmental disorders in fifty adult males (mean age 30 years) with Asperger syndrome (AS) diagnosed in childhood and followed up prospectively for almost two decades (13-26 years). Only three of the 50 men had never met criteria for an additional psychiatric/neurodevelopmental diagnosis and more than half had ongoing comorbidity (most commonly either ADHD or depression or both). Any psychiatric comorbidity increased the risk of poorer outcome. The minority of the AS group who no longer met criteria for a full diagnosis of an autism spectrum disorder were usually free of current psychiatric comorbidity. The high rate of psychiatric/neurodevelopmental comorbidities underscores the need for a full psychiatric/neurodevelopmental assessment at follow-up of males with AS.
Vinet, É; Pineau, C A; Clarke, A E; Fombonne, É; Platt, R W; Bernatsky, S
Children born to women with systemic lupus erythematosus seem to have a potentially increased risk of neurodevelopmental disorders compared to children born to healthy women. Recent experimental data suggest in utero exposure to maternal antibodies and cytokines as important risk factors for neurodevelopmental disorders. Interestingly, women with systemic lupus erythematosus display high levels of autoantibodies and cytokines, which have been shown, in animal models, to alter fetal brain development and induce behavioral anomalies in offspring. Furthermore, subjects with systemic lupus erythematosus and neurodevelopmental disorders share a common genetic predisposition, which could impair the fetal immune response to in utero immunologic insults. Moreover, systemic lupus erythematosus pregnancies are at increased risk of adverse obstetrical outcomes and medication exposures, which have been implicated as potential risk factors for neurodevelopmental disorders. In this article, we review the current state of knowledge on neurodevelopmental disorders and their potential determinants in systemic lupus erythematosus offspring. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Ratto, Allison B.; Anthony, Bruno J.; Pugliese, Cara; Mendez, Rocio; Safer-Lichtenstein, Jonathan; Dudley, Katerina M.; Kahn, Nicole F.; Kenworthy, Lauren; Biel, Matthew; Martucci, Jillian L.; Anthony, Laura G.
Low-income and ethnic minority families continue to face critical disparities in access to diagnostic and treatment services for neurodevelopmental conditions, such as autism spectrum disorder and attention deficit hyperactivity disorder. Despite the growing cultural diversity of the United States, ethnic minority children and families continue to…
Fung, Lawrence K; Quintin, Eve-Marie; Haas, Brian W; Reiss, Allan L
The overarching goal of this review is to compare and contrast the cognitive-behavioral features of fragile X syndrome (FraX) and Williams syndrome and to review the putative neural and molecular underpinnings of these features. Information is presented in a framework that provides guiding principles for conceptualizing gene-brain-behavior associations in neurodevelopmental disorders. Abnormalities, in particular cognitive-behavioral domains with similarities in underlying neurodevelopmental correlates, occur in both FraX and Williams syndrome including aberrant frontostriatal pathways leading to executive function deficits, and magnocellular/dorsal visual stream, superior parietal lobe, inferior parietal lobe, and postcentral gyrus abnormalities contributing to deficits in visuospatial function. Compelling cognitive-behavioral and neurodevelopmental contrasts also exist in these two disorders, for example, aberrant amygdala and fusiform cortex structure and function occurring in the context of contrasting social behavioral phenotypes, and temporal cortical and cerebellar abnormalities potentially underlying differences in language function. Abnormal dendritic development is a shared neurodevelopmental morphologic feature between FraX and Williams syndrome. Commonalities in molecular machinery and processes across FraX and Williams syndrome occur as well - microRNAs involved in translational regulation of major synaptic proteins; scaffolding proteins in excitatory synapses; and proteins involved in axonal development. Although the genetic variations leading to FraX and Williams syndrome are different, important similarities and contrasts in the phenotype, neurocircuitry, molecular machinery, and cellular processes in these two disorders allow for a unique approach to conceptualizing gene-brain-behavior links occurring in neurodevelopmental disorders.
Kakooza-Mwesige, Angelina; Ssebyala, Keron; Karamagi, Charles; Kiguli, Sarah; Smith, Karen; Anderson, Meredith C; Croen, Lisa A; Trevathan, Edwin; Hansen, Robin; Smith, Daniel; Grether, Judith K
Neurodevelopmental disorders are recognized to be relatively common in developing countries but little data exist for planning effective prevention and intervention strategies. In particular, data on autism spectrum disorders are lacking. For application in Uganda, we developed a 23-question screener (23Q) that includes the Ten Questions screener and additional questions on autism spectrum disorder behaviors. We then conducted household screening of 1169 children, 2-9 years of age, followed by clinical assessment of children who screened positive and a sample of those who screened negative to evaluate the validity of the screener. We found that 320 children (27% of the total) screened positive and 68 children received a clinical diagnosis of one or more moderate to severe neurodevelopmental disorders (autism spectrum disorder; cerebral palsy; epilepsy; cognitive, speech and language, hearing, or vision impairment), including 8 children with autism spectrum disorders. Prevalence and validity of the screener were evaluated under different statistical assumptions. Sensitivity of the 23Q ranged from 0.55 to 0.80 and prevalence for ≥1 neurodevelopmental disorders from 7.7/100 children to 12.8/100 children depending on which assumptions were used. The combination of screening positive on both autism spectrum disorders and Ten Questions items was modestly successful in identifying a subgroup of children at especially high risk of autism spectrum disorders. We recommend that autism spectrum disorders and related behavioral disorders be included in studies of neurodevelopmental disorders in low-resource settings to obtain essential data for planning local and global public health responses.
Full Text Available Many neurological disorders affect men and women differently regarding prevalence, progression, and severity. It is clear that many of these disorders may originate from defective signaling during fetal or perinatal brain development, which may affect males and females differently. Such sex-specific differences may originate from chromosomal or sex-hormone specific effects. This short review will focus on the estrogen receptor beta (ERβ signaling during perinatal brain development and put it in the context of sex-specific differences in neurodevelopmental disorders. We will discuss ERβ’s recent discovery in directing DNA de-methylation to specific sites, of which one such site may bear consequences for the susceptibility to the neurological reading disorder dyslexia. We will also discuss how dysregulations in sex-hormone signaling, like those evoked by endocrine disruptive chemicals, may affect this and other neurodevelopmental disorders in a sex-specific manner through ERβ.
Erdődi, Lászlό; Lajiness-O'Neill, Renée; Schmitt, Thomas A
Visual and auditory verbal learning using a selective reminding format was studied in a mixed clinical sample of children with autism spectrum disorder (ASD) (n = 42), attention-deficit hyperactivity disorder (n = 83), velocardiofacial syndrome (n = 17) and neurotypicals (n = 38) using the Test of Memory and Learning to (1) more thoroughly characterize and examine the integrity of learning and memory processes, (2) to better understand the mechanisms of learning impairment, and (3) to inform instructional practices in ASD. Contrary to expectations, children with ASD demonstrated a relative weakness in the rate of acquisition of visual in contrast to verbal learning compared to neurotypicals. They also showed a complex pattern of consolidation. Overall, between-group differences were more likely to emerge during the visual learning task, suggesting that it may be more sensitive for detecting neurodevelopmental differences. The heuristic value of assessing memory and learning across multiple trials and comparing performance during immediate and delayed recall is discussed.
Chilosi, Anna M.; Comparini, Alessandro; Scusa, Maria F.; Berrettini, Stefano; Forli, Francesca; Battini, Roberta; Cipriani, Paola; Cioni, Giovanni
Aim: The effects of sensorineural hearing loss (SNHL) are often complicated by additional disabilities, but the epidemiology of associated disorders is not clearly defined. The aim of this study was to evaluate the frequency and type of additional neurodevelopmental disabilities in a sample of children with SNHL and to investigate the relation…
Dichter Gabriel S
Full Text Available Abstract This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders, neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder, and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome. We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.
Full Text Available Previous models or hypotheses of autism spectral disorder (ASD failed to take into full consideration the chronological and causal developmental trajectory, leading to the emergence of diverse phenotypes through a complex interaction between individual etiologies and environmental factors. Those phenotypes include persistent deficits in social communication and social interaction (criteria A in DSM-5, and restricted, repetitive patterns of behavior, interests, or activities (criteria B in DSM-5. In this article, we proposed a domain-general model that can explain criteria in DSM-5 based on the assumption that the same etiological mechanism would trigger the various phenotypes observed in different individuals with ASD. In the model, we assumed the following joint causes as the etiology of autism: (1 Hypoplasia of the pons in the brainstem, occurring immediately following neural tube closure; and (2 Deficiency in the GABA (γ-aminobutyric acid developmental switch during the perinatal period. Microstructural abnormalities of the pons directly affect both the structural and functional development of the brain areas strongly connected to it, especially amygdala. The impairment of GABA switch could not only lead to the deterioration of inhibitory processing in the neural network, but could also cause abnormal cytoarchitecture. We introduced a perspective that atypical development in both brain structure and function can give full explanation of diverse phenotypes and pathogenetic mechanism of ASD. Finally, we discussed about neural mechanisms underlying the phenotypic characteristics of ASD that are not described in DSM-5 but should be considered as important foundation: sleep, global precedence, categorical perception, intelligence, interoception and motor control.
Blackmer, Allison Beck; Feinstein, James A
Neurodevelopmental disorders (NDDs) are defined as a group of disorders caused by changes in early brain development, resulting in behavioral and cognitive alterations in sensory and motor systems, speech, and language. NDDs affect approximately 1-2% of the general population. Up to 80% of children with NDDs are reported to have disrupted sleep; subsequent deleterious effects on daytime behaviors, cognition, growth, and overall development of the child are commonly reported. Examples of NDDs discussed in this review include autism spectrum disorder, cerebral palsy, Rett syndrome, Angelman syndrome, Williams syndrome, and Smith-Magenis syndrome. The etiology of sleep disorders in children with NDDs is largely heterogeneous and disease specific. The diagnosis and management of sleep disorders in this population are complex, and little high-quality data exist to guide a consistent approach to therapy. Managing sleep disorders in children with NDDs is critical both for the child and for the family but is often frustrating due to the refractory nature of the problem. Sleep hygiene must be implemented as first-line therapy; if sleep hygiene alone fails, it should be combined with pharmacologic management. The available evidence for the use of common pharmacologic interventions, such as iron supplementation and melatonin, as well as less common interventions, such as melatonin receptor agonists, clonidine, gabapentin, hypnotics, trazodone, and atypical antipsychotics is reviewed. Further, parents and caregivers should be provided with appropriate education on the nature of the sleep disorders and the expectation for modest pharmacologic benefit, at best. Additional data from well-designed trials in children with NDDs are desperately needed to gain a better understanding of sleep pharmacotherapy including efficacy and safety implications. Until then, clinicians must rely on the limited available data, as well as clinical expertise, when managing sleep disorders in the
Kajta, Małgorzata; Wójtowicz, Anna
In recent years, the major concern has been focused on persistent organic pollutants (POPs), which are present in ecosphere in increasing concentrations, especially since 1950s. Among of these pollutants are dioxins and polychlorinated biphenyls (PCBs) released during vast burning and plastics processing, as well as pesticides which were industrial chemicals intensively produced for many years. In last decade, dioxins together with PCBs and pesticides have been classified as endocrine disrupting chemicals, because they are able to alter hormone-dependent processes and disrupt functioning of endocrine glands, e.g. thyroid and gonads. Furthermore, these pollutants have been included in neural disrupting chemicals due to their ability of altering neural transmission and formation of neural networks. Since POPs may persist in the environment for dozens of years, an exposure to these organic pollutants creates a serious issue for environmental toxicologists. POP intoxication creates severe clinical problems, which became evident in dramatic circumstances, e.g. Yusho incident in Japan, Yu-Cheng incident in Tajwan, Michigan Lake poisoning. Clinical problems have been recognized as disruption of thyroid and gonadal functions, immunodeficiency as well as psychomotor deficits and increased occurrence of hormone-dependent cancers. Thus, knowledge on POP effects on human nervous system has been related mainly to toxic effects of these organic pollutants. Little is known, however, about the action of very low, so called background, doses of POPs and their effects on hormonal homeostasis in developing brain. It is of particular importance, because doses which are low for adults might become toxic for fetuses, infants or children. Recently, the public concern has been focused on POP effects on brain function, concomitantly with the increase in neuropsychiatric disorders, including autism, attention deficit and hyperactivity disorder (ADHD) as well as learning disabilities
Peralta, Victor; Cuesta, Manuel J
Motor abnormalities (MAs) of severe mental disorders have been traditionally neglected both in clinical practice and research, although they are an increasing focus of attention because of their clinical and neurobiological relevance. For historical reasons, most of the literature on MAs has been focused to a great extent on schizophrenia, and as a consequence their prevalence and featural properties in other psychiatric or neuropsychiatric disorders are poorly known. In this article, we evaluated the extent to which catatonic, extrapyramidal and neurological soft signs, and their associated clinical features, are present transdiagnostically. We examined motor-related features in neurodevelopmental (schizophrenia, obsessive compulsive disorder, autism spectrum disorders), "functional" (nonschizophrenic nonaffective psychoses, mood disorders) and neurodegenerative (Alzheimer's disease) disorders. Examination of the literature revealed that there have been very few comparisons of motor-related features across diagnoses and we had to rely mainly in disorder-specific studies to compare it transdiagnostically. One or more motor domains had a substantial prevalence in all the diagnoses examined. In "functional" disorders, MAs, and particularly catatonic signs, appear to be markers of episode severity; in chronic disorders, although with different degree of strength or evidence, all motor domains are indicators of both disorder severity and poor outcome; lastly, in Alzheimer's disease they are also indicators of disorder progression. MAs appear to represent a true transdiagnostic domain putatively sharing neurobiological mechanisms of neurodevelopmental, functional or neurodegenerative origin.
Gillberg, I. Carina; Helles, Adam; Billstedt, Eva; Gillberg, Christopher
We examined comorbid psychiatric and neurodevelopmental disorders in fifty adult males (mean age 30 years) with Asperger syndrome (AS) diagnosed in childhood and followed up prospectively for almost two decades (13-26 years). Only three of the 50 men had "never" met criteria for an additional psychiatric/neurodevelopmental diagnosis and…
Maria Luísa Bissoto
Full Text Available The neurodevelopmental disorders, mainly those genetics ones, are argued with the aim to analyze the human development conceptions that underlie these, and its impact for understanding who is the individual that carries this disorder. Methodologically, epistemological presupposition from “classical” neuropsychology and from “neuroconstructivist” neuropsychology had been compared. As results of this parallel had been considered relevant: a. the role of the individual surrounding, b. the question concerning the plasticity and dynamical character of development and c. the formal developmental process, from prenatal to postnatal period. The concluding comments claims that the Neuroconstructivist approaches allow conceiving the developmental process within genetics neurodevelopmental disorders not as a “fault” but as a differentiated and particular one. That should be understood in the Educational and Rehabilitation settings not as a nosological category but as a specific way of an individual acting while looking for a mode of being-in-the-world.
Obiols-Guardia, Aida; Guil, Sònia
Current technologies have demonstrated that only a small fraction of our genes encode for protein products. The vast majority of the human transcriptome corresponds to noncoding RNA (ncRNA) of different size, localization, and expression profile. Despite the fact that a biological function remains yet to be determined for most ncRNAs, growing evidence points to their crucial regulatory roles at all stages in gene expression regulation, including transcriptional and posttranscriptional control, so that proper cell homeostasis seems to depend largely on a variety of ncRNA-mediated regulatory networks. This is particularly relevant in the human brain, which displays the richest repertoire of ncRNA species, and where several different ncRNA molecules are known to be involved in crucial steps for brain development and maturation. Rett syndrome is a neurodevelopmental disorder characterized by loss of function mutations in the X-linked gene encoding for methyl-CpG-binding protein 2 (MeCP2). MECP2 deficiency impacts globally on gene expression programs, mainly through its role as a transcriptional repressor, and growing data also points to an important dysregulation of the noncoding transcriptome in the disease. Here, we review the current knowledge on ncRNA alterations in Rett and explore links with other pathologies that might indicate the potential use of particular noncoding transcripts as therapeutical targets, tools, or disease biomarkers.
Full Text Available Neurodevelopmental disorders represent a broad class of childhood neurological conditions that have a significant bearing on the wellbeing of children, families, and communities. In this review, we draw on evidence from two common and widely studied neurodevelopmental disorders—autism spectrum disorder (ASD and attention-deficit hyperactivity disorder (ADHD—to demonstrate the utility of genetically informed sibling designs in uncovering the nature and pathogenesis of these conditions. Specifically, we examine how twin, recurrence risk, and infant prospective tracking studies have contributed to our understanding of genetic and environmental liabilities towards neurodevelopmental morbidity through their impact on neurocognitive processes and structural/functional neuroanatomy. It is suggested that the siblings of children with ASD and ADHD are at risk not only of clinically elevated problems in these areas, but also of subthreshold symptoms and/or subtle impairments in various neurocognitive skills and other domains of psychosocial health. Finally, we close with a discussion on the practical relevance of sibling designs and how these might be used in the service of early screening, prevention, and intervention efforts that aim to alleviate the negative downstream consequences associated with disorders of neurodevelopment.
Merikangas, Alison K
Copy-number variation (CNV) is the most prevalent type of structural variation in the human genome. There is emerging evidence that copy-number variants (CNVs) provide a new vista on understanding susceptibility to neuropsychiatric disorders. Some challenges in the interpretation of current CNV studies include the use of overlapping samples, differing phenotypic definitions, an absence of population norms for CNVs and a lack of consensus in methods for CNV detection and analysis. Here, we review current CNV association study methods and results in autism spectrum disorders (ASD) and schizophrenia, and provide suggestions for design approaches to future studies that might maximize the translation of this work to etiological understanding.
Bruining, Hilgo; Passtoors, Laurien; Goriounova, Natalia; Jansen, Floor; Hakvoort, Britt; de Jonge, Maretha; Poil, Simon-Shlomo
The diuretic agent bumetanide has recently been put forward as a novel, promising treatment of behavioral symptoms in autism spectrum disorder (ASD) and related conditions. Bumetanide can decrease neuronal chloride concentrations and may thereby reinstate γ-aminobutyric acid (GABA)-ergic inhibition
Bruining, H.; Passtoors, L.; Goriounova, N.A.; Jansen, F.; Hakvoort, B.; de Jonge, M.; Poil, S.S.
The diuretic agent bumetanide has recently been put forward as a novel, abstract promising treatment of behavioral symptoms in autism spectrum disorder (ASD) and related conditions. Bumetanide can decrease neuronal chloride concentrations and may thereby reinstate g-aminobutyric acid (GABA)-ergic
Di Pietro, Nina C; Whiteley, Louise Emma; Illes, Judy
The Internet has quickly gained popularity as a major source of health-related information, but its impact is unclear. Here, we investigate the extent to which advocacy websites for three neurodevelopmental disorders—cerebral palsy (CP), autism spectrum disorder (ASD) and fetal alcohol spectrum...... disorder (FASD)—inform stakeholders about treatment options, and discuss the ethical challenges inherent in providing such information online. We identified major advocacy websites for each disorder and assessed website accountability, the number, attributes, and accessibility of treatments described...
Hori, Ikumi; Otomo, Takanobu; Nakashima, Mitsuko; Miya, Fuyuki; Negishi, Yutaka; SHIRAISHI, HIDEAKI; Nonoda, Yutaka; Magara, Shinichi; Tohyama, Jun; Okamoto, Nobuhiko; KUMAGAI, Takeshi; Shimoda, Konomi; Yukitake, Yoshiya; Kajikawa, Daigo; Morio, Tomohiro
Vici syndrome (VICIS) is a rare, autosomal recessive neurodevelopmental disorder with multisystem involvement characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency, developmental delay, and hypopigmentation. Mutations in EPG5, a gene that encodes a key autophagy regulator, have been shown to cause VICIS, however, the precise pathomechanism underlying VICIS is yet to be clarified. Here, we describe detailed clinical (including brain MRI and musc...
Byrne, Susan; Jansen, Lara; U-King-Im, Jean-Marie; Siddiqui, Ata; Lidov, Hart G. W.; Bodi, Istvan; Smith, Luke; Mein, Rachael; Cullup, Thomas; Dionisi-Vici, Carlo; Al-Gazali, Lihadh; Al-Owain, Mohammed; Bruwer, Zandre; Al Thihli, Khalid; El-Garhy, Rana
Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations...
Parker, Whitney E.; Orlova, Ksenia A.; Parker, William H.; Birnbaum, Jacqueline F.; Krymskaya, Vera P.; Goncharov, Dmitry A.; Baybis, Marianna; Helfferich, Jelte; Okochi, Kei; Strauss, Kevin A.; Crino, Peter B.
A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological evidence of heterotopic neurons in subcortical white matter and subependymal regions. PMSE is caused by a homozygous deletion of exons 9 to 13 of the LYK5/STRADA gene, which encodes the pseudokinase...
Schroeder, Stephen R.; Courtemanche, Andrea
There is a very substantial literature over the past 50 years on the advantages of early detection and intervention on the cognitive, communicative, and social-emotional development of infants and toddlers at risk for developmental delay due to premature birth or social disadvantage. Most of these studies excluded children with severe delays or other predisposing conditions, such as genetic or brain disorders. Many studies of children with biological or socio-developmental risk suggest that b...
Di Pietro, Nina C; Illes, Judy
To map the landscape of research on autism (ASD), cerebral palsy (CP), and fetal alcohol spectrum disorder (FASD) in Canadian Aboriginal children. The authors used a detailed search strategy to identify and access publications on ASD, CP, and FASD involving Canadian Aboriginal children, families, and communities from online databases. They analyzed these materials for the type of research, stated objectives, methodologies, and the level of engagement of Aboriginal Peoples. The authors found a total of 52 reports published since 1981 relevant to Aboriginal children. Of these, 51 focused exclusively on FASD. They also found a near-complete failure to acknowledge community involvement in research decisions or dissemination of results in any of the publications. The focus on FASD in Aboriginal children and the absence of research on the other 2 major childhood disorders are at odds with rates of these disorders across Canadian children. The authors argue that this trend violates fundamental principles ensuring equitable representation of all children regardless of background in research and access to benefits of research in health care and perpetuates stigma in an already marginalized population.
Moffitt, Terrie E; Houts, Renate; Asherson, Philip; Belsky, Daniel W; Corcoran, David L; Hammerle, Maggie; Harrington, HonaLee; Hogan, Sean; Meier, Madeline H; Polanczyk, Guilherme V; Poulton, Richie; Ramrakha, Sandhya; Sugden, Karen; Williams, Benjamin; Rohde, Luis Augusto; Caspi, Avshalom
Objective:Despite a prevailing assumption that adult ADHD is a childhood-onset neurodevelopmental disorder, no prospective longitudinal study has described the childhoods of the adult ADHD population...
Goriely, Anne; McGrath, John J.; Hultman, Christina M.; Wilkie, Andrew O.M.; Malaspina, Dolores
Objectives There is robust evidence from epidemiological studies that the offspring of older fathers have an increased risk of neurodevelopmental disorders such as schizophrenia and autism. Here we present a novel mechanism that may contribute to this association. Methods Narrative review. Results Because the male germ cell undergoes many more cell divisions across the reproductive age range, copy-errors taking place in the paternal germline are associated with de novo mutations in the offspring of older men. Recently it has been recognized that somatic mutations in male germ cells that modify proliferation via dysregulation of the RAS pathway can lead to within-testis expansion of mutant clonal lines. First identified in association with rare paternal age-effect disorders (e.g. Apert syndrome, achondroplasia), this process is known as ‘selfish spermatogonial selection’. This mechanism will (a) favor propagation of germ cells carrying pathogenic mutations, (b) increasingly skew the mutational profile of sperm as men age, and (c) result in an enrichment of de novo mutations in the offspring of older fathers that preferentially impact on specific cellular signaling pathways. This mechanism offers a parsimonious explanation not only for the association between advanced paternal age and various neurodevelopmental disorders, but also provides insights into the genetic architecture (role of de novo mutations), neurobiological correlates (altered cell cycle) and some epidemiological features of these disorders. We outline hypotheses to test this model. Conclusions In light of our current understanding of the genetic networks involved in neurocognitive disorders and the principles of selfish spermatogonial selection, we speculate that some pathogenic mutations associated with these disorders are the consequence of a selfish mechanism originating in the aging testis. Given the secular changes for delayed parenthood in most societies, this hypothesis has important public
Akabaliev, Valentin Hristov; Sivkov, Stefan Todorov; Mantarkov, Mladen Yordanov
Minor physical anomalies (MPAs) have been investigated by numerous studies in patients with schizophrenia in support of the neurodevelopmental hypothesis of the disorder, but have rarely been examined in patients with bipolar disorder or in direct comparisons between the two conditions. The main objective of the present study was to compare the prevalence of MPAs in psychiatrically healthy controls, patients with bipolar I disorder, and patients with schizophrenia. A slightly modified version of the Waldrop Physical Anomaly Scale was used to assess MPAs in psychiatrically healthy controls (n = 103), patients with bipolar I disorder (n = 61), and patients with schizophrenia (n = 128). In five out of six topographic regions (mouth, feet, head, eyes, and ears) there was a pattern of lowest regional MPA scores in controls, intermediate in bipolar I disorder, and highest in schizophrenia. The cephalofacial composite score and the total MPA score showed the same pattern, with all between-group differences being statistically significant. Seven individual MPAs in the discriminant analysis model contributed independently to the prediction of the triple-dependent status of 'psychiatrically healthy control, bipolar I disorder patient, schizophrenia patient': high/arched palate, fine electric hair, large gap between first and second toes, third toe ≥ second toe, epicanthus, malformed ears, and furrowed tongue. Our findings support the existence of a continuum of neurodevelopmental adversity within the clinical spectrum of psychosis, with bipolar I disorder occupying an intermediate position between psychiatric health and schizophrenia. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Baribeau, Danielle A; Doyle-Thomas, Krissy A R; Dupuis, Annie; Iaboni, Alana; Crosbie, Jennifer; McGinn, Holly; Arnold, Paul D; Brian, Jessica; Kushki, Azadeh; Nicolson, Rob; Schachar, Russell J; Soreni, Noam; Szatmari, Peter; Anagnostou, Evdokia
Several neurodevelopmental disorders are associated with social processing deficits. The objective of this study was to compare patterns of social perception abilities across obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and control participants. A total of 265 children completed the Reading the Mind in the Eyes Test-Child Version (RMET). Parents or caregivers completed established trait/symptom scales. The predicted percentage of accuracy on the RMET was compared across disorders and by item difficulty and item valence (i.e., positive/negative/neutral mental states), then analyzed for associations with trait/symptom scores. The percentage of correct RMET scores varied significantly between diagnostic groups (p social communication impairment and hyperactivity/impulsivity, but not OCD traits/symptoms, were associated with lower scores on the RMET, irrespective of diagnosis. Social perception abilities in neurodevelopmental disorders exist along a continuum. Children with ASD have the greatest deficits, whereas children with OCD may be hypersensitive to social information. Social communication deficits and hyperactive/impulsive traits are associated with impaired social perception abilities; these findings highlight overlapping cognitive and behavioral manifestations across disorders. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
Reinders, A A T S; Chalavi, S; Schlumpf, Y R; Vissia, E M; Nijenhuis, E R S; Jäncke, L; Veltman, D J; Ecker, C
To examine the two constitutes of cortical volume (CV), that is, cortical thickness (CT) and surface area (SA), in individuals with dissociative identity disorder (DID) with the view of gaining important novel insights into the underlying neurobiological mechanisms mediating DID. This study included 32 female patients with DID and 43 matched healthy controls. Between-group differences in CV, thickness, and SA, the degree of spatial overlap between differences in CT and SA, and their relative contribution to differences in regional CV were assessed using a novel spatially unbiased vertex-wise approach. Whole-brain correlation analyses were performed between measures of cortical anatomy and dissociative symptoms and traumatization. Individuals with DID differed from controls in CV, CT, and SA, with significantly decreased CT in the insula, anterior cingulate, and parietal regions and reduced cortical SA in temporal and orbitofrontal cortices. Abnormalities in CT and SA shared only about 3% of all significantly different cerebral surface locations and involved distinct contributions to the abnormality of CV in DID. Significant negative associations between abnormal brain morphology (SA and CV) and dissociative symptoms and early childhood traumatization (0 and 3 years of age) were found. In DID, neuroanatomical areas with decreased CT and SA are in different locations in the brain. As CT and SA have distinct genetic and developmental origins, our findings may indicate that different neurobiological mechanisms and environmental factors impact on cortical morphology in DID, such as early childhood traumatization. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Trent, Simon; Dean, Rachel; Veit, Bonnie; Cassano, Tommaso; Bedse, Gaurav; Ojarikre, Obah A; Humby, Trevor; Davies, William
Chromosomal deletions at Xp22.3 appear to influence vulnerability to the neurodevelopmental disorders attention deficit hyperactivity disorder (ADHD) and autism. 39,X(Y*)O mice, which lack the murine orthologue of the Xp22.3 ADHD candidate gene STS (encoding steroid sulfatase), exhibit behavioural phenotypes relevant to such disorders (e.g. hyperactivity), elevated hippocampal serotonin (5-HT) levels, and reduced serum levels of dehydroepiandrosterone (DHEA). Here we initially show that 39,X(Y*)O mice are also deficient for the recently-characterised murine orthologue of the Xp22.3 autism candidate gene ASMT (encoding acetylserotonin-O-methyltransferase). Subsequently, to specify potential behavioural correlates of elevated hippocampal 5-HT arising due to the genetic lesion, we compared 39,X(Y*)O MF1 mice to 40,XY MF1 mice on behavioural tasks taxing hippocampal and/or 5-HT function (a 'foraging' task, an object-location task, and the 1-choice serial reaction time task of impulsivity). Although Sts/Asmt deficiency did not influence foraging behaviour, reactivity to familiar objects in novel locations, or 'ability to wait', it did result in markedly increased response rates; these rates correlated with hippocampal 5-HT levels and are likely to index behavioural perseveration, a frequent feature of neurodevelopmental disorders. Additionally, we show that whilst there was no systematic relationship between serum DHEA levels and hippocampal 5-HT levels across 39,X(Y*)O and 40,XY mice, there was a significant inverse linear correlation between serum DHEA levels and activity. Our data suggest that deficiency for genes within Xp22.3 could influence core behavioural features of neurodevelopmental disorders via dissociable effects on hippocampal neurochemistry and steroid hormone levels, and that the mediating neurobiological mechanisms may be investigated in the 39,X(Y*)O model. Copyright © 2012 Elsevier Ltd. All rights reserved.
Savabieasfahani, M; Alaani, S; Tafash, M; Dastgiri, S; Al-Sabbak, M
Anthropogenic release of pollutants into the environment is especially harmful to growing fetuses and young children. These populations are at an increased risk of damage because exposure to pollutants during critical periods of development can cause many impairments. Children's exposure to mixtures of metals could be responsible for the rising numbers of neurological disorders surfacing in Iraqi children. Titanium (Ti) and magnesium (Mg) are heavily used in war industries. Exposure to Ti and Mg has been linked to the dust in occupation soldiers' lungs. Hair samples of children in Hawija, Iraq (n = 13) contained significantly higher levels of Ti compared to Iranian children (n = 13) living near the Iraqi border (2080 ± 940 vs 707 ± 421 μg/kg, p children compared to Iranian children (115,763 ± 118,155 vs 67,650 ± 46,729 μg/kg). In samples from Hawija, Ti was 1.3 times higher in children with neurodevelopmental disorders (2198 ± 1108 vs 1942 ± 779 μg/kg), and Mg was 1.9 times higher in children without neurodevelopmental disorders (155,618 ± 140,791 vs 81,602 ± 91,940 μg/kg). Lead, arsenic, and cadmium in Hawija children with neurodevelopmental disorders (n = 6) were 2.5, 2.2, and 1.37 times higher compared to non-disabled children (n = 7). To get a clear understanding of the current status of neurodevelopmental disorders in Iraqi children and to determine the magnitude of this suspected global health issue, registries should be set up to compile and aggregate data from hospitals, clinics, and health centers across the country. Functional registries can develop collaborations with researchers toward finding causes of these disorders in Iraqi children and toward preventing them.
Yewande O. Oshodi
Full Text Available Autism Spectrum Disorder (ASD is a globally prevalent neurodevelopmental disorder for which early diagnosis and intervention is the mainstay of management. In the African continent, limited data is available regarding the non-clinic based samples. Lack of information available to caregivers and inadequate skilled manpower often limit early detection and access to the few available though under resourced services in the community. Community based screening can be an important drive to create awareness and improve information dissemination regarding services available for those living with this disorder. This is a descriptive cross-sectional study utilizing data obtained from participants of a community-based autism screening exercise. The surveillance exercise was part of the annual Orange Ribbon initiative for autism awareness and screening held in 2014. Data was obtained from 85 participants involved in the Autism Surveillance screening exercise within the Lagos community. Community public service radio announcements state wide and word of mouth were used to invite and enroll eligible participants to the screening and consultation exercise. A second stage screening and a brief sociodemographic questionnaire followed by a third stage clinical interview and evaluation using the Diagnostic and Statistical Manual of Mental Disorders - 5 Edition (DSM 5 were used. Appropriate consultation and referrals to services in the community were given. Participants had a mean age of 7.53 years (SD 4.35. Twenty-nine (34.5% met the diagnosis of ASD. Other diagnosis included attention deficit hyperactivity disorder (ADHD, language and speech disorder, intellectual disability (8.3% and learning disorders (9.5%. Main health concerns to caregivers were poor language development in all (100%, of which 11 (40.7% were non-verbal; gaze avoidance was seen in 14 (48.3% and challenging behavior in 12 (42.9%. Comorbidities included seizure disorders (3.4% and ADHD (6
Mpaka, Davin Mbeya; Okitundu, Daniel Luwa E-Andjafono; Ndjukendi, Ally Omba; N'situ, Adelin Mankubu; Kinsala, Sebastien Yabassi; Mukau, Joachim Ebwel; Ngoma, Valentin Malanda; Kashala-Abotnes, Espérance; Ma-Miezi-Mampunza, Samuel; Vogels, Annick; Steyaert, Jeans
Autism spectrum disorders (ASD) is a neurodevelopmental disorder that has been rarely diagnosed in Sub-Saharan Africa. Although a proportion of children do present features of ASD in the Democratic Republic of Congo (DRC), little is known about it prevalence. Often, the co-morbidities constitute the upfront symptoms and therefore may it recognition and management difficult, aggravating as such the prognosis. The present study therefore aimed at studying the clinical profile of autism spectrum disorder (ASD) and the associated morbidities among children and adolescents in outpatient clinics in Kinshasa, the Democratic Republic of Congo. We conducted a cross sectional study in the three outpatients centers receiving patients referred for neurodevelopmental disorders in Kinshasa, DRC, from June 2008 to June 2010. A total of 450 subjects aged from 1-18 years old were referred and included in the study. The clinical diagnosis for ASD was made using the DSM-IV-R and the ADIR. Co-morbidities were identified using DSM-IV-R criteria together with an extensive clinical interview and observation. All patients were subject to an intellectual quotient evaluation and an electroencephalogram reporting. Of the 450 subjects referred, 120 (29.3%) received the diagnosis of ASD, with boys outnumbering girls (OR 3:1. The mean age was 7.9 years (SD 3.4) (psociety in Kinshasa DRC. This will help to identify and manage ASD and associated co-morbidities at an early stage for a better prognosis.
Using the conceptual tools of philosopher of science Ludwik Fleck, I argue that the reframing of autism as a neurodevelopmental spectrum disorder is constrained by two governing 'styles of thought' of contemporary psychiatry. The first is the historically conditioned 'readiness for directed perception' of, and thinking in terms of, ontologically distinct diseases. The clinical gaze of mental health professionals, the bureaucratic needs of health administration, the clinical and scientific utility of disease categories, and the practices of autism-oriented advocacy groups all imply a bias toward thinking about autism and related disorders as ontologically distinct psychiatric and scientific entities. Second, within the 'neuromolecular style of thought', mental disorders are more and more located at the neurobiological levels of the brain. In autism research, one of the biggest challenges is the identification of autism's neurobiological singularity. However, at a moment when biological and categorical approaches toward autism face serious empirical difficulties, a balance is established that holds together these two styles of thought. With a need to account for some of the most persistent uncertainties and conflicts in autism research, namely ubiquitous heterogeneity and a failure to identify disease specific biomarkers, the reframing of autism as a neurodevelopmental spectrum disorder satisfies the scientific, institutional and socio-political needs for stability and homogenization. Copyright © 2014 Elsevier Ltd. All rights reserved.
Goriely, Anne; McGrath, John J; Hultman, Christina M; Wilkie, Andrew O M; Malaspina, Dolores
There is robust evidence from epidemiological studies that the offspring of older fathers have an increased risk of neurodevelopmental disorders, such as schizophrenia and autism. The authors present a novel mechanism that may contribute to this association. Because the male germ cell undergoes many more cell divisions across the reproductive age range, copy errors taking place in the paternal germline are associated with de novo mutations in the offspring of older men. Recently it has been recognized that somatic mutations in male germ cells that modify proliferation through dysregulation of the RAS protein pathway can lead to within-testis expansion of mutant clonal lines. First identified in association with rare disorders related to paternal age (e.g., Apert syndrome, achondroplasia), this process is known as "selfish spermatogonial selection." This mechanism favors propagation of germ cells carrying pathogenic mutations, increasingly skews the mutational profile of sperm as men age, and enriches de novo mutations in the offspring of older fathers that preferentially affect specific cellular signaling pathways. This mechanism not only offers a parsimonious explanation for the association between advanced paternal age and various neurodevelopmental disorders but also provides insights into the genetic architecture (role of de novo mutations), neurobiological correlates (altered cell cycle), and some epidemiological features of these disorders. The authors outline hypotheses to test this model. Given the secular changes for delayed parenthood in most societies, this hypothesis has important public health implications.
Ahmed-Popova, Ferihan M; Mantarkov, Mladen J; Sivkov, Stefan T; Akabaliev, Valentin H
Dermatoglyphic pattern formation and differentiation are complex processes which have been in the focus of research interest ever since dermatoglyphics became a science. The patterns' early differentiation and genetic uniqueness as well as the relatively simple methods used to obtain and store fingerprints make it possible to study the relationship between certain dermatoglyphic characteristics and the underlying pathological processes in a number of diseases, including mental disorders. The present review reports published data from fundamental and clinical studies on dermatoglyphics primarily in schizophrenia and bipolar disorder to lend additional support for the neurodevelopmental hypothesis in the etiology of these disorders. Following an analysis of the theories of dermatoglyphics formation and the complex association between ridge patterns and central nervous system in early embryogenesis, an attempt is made to present dermatoglyphics as possible biological markers of impaired neurodevelopment. The contradictory data in the literature on dermatoglyphics in mental disorders suggest the need for further studies on these biological markers in order to identify their place in the neurodevelopmental etiological model of these diseases.
Reuter, Miriam S; Tawamie, Hasan; Buchert, Rebecca; Hosny Gebril, Ola; Froukh, Tawfiq; Thiel, Christian; Uebe, Steffen; Ekici, Arif B; Krumbiegel, Mandy; Zweier, Christiane; Hoyer, Juliane; Eberlein, Karolin; Bauer, Judith; Scheller, Ute; Strom, Tim M; Hoffjan, Sabine; Abdelraouf, Ehab R; Meguid, Nagwa A; Abboud, Ahmad; Al Khateeb, Mohammed Ayman; Fakher, Mahmoud; Hamdan, Saber; Ismael, Amina; Muhammad, Safia; Abdallah, Ebtessam; Sticht, Heinrich; Wieczorek, Dagmar; Reis, André; Abou Jamra, Rami
Autosomal recessive inherited neurodevelopmental disorders are highly heterogeneous, and many, possibly most, of the disease genes are still unknown. To promote the identification of disease genes through confirmation of previously described genes and presentation of novel candidates and provide an overview of the diagnostic yield of exome sequencing in consanguineous families. Autozygosity mapping in families and exome sequencing of index patients were performed in 152 consanguineous families (the parents descended from a same ancestor) with at least 1 offspring with intellectual disability (ID). The study was conducted from July 1, 2008, to June 30, 2015, and data analysis was conducted from July 1, 2015, to August 31, 2016. Of the 152 consanguineous families enrolled, 1 child (in 45 families [29.6%]) or multiple children (107 families [70.4%]) had ID; additional features were present in 140 of the families (92.1%). The mean (SD) age of the children was 10.3 (9.0) years, and 171 of 297 (57.6%) were male. In 109 families (71.7%), potentially protein-disrupting and clinically relevant variants were identified. Of these, a clear clinical genetic diagnosis was made in 56 families (36.8%) owing to 57 (likely) pathogenic variants in 50 genes already established in neurodevelopmental disorders (46 autosomal recessive, 2 X-linked, and 2 de novo) or in 7 previously proposed recessive candidates. In 5 of these families, potentially treatable disorders were diagnosed (mutations in PAH, CBS, MTHFR, CYP27A1, and HIBCH), and in 1 family, 2 disease-causing homozygous variants in different genes were identified. In another 48 families (31.6%), 52 convincing recessive variants in candidate genes that were not previously reported in regard to neurodevelopmental disorders were identified. Of these, 14 were homozygous and truncating in GRM7, STX1A, CCAR2, EEF1D, GALNT2, SLC44A1, LRRIQ3, AMZ2, CLMN, SEC23IP, INIP, NARG2, FAM234B, and TRAP1. The diagnostic yield was higher in
Andrews, G; Pine, D S; Hobbs, M J; Anderson, T M; Sunderland, M
DSM-IV and ICD-10 are atheoretical and largely descriptive. Although this achieves good reliability, the validity of diagnoses can be increased by an understanding of risk factors and other clinical features. In an effort to group mental disorders on this basis, five clusters have been proposed. We now consider the second cluster, namely neurodevelopmental disorders. We reviewed the literature in relation to 11 validating criteria proposed by a DSM-V Task Force Study Group. This cluster reflects disorders of neurodevelopment rather than a 'childhood' disorders cluster. It comprises disorders subcategorized in DSM-IV and ICD-10 as Mental Retardation; Learning, Motor, and Communication Disorders; and Pervasive Developmental Disorders. Although these disorders seem to be heterogeneous, they share similarities on some risk and clinical factors. There is evidence of a neurodevelopmental genetic phenotype, the disorders have an early emerging and continuing course, and all have salient cognitive symptoms. Within-cluster co-morbidity also supports grouping these disorders together. Other childhood disorders currently listed in DSM-IV share similarities with the Externalizing and Emotional clusters. These include Conduct Disorder, Attention Deficit Hyperactivity Disorder and Separation Anxiety Disorder. The Tic, Eating/Feeding and Elimination disorders, and Selective Mutisms were allocated to the 'Not Yet Assigned' group. Neurodevelopmental disorders meet some of the salient criteria proposed by the American Psychiatric Association (APA) to suggest a classification cluster.
Background RBFOX1 is an important splicing factor regulating developmental and tissue-specific alternative splicing in heart, muscle, and neuronal tissues. Constitutional genetic defects in RBFOX1 are implicated in multiple medical conditions. Results We identified 14 copy number variants (CNV) involving RBFOX1 from 2,124 consecutive pediatric patients referred for chromosomal microarray analysis (CMA), including 13 intragenic deletions and a single intragenic duplication. The clinical significances of the intragenic deletions of RBFOX1 were evaluated. Conclusions Our data strongly supports the associations of intragenic deletions of RBFOX1 with a diversity of neurodevelopmental and neuropsychiatric disorders, and possibly other clinical features. PMID:23822903
de Vries, Petrus J
Until recently, the neuropsychiatric phenotype of tuberous sclerosis complex (TSC) was presumed to be caused by the structural brain abnormalities and/or seizures seen in the disorder. However, advances in the molecular biology of the disorder have shown that TSC is a mammalian target of rapamycin (mTOR) overactivation syndrome, and that direct molecular pathways exist between gene mutation and cognitive/neurodevelopmental phenotype. Molecularly-targeted treatments using mTOR inhibitors (such as rapamycin) are showing great promise for the physical and neurological phenotype of TSC. Pre-clinical and early-phase clinical studies of the cognitive and neurodevelopmental features of TSC suggest that some of the neuropsychiatric phenotypes might also be reversible, even in adults with the disorder. TSC, fragile X, neurofibromatosis type 1, and disorders associated with phosphatase and tensin homo (PTEN) mutations, all signal through the mTOR signaling pathway, with the TSC1-TSC2 protein complex as a molecular switchboard at its center. Together, these disorders represent as much as 14% of autism spectrum disorders (ASD). Therefore, we suggest that this signaling pathway is a key to the underlying pathophysiology of a significant subset of individuals with ASD. The study of molecularly targeted treatments in TSC and related disorders, therefore, may be of scientific and clinical value not only to those with TSC, but to a larger population that may have a neuropsychiatric phenotype attributable to mTOR overactivation or dysregulation. (c) 2010 The American Society for Experimental NeuroTherapeutics, Inc. Published by Elsevier Inc. All rights reserved.
Mizoguchi, Yoshito; Monji, Akira
Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by deficits in social interaction, difficulties with language and repetitive/restricted behaviors. Microglia are resident innate immune cells which release many factors including proinflammatory cytokines, nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) when they are activated in response to immunological stimuli. Recent in vivo imaging has shown that microglia sculpt and refine the synaptic circuitry by removing excess and unwanted synapses and be involved in the development of neural circuits or synaptic plasticity thereby maintaining the brain homeostasis. BDNF, one of the neurotrophins, has various important roles in cell survival, neurite outgrowth, neuronal differentiation, synaptic plasticity and the maintenance of neural circuits in the CNS. Intracellular Ca2+ signaling is important for microglial functions including ramification, de-ramification, migration, phagocytosis and release of cytokines, NO and BDNF. BDNF induces a sustained intracellular Ca2+ elevation through the upregulation of the surface expression of canonical transient receptor potential 3 (TRPC3) channels in rodent microglia. BDNF might have an anti-inflammatory effect through the inhibition of microglial activation and TRPC3 could play important roles in not only inflammatory processes but also formation of synapse through the modulation of microglial phagocytic activity in the brain. This review article summarizes recent findings on emerging dual, inflammatory and non-inflammatory, roles of microglia in the brain and reinforces the importance of intracellular Ca2+ signaling for microglial functions in both normal neurodevelopment and their potential contributing to neurodevelopmental disorders such as ASDs.
Raine, Adrian; Lee, Lydia; Yang, Yaling; Colletti, Patrick
Antisocial personality disorder and psychopathy have been hypothesised to have a neurodevelopmental basis, but this proposition has not been formally tested. This study tests the hypothesis that individuals with cavum septum pellucidum (CSP), a marker of limbic neural maldevelopment, will show higher levels of psychopathy and antisocial personality. Cavum septum pellucidum was assessed using anatomical magnetic resonance imaging in a community sample. Those with CSP (n = 19) were compared with those lacking CSP (n = 68) on antisocial personality, psychopathy and criminal offending. Those with CSP had significantly higher levels of antisocial personality, psychopathy, arrests and convictions compared with controls. The pervasiveness of this association was indicated by the fact that those lacking a diagnosis of antisocial personality disorder, but who were charged or convicted for an offence, had a more extensive CSP than non-antisocial controls. Results could not be attributed to prior trauma exposure, head injury, demographic factors or comorbid psychiatric conditions. Our findings appear to be the first to provide evidence for a neurodevelopmental brain abnormality in those with antisocial personality disorder and psychopathy, and support the hypothesis that early maldevelopment of limbic and septal structures predisposes to the spectrum of antisocial behaviours.
Cruchet et al. attempt to tease out the myths and facts surrounding the growing popularity of certain dietary approaches in the management of neurodevelopmental disorders, like attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs). The authors identify a particular exclusionary-type approach that seeks to eliminate dietary gluten. Although the relationship between celiac disease (CD) and ADHD/ASD is not well established, a repeated clinical feature noted in CD is the elevated levels of nitric oxide in serum and urine. Elevated oxidative stress has also been observed in neurodevelopmental conditions, and the author of this correspondence has been the first to propose that chronic, environmental exposure to the air pollutant, nitrous oxide may contribute to these oxidative stress profiles through neural cholinergic perturbation. Therefore, the purpose of this correspondence is to highlight this biochemical connection between these conditions so as to identify the clinical populations who may realize the greatest benefit of these dietary approaches, while minimizing any potential risk of nutrient deficiencies. © 2016 S. Karger AG, Basel.
Owen, Michael J; O'Donovan, Michael C; Thapar, Anita; Craddock, Nicholas
The neurodevelopmental hypothesis of schizophrenia provided a valuable framework that allowed a condition that usually presents with frank disorder in adolescence or early adulthood to be understood...
Lazar, Steven M; Evans, David W; Myers, Scott M; Moreno-De Luca, Andres; Moore, Gregory J
Social cognition is an important aspect of social behavior in humans. Social cognitive deficits are associated with neurodevelopmental and neuropsychiatric disorders. In this study we examine the neural substrates of social cognition and face processing in a group of healthy young adults to examine the neural substrates of social cognition. Fifty-seven undergraduates completed a battery of social cognition tasks and were assessed with electroencephalography (EEG) during a face-perception task. A subset (N=22) were administered a face-perception task during functional magnetic resonance imaging. Variance in the N170 EEG was predicted by social attribution performance and by a quantitative measure of empathy. Neurally, face processing was more bilateral in females than in males. Variance in fMRI voxel count in the face-sensitive fusiform gyrus was predicted by quantitative measures of social behavior, including the Social Responsiveness Scale (SRS) and the Empathizing Quotient. When measured as a quantitative trait, social behaviors in typical and pathological populations share common neural pathways. The results highlight the importance of viewing neurodevelopmental and neuropsychiatric disorders as spectrum phenomena that may be informed by studies of the normal distribution of relevant traits in the general population. Copyright © 2014 Elsevier B.V. All rights reserved.
Chauhan, Ved; Chauhan, Abha
Extensive evidence suggests the role of oxidative stress in autism and other neurodevelopmental disorders. In this study, we investigated whether methylmercury (MeHg) and/or alcohol exposure has deleterious effects in Drosophila melanogaster (fruit flies). A diet containing different concentrations of MeHg in Drosophila induced free radical generation and increased lipid peroxidation (markers of oxidative stress) in a dose-dependent manner. This effect of MeHg on oxidative stress was enhanced by further exposure to alcohol. It was observed that alcohol alone could also induce free radical generation in flies. After alcohol exposure, MeHg did not affect the immobilization of flies, but it increased the recovery time in a concentration-dependent manner. MeHg significantly inhibited the activity of alcohol dehydrogenase (ADH) in a dose-dependent manner. Linear regression analysis showed a significant negative correlation between ADH activity and recovery time upon alcohol exposure in the flies fed a diet with MeHg. This relationship between ADH activity and recovery time after alcohol exposure was confirmed by adding 4-methyl pyrazole (an inhibitor of ADH) to the diet for the flies. These results suggest that consumption of alcohol by pregnant mothers who are exposed to MeHg may lead to increased oxidative stress and to increased length of time for alcohol clearance, which may have a direct impact on the development of the fetus, thereby increasing the risk of neurodevelopmental disorders. Published by Elsevier Ltd.
Parker, Whitney E; Orlova, Ksenia A; Parker, William H; Birnbaum, Jacqueline F; Krymskaya, Vera P; Goncharov, Dmitry A; Baybis, Marianna; Helfferich, Jelte; Okochi, Kei; Strauss, Kevin A; Crino, Peter B
A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological evidence of heterotopic neurons in subcortical white matter and subependymal regions. PMSE is caused by a homozygous deletion of exons 9 to 13 of the LYK5/STRADA gene, which encodes the pseudokinase STRADA, an upstream inhibitor of mammalian target of rapamycin complex 1 (mTORC1). We show that disrupted pathfinding in migrating mouse neural progenitor cells in vitro caused by STRADA depletion is prevented by mTORC1 inhibition with rapamycin or inhibition of its downstream effector p70 S6 kinase (p70S6K) with the drug PF-4708671 (p70S6Ki). We demonstrate that rapamycin can rescue aberrant cortical lamination and heterotopia associated with STRADA depletion in the mouse cerebral cortex. Constitutive mTORC1 signaling and a migration defect observed in fibroblasts from patients with PMSE were also prevented by mTORC1 inhibition. On the basis of these preclinical findings, we treated five PMSE patients with sirolimus (rapamycin) without complication and observed a reduction in seizure frequency and an improvement in receptive language. Our findings demonstrate a mechanistic link between STRADA loss and mTORC1 hyperactivity in PMSE, and suggest that mTORC1 inhibition may be a potential treatment for PMSE as well as other mTOR-associated neurodevelopmental disorders.
Full Text Available Psychiatric disorders are disadvantageous behavioral phenotypes in humans. Accordingly, a recent epidemiological study has reported decreased fecundity in patients with psychiatric disorders, such as schizophrenia and autism spectrum disorders. Moreover, the fecundity of the relatives of these patients is not exceedingly higher compared to the fecundity of the relatives of normal subjects. Collectively, the prevalence of psychiatric disorders among humans is expected to decrease over generations. Nevertheless, in reality, the prevalence rates of psychiatric disorders in humans either have been constant over a long period of time or have even increased more recently. Several attempts to explain this fact have been made using biological mechanisms, such as de novo gene mutations or variants, although none of these explanations is fully comprehensive. Here, we propose a hypothesis towards understanding the biological mechanisms of psychiatric disorders from evolutionary perspectives. This hypothesis considers that behavioral phenotypes associated with psychiatric disorders might have emerged in the evolution of organisms as a neurodevelopmental adaptation against adverse environmental conditions associated with stress.
Sukoff Rizzo, Stacey J; Crawley, Jacqueline N
Animal models offer heuristic research tools to understand the causes of human diseases and to identify potential treatments. With rapidly evolving genetic engineering technologies, mutations identified in a human disorder can be generated in the mouse genome. Phenotypic outcomes of the mutation are then explicated to confirm hypotheses about causes and to discover effective therapeutics. Most neurodevelopmental, neurodegenerative, and psychiatric disorders are diagnosed primarily by their prominent behavioral symptoms. Mouse behavioral assays analogous to the human symptoms have been developed to analyze the consequences of mutations and to evaluate proposed therapeutics preclinically. Here we describe the range of mouse behavioral tests available in the established behavioral neuroscience literature, along with examples of their translational applications. Concepts presented have been successfully used in other species, including flies, worms, fish, rats, pigs, and nonhuman primates. Identical strategies can be employed to test hypotheses about environmental causes and gene × environment interactions.
Millan, Mark J
Neurodevelopmental disorders (NDDs) are characterized by aberrant and delayed early-life development of the brain, leading to deficits in language, cognition, motor behaviour and other functional domains, often accompanied by somatic symptoms. Environmental factors like perinatal infection, malnutrition and trauma can increase the risk of the heterogeneous, multifactorial and polygenic disorders, autism and schizophrenia. Conversely, discrete genetic anomalies are involved in Down, Rett and Fragile X syndromes, tuberous sclerosis and neurofibromatosis, the less familiar Phelan-McDermid, Sotos, Kleefstra, Coffin-Lowry and "ATRX" syndromes, and the disorders of imprinting, Angelman and Prader-Willi syndromes. NDDs have been termed "synaptopathies" in reference to structural and functional disturbance of synaptic plasticity, several involve abnormal Ras-Kinase signalling ("rasopathies"), and many are characterized by disrupted cerebral connectivity and an imbalance between excitatory and inhibitory transmission. However, at a different level of integration, NDDs are accompanied by aberrant "epigenetic" regulation of processes critical for normal and orderly development of the brain. Epigenetics refers to potentially-heritable (by mitosis and/or meiosis) mechanisms controlling gene expression without changes in DNA sequence. In certain NDDs, prototypical epigenetic processes of DNA methylation and covalent histone marking are impacted. Conversely, others involve anomalies in chromatin-modelling, mRNA splicing/editing, mRNA translation, ribosome biogenesis and/or the regulatory actions of small nucleolar RNAs and micro-RNAs. Since epigenetic mechanisms are modifiable, this raises the hope of novel therapy, though questions remain concerning efficacy and safety. The above issues are critically surveyed in this review, which advocates a broad-based epigenetic framework for understanding and ultimately treating a diverse assemblage of NDDs ("epigenopathies") lying at the
Deidda, Gabriele; Bozarth, Ignacio F; Cancedda, Laura
During mammalian ontogenesis, the neurotransmitter GABA is a fundamental regulator of neuronal networks. In neuronal development, GABAergic signaling regulates neural proliferation, migration, differentiation, and neuronal-network wiring. In the adult, GABA orchestrates the activity of different neuronal cell-types largely interconnected, by powerfully modulating synaptic activity. GABA exerts these functions by binding to chloride-permeable ionotropic GABAA receptors and metabotropic GABAB receptors. According to its functional importance during development, GABA is implicated in a number of neurodevelopmental disorders such as autism, Fragile X, Rett syndrome, Down syndrome, schizophrenia, Tourette's syndrome and neurofibromatosis. The strength and polarity of GABAergic transmission is continuously modulated during physiological, but also pathological conditions. For GABAergic transmission through GABAA receptors, strength regulation is achieved by different mechanisms such as modulation of GABAA receptors themselves, variation of intracellular chloride concentration, and alteration in GABA metabolism. In the never-ending effort to find possible treatments for GABA-related neurological diseases, of great importance would be modulating GABAergic transmission in a safe and possibly physiological way, without the dangers of either silencing network activity or causing epileptic seizures. In this review, we will discuss the different ways to modulate GABAergic transmission normally at work both during physiological and pathological conditions. Our aim is to highlight new research perspectives for therapeutic treatments that reinstate natural and physiological brain functions in neuro-pathological conditions.
Full Text Available During mammalian ontogenesis, the neurotransmitter GABA is a fundamental regulator of neuronal networks. In neuronal development, GABAergic signaling regulates neural proliferation, migration, differentiation, and neuronal-network wiring. In the adult, GABA orchestrates the activity of different neuronal cell-types largely interconnected, by powerfully modulating synaptic activity. GABA exerts these functions by binding to chloride-permeable ionotropic GABAA receptors and metabotropic GABAB receptors. According to its functional importance during development, GABA is implicated in a number of neurodevelopmental disorders such as autism, Fragile X, Rett syndrome, Down syndrome, schizophrenia, Tourette's syndrome and neurofibromatosis.The strength and polarity of GABAergic transmission is continuously modulated during physiological, but also pathological conditions. For GABAergic transmission through GABAA receptors, strength regulation is achieved by different mechanisms such as modulation of GABAA receptors themselves, variation of intracellular chloride concentration, and alteration in GABA metabolism. In the never-ending effort to find possible treatments for GABA-related neurological diseases, of great importance would be modulating GABAergic transmission in a safe and possibly physiological way, without the dangers of either silencing network activity or causing epileptic seizures. In this review, we will discuss the different ways to modulate GABAergic transmission normally at work both during physiological and pathological conditions. Our aim is to highlight new research perspectives for therapeutic treatments that reinstate natural and physiological brain functions in neuro-pathological conditions.
Samango-Sprouse, Carole; Keen, Colleen; Mitchell, Francie; Sadeghin, Teresa; Gropman, Andrea
Fourty eight, XXXX is a rare chromosomal aneuploidy associated with neurocognitive deficits, speech and language disorders and executive dysfunction but the scarcity and variability of reported cases limit our understanding of the 48, XXXX phenotype. To our knowledge, this is the first study to report on the neurodevelopmental profile of three young females with 48, XXXX. Patient 1 (age = 11.0), Patient 2 (age = 10.9), and Patient 3 (age = 6.4) were evaluated using comprehensive neurodevelopmental assessments. Parent questionnaires were completed to assess behavioral and psychosocial domains including executive function, ADHD and anxiety. Nonverbal intelligence quotients were 56, 80, and 91 for Patients 1, 2, and 3, respectively. There were significantly impaired visual motor capacities in graphomotor and perceptual domains below the 5th centile in Patients 1 and 2, and mildly impaired visual perception skills in Patient 3. All three patients had Childhood Apraxia of Speech (CAS) but of varying severity and similar executive dysfunction, externalizing problems and social difficulties. Familial learning disabilities (FLD) in Patient 1 and the co-occurrence of ADHD in Patient's 1 and 2 may contribute to their more impaired cognitive performances relative to Patient 3 who is the second reported case of 48, XXXX to have normal intellect. These distinct and overlapping characteristics expand the phenotypic profile of 48, XXXX and may be used in the counseling of families and treatment of children with 48, XXXX. © 2015 Wiley Periodicals, Inc.
Full Text Available Sleep is important for neural plasticity, and plasticity underlies sleep-dependent memory consolidation. It is widely appreciated that protein synthesis plays an essential role in neural plasticity. Studies of sleep-dependent memory and sleep-dependent plasticity have begun to examine alterations in these functions in populations with neurological and psychiatric disorders. Such an approach acknowledges that disordered sleep may have functional consequences during wakefulness. Although neurodevelopmental disorders are not considered to be sleep disorders per se, recent data has revealed that sleep abnormalities are among the most prevalent and common symptoms and may contribute to the progression of these disorders. The main goal of this review is to highlight the role of disordered sleep in the pathology of neurodevelopmental disorders and to examine some potential mechanisms by which sleep-dependent plasticity may be altered. We will also briefly attempt to extend the same logic to the other end of the developmental spectrum and describe a potential role of disordered sleep in the pathology of neurodegenerative diseases. We conclude by discussing ongoing studies that might provide a more integrative approach to the study of sleep, plasticity, and neurodevelopmental disorders.
Byrne, Susan; Jansen, Lara; U-King-Im, Jean-Marie; Siddiqui, Ata; Lidov, Hart G W; Bodi, Istvan; Smith, Luke; Mein, Rachael; Cullup, Thomas; Dionisi-Vici, Carlo; Al-Gazali, Lihadh; Al-Owain, Mohammed; Bruwer, Zandre; Al Thihli, Khalid; El-Garhy, Rana; Flanigan, Kevin M; Manickam, Kandamurugu; Zmuda, Erik; Banks, Wesley; Gershoni-Baruch, Ruth; Mandel, Hanna; Dagan, Efrat; Raas-Rothschild, Annick; Barash, Hila; Filloux, Francis; Creel, Donnell; Harris, Michael; Hamosh, Ada; Kölker, Stefan; Ebrahimi-Fakhari, Darius; Hoffmann, Georg F; Manchester, David; Boyer, Philip J; Manzur, Adnan Y; Lourenco, Charles Marques; Pilz, Daniela T; Kamath, Arveen; Prabhakar, Prab; Rao, Vamshi K; Rogers, R Curtis; Ryan, Monique M; Brown, Natasha J; McLean, Catriona A; Said, Edith; Schara, Ulrike; Stein, Anja; Sewry, Caroline; Travan, Laura; Wijburg, Frits A; Zenker, Martin; Mohammed, Shehla; Fanto, Manolis; Gautel, Mathias; Jungbluth, Heinz
Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations (p.Met2242Cysfs*5, p.Arg417*, and p.Gln336Arg) indicated possible founder effects. Presentation was mainly neonatal, with marked hypotonia and feeding difficulties. In addition to the five principal features (callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, and immune dysfunction), we identified three equally consistent features (profound developmental delay, progressive microcephaly, and failure to thrive). The manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation and will allow informed decisions about genetic testing. Clinical progression was relentless and many children died in infancy. Survival analysis demonstrated a median survival time of 24 months (95% confidence interval 0-49 months), with only a 10th of patients surviving to 5 years of age. Survival outcomes were significantly better in patients with compound heterozygous mutations (P = 0.046), as well as in patients with the recurrent p.Gln336Arg mutation. Acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect. Two-thirds of patients had a severe seizure disorder, placing EPG5 within the rapidly expanding group of genes associated with early-onset epileptic encephalopathies. Consistent neuroradiological features comprised structural abnormalities, in particular callosal agenesis and pontine hypoplasia, delayed
Harms, Melanie D.
Individuals with neurodevelopmental disorders are challenged with memory and language deficits that impact their skills acquisition (Martin, Klusek, Estigarriba, & Roberts, 2009; Turner & Alborz, 2003). The value of music when applied as an antecedent and a reinforcer has long been established to address such memory and language deficits…
Full Text Available Background: To establish integrated healthcare pathways for patients with neurodevelopmental disorders (ND such as autism spectrum disorder and attention-deficit hyperactivity disorder is challenging. This study sets out to investigate the main concerns for healthcare professionals when integrating ND care pathways and how they resolve these concerns. Methods: Using classic grounded theory (Glaser, we analysed efforts to improve and integrate an ND care pathway for children and youth in a Swedish region over a period of 6 years. Data from 42 individual interviews with a range of ND professionals, nine group interviews with healthcare teams, participant observation, a 2-day dialogue conference, focus group meetings, regional media coverage, and reports from other Swedish regional ND projects were analysed. Results: The main concern for participants was to deal with overwhelming ND complexity by unpacking control, which is control over strategies to define patients’ status and needs. Unpacking control is key to the professionals’ strivings to expand constructive life space for patients, to squeeze health care to reach available care goals, to promote professional ideologies, and to uphold workplace integrity. Control-seeking behaviour in relation to ND unpacking is ubiquitous and complicates integration of ND care pathways. Conclusions: The Unpacking control theory expands central aspects of professions theory and may help to improve ND care development.
Waxegård, Gustaf; Thulesius, Hans
Background To establish integrated healthcare pathways for patients with neurodevelopmental disorders (ND) such as autism spectrum disorder and attention-deficit hyperactivity disorder is challenging. This study sets out to investigate the main concerns for healthcare professionals when integrating ND care pathways and how they resolve these concerns. Methods Using classic grounded theory (Glaser), we analysed efforts to improve and integrate an ND care pathway for children and youth in a Swedish region over a period of 6 years. Data from 42 individual interviews with a range of ND professionals, nine group interviews with healthcare teams, participant observation, a 2-day dialogue conference, focus group meetings, regional media coverage, and reports from other Swedish regional ND projects were analysed. Results The main concern for participants was to deal with overwhelming ND complexity by unpacking control, which is control over strategies to define patients’ status and needs. Unpacking control is key to the professionals’ strivings to expand constructive life space for patients, to squeeze health care to reach available care goals, to promote professional ideologies, and to uphold workplace integrity. Control-seeking behaviour in relation to ND unpacking is ubiquitous and complicates integration of ND care pathways. Conclusions The Unpacking control theory expands central aspects of professions theory and may help to improve ND care development. PMID:27609793
Full Text Available Background: Parents of children suffering from neurodevelopmental disorders, frequently face public stigma which is often internalized and leads to psychological burden. However, there is a lack of data on the perceptions of internalized stigma among parents of children with neurodevelopmental disorders, especially from lower-middle-income countries like India. Aims: This study aims to develop an adapted version of the Internalized Stigma of Mental Illness (ISMI scale for use in parents of children suffering from neurodevelopmental disorders and to explore the factor structure of this instrument through exploratory factor analysis (EFA. Settings and Design: A cross-sectional study was conducted in an outpatient setting in a tertiary care hospital in India. Materials and Methods: A total of 105 parents of children suffering from neurodevelopmental disorders (according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition were recruited for the study after screening for psychiatric disorder using Mini International Neuropsychiatric Interview version 6.0. A modified 16-item scale was constructed Parents' Internalized Stigma of Neurodevelopmental Disorder in Child (PISNC scale and applied on 105 parents of children suffering from neurodevelopmental disorders, after translation to Hindi and back-translation, in keeping with the World Health Organization's translation-back-translation methodology. Statistical Analysis: EFA was carried out using principal component analysis with orthogonal (varimax rotation. Internal consistency of the Hindi version of the scale was estimated in the form of Cronbach's alpha. Spearman–Brown coefficient and Guttman split-half coefficient were calculated to evaluate the split-half reliability. Results: The initial factor analysis yielded three-factor models with an eigenvalue of >1 and the total variance explained by these factors was 62.017%. The internal consistency of the 16-item scale was 0
Gabriel, Elke; Gopalakrishnan, Jay
The restricted availability of suitable in vitro models that can reliably represent complex human brain development is a significant bottleneck that limits the translation of basic brain research into clinical application. While induced pluripotent stem cells (iPSCs) have replaced the ethically questionable human embryonic stem cells, iPSC-based neuronal differentiation studies remain descriptive at the cellular level but fail to adequately provide the details that could be derived from a complex, 3D human brain tissue. This gap is now filled through the application of iPSC-derived, 3D brain organoids, "Brains in a dish," that model many features of complex human brain development. Here, a method for generating iPSC-derived, 3D brain organoids is described. The organoids can help with modeling autosomal recessive primary microcephaly (MCPH), a rare human neurodevelopmental disorder. A widely accepted explanation for the brain malformation in MCPH is a depletion of the neural stem cell pool during the early stages of human brain development, a developmental defect that is difficult to recreate or prove in vitro. To study MCPH, we generated iPSCs from patient-derived fibroblasts carrying a mutation in the centrosomal protein CPAP. By analyzing the ventricular zone of microcephaly 3D brain organoids, we showed the premature differentiation of neural progenitors. These 3D brain organoids are a powerful in vitro system that will be instrumental in modeling congenital brain disorders induced by neurotoxic chemicals, neurotrophic viral infections, or inherited genetic mutations.
Harvey, Louise; Boksa, Patricia
Epidemiological evidence has established links between immune activation during the prenatal or early postnatal period and increased risk of developing a range of neurodevelopment disorders in later life. Animal models have been used to great effect to explore the ramifications of immune activation during gestation and neonatal life. A range of behavioral, neurochemical, molecular, and structural outcome measures associated with schizophrenia, autism, cerebral palsy, and epilepsy have been assessed in models of prenatal and postnatal immune activation. However, the epidemiology-driven disease-first approach taken by some studies can be limiting and, despite the wealth of data, there is a lack of consensus in the literature as to the specific dose, timing, and nature of the immunogen that results in replicable and reproducible changes related to a single disease phenotype. In this review, we highlight a number of similarities and differences in models of prenatal and postnatal immune activation currently being used to investigate the origins of schizophrenia, autism, cerebral palsy, epilepsy, and Parkinson's disease. However, we describe a lack of synthesis not only between but also within disease-specific models. Our inability to compare the equivalency dose of immunogen used is identified as a significant yet easily remedied problem. We ask whether early life exposure to infection should be described as a disease-specific or general vulnerability factor for neurodevelopmental disorders and discuss the implications that either classification has on the design, strengths and limitations of future experiments. Copyright © 2012 Wiley Periodicals, Inc.
Full Text Available Brain function and behaviour undergo significant plasticity and refinement, particularly during specific critical and sensitive periods. In autistic and intellectual disability neurodevelopmental disorders (NDDs and their corresponding genetic mouse models, impairments in many neuronal and behavioural phenotypes are temporally regulated and in some cases, transient. However, the links between neurobiological mechanisms governing typically normal brain and behavioural development (referred to also as ‘neurotypical’ development and timing of NDD impairments are not fully investigated.This perspective highlights temporal patterns of synaptic and neuronal impairment, with a restricted focus on autism and intellectual disability types of NDDs. Given the varying known genetic and environmental causes for NDDs, this perspective proposes two strategies for investigation: (1 a focus on neurobiological mechanisms underlying known critical periods in the (typically normal-developing brain (2 investigation of spatio-temporal expression profiles of genes implicated in monogenic syndromes throughout affected brain regions.This approach may help explain why many NDDs with differing genetic causes can result in overlapping phenotypes at similar developmental stages and better predict vulnerable periods within these disorders, with implications for both therapeutic rescue and ultimately, prevention.
Full Text Available Insulin-Like Growth Factor 1 (IGF-1 is a neurotrophic polypeptide with crucial roles to play in Central Nervous System (CNS growth, development and maturation. Following interrogation of the neurobiology underlying several neurodevelopmental disorders and Autism Spectrum Disorders (ASD, both recombinant IGF-1 (mecasermin and related derivatives, such as (1-3 IGF-1, have emerged as potential therapeutic approaches. Clinical pilot studies and early reports have supported the safety/preliminary efficacy of IGF-1 and related compounds in the treatment of Rett Syndrome, with evidence mounting for its use in Phelan McDermid Syndrome and Fragile X Syndrome. In broader ASD, clinical trials are ongoing. Here, we review the role of IGF-1 in the molecular etiologies of these conditions in addition to the accumulating evidence from early clinical studies highlighting the possibility of IGF-1 and related compounds as potential treatments for these childhood-onset neurodevelopmental disorders.
Susie Ruth Berkowicz
Full Text Available Background: Brinps 1 – 3, and Astrotactins (Astn 1 and 2, are members of the Membrane Attack Complex / Perforin (MACPF superfamily that are predominantly expressed in the mammalian brain during development. Genetic variation at the human BRINP2/ASTN1 and BRINP1/ASTN2 loci has been implicated in neurodevelopmental disorders. We, and others, have previously shown that Brinp1-/- mice exhibit behaviour reminiscent of autism spectrum disorder (ASD and attention deficit hyperactivity disorder (ADHD.Method: We created Brinp2-/- mice and Brinp3-/- mice via the Cre-mediated LoxP system to investigate the effect of gene deletion on anatomy and behaviour. Additionally, Brinp2-/-Brinp3-/- double knock-out mice were generated by interbreeding Brinp2-/- and Brinp3-/- mice. Genomic validation was carried out for each knock-out line, followed by histological, weight and behavioural examination. Brinp1-/-Brinp2-/-Brinp3-/- triple knock-out mice were also generated by crossing Brinp2/3 double knock-out mice with previously generated Brinp1-/- mice, and examined by weight and histological analysis.Results: Brinp2-/- and Brinp3-/- mice differ in their behaviour: Brinp2-/- mice are hyperactive, whereas Brinp3-/- mice exhibit marked changes in anxiety-response on the elevated plus maze. Brinp3-/- mice also show evidence of altered sociability. Both Brinp2-/- and Brinp3-/- mice have normal short-term memory, olfactory responses, pre-pulse inhibition and motor learning. The double knock-out mice show behaviours of Brinp2-/- and Brinp3-/- mice, without evidence of new or exacerbated phenotypes. Conclusion: Brinp3 is important in moderation of anxiety, with potential relevance to anxiety disorders. Brinp2 dysfunction resulting in hyperactivity may be relevant to the association of ADHD with chromosome locus 1q25.2. Brinp2-/- and Brinp3-/- genes do not compensate in the mammalian brain and likely have distinct molecular or cell-type specific functions.
Full Text Available BackgroundEarly detection of movement deficits during step initiation will facilitate the selection of the optimal physiotherapy management strategy. The main aim of the study was to assess potential differences in step initiation between 5- and 6-year-old children with faulty posture who had been diagnosed with neurodevelopmental disorders during infancy and healthy children.MethodsThe experimental group consisted of 19 children aged 5–6 years with faulty posture, who had been diagnosed with neurodevelopmental disorders during infancy and were given physiotherapy in the first year of their lives. The control group comprised 19 nursery school children aged 5–6 years with no postural defects, no history of postural control or movement deficits, and no physiotherapy interventions in the first year of their lives. Step initiation was performed on force platforms under various conditions, i.e., with and without an obstacle, stepping up onto a platform placed at a higher level, stepping down onto a platform placed on a lower level. The recording of center of foot pressure (COP displacements was divided into three phases: phase 1 (P1—quiet standing before step initiation, phase 2 (P2—transit, phase 3 (P3—quiet standing until measurement completion.ResultsThe Tukey post hoc test showed that the means of sway range (raCOP and mean velocity (vCOP in sagittal (AP plane for phase 1 and vCOP in frontal (ML plane for phase 3 registered in the step-up trial were significantly higher (p < 0.05 in children with faulty posture compared to children with typical development. P1vCOPML, P3vCOPAP, P3raCOPML, and P3vCOPMLof the step-down trial were also significantly higher in children with faulty posture (p < 0.05.ConclusionInclusion of functional movement exercises (stair-walking tasks in physiotherapy interventions for children with postural defects seems well justified.The trial was registered in the Australian and New Zealand Clinical Trials
Arim, Rubab G; Kohen, Dafna E; Garner, Rochelle E; Lach, Lucyna M; Brehaut, Jamie C; MacKenzie, Michael J; Rosenbaum, Peter L
This study examines psychosocial functioning in children with neurodevelopmental disorders (NDDs) and/or externalizing behavior problems (EBPs) as compared to children with neither condition. The longitudinal sample, drawn from the Canadian National Longitudinal Survey of Children and Youth, included children who were 6 to 9 years old in Cycle 1 who were followed-up biennially in Cycles 2 and 3 (N = 3476). The associations between NDDs and/or EBPs, child and family socio-demographic characteristics and parenting behaviors (consistency and ineffective parenting), were examined across several measures of child psychosocial functioning: peer relationships, general self-esteem, prosocial behavior and anxiety-emotional problems. Children with NDDs, EBPs, and both NDDs and EBPs self-reported lower scores on general self-esteem. Children with NDDs and both NDDs and EBPs reported lower scores on peer relationships and prosocial behavior. Lastly, children with both NDDs and EBPs self-reported higher scores on anxiety-emotional behaviors. After considering family socio-demographic characteristics and parenting behaviors, these differences remained statistically significant only for children with both NDDs and EBPs. Child age and gender, household income and parenting behaviors were important in explaining these associations. Psychosocial functioning differs for children with NDDs and/or EBPs. Children with both NDDs and EBPs appear to report poorer psychosocial functioning compared to their peers with neither condition. However, it is important to consider the context of socio-demographic characteristics, parenting behaviors and their interactions to understand differences in children's psychosocial functioning. Implication for Rehabilitation: Practitioners may wish to consider complexity in child health by examining a comprehensive set of determinants of psychosocial outcomes as well as comorbid conditions, such as neurodevelopmental disorders (NDDs) and externalizing
Full Text Available AGAP1 is an Arf1 GTPase activating protein that interacts with the vesicle-associated protein complexes adaptor protein 3 (AP-3 and Biogenesis of Lysosome Related Organelles Complex-1 (BLOC-1. Overexpression of AGAP1 in non-neuronal cells results in an accumulation of endosomal cargoes, which suggests a role in endosome-dependent traffic. In addition, AGAP1 is a candidate susceptibility gene for two neurodevelopmental disorders, autism spectrum disorder (ASD and schizophrenia (SZ; yet its localization and function in neurons have not been described. Here, we describe that AGAP1 localizes to axons, dendrites, dendritic spines, and synapses, colocalizing preferentially with markers of early and recycling endosomes. Functional studies reveal overexpression and down-regulation of AGAP1 affects both neuronal endosomal trafficking and dendritic spine morphology, supporting a role for AGAP1 in the recycling endosomal trafficking involved in their morphogenesis. Finally, we determined the sensitivity of AGAP1 expression to mutations in the DTNBP1 gene, which is associated with neurodevelopmental disorder, and found that AGAP1 mRNA and protein levels are selectively reduced in the null allele of the mouse orthologue of DTNBP1. We postulate that endosomal trafficking contributes to the pathogenesis of neurodevelopmental disorders affecting dendritic spine morphology, and thus excitatory synapse structure and function.
Full Text Available Empirical evidence indicates that sleep spindles facilitate neuroplasticity and “off-line” processing during sleep, which supports learning, memory consolidation, and intellectual performance. Children with neurodevelopmental disorders (NDDs exhibit characteristics that may increase both the risk for and vulnerability to abnormal spindle generation. Despite the high prevalence of sleep problems and cognitive deficits in children with NDD, only a few studies have examined the putative association between spindle characteristics and cognitive function. This paper reviews the literature regarding sleep spindle characteristics in children with NDD and their relation to cognition in light of what is known in typically developing children and based on the available evidence regarding children with NDD. We integrate available data, identify gaps in understanding, and recommend future research directions. Collectively, studies are limited by small sample sizes, heterogeneous populations with multiple comorbidities, and nonstandardized methods for collecting and analyzing findings. These limitations notwithstanding, the evidence suggests that future studies should examine associations between sleep spindle characteristics and cognitive function in children with and without NDD, and preliminary findings raise the intriguing question of whether enhancement or manipulation of sleep spindles could improve sleep-dependent memory and other aspects of cognitive function in this population.
William B. Grant
Full Text Available People with neurodevelopmental disorders and intellectual disabilities have much greater health care needs. Mainly staying indoors, such people generally have low 25-hydroxyvitamin D (25(OHD concentrations. The Vitamin D Task Force of the American Academy of Developmental Medicine and Dentistry (AADMD reviewed the evidence of 25(OHD concentrations that benefit the health of persons with developmental disabilities. Maintaining recommended optimal serum 25(OHD concentrations year long will benefit skeletal development in infants, children, and adolescents, and benefit musculoskeletal health and neuromuscular coordination in adult patients, and decrease risk of falls. Maintaining optimal concentrations decreases risks and severities of autoimmune diseases, cardiovascular disease, many types of cancer, dementia, types 1 and 2 diabetes mellitus, and respiratory tract infections. Other benefits include improved dental and oral health and improved physical performance. The Task Force recommends that 25(OHD concentrations for optimal health to be in the range of 75 to 125 nmol/L, which can be achieved using between 800 and 4000 IU/day vitamin D3 and sensible exposure to solar UVB radiation. The paper also discusses the potential risks of higher 25(OHD concentrations, the evidence from and limitations of randomized controlled trials, and the recommendations by various groups and agencies.
Hori, Ikumi; Otomo, Takanobu; Nakashima, Mitsuko; Miya, Fuyuki; Negishi, Yutaka; Shiraishi, Hideaki; Nonoda, Yutaka; Magara, Shinichi; Tohyama, Jun; Okamoto, Nobuhiko; Kumagai, Takeshi; Shimoda, Konomi; Yukitake, Yoshiya; Kajikawa, Daigo; Morio, Tomohiro; Hattori, Ayako; Nakagawa, Motoo; Ando, Naoki; Nishino, Ichizo; Kato, Mitsuhiro; Tsunoda, Tatsuhiko; Saitsu, Hirotomo; Kanemura, Yonehiro; Yamasaki, Mami; Kosaki, Kenjiro; Matsumoto, Naomichi; Yoshimori, Tamotsu; Saitoh, Shinji
Vici syndrome (VICIS) is a rare, autosomal recessive neurodevelopmental disorder with multisystem involvement characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency, developmental delay, and hypopigmentation. Mutations in EPG5, a gene that encodes a key autophagy regulator, have been shown to cause VICIS, however, the precise pathomechanism underlying VICIS is yet to be clarified. Here, we describe detailed clinical (including brain MRI and muscle biopsy) and genetic features of nine Japanese patients with VICIS. Genetic dissection of these nine patients from seven families identified 14 causative mutations in EPG5. These included five nonsense, two frameshift, three splicing, one missense, and one multi-exon deletion mutations, and two initiation codon variants. Furthermore, cultured skin fibroblasts (SFs) from two affected patients demonstrated partial autophagic dysfunction. To investigate the function of EPG5, siRNA based EPG5 knock-down, and CRISPR/Cas9 mediated EPG5 knock-out HeLa cells were generated. EPG5-depleted cells exhibited a complete block of autophagic flux caused by defective autophagosome-lysosome fusion. Unexpectedly, endocytic degradation was normal in both VICIS SFs and EPG5 depleted cells, suggesting that EPG5 function is limited to the regulation of autophagosome-lysosome fusion.
Grant, William B; Wimalawansa, Sunil J; Holick, Michael F; Cannell, John J; Pludowski, Pawel; Lappe, Joan M; Pittaway, Mary; May, Philip
People with neurodevelopmental disorders and intellectual disabilities have much greater health care needs. Mainly staying indoors, such people generally have low 25-hydroxyvitamin D (25(OH)D) concentrations. The Vitamin D Task Force of the American Academy of Developmental Medicine and Dentistry (AADMD) reviewed the evidence of 25(OH)D concentrations that benefit the health of persons with developmental disabilities. Maintaining recommended optimal serum 25(OH)D concentrations year long will benefit skeletal development in infants, children, and adolescents, and benefit musculoskeletal health and neuromuscular coordination in adult patients, and decrease risk of falls. Maintaining optimal concentrations decreases risks and severities of autoimmune diseases, cardiovascular disease, many types of cancer, dementia, types 1 and 2 diabetes mellitus, and respiratory tract infections. Other benefits include improved dental and oral health and improved physical performance. The Task Force recommends that 25(OH)D concentrations for optimal health to be in the range of 75 to 125 nmol/L, which can be achieved using between 800 and 4000 IU/day vitamin D3 and sensible exposure to solar UVB radiation. The paper also discusses the potential risks of higher 25(OH)D concentrations, the evidence from and limitations of randomized controlled trials, and the recommendations by various groups and agencies.
Grant, William B.; Wimalawansa, Sunil J.; Holick, Michael F.; Cannell, John J.; Pludowski, Pawel; Lappe, Joan M.; Pittaway, Mary; May, Philip
People with neurodevelopmental disorders and intellectual disabilities have much greater health care needs. Mainly staying indoors, such people generally have low 25-hydroxyvitamin D (25(OH)D) concentrations. The Vitamin D Task Force of the American Academy of Developmental Medicine and Dentistry (AADMD) reviewed the evidence of 25(OH)D concentrations that benefit the health of persons with developmental disabilities. Maintaining recommended optimal serum 25(OH)D concentrations year long will benefit skeletal development in infants, children, and adolescents, and benefit musculoskeletal health and neuromuscular coordination in adult patients, and decrease risk of falls. Maintaining optimal concentrations decreases risks and severities of autoimmune diseases, cardiovascular disease, many types of cancer, dementia, types 1 and 2 diabetes mellitus, and respiratory tract infections. Other benefits include improved dental and oral health and improved physical performance. The Task Force recommends that 25(OH)D concentrations for optimal health to be in the range of 75 to 125 nmol/L, which can be achieved using between 800 and 4000 IU/day vitamin D3 and sensible exposure to solar UVB radiation. The paper also discusses the potential risks of higher 25(OH)D concentrations, the evidence from and limitations of randomized controlled trials, and the recommendations by various groups and agencies. PMID:25734565
Andrew T Olagunju
Full Text Available Background: Children with neurodevelopmental disorders (CNDs are a group requiring more attention as their care is often challenging, particularly for parents with primary caregiving roles in resource-restricted settings. This study had set out to investigate the burden and psychological distress among caregivers of children with neurodevelopmental delays. Materials and Methods: A total of 68 caregivers were recruited during the 2013 annual autism health program organized by the College of Medicine, University of Lagos in collaboration with Guaranty Trust Bank, Nigeria and Blazing Trails, USA. Of these caregivers, 60 respondents (caregivers and children were included in the final analyses due to poorly completed questionnaires. The Zarit Caregivers Burden Scale (ZCBS and General Health Questionnaire version 12 (GHQ-12 were administered to elicit caregivers' experience with respect to burden and psychological distress, respectively. Results: Of the 60 participants included in the final analyses, the majority constituted parents (96.3% with mothers accounting for 71.7%; 28 (46.7% participants were government workers and 3 (5% were full-time housewives. The mean age of CNDs was 6.8 (±3.2 years, and 33 (55.0% were males. Delivery by cesarian section was reported in 19 (31.8%. The common presenting complaints by caregivers were inability to walk (32.7%, repetitive behavior (25.5%, difficulty with verbal communication (10.9%, nonsocialization (9.1%, seizures (9.1%, and hyperactivity (3.6%. Problems were noticed at ≤ 1 year in 46.7% while they were noticed after 2 years in more than half the children, and a little above one-eighth (14% had siblings with similar problems. On the ZCBS, nine (15.0% caregivers reported a significant burden. In addition, 23 (38.3% caregivers had psychological distress. Caregivers' burden was significantly related to the report of psychological distress in caregivers (P < 0.001 and there was a trend toward the presence of
Erdodi, Laszlo; Lajiness-O'Neill, Renee; Schmitt, Thomas A.
Visual and auditory verbal learning using a selective reminding format was studied in a mixed clinical sample of children with autism spectrum disorder (ASD) (n = 42), attention-deficit hyperactivity disorder (n = 83), velocardiofacial syndrome (n = 17) and neurotypicals (n = 38) using the Test of Memory and Learning to (1) more thoroughly…
Sun, Jing; Buys, Nicholas
The purpose of this study is to examine the association of deficits of executive function (EF) and neurodevelopmental disorders in preterm children and the potential of assessing EF in infants as means of early identification. EF refers to a collection of related but somewhat discrete abilities, the main ones being working memory, inhibition, and planning. There is a general consensus that EF governs goal-directed behavior that requires holding those plans or programs on-line until executed, inhibiting irrelevant action and planning a sequence of actions. EF plays an essential role in cognitive development and is vital to individual social and intellectual success. Most researchers believe in the coordination and integrate cognitive-perceptual processes in relation to time and space, thus regulating higher-order cognitive processes, such as problem solving, reasoning, logical and flexible thinking, and decision-making. The importance of the maturation of the frontal lobe, particularly the prefrontal cortex, to the development of EF in childhood has been emphasized. Therefore, any abnormal development in the prefrontal lobes of infants and children could be expected to result in significant deficits in cognitive functioning. As this is a late-maturing part of the brain, various neurodevelopmental disorders, such as autism spectrum disorders, attention deficit hyperactivity disorder, language disorders, and schizophrenia, as well as acquired disorders of the right brain (and traumatic brain injury) impair EF, and the prefrontal cortex may be particularly susceptible to delayed development in these populations. The deficits of EF in infants are persistent into childhood and related to neurodevelopmental disorders in childhood and adolescence.
Sugranyes, Gisela; de la Serna, Elena; Borras, Roger; Sanchez-Gistau, Vanessa; Pariente, Jose C; Romero, Soledad; Baeza, Inmaculada; Díaz-Caneja, Covadonga M; Rodriguez-Toscano, Elisa; Moreno, Carmen; Bernardo, Miguel; Moreno, Dolores; Vieta, Eduard; Castro-Fornieles, Josefina
Studies in child and adolescent offspring of patients with schizophrenia or bipolar disorders may help understand the influence of neurodevelopmental factors on the premorbid phenotype of these disorders. To assess whether a combination of neurodevelopmental factors discriminates between young offspring of patients with schizophrenia (SzO) or bipolar disorder (BpO) and community controls (CcO). To assess the association between these factors and rates of psychiatric diagnoses in high risk (HR) youth. One hundred thirty-three HR offspring (47 SzO and 86 BpO) and 84 CcO, aged 6-17, underwent cross-sectional clinical, neurocognitive, and structural neuroimaging assessment. Information on perinatal events and early childhood development was also obtained. General linear mixed models were performed to assess group discrimination and association with lifetime axis I psychiatric disorders. Multivariate analyses revealed that greater neurological soft signs (NSS), less total grey matter volume (GMV) and a higher frequency of obstetric complications discriminated HR offspring from CcO. When comparing each group individually, greater NSS and a higher frequency of obstetric complications discriminated SzO from CcO, and BpO from CcO, while lower intelligence also discriminated SzO from CcO and from BpO. Within HR offspring, lower intelligence and less total GMV were associated with lifetime incidence of psychiatric disorders. Both SzO and BpO showed evidence of neurodevelopmental insult, although this may have a greater impact in SzO. Lower intelligence and less total GMV hold potential as biomarkers of risk for psychiatric disorders in HR youth.
Ravi Philip Rajkumar
Full Text Available Gender identity disorder (GID, recently renamed gender dysphoria (GD, is a rare condition characterized by an incongruity between gender identity and biological sex. Clinical evidence suggests that schizophrenia occurs in patients with GID at rates higher than in the general population and that patients with GID may have schizophrenia-like personality traits. Conversely, patients with schizophrenia may experience alterations in gender identity and gender role perception. Neurobiological research, including brain imaging and studies of finger length ratio and handedness, suggests that both these disorders are associated with altered cerebral sexual dimorphism and changes in cerebral lateralization. Various mechanisms, such as Toxoplasma infection, reduced levels of brain-derived neurotrophic factor (BDNF, early childhood adversity, and links with autism spectrum disorders, may account for some of this overlap. The implications of this association for further research are discussed.
Rajkumar, Ravi Philip
Gender identity disorder (GID), recently renamed gender dysphoria (GD), is a rare condition characterized by an incongruity between gender identity and biological sex. Clinical evidence suggests that schizophrenia occurs in patients with GID at rates higher than in the general population and that patients with GID may have schizophrenia-like personality traits. Conversely, patients with schizophrenia may experience alterations in gender identity and gender role perception. Neurobiological research, including brain imaging and studies of finger length ratio and handedness, suggests that both these disorders are associated with altered cerebral sexual dimorphism and changes in cerebral lateralization. Various mechanisms, such as Toxoplasma infection, reduced levels of brain-derived neurotrophic factor (BDNF), early childhood adversity, and links with autism spectrum disorders, may account for some of this overlap. The implications of this association for further research are discussed. PMID:25548672
Rajkumar, Ravi Philip
Gender identity disorder (GID), recently renamed gender dysphoria (GD), is a rare condition characterized by an incongruity between gender identity and biological sex. Clinical evidence suggests that schizophrenia occurs in patients with GID at rates higher than in the general population and that patients with GID may have schizophrenia-like personality traits. Conversely, patients with schizophrenia may experience alterations in gender identity and gender role perception. Neurobiological research, including brain imaging and studies of finger length ratio and handedness, suggests that both these disorders are associated with altered cerebral sexual dimorphism and changes in cerebral lateralization. Various mechanisms, such as Toxoplasma infection, reduced levels of brain-derived neurotrophic factor (BDNF), early childhood adversity, and links with autism spectrum disorders, may account for some of this overlap. The implications of this association for further research are discussed.
Hannigan, J H; Berman, R F
Fetal alcohol syndrome (FAS) and alcohol-related neurodevelopmental disorders (ARNDs) in children are characterized by life-long compromises in learning, memory, and adaptive responses. Until the advent of effective prevention measures, it will remain necessary to seek ways to treat the life-long neurobehavioral consequences of prenatal alcohol exposure. To date, there are no clinical remedies to recommend for either specific or global fetal alcohol effects. This article reviews our basic research in animal models that assesses the potential of global environmental manipulations or specific psychopharmacological treatments to ameliorate the neurobehavioral effects of prenatal exposure to alcohol. Postweaning environmental enrichment can improve behavioral performance and ameliorate or even eliminate deficits in prenatal alcohol-exposed rats, although there is persistent impairment in neuronal plasticity, as indicated by the failure of hippocampal pyramidal cells to increase dendrite spine density. Behavioral and neural responses to CNS stimulants differ in rats exposed prenatally to alcohol, although it is not clear that these shifts in dose-response curves would predict benefit to children. Although the present results may sound a note of optimism for the development of effective treatment strategies for children with FAS or ARNDs, it is important to consider that application of these findings in rodents may not be straightforward. We also need to know the critical features of specific environments that influence brain development, and the limits of pharmacotherapy, as well as critical periods of exposure. Continued study of the beneficial, ameliorative effects of environmental enrichment, rehabilitative training, and of pharmacological therapies in animal models, will remain a valuable source of information for eventually devising treatments specific for children with FAS and ARNDs.
Khandaker, Golam M.; Stochl, Jan; Zammit, Stanley; Lewis, Glyn; Jones, Peter B
Background Schizophrenia has a neurodevelopmental component to its origin, and may share overlapping pathogenic mechanisms with childhood neurodevelopmental disorders (ND). Yet longitudinal studies of psychotic outcomes among individuals with ND are limited. We report a population-based prospective study of six common childhood ND, subsequent neurocognitive performance and the risk of psychotic experiences (PEs) in early adolescence. Methods PEs were assessed by semi-structured interviews at age 13 years. IQ and working memory were measured between ages 9 and 11 years. The presence of six neurodevelopmental disorders (autism spectrum, dyslexia, dyspraxia, dysgraphia, dysorthographia, dyscalculia) was determined from parent-completed questionnaire at age 9 years. Linear regression calculated mean difference in cognitive scores between those with and without ND. The association between ND and PEs was expressed as odds ratio (OR); effects of cognitive deficits were examined. Potential confounders included age, gender, father’s social class, ethnicity and maternal education. Results Out of 8,220 children, 487 (5.9%) were reported to have ND at age 9 years. Children with, compared with those without ND performed worse on all cognitive measures; adjusted mean difference in total IQ 6.84 (95% CI 5.00- 8.69). The association between total IQ and ND was linear (p<0.0001). The risk of PEs was higher in those with, compared with those without ND; adjusted OR for definite PEs 1.76 (95% CI 1.11- 2.79). IQ (but not working memory) deficit partly explained this association. Conclusion Higher risk of PEs in early adolescence among individuals with childhood ND is consistent with the neurodevelopmental hypothesis of schizophrenia. PMID:25066026
Gettings, Sheryl; Franco, Fabia; Santosh, Paramala J
Siblings of children with chronic illness and disabilities are at increased risk of negative psychological effects. Support groups enable them to access psycho-education and social support. Barriers to this can include the distance they have to travel to meet face-to-face. Audio-conferencing, whereby three or more people can connect by telephone in different locations, is an efficient means of groups meeting and warrants exploration in this healthcare context. This study explored the feasibility of audio-conferencing as a method of facilitating sibling support groups. A longitudinal design was adopted. Participants were six siblings (aged eight to thirteen years) and parents of children with complex neurodevelopmental disorders attending the Centre for Interventional Paediatric Psychopharmacology (CIPP). Four of the eight one-hour weekly sessions were held face-to-face and the other four using audio-conferencing. Pre- and post-intervention questionnaires and interviews were completed and three to six month follow-up interviews were carried out. The sessions were audio-recorded, transcribed and thematic analysis was undertaken. Audio-conferencing as a form of telemedicine was acceptable to all six participants and was effective in facilitating sibling support groups. Audio-conferencing can overcome geographical barriers to children being able to receive group therapeutic healthcare interventions such as social support and psycho-education. Psychopathology ratings increased post-intervention in some participants. Siblings reported that communication between siblings and their family members increased and siblings' social network widened. Audio-conferencing is an acceptable, feasible and effective method of facilitating sibling support groups. Siblings' clear accounts of neuropsychiatric symptoms render them reliable informants. Systematic assessment of siblings' needs and strengthened links between Child and Adolescent Mental Health Services, school counsellors and
Weaving, Linda S.; Christodoulou, John; Williamson, Sarah L.; Friend, Kathie L.; McKenzie, Olivia L. D.; Archer, Hayley; Evans, Julie; Clarke, Angus; Pelka, Gregory J.; Tam, Patrick P. L.; Watson, Catherine; Lahooti, Hooshang; Ellaway, Carolyn J.; Bennetts, Bruce; Leonard, Helen; Gécz, Jozef
Rett syndrome (RTT) is a severe neurodevelopmental disorder caused, in most classic cases, by mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2). A large degree of phenotypic variation has been observed in patients with RTT, both those with and without MECP2 mutations. We describe a family consisting of a proband with a phenotype that showed considerable overlap with that of RTT, her identical twin sister with autistic disorder and mild-to-moderate intellectual disability, and a brother with profound intellectual disability and seizures. No pathogenic MECP2 mutations were found in this family, and the Xq28 region that contains the MECP2 gene was not shared by the affected siblings. Three other candidate regions were identified by microsatellite mapping, including 10.3 Mb at Xp22.31-pter between Xpter and DXS1135, 19.7 Mb at Xp22.12-p22.11 between DXS1135 and DXS1214, and 16.4 Mb at Xq21.33 between DXS1196 and DXS1191. The ARX and CDKL5 genes, both of which are located within the Xp22 region, were sequenced in the affected family members, and a deletion of nucleotide 183 of the coding sequence (c.183delT) was identified in CDKL5 in the affected family members. In a screen of 44 RTT cases, a single splice-site mutation, IVS13-1G→A, was identified in a girl with a severe phenotype overlapping RTT. In the mouse brain, Cdkl5 expression overlaps—but is not identical to—that of Mecp2, and its expression is unaffected by the loss of Mecp2. These findings confirm CDKL5 as another locus associated with epilepsy and X-linked mental retardation. These results also suggest that mutations in CDKL5 can lead to a clinical phenotype that overlaps RTT. However, it remains to be determined whether CDKL5 mutations are more prevalent in specific clinical subgroups of RTT or in other clinical presentations. PMID:15492925
Khandaker, G M; Stochl, J; Zammit, S; Lewis, G; Jones, P B
Schizophrenia has a neurodevelopmental component to its origin, and may share overlapping pathogenic mechanisms with childhood neurodevelopmental disorders (NDs). Nevertheless, longitudinal studies of psychotic outcomes among individuals with NDs are limited. We report a population-based prospective study of six common childhood NDs, subsequent neurocognitive performance and the risk of psychotic experiences (PEs) in early adolescence. PEs were assessed by semi-structured interviews at age 13 years. IQ and working memory were measured between ages 9 and 11 years. The presence of six NDs (autism spectrum, dyslexia, dyspraxia, dysgraphia, dysorthographia, dyscalculia) was determined from parent-completed questionnaires at age 9 years. Linear regression calculated the mean difference in cognitive scores between children with and without NDs. Associations between NDs and PEs were expressed as odds ratios (ORs) with 95% confidence intervals (CIs); effects of cognitive deficits were examined. Potential confounders included age, gender, father's social class, ethnicity and maternal education. Out of 8220 children, 487 (5.9%) were reported to have NDs at age 9 years. Children with, compared with those without, NDs performed worse on all cognitive measures; the adjusted mean difference in total IQ was 6.84 (95% CI 5.00-8.69). The association between total IQ and NDs was linear (p memory) deficit partly explained this association. Higher risk of PEs in early adolescence among individuals with childhood ND is consistent with the neurodevelopmental hypothesis of schizophrenia.
Dan, Bernard; Pelc, Karine; de Meirleir, Linda; Cheron, Guy
Careful study of the phenotype can have implications at several levels, namely clinical diagnosis, pathophysiological reasoning, management planning, and outcome measurement. Behavioural phenotypes involve cognition, communication, social skills, and motor control. They can be documented in a host of neurodevelopmental conditions and approached with the recently refined perception-action-cognition-environment (PACE) paradigm, which focuses on the neurodevelopmental processes that underlie learning and adaption to the environment through perception, action, and cognitive processing. Although this paradigm was originally developed in the context of cerebral palsy, it can be applied along developmental trajectories in several neurogenetic conditions, including Down syndrome, fragile X syndrome, Rett syndrome, Angelman syndrome, and Williams syndrome, to name but a few. It must be recognized, however, that relevant, valid tools for assessment and management strategies still need to be developed. © 2015 The Authors. Developmental Medicine & Child Neurology © 2015 Mac Keith Press.
Full Text Available Over the past 30 years, preterm births have drastically increased and today represent 12.5% of total births. About 1.2% of preterm births characterize very preterm births (GA<32weeks that, with very low birth weight (BW<1500grams, are constantly found as risk factors of unfavourable neurological outcomes in longitudinal follow up studies. Actually, also “late preterm” children (preterm born from 33 to 36 weeks of gestational age, normally considered at low risk for neurodevelopmental disabilities, are supposed to represent a population of children to be monitored. Previous findings of a general cognitive impairment in children born preterm have gradually addressed the assessment of more specific neuropsychological skills and pointed out the importance to follow these children up to adolescent age. The neuroanatomical prerequisite of an abnormality in frontal lobe development and the correlation with various neuropsychological dysfunctions (fine and gross motor disabilities, executive function and working memory deficits, visual-constructional and attentional dysfunctions underline the interference of preterm birth with normal brain maturational phases. Though showing more demanding neurodevelopmental pathways than term peers, a large number of preterm children tend to functionally normalize in adolescence. The review supports the hypothesis of a neurodevelopmental model that can be at risk to influence dysfunctional neuropsychological outcome.
Andersen, Stine Linding; Carlé, Allan; Karmisholt, Jesper; Pedersen, Inge Bülow; Andersen, Stig
Fetal programming is a long-standing, but still evolving, concept that links exposures during pregnancy to the later development of disease in the offspring. A fetal programming effect has been considered within different endocrine axes and in relation to different maternal endocrine diseases. In this critical review, we describe and discuss the hypothesis of fetal programming by maternal thyroid dysfunction in the context of fetal brain development and neurodevelopmental disorders in the offspring. Thyroid hormones are important regulators of early brain development, and evidence from experimental and observational human studies have demonstrated structural and functional abnormalities in the brain caused by the lack or excess of thyroid hormone during fetal brain development. The hypothesis that such abnormalities introduced during early fetal brain development increase susceptibility for the later onset of neurodevelopmental disorders in the offspring is biologically plausible. However, epidemiological studies on the association between maternal thyroid dysfunction and long-term child outcomes are observational in design, and are challenged by important methodological aspects. © 2017 European Society of Endocrinology.
Rasmussen, Malene B; Nielsen, Jakob V; Lourenço, Charles M; Melo, Joana B; Halgren, Christina; Geraldi, Camila V L; Marques, Wilson; Rodrigues, Guilherme R; Thomassen, Mads; Bak, Mads; Hansen, Claus; Ferreira, Susana I; Venâncio, Margarida; Henriksen, Karen F; Lind-Thomsen, Allan; Carreira, Isabel M; Jensen, Niels A; Tommerup, Niels
Recently, a number of patients have been described with structural rearrangements at 3q13.31, delineating a novel microdeletion syndrome with common clinical features including developmental delay and other neurodevelopmental disorders (NDD). A smallest region of overlapping deletions (SRO) involved five RefSeq genes, including the transcription factor gene ZBTB20 and the dopamine receptor gene DRD3, considered as candidate genes for the syndrome. We used array comparative genomic hybridization and next-generation mate-pair sequencing to identify key structural rearrangements involving ZBTB20 in two patients with NDD. In a patient with developmental delay, attention-deficit hyperactivity disorder, psychosis, Tourette's syndrome and autistic traits, a de novo balanced t(3;18) translocation truncated ZBTB20. The other breakpoint did not disrupt any gene. In a second patient with developmental delay and autism, we detected the first microdeletion at 3q13.31, which truncated ZBTB20 but did not involve DRD3 or the other genes within the previously defined SRO. Zbtb20 directly represses 346 genes in the developing murine brain. Of the 342 human orthologous ZBTB20 candidate target genes, we found 68 associated with NDD. Using chromatin immunoprecipitation and quantitative PCR, we validated the in vivo binding of Zbtb20 in evolutionary conserved regions in six of these genes (Cntn4, Gad1, Nrxn1, Nrxn3, Scn2a, Snap25). Our study links dosage imbalance of ZBTB20 to a range of neurodevelopmental, cognitive and psychiatric disorders, likely mediated by dysregulation of multiple ZBTB20 target genes, and provides new knowledge on the genetic background of the NDD seen in the 3q13.31 microdeletion syndrome. 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.
Full Text Available The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic cues play important roles in shaping and wiring neural connections. The perinatal period constitutes a critical time in central nervous system development with extensive refinement of neural connections, which are highly sensitive to fetal and neonatal compromise, such as inflammatory challenges. Emerging evidence suggests that inflammatory cells in the brain such as microglia and astrocytes are pivotal in regulating synaptic structure and function. In this article, we will review the role of glia cells in synaptic physiology and pathophysiology, including microglia-mediated elimination of synapses. We propose that activation of the immune system dynamically affects synaptic organization and function in the developing brain. We will discuss the role of neuroinflammation in altered synaptic plasticity following perinatal inflammatory challenges and potential implications for neurodevelopmental and neurodegenerative disorders.
Golembo-Smith, Shana; Schiffman, Jason; Kline, Emily
of 265 Danish children in 1972, when participants were 10-13years old. Parent psychiatric diagnoses were also obtained in order to evaluate the predictive strength of neurodevelopmental factors in combination with genetic risk. Adult diagnostic information was available for 244 members of the sample...... included minor physical anomalies (MPAs), coordination, ocular alignment, laterality, and IQ. Adult diagnoses were assessed through psychiatric interviews in 1992, as well as through a scan of the national psychiatric registry through 2007. Through a combination of multiple childhood predictors, the model...... correctly classified 73% (24 of 33) of the participants who eventually developed a schizophrenia-spectrum outcome in adulthood. Results suggest that, with replication, multivariate premorbid prediction could potentially be a useful complementary approach to identifying individuals at risk for developing...
Schmeisser, Kathrin; Fardghassemi, Yasmin; Parker, J Alex
Autism spectrum disorder (ASD) is the most common neurodevelopmental disorder with a constantly increasing prevalence. Model organisms may be tools to identify underlying cellular and molecular mechanisms, as well as aid the discovery and development of novel therapeutic approaches. A simple animal such as the nematode Caenorhabditis elegans may provide insights into the extreme complexity of ASD genetics. Despite its potential, using C. elegans in ASD research is a controversial approach and has not yet been used extensively in this context. In this study, we present a screening approach of potential C. elegans mutants as potential ASD models. We screened these mutants for motor-deficiency phenotypes, which can be exploited to study underlying mechanisms of the disorder. Selected motor-deficient mutants were then used in a comprehensive drug screen of over 3900 compounds, including many FDA-approved and natural molecules, that were analyzed for their ability to suppress motility defects caused by ASD-associated gene orthologues. This genetic-chemical approach, i.e. establishing C. elegans models for ASD and screening of a well-characterized compound library, might be a promising first step to understand the mechanisms of how gene variations cause neuronal dysfunction, leading to ASD and other neurological disorders. Positively acting compounds could also be promising candidates for preclinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.
David A. Geier
Full Text Available A hypothesis testing case-control study evaluated concerns about the toxic effects of organic-mercury (Hg exposure from thimerosal-containing (49.55% Hg by weight vaccines on the risk of neurodevelopmental disorders (NDs. Automated medical records were examined to identify cases and controls enrolled from their date-of-birth (1991–2000 in the Vaccine Safety Datalink (VSD project. ND cases were diagnosed with pervasive developmental disorder (PDD, specific developmental delay, tic disorder or hyperkinetic syndrome of childhood. In addition, putative non-thimerosal-related outcomes of febrile seizure, failure to thrive and cerebral degenerations were examined. The cumulative total dose of Hg exposure from thimerosal-containing hepatitis B vaccine (T-HBV administered within the first six months of life was calculated. On a per microgram of organic-Hg basis, PDD (odds ratio (OR = 1.054, specific developmental delay (OR = 1.035, tic disorder (OR = 1.034 and hyperkinetic syndrome of childhood (OR = 1.05 cases were significantly more likely than controls to receive increased organic-Hg exposure. By contrast, none of the non-thimerosal related outcomes were significantly more likely than the controls to have received increased organic-Hg exposure. Routine childhood vaccination may be an important public health tool to reduce infectious disease-associated morbidity/mortality, but the present study significantly associates organic-Hg exposure from T-HBV with an increased risk of an ND diagnosis.
Arim, Rubab G; Miller, Anton R; Guèvremont, Anne; Lach, Lucyna M; Brehaut, Jamie C; Kohen, Dafna E
The aim of this study was to identify children with neurodevelopmental disorders and disabilities (NDD/D) and compare their healthcare service utilization to children without NDD/D using provincial linked administrative data. The sample included children aged 6 to 10 years (n=183 041), who were registered with the British Columbia Medical Services Plan. Diagnostic information was used for the identification and classification of NDD/D in six functional domains. Healthcare service utilization included outcomes based on physician claims, prescription medication use, and hospitalization. Overall, 8.3% of children were identified with NDD/D. Children with NDD/D had higher healthcare service utilization rates than those without NDD/D. Effect sizes were: very large for the number of days a prescription medication was dispensed; large for the number of prescriptions; medium for the number of physician visits, different specialists visited, number of different prescription medications, and ever hospitalized; and small for the number of laboratory visits, X-ray visits, and number of days hospitalized. The findings have policy implications for service and resource planning. Given the high use of psychostimulants, specialized services for both NDD/D and psychiatric conditions may be the most needed services for children with NDD/D. Future studies may examine patterns of physician behaviours and costs attributable to healthcare service utilization for children with NDD/D. Children with neurodevelopmental disorders and disabilities (NDD/D) have higher healthcare service utilization than those without. Based on provincial population-based linked administrative health data, a sizeable number of children are living with NDD/D. Given the high use of psychostimulants, specialized services for children with both NDD/D and psychiatric conditions may be the most needed services for children with NDD/D. © 2017 Mac Keith Press.
Holland, A.; Whittington, J.; Cohen, O.; Curfs, L.; Delahaye, F.; Dudley, O.; Horsthemke, B.; Lindgren, A. -C.; Nourissier, C.; Sharma, N.; Vogels, A.
Background: Prader-Willi Syndrome (PWS) is a rare genetically determined neurodevelopmental disorder with a complex phenotype that changes with age. The rarity of the syndrome and the need to control for different variables such as genetic sub-type, age and gender limits clinical studies of sufficient size in any one country. A clinical research…
Bell, Emily; Wallace, Tessa; Chouinard, Isabelle; Shevell, Michael; Racine, Eric
Faced with the limitations of currently available mainstream medical treatments and interventions, parents of children with neurodevelopmental disorders often seek information about unproven interventions. These interventions frequently have undetermined efficacy and uncertain safety profiles. In this article, we present a general background and…
Full Text Available Recent studies of the hippocampus have suggested that a network of genes is associated with the regulation of the GAD₆₇ (GAD1 expression and may play a role in γ-amino butyric acid (GABA dysfunction in schizophrenia (SZ and bipolar disorder (BD. To obtain a more detailed understanding of how GAD₆₇ regulation may result in GABAergic dysfunction, we have developed an in vitro model in which GABA cells are differentiated from the hippocampal precursor cell line, HiB5. Growth factors, such as PDGF, and BDNF, regulate the GABA phenotype by inducing the expression of GAD₆₇ and stimulating the growth of cellular processes, many with growth cones that form appositions with the cell bodies and processes of other GAD₆₇-positive cells. These changes are associated with increased expression of acetylated tubulin, microtubule-associated protein 2 (MAP2 and the post-synaptic density protein 95 (PSD95. The addition of BDNF, together with PDGF, increases the levels of mRNA and protein for GAD₆₇, as well as the high affinity GABA uptake protein, GAT1. These changes are associated with increased concentrations of GABA in the cytoplasm of "differentiated" HiB5 neurons. In the presence of Ca²⁺ and K⁺, newly synthesized GABA is released extracellularly. When the HiB5 cells appear to be fully differentiated, they also express GAD₆₅, parvalbumin and calbindin, and GluR subtypes as well as HDAC1, DAXX, PAX5, Runx2, associated with GAD₆₇ regulation. Overall, these results suggest that the HiB5 cells can differentiate into functionally mature GABA neurons in the presence of gene products that are associated with GAD₆₇ regulation in the adult hippocampus.
Hempel, A.; Pagnamenta, A.T.; Blyth, M; Mansour, S; McConnell, V; Kou, I; Ikegawa, S.; Tsurusaki, Y.; Matsumoto, N.; Lo-Castro, A.; Plessis, G; Albrecht, B; Battaglia, A.; Taylor, J C; Howard, M. F.
Background \\ud \\ud SOX11 is a transcription factor proposed to play a role in brain development. The relevance of SOX11 to human developmental disorders was suggested by a recent report of SOX11 mutations in two patients with Coffin–Siris syndrome. Here we further investigate the role of SOX11 variants in neurodevelopmental disorders.\\ud \\ud Methods \\ud \\ud We used array based comparative genomic hybridisation and trio exome sequencing to identify children with intellectual disability who hav...
Sollis, Elliot; Graham, Sarah A; Vino, Arianna; Froehlich, Henning; Vreeburg, Maaike; Dimitropoulou, Danai; Gilissen, Christian; Pfundt, Rolph; Rappold, Gudrun A; Brunner, Han G; Deriziotis, Pelagia; Fisher, Simon E
De novo disruptions of the neural transcription factor FOXP1 are a recently discovered, rare cause of sporadic intellectual disability (ID). We report three new cases of FOXP1-related disorder identified through clinical whole-exome sequencing. Detailed phenotypic assessment confirmed that global developmental delay, autistic features, speech/language deficits, hypotonia and mild dysmorphic features are core features of the disorder. We expand the phenotypic spectrum to include sensory integration disorder and hypertelorism. Notably, the etiological variants in these cases include two missense variants within the DNA-binding domain of FOXP1. Only one such variant has been reported previously. The third patient carries a stop-gain variant. We performed functional characterization of the three missense variants alongside our stop-gain and two previously described truncating/frameshift variants. All variants severely disrupted multiple aspects of protein function. Strikingly, the missense variants had similarly severe effects on protein function as the truncating/frameshift variants. Our findings indicate that a loss of transcriptional repression activity of FOXP1 underlies the neurodevelopmental phenotype in FOXP1-related disorder. Interestingly, the three novel variants retained the ability to interact with wild-type FOXP1, suggesting these variants could exert a dominant-negative effect by interfering with the normal FOXP1 protein. These variants also retained the ability to interact with FOXP2, a paralogous transcription factor disrupted in rare cases of speech and language disorder. Thus, speech/language deficits in these individuals might be worsened through deleterious effects on FOXP2 function. Our findings highlight that de novo FOXP1 variants are a cause of sporadic ID and emphasize the importance of this transcription factor in neurodevelopment. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email
James, William H
It has been suggested that reading disability (RD), autism spectrum disorder (ASD), and attention-deficit-hyperactivity disorder (ADHD) share a measure of genetic overlap. They also share some epidemiological features, and have all been suspected of multifactorial (genetic and environmental) threshold origins. It has also been hypothesized that ASD, pervasive developmental disorder - not otherwise specified, and ADHD are partially caused by high maternal intrauterine testosterone levels. Here I offer a new method of testing this latter hypothesis on some of these disorders (RD, ADHD, and ASD). All these disorders occur more commonly in males. If the intrauterine testosterone hypothesis was correct, then probands should have a statistically significant excess of brothers among their siblings. Data are adduced here to test this. When treated as individual disorders, the data are significant only in the case of RD. However, the data are highly significant when pooled as RD + ADHD or RD + ADHD + ASD. Taken alone, the data on ASD are not significant. These results suggest that: (1) taxonomically, RD and ADHD are moresimilar to one another than either is to ASD; and (2) probands in the pooled samples have a very highly significant excess of brothers. This result stands in need of explanation. Provisionally, the data may be interpreted as suggesting that RD may be caused by high intrauterine testosterone levels, and confirming the hypothesis that ADHD is partially caused by high intrauterine testosterone.
Carballal Mariño, Marta; Gago Ageitos, Ana; Ares Alvarez, Josefa; Del Rio Garma, Mercedes; García Cendón, Clara; Goicoechea Castaño, Ana; Pena Nieto, Josefina
To determine the prevalence of psychiatric disorders in primary care pediatrics in Atlantic Galicia. An observational, descriptive, cross-sectional prevalence study was carried out in 9 outpatient clinics in A Coruña and Pontevedra with a population of 8293 children between September and November 2015. A total of 1286 randomly selected patients from 0 to 14 years of age were included. From the medical history was registered: age, sex, psychiatric diagnosis established by DSM-IV-TR criteria in its five axes, professionals who participated in the diagnosis and treatment of the process and what type of treatment was received. Authorization was obtained from the Research Ethics Committee of Galicia number 2015/427. 148 of 1286 patients presented psychiatric pathology (11,5% IC 95% 9.73-13,29), 68% male. Between 0 and 5years, the prevalence was 4.5%; between 6y and 10y, 18.5% and between 11y and 14y 22%. Symptoms lasted a median of 25 months. The most frequent pathologies in 1286 patients were ADHD (5.36%), language disorders (3.42%), learning disorders (3.26%), anxiety-depressive disorders (2.4%) and behavior disorders (1.87%). Of the 148 cases, 47% had comorbidity with another mental disorder. Most of them required attention by multiple social, health and educational professionals; 33% received psychopharmacological treatment. The prevalence of psychiatric disorders in pediatric primary care is frequent, chronic and complex, increases with age and requires many health, educational and social resources. Copyright © 2017. Publicado por Elsevier España, S.L.U.
Spooren, Will; Lindemann, Lothar; Ghosh, Anirvan; Santarelli, Luca
Autism and autism spectrum disorders (ASDs) affect millions of individuals worldwide. Despite increased autism diagnoses over the past 30 years, therapeutic intervention is often 'trial and error'. This approach has identified some beneficial agents, but complex heterogeneous disorders require a more personalized treatment regimen. Many ASD risk factors are genetic, implicating impaired synaptic development and function. Monogenetic disorders (e.g., fragile X syndrome, Rett syndrome, and neurofibromatosis) that have phenotypic overlap with autism provide insights into ASD pathology through the identification novel drug targets (e.g., glutamatergic receptors). Encouragingly, some of these novel drug targets provide symptomatic improvement, even in patients who have lived with ASDs for protracted periods of time. Consequently, a targeted drug discovery approach is expected to deliver improved agents for the treatment and management of ASDs. Here, we review the opportunities and challenges in drug development for autism and provide insight into the neurobiology of ASDs. Copyright © 2012 Elsevier Ltd. All rights reserved.
Perra, Oliver; Williams, Justin H. G.; Whiten, Andrew; Fraser, Lesley; Benzie, Helen; Perrett, David I.
Several studies have reported imitative deficits in autism spectrum disorder (ASD). However, it is still debated if imitative deficits are specific to ASD or shared with clinical groups with similar mental impairment and motor difficulties. We investigated whether imitative tasks can be used to discriminate ASD children from typically developing…
Iqbal, Z.; Vandeweyer, G.; Voet, M. van der; Waryah, A.M.; Zahoor, M.Y.; Besseling, J.A.; Roca, L.T.; Silfhout, A.T. van; Nijhof, B.; Kramer, J.M.; Aa, N. van der; Ansar, M.; Peeters, H.; Helsmoortel, C.; Gilissen, C.F.H.A.; Vissers, L.E.L.M.; Veltman, J.A.; Brouwer, A.P.M. de; Kooy, R. van; Riazuddin, S.; Schenck, A.; Bokhoven, H. van; Rooms, L.
AnkyrinG, encoded by the ANK3 gene, is involved in neuronal development and signaling. It has previously been implicated in bipolar disorder and schizophrenia by association studies. Most recently, de novo missense mutations in this gene were identified in autistic patients. However, the causative
Gillet, Virginie; Hunting, Darel John; Takser, Larissa
The prevention of neurodevelopmental disorders (NDD) of prenatal origin suffers from the lack of objective tools for early detection of susceptible individuals and the long time lag, usually in years, between the neurotoxic exposure and the diagnosis of mental dysfunction. Human data on the effects of alcohol, lead, and mercury and experimental data from animals on developmental neurotoxins and their long-term behavioral effects have achieved a critical mass, leading to the concept of the Developmental Origin of Health and Disease (DOHaD). However, there is currently no way to evaluate the degree of brain damage early after birth. We propose that extracellular vesicles (EVs) and particularly exosomes, released by brain cells into the fetal blood, may offer us a non-invasive means of assessing brain damage by neurotoxins. We are inspired by the strategy applied by Alan Turing (a cryptanalyst working for the British government), who created a first computer to decrypt German intelligence communications during World War II. Given the growing evidence that microRNAs (miRNAs), which are among the molecules carried by EVs, are involved in cell-cell communication, we propose that decrypting messages from EVs can allow us to detect damage thus offering an opportunity to cure, reverse, or prevent the development of NDD. This review summarizes recent findings on miRNAs associated with selected environmental toxicants known to be involved in the pathophysiology of NDD.
Bakare, Muideen O; Munir, Kerim M; Bello-Mojeed, Mashudat A
Sub-Saharan African (SSA) population consists of about 45% children, while in Europe and North America children population is 10-15%. Lately, attention has been directed at mitigating childhood infectious and communicable diseases to reduce under-five mortality. As the under-five mortality index in Sub-Saharan Africa has relatively improved over the last two decades, more Sub-Saharan African children are surviving beyond the age of five and, apparently, a sizeable percentage of this population would be living with one or more childhood neurodevelopmental disorders (NDD). The distribution of child mental health service resources across the world is unequal. This manifests in the treatment gap of major childhood onset mental health problems in SSA, with the gap being more pronounced for childhood NDD. It is important to balance the public health focus and research funding priorities in Sub-Saharan Africa. We urgently need to define the burden of childhood NDD in the region for healthcare planning and policy formulation.
Muideen O. Bakare
Full Text Available Sub-Saharan African (SSA population consists of about 45% children, while in Europe and North America children population is 10- 15%. Lately, attention has been directed at mitigating childhood infectious and communicable diseases to reduce under-five mortality. As the under-five mortality index in Sub-Saharan Africa has relatively improved over the last two decades, more Sub-Saharan African children are surviving beyond the age of five and, apparently, a sizeable percentage of this population would be living with one or more childhood neurodevelopmental disorders (NDD. The distribution of child mental health service resources across the world is unequal. This manifests in the treatment gap of major childhood onset mental health problems in SSA, with the gap being more pronounced for childhood NDD. It is important to balance the public health focus and research funding priorities in Sub-Saharan Africa. We urgently need to define the burden of childhood NDD in the region for healthcare planning and policy formulation.
Johnels, Jakob Åsberg; Hagberg, Bibbi; Gillberg, Christopher; Miniscalco, Carmela
Oral narrative retelling is often problematic for children with communicative and neurodevelopmental disorders. However, beyond a suggested role of language level, little is known about the basis of narrative performance. In this study we examine whether oral narrative retelling might be associated not just with language level but also with skills related to nonverbal narrative temporal sequencing. A diagnostically heterogeneous sample of Swedish-speaking children with a full scale IQ >70 was included in the study (N = 55; age 6-9 years). Narrative retelling skills were measured using the three subscores from the bus story test (BST). Independent predictors included (1) temporal sequencing skills according to a picture arrangement test and (2) a language skills factor consisting of definitional vocabulary and receptive grammar. Regression analyses show that language skills predicted BST Sentence Length and Subordinate Clauses subscores, while both temporal sequencing and language were independently linked with the BST Information subscore. When subdividing the sample based on nonverbal temporal sequencing level, a significant subgroup difference was found only for BST Information. Finally, a principal component analysis shows that temporal sequencing and BST Information loaded on a common factor, separately from the language measures. It is concluded that language level is an important correlate of narrative performance more generally in this diagnostically heterogeneous sample, and that nonverbal temporal sequencing functions are important especially for conveying story information. Theoretical and clinical implications are discussed. © 2013 The Scandinavian Psychological Associations.
notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does...disorders such as ASD. 15. SUBJECT TERMS Autism, placenta, tryptophan, serotonin, kynurenine, maternal immune activation, fetal brain 16...Several reference genes were tested, and TPB was found to be the most stable between treatment groups and time points in our samples. In order for
Savabieasfahani, M.; Alaani, S.; Tafash, M.; Dastgiri, S; Al-Sabbak, M.
Anthropogenic release of pollutants into the environment is especially harmful to growing fetuses and young children. These populations are at an increased risk of damage because exposure to pollutants during critical periods of development can cause many impairments. Children’s exposure to mixtures of metals could be responsible for the rising numbers of neurological disorders surfacing in Iraqi children. Titanium (Ti) and magnesium (Mg) are heavily used in war industries. Exposure to Ti and...
Romeo, Domenico M; Brogna, Claudia; Quintiliani, Michela; Baranello, Giovanni; Pagliano, Emanuela; Casalino, Tiziana; Sacco, Annalisa; Ricci, Daniela; Mallardi, Maria; Musto, Elisa; Sivo, Serena; Cota, Francesco; Battaglia, Domenica; Bruni, Oliviero; Mercuri, Eugenio
We aimed to estimate the frequency of sleep disorders in children with cerebral palsy (CP) using the Sleep Disturbance Scale for Children (SDSC) and to evaluate the relations between sleep disorders and motor, cognitive, and behavioral problems. One hundred and sixty-five children with CP ages 6-16 years (mean age, 11years) were assessed using the SDSC, the Gross Motor Function Classification System (GMFCS), the Wechsler Intelligence Scale for Children and the Child Behavior Check List (CBCL) to assess sleep, motor, cognitive, and behavioral problems, respectively. An abnormal total sleep score was found in 19% of children with CP; more than 40% of children had an abnormal score on at least one SDSC factor. The SDSC total score was significantly associated (P<.01) with mental retardation, epilepsy, CBCL scores, and level 5 on the GMFCS. Our results confirm that sleep disorders are common in children with cerebral palsy. The relationship between motor and cognitive behavior and epilepsy should be further explored to better understand how these factors influence one another to identify effective treatments and to improve the well-being of the child. Copyright © 2014 Elsevier B.V. All rights reserved.
Ye, Xin Cynthia; Ng, Isaiah; Seid-Karbasi, Puya; Imam, Tuhina; Lee, Cheryl E; Chen, Shirley Yu; Herman, Adam; Sharma, Balraj; Johal, Gurinder; Gu, Bobby; Wasserman, Wyeth W
The Portal for Families Overcoming Neurodevelopmental Disorders (PFOND) provides a structured Internet interface for the sharing of information with individuals struggling with the consequences of rare developmental disorders. Large disease-impacted communities can support fundraising organizations that disseminate Web-based information through elegant websites run by professional staff. Such quality resources for families challenged by rare disorders are infrequently produced and, when available, are often dependent upon the continued efforts of a single individual. The project endeavors to create an intuitive Web-based software system that allows a volunteer with limited technical computer skills to produce a useful rare disease website in a short time period. Such a system should provide access to emerging news and research findings, facilitate community participation, present summary information about the disorder, and allow for transient management by volunteers who are likely to change periodically. The prototype portal was implemented using the WordPress software system with both existing and customized supplementary plug-in software modules. Gamification scoring features were implemented in a module, allowing editors to measure progress. The system was installed on a Linux-based computer server, accessible across the Internet through standard Web browsers. A prototype PFOND system was implemented and tested. The prototype system features a structured organization with distinct partitions for background information, recent publications, and community discussions. The software design allows volunteer editors to create a themed website, implement a limited set of topic pages, and connect the software to dynamic RSS feeds providing information about recent news or advances. The prototype was assessed by a fraction of the disease sites developed (8 out of 27), including Aarskog-Scott syndrome, Aniridia, Adams-Oliver syndrome, Cat Eye syndrome, Kabuki syndrome
Imam, Tuhina; Lee, Cheryl E; Chen, Shirley Yu; Herman, Adam; Sharma, Balraj; Johal, Gurinder; Gu, Bobby
Background The Portal for Families Overcoming Neurodevelopmental Disorders (PFOND) provides a structured Internet interface for the sharing of information with individuals struggling with the consequences of rare developmental disorders. Large disease-impacted communities can support fundraising organizations that disseminate Web-based information through elegant websites run by professional staff. Such quality resources for families challenged by rare disorders are infrequently produced and, when available, are often dependent upon the continued efforts of a single individual. Objective The project endeavors to create an intuitive Web-based software system that allows a volunteer with limited technical computer skills to produce a useful rare disease website in a short time period. Such a system should provide access to emerging news and research findings, facilitate community participation, present summary information about the disorder, and allow for transient management by volunteers who are likely to change periodically. Methods The prototype portal was implemented using the WordPress software system with both existing and customized supplementary plug-in software modules. Gamification scoring features were implemented in a module, allowing editors to measure progress. The system was installed on a Linux-based computer server, accessible across the Internet through standard Web browsers. Results A prototype PFOND system was implemented and tested. The prototype system features a structured organization with distinct partitions for background information, recent publications, and community discussions. The software design allows volunteer editors to create a themed website, implement a limited set of topic pages, and connect the software to dynamic RSS feeds providing information about recent news or advances. The prototype was assessed by a fraction of the disease sites developed (8 out of 27), including Aarskog-Scott syndrome, Aniridia, Adams-Oliver syndrome
Roche, Laura; Sigafoos, Jeff; Lancioni, Giulio E; O'Reilly, Mark F; Schlosser, Ralf W; Stevens, Michelle; van der Meer, Larah; Achmadi, Donna; Kagohara, Debora; James, Ruth; Carnett, Amarie; Hodis, Flaviu; Green, Vanessa A; Sutherland, Dean; Lang, Russell; Rispoli, Mandy; Machalicek, Wendy; Marschik, Peter B
Children with neurodevelopmental disorders often present with little or no speech. Augmentative and alternative communication (AAC) aims to promote functional communication using non-speech modes, but it might also influence natural speech production. To investigate this possibility, we provided AAC intervention to two boys with neurodevelopmental disorders and severe communication impairment. Intervention focused on teaching the boys to use a tablet computer-based speech-generating device (SGD) to request preferred stimuli. During SGD intervention, both boys began to utter relevant single words. In an effort to induce more speech, and investigate the relation between SGD availability and natural speech production, the SGD was removed during some requesting opportunities. With intervention, both participants learned to use the SGD to request preferred stimuli. After learning to use the SGD, both participants began to respond more frequently with natural speech when the SGD was removed. The results suggest that a rehabilitation program involving initial SGD intervention, followed by subsequent withdrawal of the SGD, might increase the frequency of natural speech production in some children with neurodevelopmental disorders. This effect could be an example of response generalization. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.
Carpente, John; Manne, Stela; Gattino, Gustavo
Background: The Individual Music-Centered Assessment Profile for Neurodevelopmental Disorders (IMCAP-ND) is an evaluation instrument made up of three criterion-referenced rating scales designed to examine how clients perceive, interpret, and make music with the therapist while participating...... in individual improvisational music therapy. For this assessment instrument to be considered clinically relevant, it is essential to examine the degree of inter-rater reliability for each of the three rating scales. Objective: The purposes of this study are as follows: a) to determine the inter......-rater reliability of the three scales that make up the IMCAP-ND: Scale I: Musical Emotional Assessment Rating Scale (MEARS), Scale II: Musical Cognitive Perception Scale (MCPS), and Scale III: Musical Responsive Scale (MRS); b) to examine the inter-rater reliabilities of the unweighted and weighted overall MEARS...
Mühleisen, Thomas W; Reinbold, Céline S; Forstner, Andreas J; Abramova, Lilia I; Alda, Martin; Babadjanova, Gulja; Bauer, Michael; Brennan, Paul; Chuchalin, Alexander; Cruceanu, Cristiana; Czerski, Piotr M; Degenhardt, Franziska; Fischer, Sascha B; Fullerton, Janice M; Gordon, Scott D; Grigoroiu-Serbanescu, Maria; Grof, Paul; Hauser, Joanna; Hautzinger, Martin; Herms, Stefan; Hoffmann, Per; Kammerer-Ciernioch, Jutta; Khusnutdinova, Elza; Kogevinas, Manolis; Krasnov, Valery; Lacour, André; Laprise, Catherine; Leber, Markus; Lissowska, Jolanta; Lucae, Susanne; Maaser, Anna; Maier, Wolfgang; Martin, Nicholas G; Mattheisen, Manuel; Mayoral, Fermin; McKay, James D; Medland, Sarah E; Mitchell, Philip B; Moebus, Susanne; Montgomery, Grant W; Müller-Myhsok, Bertram; Oruc, Lilijana; Pantelejeva, Galina; Pfennig, Andrea; Pojskic, Lejla; Polonikov, Alexey; Reif, Andreas; Rivas, Fabio; Rouleau, Guy A; Schenk, Lorena M; Schofield, Peter R; Schwarz, Markus; Streit, Fabian; Strohmaier, Jana; Szeszenia-Dabrowska, Neonila; Tiganov, Alexander S; Treutlein, Jens; Turecki, Gustavo; Vedder, Helmut; Witt, Stephanie H; Schulze, Thomas G; Rietschel, Marcella; Nöthen, Markus M; Cichon, Sven
Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci. We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan. Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (P FDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (P FDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system. Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients. Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD. Copyright © 2017 Elsevier B.V. All rights reserved.
Kerns, Kimberly A; Macoun, Sarah; MacSween, Jenny; Pei, Jacqueline; Hutchison, Marnie
The current study investigated the efficacy of a game-based process specific intervention for improving attention and working memory in children with Fetal Alcohol Spectrum Disorders (FASD) and Autism Spectrum Disorders (ASD). The Caribbean Quest (CQ) is a 'serious game' that consists of five hierarchically structured tasks, delivered in an adaptive format, targeting different aspects of attention and/or working memory. In addition to game play, the intervention incorporates metacognitive strategies provided by trained educational assistants (EAs), to facilitate generalization and far transfer to academic and daily skills. EAs delivered the intervention to children (ages 6-13) during their regular school day, providing children with instruction in metacognitive strategies to improve game play, with participants completing approximately 12 hours of training over an 8 to 12 school week period. Pre- and post-test analyses revealed significant improvement on measures of working memory and attention, including reduced distractibility and improved divided attention skills. Additionally, children showed significant gains in performance on an academic measure of reading fluency, suggesting that training-related gains in attention and working memory transferred to classroom performance. Exit interviews with EAs revealed that the intervention was easily delivered within the school day, that children enjoyed the intervention, and that children transferred metacognitive strategies learned in game play into the classroom. Preliminary results support this game-based process specific intervention as a potentially effective treatment and useful tool for supporting cognitive improvements in children with FASD or ASD, when delivered as part of an overall treatment plan.
Miller, Anton; Shen, Jane; Mâsse, Louise C
Allocation of resources for services and supports for children with neurodevelopmental disorders/disabilities (NDD/D) is often based on the presence of specific health conditions. This study investigated the relative roles of a child's diagnosed health condition and neurodevelopmental and related functional characteristics in explaining child and family health and well-being. The data on children with NDD/D (ages 5 to 14; weighted n = 120,700) are from the 2006 Participation and Activity Limitation Survey (PALS), a population-based Canadian survey of parents of children with functional limitations/disabilities. Direct and indirect effects of child diagnosis status-autism spectrum disorder (ASD)/not ASD-and functional characteristics (particularly, ASD-related impairments in speech, cognition, and emotion and behaviour) on child participation and family health and well-being were investigated in a series of structural equation models, while controlling for covariates. All models adequately fitted the data. Child ASD diagnosis was significantly associated with child participation and family health and well-being. When ASD-related child functional characteristics were added to the model, all direct effects from child diagnosis on child and family outcomes disappeared; the effect of child diagnosis on child and family outcomes was fully mediated via ASD-related child functional characteristics. Children's neurodevelopmental functional characteristics are integral to understanding the child and family health-related impact of neurodevelopmental disorders such as ASD. These findings have implications for the relative weighting given to functional versus diagnosis-specific factors in considering needs for services and supports.
Atladóttir, H. Ó.; Schendel, D. E.; Parner, E. T.; Henriksen, T. B.
The aim of this study was to describe the profile of specific neonatal morbidities in children later diagnosed with autism spectrum disorder (ASD), and to compare this profile with the profile of children with hyperkinetic disorder, cerebral palsy, epilepsy or intellectual disability. This is a Danish population based cohort study, including all…
Karen S. Ho
Full Text Available Copy number variants (CNVs detected by chromosomal microarray analysis (CMA significantly contribute to understanding the etiology of autism spectrum disorder (ASD and other related conditions. In recognition of the value of CMA testing and its impact on medical management, CMA is in medical guidelines as a first-tier test in the evaluation of children with these disorders. As CMA becomes adopted into routine care for these patients, it becomes increasingly important to report these clinical findings. This study summarizes the results of over 4 years of CMA testing by a CLIA-certified clinical testing laboratory. Using a 2.8 million probe microarray optimized for the detection of CNVs associated with neurodevelopmental disorders, we report an overall CNV detection rate of 28.1% in 10,351 consecutive patients, which rises to nearly 33% in cases without ASD, with only developmental delay/intellectual disability (DD/ID and/or multiple congenital anomalies (MCA. The overall detection rate for individuals with ASD is also significant at 24.4%. The detection rate and pathogenic yield of CMA vary significantly with the indications for testing, age, and gender, as well as the specialty of the ordering doctor. We note discrete differences in the most common recurrent CNVs found in individuals with or without a diagnosis of ASD.
Full Text Available Inherited encephalopathies include a broad spectrum of heterogeneous disorders. To provide a correct diagnosis, an integrated approach including genetic testing is warranted. We report seven patients with difficult to diagnose inborn paediatric encephalopathies. The diagnosis could not be attained only by means of clinical and laboratory investigations and MRI. Additional genetic testing was required. Cytogenetics, PCR based tests, and array-based comparative genome hybridization were performed. In 4 patients with impaired language abilities we found the presence of microduplication in the region 16q23.1 affecting two dose-sensitive genes: WWOX (OMIM 605131 and MAF (OMIM 177075 (1 case, an interstitial deletion of the 17p11.2 region (2 patients further diagnosed as Smith-Magenis syndrome, and deletion encompassing first three exons of Myocyte Enhancer Factor gene 2MEF2C (1 case. The two other cases represented progressing dystonia. Characteristic GAG deletion in DYT1 consistently with the diagnosis of torsion dystonia was confirmed in 1 case. Last enrolled patient presented with clinical picture consistent with Krabbe disease confirmed by finding of two pathogenic variants of GALC gene and the absence of mutations in PSAP. The integrated diagnostic approach including genetic testing in selected examples of complicated hereditary diseases of the brain is largely discussed in this paper.
Rossignol, Rafaëlle; Ranchon-Cole, Isabelle; Pâris, Arnaud; Herzine, Ameziane; Perche, Astrid; Laurenceau, David; Bertrand, Pauline; Cercy, Christine; Pichon, Jacques; Mortaud, Stéphane; Briault, Sylvain; Menuet, Arnaud; Perche, Olivier
Visual sensory impairments are common in Mental Deficiency (MD) and Autism Spectrum Disorder (ASD). These defects are linked to cerebral dysfunction in the visual cortical area characterized by the deregulation of axon growth/guidance and dendrite spine immaturity of neurons. However, visual perception had not been addressed, although the retina is part of the central nervous system with a common embryonic origin. Therefore, we investigated retinal perception, the first event of vision, in a murine model of MD with autistic features. We document that retinal function is altered in Fmr1 KO mice, a model of human Fragile X Syndrome. Indeed, In Fmr1 KO mice had a lower retinal function characterized by a decreased photoreceptors neuron response, due to a 40% decrease in Rhodopsin content and to Rod Outer Segment destabilization. In addition, we observed an alteration of the visual signal transmission between photoreceptors and the inner retina which could be attributed to deregulations of pre- and post- synaptic proteins resulting in retinal neurons synaptic destabilization and to retinal neurons immaturity. Thus, for the first time, we demonstrated that retinal perception is altered in a murine model of MD with autistic features and that there are strong similarities between cerebral and retinal cellular and molecular defects. Our results suggest that both visual perception and integration must be taken into account in assessing visual sensory impairments in MD and ASD.
Lionel, Anath C; Tammimies, Kristiina; Vaags, Andrea K
during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89,985 individuals across 10 sites, including 64,114 neurodevelopmental disorder...... in the neurodevelopmental disorder subjects (p=0.002) compared with 44,085 population-based controls. Frequent phenotypes observed in individuals with such deletions included Autism Spectrum Disorders (ASD), Attention Deficit Hyperactivity Disorder (ADHD), speech delay, anxiety and Obsessive Compulsive Disorder (OCD......). The 3'-terminal ASTN2 deletions were significantly enriched compared with controls in males with neurodevelopmental disorders, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin...
Kerekes, Nóra; Lundström, Sebastian; Chang, Zheng; Tajnia, Armin; Jern, Patrick; Lichtenstein, Paul; Nilsson, Thomas; Anckarsäter, Henrik
Background. Previous research has supported gender-specific aetiological factors in oppositional defiant disorder (ODD) and conduct disorder (CD). The aims of this study were to identify gender-specific associations between the behavioural problems-ODD/CD-like problems-and the neurodevelopmental disorders-attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD)-and to investigate underlying genetic effects. Methods. 17,220 twins aged 9 or 12 were screened using the Autism-Tics, AD/HD and other Comorbidities inventory. The main covariates of ODD- and CD-like problems were investigated, and the relative importance of unique versus shared hereditary and environmental effects was estimated using twin model fitting. Results. Social interaction problems (one of the ASD subdomains) was the strongest neurodevelopmental covariate of the behavioural problems in both genders, while ADHD-related hyperactivity/impulsiveness in boys and inattention in girls stood out as important covariates of CD-like problems. Genetic effects accounted for 50%-62% of the variance in behavioural problems, except in CD-like problems in girls (26%). Genetic and environmental effects linked to ADHD and ASD also influenced ODD-like problems in both genders and, to a lesser extent, CD-like problems in boys, but not in girls. Conclusions. The gender-specific patterns should be considered in the assessment and treatment, especially of CD.
Iossifov, Ivan; Zheng, Tian; Baron, Miron; Gilliam, T. Conrad; Rzhetsky, Andrey
Common hereditary neurodevelopmental disorders such as autism, bipolar disorder, and schizophrenia are most likely both genetically multifactorial and heterogeneous. Because of these characteristics traditional methods for genetic analysis fail when applied to such diseases. To address the problem we propose a novel probabilistic framework that combines the standard genetic linkage formalism with whole-genome molecular-interaction data to predict pathways or networks of interacting genes that...
Full Text Available Background. Previous research has supported gender-specific aetiological factors in oppositional defiant disorder (ODD and conduct disorder (CD. The aims of this study were to identify gender-specific associations between the behavioural problems–ODD/CD-like problems–and the neurodevelopmental disorders–attention deficit hyperactivity disorder (ADHD, autism spectrum disorder (ASD–and to investigate underlying genetic effects.Methods. 17,220 twins aged 9 or 12 were screened using the Autism–Tics, AD/HD and other Comorbidities inventory. The main covariates of ODD- and CD-like problems were investigated, and the relative importance of unique versus shared hereditary and environmental effects was estimated using twin model fitting.Results. Social interaction problems (one of the ASD subdomains was the strongest neurodevelopmental covariate of the behavioural problems in both genders, while ADHD-related hyperactivity/impulsiveness in boys and inattention in girls stood out as important covariates of CD-like problems. Genetic effects accounted for 50%–62% of the variance in behavioural problems, except in CD-like problems in girls (26%. Genetic and environmental effects linked to ADHD and ASD also influenced ODD-like problems in both genders and, to a lesser extent, CD-like problems in boys, but not in girls.Conclusions. The gender-specific patterns should be considered in the assessment and treatment, especially of CD.
Lance, Eboni I; Shapiro, Bruce K
We report the case of a school-age child with a history of hearing loss presenting with staring spells. Electroencephalography (EEG) revealed a pattern consistent with absence epilepsy, and the patient was started on antiepileptic medication with decreased frequency of staring spells but he then continued to have behavioral issues. The patient was diagnosed subsequently with combined-type attention-deficit hyperactivity disorder (ADHD) and started on stimulant medication with subsequent improvement in attention and school performance. Multiple confounding diagnoses are common in children with neurodevelopmental disabilities, and comprehensive evaluation is required for appropriate management.
Alterations in the expression of a neurodevelopmental gene exert long-lasting effects on cognitive-emotional phenotypes and functional brain networks: translational evidence from the stress-resilient Ahi1 knockout mouse.
Lotan, A; Lifschytz, T; Mernick, B; Lory, O; Levi, E; Ben-Shimol, E; Goelman, G; Lerer, B
Many psychiatric disorders are highly heritable and may represent the clinical outcome of early aberrations in the formation of neural networks. The placement of brain connectivity as an 'intermediate phenotype' renders it an attractive target for exploring its interaction with genomics and behavior. Given the complexity of genetic make up and phenotypic heterogeneity in humans, translational studies are indicated. Recently, we demonstrated that a mouse model with heterozygous knockout of the key neurodevelopmental gene Ahi1 displays a consistent stress-resilient phenotype. Extending these data, the current research describes our multi-faceted effort to link early variations in Ahi1 expression with long-term consequences for functional brain networks and cognitive-emotional phenotypes. By combining behavioral paradigms with graph-based analysis of whole-brain functional networks, and then cross-validating the data with robust neuroinformatic data sets, our research suggests that physiological variation in gene expression during neurodevelopment is eventually translated into a continuum of global network metrics that serve as intermediate phenotypes. Within this framework, we suggest that organization of functional brain networks may result, in part, from an adaptive trade-off between efficiency and resilience, ultimately culminating in a phenotypic diversity that encompasses dimensions such as emotional regulation and cognitive function.
Appleton, R E; Jones, A P; Gamble, C; Williamson, P R; Wiggs, L; Montgomery, P; Sutcliffe, A; Barker, C; Gringras, P
Difficulties in initiating and maintaining sleep are common in children with neurodevelopmental disorders. Melatonin is unlicensed in children yet widely prescribed for sleep problems. To determine whether or not immediate-release melatonin is beneficial compared with placebo in improving total duration of night-time sleep in children with neurodevelopmental problems. Randomised, double-blind, placebo-controlled, parallel study. Hospitals throughout England and Wales recruited patients referred by community paediatricians and other clinical colleagues. Children with neurodevelopmental problems aged from 3 years to 15 years 8 months who did not fall asleep within 1 hour of lights out or who had children were screened to enter the trial; 263 (96%) children were registered and completed the 4- to 6-week behaviour therapy period and 146 (56%) children were randomised, of whom 110 (75%) contributed data for the primary outcome. The difference in TST time between the melatonin and placebo groups adjusted for baseline was 22.43 minutes [95% confidence interval (CI) 0.52 to 44.34 minutes; p = 0.04] measured using sleep diaries. A reduction in SOL, adjusted for baseline, was seen for melatonin compared with placebo when measured by sleep diaries (-37.49 minutes, 95% CI -55.27 to -19.71 minutes; p children treated with melatonin slept 23 minutes longer than those in the placebo group; however, the upper limit of the confidence interval was less than 1 hour, the minimum clinically worthwhile difference specified at the outset of the trial. Melatonin is effective in reducing SOL in children with neurodevelopmental delay by a mean of 45 minutes; a value of 30 minutes was specified a priori to be clinically important. Future studies should be conducted over longer periods and directly compare different formulations of melatonin with conventional hypnotic and sedative medications. It would also be important to study groups of children with specific neurological disorders. Current
Aman, Michael G.; Vinks, Alexander A.; Remmerie, Bart; Mannaert, Erik; Ramadan, Yaser; Masty, Jessica; Lindsay, Ronald L.; Malone, Krista
Background Risperidone is a second-generation antipsychotic agent widely used in the treatment of schizophrenia and other psychotic disorders in adults. Risperidone is probably the most frequently used atypical antipsychotic in the pediatric population. Objectives The goals of this study were to estimate the pharmacokinetic parameters of risperidone and its enantiomers in a pediatric population and explore relationships between saliva and plasma concentrations. Methods Eligible patients, between 4 and 15 years of age, included those taking a stable dose of oral risperidone ranging from 0.01 to 0.07 mg/kg BID for ≥4 weeks to treat psychiatric or neurodevelopmental conditions. A trough blood level and predose saliva sample were collected at study initiation; the regular risperidone dose was administered; and paired samples of blood and saliva were collected at 1, 2, 4, and 7 hours postdose. Plasma/saliva concentrations of risperidone and enantiomers of its principal active metabolite, 9-hydroxyrisperidone (9-OH-risperidone), were measured using a chiral liquid chromatography–tandem mass spectrometry assay. Standard pharmacokinetic parameters were calculated. Cytochrome P450 2D6 genotypes of *3,*4,*5 deletion and duplication were determined. Results The study included 19 patients (age range, 4 years 2 months to 15 years 11 months). Mean (SD) values for Cmax, t1/2, and AUC 0 to 12 hours for risperidone in plasma were 15.9 (22.2) ng/mL, 3.0 (2.3) h, and 92.1 (200.6) ng · h/mL, respectively. Corresponding values in saliva were 12.0 (21.0) ng/mL, 3.4 (3.2) h, and 27.8 (38.7) ng · h/mL, respectively. Mean (SD) plasma enantiomer values for Cmax and AUC calculated up to the last observation were: (+)-9-OH-risperidone, 13.6 (10.0) ng/mL and 73.6 (52.3) ng · h/mL; (−)-9-OH-risperidone, 4.9 (3.1) ng/mL and 29.3 (19.1) ng · h/mL. Corresponding enantiomer values in saliva were: (+)-9-OH-risperidone, 5.2 (8.8) ng/mL and 15.6 (8.9) ng · h/mL; (−)-9-OH-risperidone, 5
Bilder, Deborah A.; Bakian, Amanda V.; Stevenson, David A.; Carbone, Paul S.; Cunniff, Christopher; Goodman, Alyson B.; McMahon, William M.; Fisher, Nicole P.; Viskochil, David
Neurofibromatosis type 1 (NF1) is an inherited neurocutaneous disorder associated with neurodevelopmental disorders including autism spectrum disorder (ASD). The frequency of ASD/NF1 co-occurrence has been subject to debate since the 1980s. This relationship was investigated in a large population-based sample of 8-year-old children identified with ASD (N = 12,271) by the Centers for Disease Control and Prevention’s Autism and Developmental Disabilities Monitoring (ADDM) Network. Twenty-two (1...
Neurodevelopmental Disorders across the Lifespan: A Neuroconstructivist Approach. Edited by Emily K. Farran and Annette Karmiloff-Smith, Oxford University Press, 2012; 394 pages. Price: £49.99, ISBN 978-0-19-959481-8
Full Text Available The first book to consider atypical development across multiple levels (genes, brain, behavior, environment, encouraging readers to think dynamically and developmentally, rather than examining static snapshots of neurodevelopmental disorders.Provides the most comprehensive review of development across cognitive domains (and their interactions, making clinicians more sensitive to looking for underlying cognitive and neural differences even when behavioral scores are in the normal range.Considers development from infancy to adulthood, encouraging the reader to think about the importance of development in understanding neurodevelopmental disorders, for example, by considering the impact that differences in low-level processes in infancy can have on later developing cognitive processes.
Allen, J L; Oberdorster, G; Morris-Schaffer, K; Wong, C; Klocke, C; Sobolewski, M; Conrad, K; Mayer-Proschel, M; Cory-Slechta, D A
Accumulating evidence from both human and animal studies show that brain is a target of air pollution. Multiple epidemiological studies have now linked components of air pollution to diagnosis of autism spectrum disorder (ASD), a linkage with plausibility based on the shared mechanisms of inflammation. Additional plausibility appears to be provided by findings from our studies in mice of exposures from postnatal day (PND) 4-7 and 10-13 (human 3rd trimester equivalent), to concentrated ambient ultrafine (UFP) particles, considered the most reactive component of air pollution, at levels consistent with high traffic areas of major U.S. cities and thus highly relevant to human exposures. These exposures, occurring during a period of marked neuro- and gliogenesis, unexpectedly produced a pattern of developmental neurotoxicity notably similar to multiple hypothesized mechanistic underpinnings of ASD, including its greater impact in males. UFP exposures induced inflammation/microglial activation, reductions in size of the corpus callosum (CC) and associated hypomyelination, aberrant white matter development and/or structural integrity with ventriculomegaly (VM), elevated glutamate and excitatory/inhibitory imbalance, increased amygdala astrocytic activation, and repetitive and impulsive behaviors. Collectively, these findings suggest the human 3rd trimester equivalent as a period of potential vulnerability to neurodevelopmental toxicity to UFP, particularly in males, and point to the possibility that UFP air pollution exposure during periods of rapid neuro- and gliogenesis may be a risk factor not only for ASD, but also for other neurodevelopmental disorders that share features with ASD, such as schizophrenia, attention deficit disorder, and periventricular leukomalacia. Copyright © 2015 Elsevier B.V. All rights reserved.
Full Text Available Contemporary aetiopathogenetic considerations, based on neuro-imaging genetic and developmental neurobiology studies, suggest neurodevelopmental origin of schizophrenia. Several lines of evidence including structural abnormalities on in vivo brain imaging, the excess of prenatal and obstetric complications and the association of congenital and minor physical anomalies with schizophrenia, strongly indicate the neurodevelopmental pathogenesis of schizophrenia. On the other hand, controversial concept of psychotic continuum suggests schizophrenia and depression sharing the same genetic contribution to the pathogenesis. If this would be the case, depression could also be considered as neuro developmental disorder. The aims of the study were to investigate the association between: a pregnancy and birth complications (PBC, and b minor physical anomalies (MPA and schizophrenia or depression. Experimental groups consisted of 60 schizophrenic, 28 major depression patients and 30 healthy controls. All patients were diagnosed according to DSM-IV. Schizophrenic group was divided with regard to PANSS score into positive (n=32 and negative form (n=28 subgroups. PBC information were gathered from maternal recall while MPA were examined by using Waldrop scale for adults. The results showed that negative and positive schizophrenic subgroups had significantly more PBC than depressive group (p<0,05, as well than controls (p<0,001; p<0,05; respectively. There was no significant trend for more PBC in negative than in positive subgroup. All schizophrenic patients had higher rates of MPA than depressives (p<0,05. This trend for more MPA was not significant in comparison with healthy controls. These findings suggest that schizophrenia, especially its negative forms, could be considered as a member of the spectrum of neuro developmental disorders, which does not seem to be the case with depression. PBC and MPA could also be valuable in evaluation of risks for
Farmer, Cristan; Golden, Christine; Thurm, Audrey
Estimates of intelligence in young children with neurodevelopmental disorders are critical for making diagnoses, in characterizing symptoms of disorders, and in predicting future outcomes. The limitations of standardized testing for children with developmental delay or cognitive impairment are well known: Tests do not exist that provide developmentally appropriate material along with norms that extend to the lower reaches of ability. Two commonly used and interchanged instruments are the Mullen Scales of Early Learning (MSEL), a test of developmental level, and the Differential Ability Scales, second edition (DAS-II), a more traditional cognitive test. We evaluated the correspondence of contemporaneous MSEL and the DAS-II scores in a mixed sample of children aged 2-10 years with autism spectrum disorder (ASD), non-ASD developmental delays, and typically developing children across the full spectrum of cognitive ability. Consistent with published data on the original DAS and the MSEL, scores on the DAS-II and MSEL were highly correlated. However, curve estimation revealed large mean differences that varied as a function of the child's cognitive ability level. We conclude that interchanging MSEL and DAS-II scores without regard to the discrepancy in scores may produce misleading results in both cross-sectional and longitudinal studies of children with and without ASD, and, thus, this practice should be implemented with caution.
Vannucci, Anna; Nelson, Eric E.; Bongiorno, Diana M.; Pine, Daniel S.; Yanovski, Jack A.; Tanofsky-Kraff, Marian
Background Pediatric loss-of-control eating is a robust behavioral precursor to binge-type eating disorders. Elucidating precursors to loss-of-control eating and binge-type eating disorders may refine developmental risk models of eating disorders and inform interventions. Method We review evidence within constructs of the Negative Valence Systems (NVS)-domain, as specified by the Research Domain Criteria framework. Based on published studies, we propose an integrated NVS model of binge-type eating disorder risk. Results Data implicate altered corticolimbic functioning, neuroendocrine dysregulation, and self-reported negative affect as possible risk-factors. However, neuroimaging and physiological data in children and adolescents are sparse, and most prospective studies are limited to self-report measures. Conclusions We discuss a broad NVS framework for conceptualizing early risk for binge-type eating disorders. Future neural and behavioral research on the developmental trajectory of loss-of-control and binge-type eating disorders is required. PMID:26040923
Sollis, E; Graham, S.A.; Vino, A.; Froehlich, H.; Vreeburg, M.; Dimitropoulou, D.; Gilissen, C.; Pfundt, R.; Rappold, G.A.; Brunner, H.G; Deriziotis, P.; Fisher, S.E.
De novo disruptions of the neural transcription factor FOXP1 are a recently discovered, rare cause of sporadic intellectual disability (ID). We report three new cases of FOXP1-related disorder identified through clinical whole-exome sequencing. Detailed phenotypic assessment confirmed that global
Isles, Anthony R; Ingason, Andrés; Lowther, Chelsea
Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications m...
Lakes, Kimberley D; Abdullah, Maryam M; Youssef, Julie; Donnelly, Joseph H; Taylor-Lucas, Candice; Goldberg, Wendy A; Cooper, Dan; Aizik, Shlomit
The purpose of this study was to examine a new tool (PPPAS = Parent Perceptions of Physical Activity Scale-Preschool) developed to study parental perceptions of physical activity (PA) among parents of toddler and preschool age children. 143 children (mean age 31.65 months; 75% male) and their parents were recruited from a neurodevelopmental clinic. Parents completed questionnaires, and both a psychologist and a physician evaluated the children. Eighty-three percent of the children received a diagnosis of Autism Spectrum Disorder; 20% of the children had a BMI > 85th percentile. Analyses were conducted to evaluate the reliability, concurrent validity, discriminant validity, and predictive validity of PPPAS scores. Results supported a two-factor structure: Perceptions of the Benefits of PA and the Barriers to PA. The internal consistency of scores was good for both PPPAS subscales, derived from the two factors. Parent perceptions of barriers to PA were significantly correlated with delays in overall adaptive functioning, daily living skills, socialization, and motor skills. When a child's motor skills were delayed, parents were less likely to believe PA was beneficial and perceived more barriers to PA. Parent perceptions of barriers to PA predicted parent-reported weekly unstructured PA and ratings of how physically active their child was compared with other children. We present the PPPAS-Preschool for use in pediatric exercise research and discuss potential applications for the study of parent perceptions of PA in young children.
Bojović, Katarina; Stanković, Biljana; Kotur, Nikola; Krstić-Milošević, Dijana; Gašić, Vladimir; Pavlović, Sonja; Zukić, Branka; Ignjatović, Đurđica
Gastrointestinal disturbances, nutritional deficiencies, and food intolerances are frequently observed in children with neurodevelopmental disorders (NDD). To reveal possible association of celiac disease risk variants (HLA-DQ), lactose intolerance associated variant (LCT-13910C>T) as well as variant associated with vitamin D function (VDR FokI) with NDD, polymerase chain reaction-based methodology was used. Additionally, intestinal peptide permeability was estimated in NDD patients and healthy children by measuring the level of peptides in urine using high-performance liquid chromatography. Levels of opioid peptides, casomorphin 8, and gluten exorphin C were significantly elevated in urine samples of NDD patients (P = 0.004 and P = 0.005, respectively), but no association of genetic risk variants for celiac disease and lactose intolerance with NDD was found. Our results indicate that increased intestinal peptide permeability observed in analyzed NDD patients is not associated with genetic predictors of celiac disease or lactose intolerance. We have also found that FF genotype of VDR FokI and lower serum levels of vitamin D (25-OH) showed association with childhood autism (CHA), a subgroup of NDD. We hypothesize that vitamin D might be important for the development of CHA.
Gillberg, Christopher; Lundström, Sebastian; Fernell, Elisabeth; Nilsson, Gill; Neville, Brian
There is a recently well-documented association between childhood epilepsy and earlysymptomaticsyndromeselicitingneurodevelopmentalclinicalexaminations (ESSENCE) including autism spectrum disorder, but the relationship between febrile seizures and ESSENCE is less clear. The Child and Adolescent Twin Study in Sweden (CATSS) is an ongoing population-based study targeting twins born in Sweden since July 1, 1992. Parents of 27,092 twins were interviewed using a validated DSM-IV-based interview for ESSENCE, in connection with the twins' ninth or twelfth birthday. Diagnoses of febrile seizures (n = 492) and epilepsy (n = 282) were based on data from the Swedish National Patient Register. Prevalence of ESSENCE in individuals with febrile seizures and epilepsy was compared with prevalence in the twin population without seizures. The association between febrile seizures and ESSENCE was considered before and after adjustment for epilepsy. Age of diagnosis of febrile seizures and epilepsy was considered as a possible correlate of ESSENCE in febrile seizures and epilepsy. The rate of ESSENCE in febrile seizures and epilepsy was significantly higher than in the total population without seizures (all P < 0.001). After adjusting for epilepsy, a significant association between febrile seizures and autism spectrum disorder, developmental coordination disorder, and intellectual disability remained. Earlier age of onset was associated with all ESSENCE except attention-deficit/hyperactivity disorder in epilepsy but not with ESSENCE in febrile seizures. In a nationally representative sample of twins, there was an increased rate of ESSENCE in childhood epilepsy and in febrile seizures. Febrile seizures alone could occur as a marker for a broader ESSENCE phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.
Ronca, April E.
Intrauterine complications have been implicated in the etiology of neuripsychiatric disorders including schizophrenia, autism and ADHD. This presentation will describe new translational studies derived from in vivo magnetic resonance imaging of developing and adult brain following perinatal asphyxia (PA). Our findings reveal significant effects of PA on neurometabolic profiles at one week of age, and significant relationships between early metabolites and later life phenotypes including behavior and brain morphometry
Ballendine, Stephanie A; Greba, Quentin; Dawicki, Wojciech; Zhang, Xiaobei; Gordon, John R; Howland, John G
Research suggests that maternal immune activation (MIA) during pregnancy increases the risk of neurodevelopmental disorders including schizophrenia and autism in the offspring. Current theories suggest that inflammatory mediators including cytokines and chemokines may underlie the increased risk of these disorders in humans. For example, elevated maternal interleukin-8 (IL-8) during pregnancy is associated with increased risk of schizophrenia in the offspring. Given this association, the present experiments examined ELR-CXC chemokines CXCL1 and CXCL2, rodent homologues of human IL-8, and activation of their receptors (CXCR1 and CXCR2) in an established rodent model of MIA. Pregnant Long Evans rats were treated with the viral mimetic polyinosinic-polycytidylic acid (polyI:C; 4 mg/kg, i.v.) on gestational day 15. Protein analysis using multiplex assays and ELISA showed that polyI:C significantly increased maternal serum concentrations of interleukin-1β, tumor necrosis factor, and CXCL1 3h after administration. Subsequent experiments tested the role of elevated maternal CXCL1 on behavior of the offspring by administering a CXCR1/CXCR2 antagonist (G31P; 500 μg/kg, i.p.; 1h before, 48 and 96 h after polyI:C treatment). The male offspring of dams treated with polyI:C demonstrated subtle impairments in prepulse inhibition (PPI), impaired associative and crossmodal recognition memory, and altered behavioral flexibility in an operant test battery. While G31P did not completely reverse the behavioral impairments caused by polyI:C, it enhanced PPI during adolescence and strategy set-shifting and reversal learning during young adulthood. These results suggest that while polyI:C treatment significantly increases maternal CXCL1, elevations of this chemokine are not solely responsible for the effects of polyI:C on the behavior of the offspring. Copyright © 2014 Elsevier Inc. All rights reserved.
Hempel, Annmarie; Pagnamenta, Alistair T; Blyth, Moira; Mansour, Sahar; McConnell, Vivienne; Kou, Ikuyo; Ikegawa, Shiro; Tsurusaki, Yoshinori; Matsumoto, Naomichi; Lo-Castro, Adriana; Plessis, Ghislaine; Albrecht, Beate; Battaglia, Agatino; Taylor, Jenny C; Howard, Malcolm F; Keays, David; Sohal, Aman Singh; Kühl, Susanne J; Kini, Usha; McNeill, Alisdair
SOX11 is a transcription factor proposed to play a role in brain development. The relevance of SOX11 to human developmental disorders was suggested by a recent report of SOX11 mutations in two patients with Coffin-Siris syndrome. Here we further investigate the role of SOX11 variants in neurodevelopmental disorders. We used array based comparative genomic hybridisation and trio exome sequencing to identify children with intellectual disability who have deletions or de novo point mutations disrupting SOX11. The pathogenicity of the SOX11 mutations was assessed using an in vitro gene expression reporter system. Loss-of-function experiments were performed in xenopus by knockdown of Sox11 expression. We identified seven individuals with chromosome 2p25 deletions involving SOX11. Trio exome sequencing identified three de novo SOX11 variants, two missense (p.K50N; p.P120H) and one nonsense (p.C29*). The biological consequences of the missense mutations were assessed using an in vitro gene expression system. These individuals had microcephaly, developmental delay and shared dysmorphic features compatible with mild Coffin-Siris syndrome. To further investigate the function of SOX11, we knocked down the orthologous gene in xenopus. Morphants had significant reduction in head size compared with controls. This suggests that SOX11 loss of function can be associated with microcephaly. We thus propose that SOX11 deletion or mutation can present with a Coffin-Siris phenotype. 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/
Iossifov, Ivan; Zheng, Tian; Baron, Miron; Gilliam, T Conrad; Rzhetsky, Andrey
Common hereditary neurodevelopmental disorders such as autism, bipolar disorder, and schizophrenia are most likely both genetically multifactorial and heterogeneous. Because of these characteristics traditional methods for genetic analysis fail when applied to such diseases. To address the problem we propose a novel probabilistic framework that combines the standard genetic linkage formalism with whole-genome molecular-interaction data to predict pathways or networks of interacting genes that contribute to common heritable disorders. We apply the model to three large genotype-phenotype data sets, identify a small number of significant candidate genes for autism (24), bipolar disorder (21), and schizophrenia (25), and predict a number of gene targets likely to be shared among the disorders.
Whitaker, Ashley M; Bell, Terece S; Houskamp, Beth M; O'Callaghan, Erin T
Intellectual giftedness is associated with strong strategic verbal memory while attention-deficit hyperactivity disorder (ADHD) is associated with strategic verbal memory deficits; however, no previous research has explored how this contradiction manifests in gifted populations with diagnoses of ADHD. The purpose of this study was to explore strategic verbal memory processes among intellectually gifted youth with and without ADHD to provide clarification regarding this specific aspect of neuropsychological functioning within this population. One hundred twenty-five youth completed neuropsychological evaluations including the Wechsler Intelligence Scale for Children-Fourth Edition and California Verbal Learning Test-Children's Version (CVLT-C). Results revealed significant differences between groups, with intellectually gifted youth with ADHD achieving lower T scores on CVLT-C Trials 1 through 5 compared with intellectually gifted youth without ADHD, and intellectually gifted youth with ADHD achieving higher T scores than youth of average intellectual abilities with ADHD. Additionally, repeated-measures analysis of variance revealed a main effect improvement among gifted youth with ADHD in short-delay recall when provided with organizational cues. Findings revealed new evidence about the role of twice exceptionality (specifically intellectual giftedness and ADHD) in strategic verbal memory and have important implications for parents, educators, psychologists and neuropsychologists, and other mental health professionals working with this population.
Anthony R Isles
Full Text Available Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS region have been associated with developmental delay (DD, autism spectrum disorder (ASD and schizophrenia (SZ. Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA, but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15 or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of
Isles, Anthony R.; Ingason, Andrés; Lowther, Chelsea; Gawlick, Micha; Stöber, Gerald; Potter, Harry; Georgieva, Lyudmila; Pizzo, Lucilla; Ozaki, Norio; Kushima, Itaru; Ikeda, Masashi; Iwata, Nakao; Levinson, Douglas F.; Gejman, Pablo V.; Shi, Jianxin; Sanders, Alan R.; Duan, Jubao; Sisodiya, Sanjay; Costain, Gregory; Degenhardt, Franziska; Giegling, Ina; Rujescu, Dan; Hreidarsson, Stefan J.; Saemundsen, Evald; Ahn, Joo Wook; Ogilvie, Caroline; Stefansson, Hreinn; Stefansson, Kari; O’Donovan, Michael C.; Owen, Michael J.; Bassett, Anne; Kirov, George
Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally
Kunitz, Selma C.; Havekost, Charles L.; Gross, Cynthia R.
National pilot data bank networks for stroke and traumatic coma have recently been initiated at multiple centers by the National Institute of Neurological and Communicative Disorders and Stroke. The characteristics of these pilot data bank projects include: 1) the overall development and statement of research issues by a multidisciplinary team; 2) dual emphasis on patient management and clinical research; 3) the definition and use of a uniform clinical vocabulary; 4) the use of a clinically-oriented data base management system; and 5) the use of intelligent terminals for data entry, retrieval, and patient management. This paper will describe the data bank approach used by the neurological disorders programs.
Nørgaard, Martin; Ganz, Melanie; Svarer, Claus
Background: Seasonal Affective Disorder (SAD) is a subtype of Major Depressive Disorder characterized by seasonally occurring depression that often presents with atypical vegetative symptoms such as hypersomnia and carbohydrate craving. It has recently been shown that unlike healthy people......, patients with SAD fail to globally downregulate their cerebral serotonin transporter (5-HTT) in winter, and that this effect seemed to be particularly pronounced in female S-carriers of the 5-HTTLPR genotype. The purpose of this study was to identify a 5-HTT brain network that accounts for the adaption...
Kevin R. McLeod
Full Text Available Developmental coordination disorder (DCD and attention-deficit hyperactivity disorder (ADHD are highly comorbid neurodevelopmental disorders; however, the neural mechanisms of this comorbidity are poorly understood. Previous research has demonstrated that children with DCD and ADHD have altered brain region communication, particularly within the motor network. The structure and function of the motor network in a typically developing brain exhibits hemispheric dominance. It is plausible that functional deficits observed in children with DCD and ADHD are associated with neurodevelopmental alterations in within- and between-hemisphere motor network functional connection strength that disrupt this hemispheric dominance. We used resting-state functional magnetic resonance imaging to examine functional connections of the left and right primary and sensory motor (SM1 cortices in children with DCD, ADHD and DCD + ADHD, relative to typically developing children. Our findings revealed that children with DCD, ADHD and DCD + ADHD exhibit atypical within- and between-hemisphere functional connection strength between SM1 and regions of the basal ganglia, as well as the cerebellum. Our findings further support the assertion that development of atypical motor network connections represents common and distinct neural mechanisms underlying DCD and ADHD. In children with DCD and DCD + ADHD (but not ADHD, a significant correlation was observed between clinical assessment of motor function and the strength of functional connections between right SM1 and anterior cingulate cortex, supplementary motor area, and regions involved in visuospatial processing. This latter finding suggests that behavioral phenotypes associated with atypical motor network development differ between individuals with DCD and those with ADHD.
Fejzo, Marlena S; Magtira, Aromalyn; Schoenberg, Frederic Paik; Macgibbon, Kimber; Mullin, Patrick M
The purpose of this study is to determine the frequency of emotional, behavioral, and learning disorders in children exposed in utero to hyperemesis gravidarum (HG) and to identify prognostic factors for these disorders. Neurodevelopmental outcomes of 312 children from 203 mothers with HG were compared to neurodevelopmental outcomes from 169 children from 89 unaffected mothers. Then the clinical profiles of patients with HG and a normal child outcome were compared to the clinical profiles of patients with HG and a child with neurodevelopmental delay to identify prognostic factors. Binary responses were analyzed using either a Chi-square or Fisher Exact test and continuous responses were analyzed using a t-test. Children exposed in utero to HG have a 3.28-fold increase in odds of a neurodevelopmental diagnosis including attention disorders, learning delay, sensory disorders, and speech and language delay (Ppregnancies, only early onset of symptoms (prior to 5 weeks gestation) was significantly linked to neurodevelopmental delay. We found no evidence for increased risk of 13 emotional, behavioral, and learning disorders, including autism, intellectual impairment, and obsessive-compulsive disorder. However, the study was not sufficiently powered to detect rare conditions. Medications, treatments, and preterm birth were not associated with an increased risk for neurodevelopmental delay. Women with HG are at a significantly increased risk of having a child with neurodevelopmental delay. Common antiemetic treatments were not linked to neurodevelopmental delay, but early symptoms may play a role. There is an urgent need to address whether aggressive treatment that includes vitamin and nutrient supplementation in women with early symptoms of severe nausea of pregnancy decreases the risk of neurodevelopmental delay. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Di Martino, Adriana; Zuo, Xi-Nian; Kelly, Clare; Grzadzinski, Rebecca; Mennes, Maarten; Schvarcz, Ariel; Rodman, Jennifer; Lord, Catherine; Castellanos, F Xavier; Milham, Michael P
Individuals with autism spectrum disorders (ASD) often exhibit symptoms of attention-deficit/hyperactivity disorder (ADHD). Across both disorders, observations of distributed functional abnormalities suggest aberrant large-scale brain network connectivity. Yet, common and distinct network correlates of ASD and ADHD remain unidentified. Here, we aimed to examine patterns of dysconnection in school-age children with ASD and ADHD and typically developing children who completed a resting state functional magnetic resonance imaging scan. We measured voxelwise network centrality, functional connectivity metrics indexing local (degree centrality [DC]) and global (eigenvector centrality) functional relationships across the entire brain connectome, in resting state functional magnetic resonance imaging data from 56 children with ASD, 45 children with ADHD, and 50 typically developing children. A one-way analysis of covariance, with group as fixed factor (whole-brain corrected), was followed by post hoc pairwise comparisons. Cortical and subcortical areas exhibited centrality abnormalities, some common to both ADHD and ASD, such as in precuneus. Others were disorder-specific and included ADHD-related increases in DC in right striatum/pallidum, in contrast with ASD-related increases in bilateral temporolimbic areas. Secondary analyses differentiating children with ASD into those with or without ADHD-like comorbidity (ASD(+) and ASD(-), respectively) revealed that the ASD(+) group shared ADHD-specific abnormalities in basal ganglia. By contrast, centrality increases in temporolimbic areas characterized children with ASD regardless of ADHD-like comorbidity. At the cluster level, eigenvector centrality group patterns were similar to DC. ADHD and ASD are neurodevelopmental disorders with distinct and overlapping clinical presentations. This work provides evidence for both shared and distinct underlying mechanisms at the large-scale network level. Copyright © 2013 Society of
Bouna-Pyrrou, Polyxeni; Mühle, Christiane; Kornhuber, Johannes; Lenz, Bernd
The internet age bears new challenges that include health risks. It is agreed that excessive internet use may reach pathological levels. However, the concept of internet addiction lacks specificity and, therefore, warrants studies on its diagnostic and etiologic classification. This study was conducted to characterize the novel DSM-5 criteria for internet gaming disorder and the adapted criteria for the "social network disorder". Based on the established association of handedness and substance use disorders, we also explored whether internet use related to laterality. For this study, 3,287 volunteers participated in the online survey and gave particulars concerning their internet use in general, internet gaming and use of social networks, laterality markers (hand, foot, eye, ear, rotational preference in gymnastics, and head turning asymmetry) and health status. Of the participants, 1.1 % fulfilled the criteria for internet gaming disorder, and 1.8 % fulfilled the criteria for social network disorder. The applied criteria were highly correlated with the time spent on the respective internet activities (p gaming and social network use and provide evidence that biological markers of substance use disorders are involved in internet addiction.
Camacho, Ricardo; McCauley, Brandon; Szczech Moser, Christy
Over 70 years ago Dr. Karel Bobath and his wife Bertha Bobath began to craft the therapeutic intervention now known as neurodevelopmental treatment (NDT). This edition of Reviews, Tools, and Resources will highlight a historical review of research studies that have been completed, current websites, books, and blogs focusing on NDT.
Novel de novo variant in EBF3 is likely to impact DNA binding in a patient with a neurodevelopmental disorder and expanded phenotypes: patient report, in silico functional assessment, and review of published cases
Blackburn, Patrick; Barnett, Sarah S.; Zimmermann, Michael T.; Cousin, Margot A.; Kaiwar, Charu; Pinto e Vairo,Filippo; Niu, Zhiyv; Ferber, Matthew J.; Urrutia, Raul A.; Selcen, Duygu; Eric W. Klee; Pichurin, Pavel N.
Pathogenic variants in EBF3 were recently described in three back-to-back publications in association with a novel neurodevelopmental disorder characterized by intellectual disability, speech delay, ataxia, and facial dysmorphisms. In this report, we describe an additional patient carrying a de novo missense variant in EBF3 (c.487C>T, p.(Arg163Trp)) that falls within a conserved residue in the zinc knuckle motif of the DNA binding domain. Without a solved structure of the DNA binding domain, ...
Angelica eDe La Fuente
Full Text Available Attention-Deficit/Hyperactivity disorder (ADHD is the most commonly diagnosed neurodevelopmental disorder in childhood, which affects more than 5% of the population worldwide. ADHD is characterized by developmentally inappropriate behaviors of inattention, and/or impulsivity and hyperactivity. These behavioral manifestations contribute to diminished academic, occupational and social functioning, and have neurobiological bases. Neuronal deficits, especially in the attention and executive function processing networks, have been implicated in both children and adults with ADHD by using sophisticated structural and functional neuroimaging approaches. These structural and functional abnormalities in the brain networks have been associated with the impaired cognitive, affective, and motor behaviors seen in the disorder. The goal of this review is to summarize and integrate emerging themes from the existing neuroimaging connectivity studies based on advanced imaging techniques, applied in data of structural Magnetic Resonance Imaging (MRI, functional MRI (fMRI, Diffusion Tensor Imaging (DTI, Electroencephalography (EEG and Event Related Potential (ERP; and to discuss the results of these studies when considering future directions for understanding pathophysiological mechanisms and developmental trajectories of the behavioral manifestations in ADHD. We conclude this review by suggesting that future research should put more effort on understanding the roles of the subcortical structures and their structural/functional pathways in ADHD.
Albin, Roger L
Tourette syndrome is a common neurodevelopmental disorder defined by characteristic involuntary movements, tics, with both motor and phonic components. Tourette syndrome is usually conceptualized as a basal ganglia disorder, with an emphasis on striatal dysfunction. While considerable evidence is consistent with these concepts, imaging data suggest diffuse functional and structural abnormalities in Tourette syndrome brain. Tourette syndrome exhibits features that are difficult to explain solely based on basal ganglia circuit dysfunctions. These features include the natural history of tic expression, with typical onset of tics around ages 5 to 7 years and exacerbation during the peri-pubertal years, marked sex disparity with higher male prevalence, and the characteristic distribution of tics. The latter are usually repetitive, somewhat stereotyped involuntary eye, facial and head movements, and phonations. A major functional role of eye, face, and head movements is social signalling. Prior work in social neuroscience identified a phylogenetically conserved network of sexually dimorphic subcortical nuclei, the Social Behaviour Network, mediating many social behaviours. Social behaviour network function is modulated developmentally by gonadal steroids and social behaviour network outputs are stereotyped sex and species specific behaviours. In 2011 O'Connell and Hofmann proposed that the social behaviour network interdigitates with the basal ganglia to form a greater network, the social decision-making network. The social decision-making network may have two functionally complementary limbs: the basal ganglia component responsible for evaluation of socially relevant stimuli and actions with the social behaviour network component responsible for the performance of social acts. Social decision-making network dysfunction can explain major features of the neurobiology of Tourette syndrome. Tourette syndrome may be a disorder of social communication resulting from
Full Text Available Autism spectrum disorder (ASD is a neurodevelopmental disorder characterized by behavioral impairment in social interactions. Although theoretical and empirical evidence suggests that impairment in the social brain network could be the neural underpinnings of ASD, previous structural magnetic resonance imaging (MRI studies in adults with ASD have not provided clear support for this, possibly due to confounding factors, such as language impairments. To further explore this issue, we acquired structural MRI data and analyzed gray matter volume in adults with ASD (n = 36 who had no language impairments (diagnosed with Asperger’s disorder or pervasive developmental disorder not otherwise specified, with symptoms milder than those of Asperger’s disorder, had no comorbidity, and were not taking medications, and in age- and sex-matched typically developing (TD controls (n = 36. Univariate voxel-based morphometry analyses revealed that regional gray matter volume was lower in the ASD than in the control group in several brain regions, including the right inferior occipital gyrus, left fusiform gyrus, right middle temporal gyrus, bilateral amygdala, right inferior frontal gyrus, right orbitofrontal cortex, and left dorsomedial prefrontal cortex. A multivariate approach using a partial least squares (PLS method showed that these regions constituted a network that could be used to discriminate between the ASD and TD groups. A PLS discriminant analysis using information from these regions showed high accuracy, sensitivity, specificity, and precision (>80% in discriminating between the groups. These results suggest that reduced gray matter volume in the social brain network represents the neural underpinnings of behavioral social malfunctioning in adults with ASD.
Full Text Available Autism spectrum disorders (ASD are neurodevelopmental disorders with phenotypic and genetic heterogeneity. Recent studies have reported rare and de novo mutations in ASD, but the allelic architecture of ASD remains unclear. To assess the role of common and rare variations in ASD, we constructed a gene co-expression network based on a widespread survey of gene expression in the human brain. We identified modules associated with specific cell types and processes. By integrating known rare mutations and the results of an ASD genome-wide association study (GWAS, we identified two neuronal modules that are perturbed by both rare and common variations. These modules contain highly connected genes that are involved in synaptic and neuronal plasticity and that are expressed in areas associated with learning and memory and sensory perception. The enrichment of common risk variants was replicated in two additional samples which include both simplex and multiplex families. An analysis of the combined contribution of common variants in the neuronal modules revealed a polygenic component to the risk of ASD. The results of this study point toward contribution of minor and major perturbations in the two sub-networks of neuronal genes to ASD risk.
Uhlhaas, Peter J; Singer, Wolf
Recent data from developmental cognitive neuroscience highlight the profound changes in the organization and function of cortical networks during the transition from adolescence to adulthood. While previous studies have focused on the development of gray and white matter, recent evidence suggests that brain maturation during adolescence extends to fundamental changes in the properties of cortical circuits that in turn promote the precise temporal coding of neural activity. In the current article, we will highlight modifications in the amplitude and synchrony of neural oscillations during adolescence that may be crucial for the emergence of cognitive deficits and psychotic symptoms in schizophrenia. Specifically, we will suggest that schizophrenia is associated with impaired parameters of synchronous oscillations that undergo changes during late brain maturation, suggesting an important role of adolescent brain development for the understanding, treatment, and prevention of the disorder. © The Author 2011. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
Psychiatric disorders such as schizophrenia and autism are characterised by cellular disorganisation and dysconnectivity across the brain and can be caused by mutations in genes that control neurodevelopmental processes. To examine how neurodevelopmental defects can affect brain function and behaviour, we have comprehensively investigated the consequences of mutation of one such gene, Semaphorin-6A, on cellular organisation, axonal projection patterns, behaviour and physiology in mice. These analyses reveal a spectrum of widespread but subtle anatomical defects in Sema6A mutants, notably in limbic and cortical cellular organisation, lamination and connectivity. These mutants display concomitant alterations in the electroencephalogram and hyper-exploratory behaviour, which are characteristic of models of psychosis and reversible by the antipsychotic clozapine. They also show altered social interaction and deficits in object recognition and working memory. Mice with mutations in Sema6A or the interacting genes may thus represent a highly informative model for how neurodevelopmental defects can lead to anatomical dysconnectivity, resulting, either directly or through reactive mechanisms, in dysfunction at the level of neuronal networks with associated behavioural phenotypes of relevance to psychiatric disorders. The biological data presented here also make these genes plausible candidates to explain human linkage findings for schizophrenia and autism.
Angriman, Marco; Caravale, Barbara; Novelli, Luana; Ferri, Raffaele; Bruni, Oliviero
This review describes recent research in pediatric sleep disorders associated with neurodevelopmental disabilities (NDDs) and their treatment. NDDs affect more than 2% of the general population and represent more than 35% of the total cases of children referred to a neuropsychiatric center for sleep problems. Specific clinical and therapeutic aspects of sleep disorders associated with Down syndrome, Fragile X syndrome, Prader-Willi syndrome, Angelman syndrome, Rett syndrome, Smith-Magenis syndrome, cerebral palsy, and autism spectrum disorders are described. Furthermore, the drugs commonly used for sleep disorders in children with NDDs are described. The review clearly highlighted that children with NDDs are often affected by sleep disorders that require appropriate clinical and therapeutic approach to improve quality of life in both patients and families. Georg Thieme Verlag KG Stuttgart · New York.
Sylvester, C.M.; Corbetta, M.; Raichle, M.E.; Rodebaugh, T.; Schlaggar, B L; Sheline, Y I; Zorumski, C F; Lenze, E.J.
A recent paradigm shift in systems neuroscience is the division of the human brain into functional networks. Functional networks are collections of brain regions with strongly correlated activity both at rest and during cognitive tasks, and each network is believed to implement a different aspect of cognition. Here, we propose that anxiety disorders and high trait anxiety are associated with a particular pattern of functional network dysfunction: increased functioning of the cingulo-opercular...
Pearl, Phillip L; Sable, Craig; Evans, Sarah; Knight, Joseph; Cunningham, Parker; Lotrecchiano, Gaetano R; Gropman, Andrea; Stuart, Sheela; Glass, Penny; Conway, Anne; Ramadan, Issam; Paiva, Tania; Batshaw, Mark L; Packer, Roger J
A telemedicine program was developed between the Children's National Medical Center (CNMC) in Washington, DC, and the Sheikh Khalifa Bin Zayed Foundation in the United Arab Emirates (UAE). A needs assessment and a curriculum of on-site training conferences were devised preparatory to an ongoing telemedicine consultation program for children with neurodevelopmental disabilities in the underserved eastern region of the UAE. Weekly telemedicine consultations are provided by a multidisciplinary faculty. Patients are presented in the UAE with their therapists and families. Real-time (video over Internet protocol; average connection, 768 kilobits/s) telemedicine conferences are held weekly following previews of medical records. A full consultation report follows each telemedicine session. Between February 29, 2012 and June 26, 2013, 48 weekly 1-h live interactive telemedicine consultations were conducted on 48 patients (28 males, 20 females; age range, 8 months-22 years; median age, 5.4 years). The primary diagnoses were cerebral palsy, neurogenetic disorders, autism, neuromuscular disorders, congenital anomalies, global developmental delay, systemic disease, and epilepsy. Common comorbidities were cognitive impairment, communication disorders, and behavioral disorders. Specific recommendations included imaging and DNA studies, antiseizure management, spasticity management including botulinum toxin protocols, and specific therapy modalities including taping techniques, customized body vests, and speech/language and behavioral therapy. Improved outcomes reported were in clinician satisfaction, achievement of therapy goals for patients, and requests for ongoing sessions. Weekly telemedicine sessions coupled with triannual training conferences were successfully implemented in a clinical program dedicated to patients with neurodevelopmental disabilities by the Center for Neuroscience at CNMC and the UAE government. International consultations in neurodevelopmental
Kristofiková, Zdena; Stástný, Frantisek; Bubeniková, Vera; Druga, Rastislav; Klaschka, Jan; Spaniel, Filip
Studies suggest age- and sex-dependent structural and functional patterns of human cerebral lateralization underlie hemisphere specialization and its alterations in schizophrenia. Recent works report sexual dimorphism of neurons in the hippocampal formation and specialization of hemispheres in rats. Our experiments indicate for the first time functional lateralization of the high-affinity choline uptake (HACU) system directly associated with a synthesis of acetylcholine in the hippocampus of Wistar rats. The markedly increased HACU activity was found in the left compared to the right hippocampus of adult male but not female animals. Lineweaver-Burk plot analysis revealed a statistically significant increase of Vmax in the left hippocampus of 14-day-old when compared to 7-day-old males. It appears that laterality of HACU occurs during late postnatal maturation, and its degree is markedly enhanced after puberty and attenuated during aging. Quinolinic acid (QUIN), an endogenous agonist of N-methyl-D-aspartate type glutamate receptors, was used in this study to evaluate the neurodevelopmental hypothesis of schizophrenia. It is known that elevated levels of QUIN accompany viral infections, increasing the risk of developing schizophrenia. Bilateral intracerebroventricular application of QUIN (250 nmoles/ventricle) to pups aged 12 days significantly impaired the cholinergic hippocampal system of adolescent male and female rats and reversed lateralization of male HACU. Morphological analysis indicated marked changes in brain lesion sizes (extensive 24 h and moderate 38 days after the operation). Asymmetry of lesions was observed in the majority of cases, but the left hemisphere was not generally more vulnerable to QUIN effects than the right side. Moreover, no lateral differences were found between lesioned hippocampi in the specific binding of [3H]hemicholinium-3 (10%-15% loss of binding sites when compared to sham-operated animals). In summary, our results indicate a
Baldwin, David S.; Allgulander, Christer; Altamura, Alfredo Carlo; Angst, Jules; Bandelow, Borwin; den Boer, Johan; Boyer, Patrice; Davies, Simon; dell'Osso, Bernardo; Eriksson, Elias; Fineberg, Naomi; Fredrikson, Mats; Herran, Andres; Maron, Eduard; Metspalu, Andres; Nutt, David; van der Wee, Nic; Luis Vazquez-Barquero, Jose; Zohar, Joseph
Despite the size, burden and costs of anxiety disorders, many patients remain unrecognised, and the effectiveness of evidence-based interventions in routine clinical practice can be disappointing. The European College of Neuropsychopharmacology (ECNP) has established the ECNP Network Initiative
Kennis, M.; Van Rooij, S. J H; Van Den Heuvel, M. P.; Kahn, R. S.; Geuze, E.
Posttraumatic stress disorder (PTSD) is a disabling disorder associated with resting state functional connectivity alterations. However, whether specific brain regions are altered in PTSD or whether the whole brain network organization differs remains unclear. PTSD can be treated with trauma-focused
Catani, Marco; Dell'Acqua, Flavio; Budisavljevic, Sanja; Howells, Henrietta; Thiebaut De Schotten, Michel; Froudist-Walsh, Seán; D'Anna, Lucio; Thompson, Abigail; Sandrone, Stefano; Bullmore, Edward T.; Suckling, John; Baron-Cohen, Simon; Lombardo, Michael V.; Wheelwright, Sally J.; Chakrabarti, Bhismadev; Lai, Meng Chuan; Ruigrok, Amber N V; Leemans, Alexander|info:eu-repo/dai/nl/340300108; Ecker, Christine; Craig, Michael C.; Murphy, Declan G M; Bailey, Anthony J.; Bolton, Patrick F.; Carrington, Sarah; Daly, Eileen M.; Deoni, Sean C.; Happé, Francesca; Henty, Julian; Jezzard, Peter; Johnston, Patrick; Jones, Derek K.; Madden, Anya; Mullins, Diane; Murphy, Clodagh M.; Murphy, Declan G M; Pasco, Greg; Ruigrok, Amber N V; Sadek, Susan A.; Spain, Debbie; Stewart, Rose; Williams, Steven C.
It has been postulated that autism spectrum disorder is underpinned by an 'atypical connectivity' involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism
Novel de novo variant in EBF3 is likely to impact DNA binding in a patient with a neurodevelopmental disorder and expanded phenotypes: patient report, in silico functional assessment, and review of published cases.
Blackburn, Patrick R; Barnett, Sarah S; Zimmermann, Michael T; Cousin, Margot A; Kaiwar, Charu; Pinto E Vairo, Filippo; Niu, Zhiyv; Ferber, Matthew J; Urrutia, Raul A; Selcen, Duygu; Klee, Eric W; Pichurin, Pavel N
Pathogenic variants in EBF3 were recently described in three back-to-back publications in association with a novel neurodevelopmental disorder characterized by intellectual disability, speech delay, ataxia, and facial dysmorphisms. In this report, we describe an additional patient carrying a de novo missense variant in EBF3 (c.487C>T, p.(Arg163Trp)) that falls within a conserved residue in the zinc knuckle motif of the DNA binding domain. Without a solved structure of the DNA binding domain, we generated a homology-based atomic model and performed molecular dynamics simulations for EBF3, which predicted decreased DNA affinity for p.(Arg163Trp) compared with wild-type protein and control variants. These data are in agreement with previous experimental studies of EBF1 showing the paralogous residue is essential for DNA binding. The conservation and experimental evidence existing for EBF1 and in silico modeling and dynamics simulations to validate comparable behavior of multiple variants in EBF3 demonstrates strong support for the pathogenicity of p.(Arg163Trp). We show that our patient presents with phenotypes consistent with previously reported patients harboring EBF3 variants and expands the phenotypic spectrum of this newly identified disorder with the additional feature of a bicornuate uterus.
Mikkelsen, Stine Schou; Tolstrup, Janne S; Becker, Ulrik
in a prospective design. METHODS: Information on social network and covariates was obtained from 9589 men and women aged 21-99 years in the Copenhagen City Heart Study, followed for registration of alcohol use disorder in the Danish National Patient Registry and the WINALCO database. RESULTS: Men who lived alone......OBJECTIVE: Social network has been linked to alcohol use disorder in several studies. However, since the majority of such findings are cross-sectional, causal interpretation is difficult. The aim of the present study was to test if social network characteristics predict alcohol use disorder......, were separated or divorced or widowers had a higher risk of developing alcohol use disorder: HR among men living alone vs. men not living alone was 2.28 (95% CI: 1.59-3.27), and HR among separated/divorced men vs. married men was 2.55 (95% CI: 1.33-4.89). No such associations were found among women...
Beroz, Farzan; Jawerth, Louise M.; Münster, Stefan; Weitz, David A.; Broedersz, Chase P.; Wingreen, Ned S.
Cells actively probe and respond to the stiffness of their surroundings. Since mechanosensory cells in connective tissue are surrounded by a disordered network of biopolymers, their in vivo mechanical environment can be extremely heterogeneous. Here we investigate how this heterogeneity impacts mechanosensing by modelling the cell as an idealized local stiffness sensor inside a disordered fibre network. For all types of networks we study, including experimentally-imaged collagen and fibrin architectures, we find that measurements applied at different points yield a strikingly broad range of local stiffnesses, spanning roughly two decades. We verify via simulations and scaling arguments that this broad range of local stiffnesses is a generic property of disordered fibre networks. Finally, we show that to obtain optimal, reliable estimates of global tissue stiffness, a cell must adjust its size, shape, and position to integrate multiple stiffness measurements over extended regions of space.
Hamaguchi, Kosuke; Hatchett, J. P. L.; Okada, Masato
The replica method has played a key role in analyzing systems with disorder, e.g., the Sherrington-Kirkpatrick (SK) model, and associative neural networks. Here we study the influence of disorder in the lateral inhibition type interactions on the cooperative and uncooperative behavior of recurrent neural networks by using the replica method. Although the interaction between neurons has a dependency on distance, our model can be solved analytically. Bifurcation analysis identifies the boundaries between paramagnetic, ferromagnetic, spin-glass, and localized phases. In the localized phase, the network shows a bump like activity, which is often used as a model of spatial working memory or columnar activity in the visual cortex. Simulation results show that disordered interactions can stabilize the drift the of bump position, which is commonly observed in conventional lateral inhibition type neural networks.
Kable, Julie A; Mukherjee, Raja A S
Neurobehavioral Disorder associated with Prenatal Alcohol Exposure (ND-PAE) was proposed as a diagnostic formulation intended to capture the range of mental health problems occurring in alcohol-affected individuals with a history of prenatal alcohol exposure. The proposed criteria for the disorder are reviewed as well as various factors considered in the development of the disorder and its associated criteria. The taxonomic research related to the disorder is reviewed with preliminary analyses indicating that clinicians are readily able to agree when applying the diagnostic criteria but that the adaptive functioning criteria may need to be modified to expand its coverage of alcohol-affected individuals and to aid in discriminating these individuals from others not alcohol-affected. Finally, the challenges with translating the diagnosis into European medical and mental healthcare systems are discussed and recommendations for facilitating implementation are made. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Modern network science has revealed fundamental aspects of normal brain-network organization, such as small-world and scale-free patterns, hierarchical modularity, hubs and rich clubs. The next challenge is to use this knowledge to gain a better understanding of brain disease. Recent developments in
Cornwell, Erin York
Family relationships, social interactions, and exchanges of support often revolve around the household context, but scholars rarely consider the social relevance of this physical space. In this article the author considers social causes and consequences of household disorder in the dwellings of older adults. Drawing from research on neighborhood disorder and social connectedness in later life, she describes how network characteristics may contribute to household disorder and how household disorder may weaken relationships and reduce access to support. This is explored empirically by estimating cross-lagged panel models with data from 2 waves of the National Social Life, Health, and Aging Project. The results reveal that household disorder reflects a lack of social support, and it leads to more kin-centered networks and more strain within family relationships. The author concludes by urging greater attention to how the household context shapes-and is shaped by-the social interactions and processes that occur within it.
Stern, Francine Martin; Gorga, Delia
Use of neurodevelopmental treatment, also known as the Bobath method, is discussed, including its history, philosophy, goals, and treatment emphasis with infants and children with movement disorders. Examples of children before and after therapeutic intervention illustrate use of the technique, and controversies in measuring therapy efficacy are…
Autism is a developmental disorder with variable severity, occurring at all levels of cognitive ability and having a number of slightly different clinical presentations. It is associated with neuropsychological deficits that occur in other conditions also, but its pattern may be specific to autism. Genetic and environmental early insults to brain development are etiological determinants of the disorder. Brain circuitries important for social, communicative, and integrational purposes have been suggested to be dysfunctional in autism. There could be at least two different pathways to autism, one connected with primary temporofrontal dysfunction (and late prenatal-early postnatal origins) and another linked to primary brain-stem dysfunction (and early prenatal origins). Further study of neurodevelopmental and neuropsychological processes in autism will help elucidate not only the pathological mechanisms involved in the specific syndromes but also the underpinnings of normal brain development.
Catani, Marco; Dell'Acqua, Flavio; Budisavljevic, Sanja; Howells, Henrietta; Thiebaut de Schotten, Michel; Froudist-Walsh, Seán; D'Anna, Lucio; Thompson, Abigail; Sandrone, Stefano; Bullmore, Edward T; Suckling, John; Baron-Cohen, Simon; Lombardo, Michael V; Wheelwright, Sally J; Chakrabarti, Bhismadev; Lai, Meng-Chuan; Ruigrok, Amber N V; Leemans, Alexander; Ecker, Christine; Consortium, Mrc Aims; Craig, Michael C; Murphy, Declan G M
It has been postulated that autism spectrum disorder is underpinned by an 'atypical connectivity' involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a 'whole brain' non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate--predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these
Catani, Marco; Dell’Acqua, Flavio; Budisavljevic, Sanja; Howells, Henrietta; Thiebaut de Schotten, Michel; Froudist-Walsh, Seán; D’Anna, Lucio; Thompson, Abigail; Sandrone, Stefano; Bullmore, Edward T.; Suckling, John; Baron-Cohen, Simon; Lombardo, Michael V.; Wheelwright, Sally J.; Chakrabarti, Bhismadev; Lai, Meng-Chuan; Ruigrok, Amber N. V.; Leemans, Alexander; Ecker, Christine; Consortium, MRC AIMS; Craig, Michael C.
It has been postulated that autism spectrum disorder is underpinned by an ‘atypical connectivity’ involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a ‘whole brain’ non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate—predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms
Wilska, M L; Kaski, M K
One of the most important tasks of a physician who has patients with delayed development is to assess the cause of the problem. To help with this work, an aetiological classification based on timing and type of the injury to the central nervous system (CNS), has been created. The main divisions are: genetic causes; CNS malformations and multiple malformation syndromes of unknown origin; external prenatal factors; paranatally acquired disorders (-1 to +4 weeks from delivery); postnatally acquired disorders; and untraceable or unclassified causes. In the classification, the earliest factor injuring the CNS is the primary diagnosis. The first stage, which consists of a quite simple workup, reveals the timing of the injury and allows the possibility for family counselling. The overview of the second stage assessment is also given. The 'aetiological tree' illustrates the classification method and serves as a reference and teaching aid. It can also be used for genetic counselling to demonstrate the situation. This method has been used for almost 20 years and has been proven to enhance diagnostic activity and family counselling.
Full Text Available INTRODUCTION: The vast number of psychopathological syndromes that can be observed in clinical practice can be described in terms of a limited number of elementary syndromes that are differentially expressed. Previous attempts to identify elementary syndromes have shown limitations that have slowed progress in the taxonomy of psychiatric disorders. AIM: To examine the ability of network community detection (NCD to identify elementary syndromes of psychopathology and move beyond the limitations of current classification methods in psychiatry. METHODS: 192 patients with unselected mental disorders were tested on the Comprehensive Psychopathological Rating Scale (CPRS. Principal component analysis (PCA was performed on the bootstrapped correlation matrix of symptom scores to extract the principal component structure (PCS. An undirected and weighted network graph was constructed from the same matrix. Network community structure (NCS was optimized using a previously published technique. RESULTS: In the optimal network structure, network clusters showed a 89% match with principal components of psychopathology. Some 6 network clusters were found, including "Depression", "Mania", "Anxiety", "Psychosis", "Retardation", and "Behavioral Disorganization". Network metrics were used to quantify the continuities between the elementary syndromes. CONCLUSION: We present the first comprehensive network graph of psychopathology that is free from the biases of previous classifications: a 'Psychopathology Web'. Clusters within this network represent elementary syndromes that are connected via a limited number of bridge symptoms. Many problems of previous classifications can be overcome by using a network approach to psychopathology.
Goekoop, Rutger; Goekoop, Jaap G
The vast number of psychopathological syndromes that can be observed in clinical practice can be described in terms of a limited number of elementary syndromes that are differentially expressed. Previous attempts to identify elementary syndromes have shown limitations that have slowed progress in the taxonomy of psychiatric disorders. To examine the ability of network community detection (NCD) to identify elementary syndromes of psychopathology and move beyond the limitations of current classification methods in psychiatry. 192 patients with unselected mental disorders were tested on the Comprehensive Psychopathological Rating Scale (CPRS). Principal component analysis (PCA) was performed on the bootstrapped correlation matrix of symptom scores to extract the principal component structure (PCS). An undirected and weighted network graph was constructed from the same matrix. Network community structure (NCS) was optimized using a previously published technique. In the optimal network structure, network clusters showed a 89% match with principal components of psychopathology. Some 6 network clusters were found, including "Depression", "Mania", "Anxiety", "Psychosis", "Retardation", and "Behavioral Disorganization". Network metrics were used to quantify the continuities between the elementary syndromes. We present the first comprehensive network graph of psychopathology that is free from the biases of previous classifications: a 'Psychopathology Web'. Clusters within this network represent elementary syndromes that are connected via a limited number of bridge symptoms. Many problems of previous classifications can be overcome by using a network approach to psychopathology.
Lehner, Małgorzata; Taracha, Ewa; Wisłowska, Aleksandra; Zienowicz, Małgorzata; Maciejak, Piotr; Skórzewska, Anna; Płaźnik, Adam
Schizophrenia is a complex disorder of unknown origin, characterised by abnormalities in the realms of perception, thinking and the experience of emotions that onset is restricted to young adulthood. Many techniques that range from neuropathology to neuroimaging identified subtle brain abnormalities particularly in frontal, temporal cortex, hippocampus, basal ganglia and cerebellum. Neurodevelopmental models of schizophrenia test hypotheses that this disease is caused by a defect in cerebral development which results in altered neural connectivity, brain neurochemistry and aberrant behaviour observed in adult life. Recent evidence indicates that neonatal hippocampal damage may affect prefrontal neuronal integrity. The developmental lesion model appears to have predictive validity because treatment with antipsychotic drugs normalises some abnormal behaviour changes. Therefore it will be a useful paradigm in the work on new therapies and in providing new insights about pathophysiology and etiology of schizophrenia.
Elizabeth B. Torres
Full Text Available Background: The approximate 5:1 male to female ratio in clinical detection of Autism Spectrum Disorder (ASD prevents research from characterizing the female phenotype. Current open access repositories [such as those in the Autism Brain Imaging Data Exchange (ABIDE I-II] contain large numbers of females to help begin providing a new characterization of females on the autistic spectrum. Here we introduce new methods to integrate data in a scale-free manner from continuous biophysical rhythms of the nervous systems and discrete (ordinal observational scores.Methods: New data-types derived from image-based involuntary head motions and personalized statistical platform were combined with a data-driven approach to unveil sub-groups within the female cohort. Further, to help refine the clinical DSM-based ASD vs. Asperger's Syndrome (AS criteria, distributional analyses of ordinal score data from Autism Diagnostic Observation Schedule (ADOS-based criteria were used on both the female and male phenotypes.Results: Separate clusters were automatically uncovered in the female cohort corresponding to differential levels of severity. Specifically, the AS-subgroup emerged as the most severely affected with an excess level of noise and randomness in the involuntary head micro-movements. Extending the methods to characterize males of ABIDE revealed ASD-males to be more affected than AS-males. A thorough study of ADOS-2 and ADOS-G scores provided confounding results regarding the ASD vs. AS male comparison, whereby the ADOS-2 rendered the AS-phenotype worse off than the ASD-phenotype, while ADOS-G flipped the results. Females with AS scored higher on severity than ASD-females in all ADOS test versions and their scores provided evidence for significantly higher severity than males. However, the statistical landscapes underlying female and male scores appeared disparate. As such, further interpretation of the ADOS data seems problematic, rather suggesting the
Bilder, Deborah A.; Bakian, Amanda V.; Stevenson, David A.; Carbone, Paul S.; Cunniff, Christopher; Goodman, Alyson B.; McMahon, William M.; Fisher, Nicole P.; Viskochil, David
Neurofibromatosis type 1 (NF1) is an inherited neurocutaneous disorder associated with neurodevelopmental disorders including autism spectrum disorder (ASD). The frequency of ASD/NF1 co-occurrence has been subject to debate since the 1980s. This relationship was investigated in a large population-based sample of 8-year-old children identified with…
Amianto, F; D'Agata, F; Lavagnino, L; Caroppo, P; Abbate-Daga, G; Righi, D; Scarone, S; Bergui, M; Mortara, P; Fassino, S
Cerebellum seems to have a role both in feeding behavior and emotion regulation; therefore, it is a region that warrants further neuroimaging studies in eating disorders, severe conditions that determine a significant impairment in the physical and psychological domain. The aim of this study was to examine the cerebellum intrinsic connectivity during functional magnetic resonance imaging resting state in anorexia nervosa (AN), bulimia nervosa (BN), and healthy controls (CN). Resting state brain activity was decomposed into intrinsic connectivity networks (ICNs) using group spatial independent component analysis on the resting blood oxygenation level dependent time courses of 12 AN, 12 BN, and 10 CN. We extracted the cerebellar ICN and compared it between groups. Intrinsic connectivity within the cerebellar network showed some common alterations in eating disordered compared to healthy subjects (e.g., a greater connectivity with insulae, vermis, and paravermis and a lesser connectivity with parietal lobe); AN and BN patients were characterized by some peculiar alterations in connectivity patterns (e.g., greater connectivity with the insulae in AN compared to BN, greater connectivity with anterior cingulate cortex in BN compared to AN). Our data are consistent with the presence of different alterations in the cerebellar network in AN and BN patients that could be related to psychopathologic dimensions of eating disorders.
Sandberg, D E; Callens, N; Wisniewski, A B
Syndromes resulting in Disorders of Sex Development (DSD) are individually rare. Historically, this fact has hindered both clinical research and the delivery of evidence-based care. Recognizing the need for advancement, members of European and North American medical societies produced policy statements, notably the Consensus Statement on Management of Intersex Disorders, which recognize that optimal healthcare in DSD requires multidisciplinary teams in conjunction with networking of treatment centers and continued development of patient registries. This paper summarizes efforts in Europe and the U.S. toward creating networks focused on expanding discovery and improving healthcare and quality of life outcomes in DSD. The objectives and function of registry-based networks (EuroDSD/I-DSD), learning collaboratives (DSD-net), clinical outcomes research (DSD-Life), and networking hybrids (DSD-TRN) are reviewed. Opportunities for, and barriers to standardization in research and care are highlighted in light of practical considerations, for example, limitations in reliably classifying anatomic phenotypes and gaps in behavioral health staffing resources. The role of patient-reported outcomes is considered, with emphasis on integrating patient perspectives, given findings of limited agreement in outcome ratings by healthcare providers and patients. Finally, the characteristics of clinical centers likely to deliver the highest quality outcomes are discussed. © Georg Thieme Verlag KG Stuttgart · New York.
theory of principles and parameters, basically argue for a core syntactic module, the operations of which are con- ... explicit theories accounting for this (social interactive) perspective are still in the making. (i) Lesion ..... Disabilities in India: Willing the Mind to Learn (eds) P. Karanth and J Rozario (New Delhi: Sage) pp 62–76.
Richard E Frye
Full Text Available Tetrahydrobiopterin (BH4 is a naturally occurring cofactor essential for critical metabolic pathways. Studies suggest that BH4 supplementation may ameliorate autism symptoms; the biological mechanism for such an effect is unknown. To help understand the relation between central BH4 concentration and systemic metabolism and to develop a biomarker of central BH4 concentration, the relationship between cerebrospinal fluid BH4 concentration and serum amino acids was studied. BH4 concentration was found to be distributed in two groups, a lower and higher BH4 concentration group. Two serum amino acids, citrulline and methionine, differentiated these groups, and the ratio of serum citrulline-to-methionine was found to correlate with the cerebrospinal fluid BH4 concentration (r = -0.67, p < 0.05. Both citrulline and methionine are substrates in inflammation and oxidative stress pathways - two pathways that utilize BH4 and are abnormally activated in autism. These data suggests that central BH4 concentration may be related to systemic inflammation and oxidative stress pathways.
The article analyzes the importance of early care in child development, guiding a neuropsychological perspective of development. The early care model seeks to refer to the set of interventions aimed at children and their work in conjunction with a multidisciplinary team. It presents recommendations for the implementation of programs that allow…
Full Text Available The article analyzes the importance of early care in child development, guiding a neuropsychological perspective of development. The early care model seeks to refer to the set of interventions aimed at children and their work in conjunction with a multidisciplinary team. It presents recommendations for the implementation of programs that allow early intervention in the early years, so that the process of care for the affected children can be optimized by the different early developmental and learning alterations.
Rapoport, J L; Giedd, J N; Gogtay, N
... greatest potential to modify or extend, the neurodevelopmental model of schizophrenia. Longitudinal whole-population studies support a dimensional, rather than categorical, concept of psychosis...
Bay, Bjørn; Mortensen, Erik Lykke; Kesmodel, Ulrik Schiøler
To systematically review the existing literature on neurodevelopmental outcomes in children born after medically assisted reproduction compared with those of children born after spontaneous conception. Systematic review. Not applicable. Children born after medically assisted reproduction vs. reference groups of spontaneously conceived children. Data were reviewed from worldwide published articles, without restrictions as to publication year or language. A total of 80 studies included between 31 and 2,446,044 children. Child neurodevelopmental outcomes categorized as cognitive, behavioral, emotional or psychomotor development, or diagnoses of mental disorders. For infants, studies on psychomotor development showed no deficits, but few investigated cognitive or behavioral development. Studies on toddlers generally reported normal cognitive, behavioral, socio-emotional, and psychomotor development. For children in middle childhood, development seems comparable in children born after assisted reproduction and controls, although fewer studies have been conducted with follow-up to this age. Very few studies have assessed neurodevelopmental outcomes among teens, and the results are inconclusive. Studies investigating the risk of diagnoses of mental disorders are generally large, with long follow-up, but the results are inconsistent. It may tentatively be concluded that the neurodevelopment of children born after fertility treatment is overall comparable to that in children born after spontaneous conception. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Full Text Available Episodic retrieval is characterized by the subjective experience of remembering. This experience enables the co-ordination of memory retrieval processes and can be acted on metacognitively. In successful retrieval, the feeling of remembering may be accompanied by recall of important contextual information. On the other hand, when people fail (or struggle to retrieve information, other feelings, thoughts and information may come to mind. In this review, we examine the subjective and metacognitive basis of episodic memory function from a neurodevelopmental perspective, looking at recollection paradigms (such as source memory, and the report of recollective experience and metacognitive paradigms such as the feeling of knowing. We start by considering healthy development, and provide a brief review of the development of episodic memory, with a particular focus on the ability of children to report first-person experiences of remembering. We then consider neurodevelopmental disorders such as amnesia acquired in infancy, autism, Williams syndrome, Down syndrome or 22q11.2 deletion syndrome. This review shows that different episodic processes develop at different rates, and that across a broad set of different neurodevelopmental disorders there are various types of episodic memory impairment, each with possibly a different character. This literature is in agreement with the idea that episodic memory is a multifaceted process.
Bay, Bjørn; Mortensen, Erik Lykke; Kesmodel, Ulrik Schiøler
To systematically review the existing literature on neurodevelopmental outcomes in children born after medically assisted reproduction compared with those of children born after spontaneous conception.......To systematically review the existing literature on neurodevelopmental outcomes in children born after medically assisted reproduction compared with those of children born after spontaneous conception....
Zlatic, Stephanie; Comstra, Heather Skye; Gokhale, Avanti; Petris, Michael J.; Faundez, Victor
ATP7A mutations impair copper metabolism resulting in three distinct genetic disorders in humans. These diseases are characterized by neurological phenotypes ranging from intellectual disability to neurodegeneration. Severe ATP7A loss-of function alleles trigger Menkes disease, a copper deficiency condition where systemic and neurodegenerative phenotypes dominate clinical outcomes. The pathogenesis of these manifestations has been attributed to hypoactivity of a limited number of copper-dependent enzymes, a hypothesis that we refer as the oligoenzymatic pathogenic hypothesis. This hypothesis, which has dominated the field for 25 years, only explains some systemic Menkes phenotypes. However, we argue that this hypothesis does not fully account for the Menkes neurodegeneration or neurodevelopmental phenotypes. Here, we propose revisions of the oligoenzymatic hypothesis that could illuminate the pathogenesis of Menkes neurodegeneration and neurodevelopmental defects through unsuspected overlap with other neurological conditions including Parkinson’s, intellectual disability, and schizophrenia. PMID:25583185
Simacek, Jessica; Dimian, Adele F.; McComas, Jennifer J.
Young children with neurodevelopmental disorders such as autism spectrum disorders (ASD) and Rett syndrome often experience severe communication impairments. This study examined the efficacy of parent-implemented communication assessment and intervention with remote coaching via telehealth on the acquisition of early communication skills of three…
Hobbs, Linn W.
This report summarizes results of a research program investigating the fundamental principles underlying the phenomenon of topological disordering in a radiation environment. This phenomenon is known popularly as amorphization, but is more formally described as a process of radiation-induced structural arrangement that leads in crystals to loss of long-range translational and orientational correlations and in glasses to analogous alteration of connectivity topologies. The program focus has been on a set compound ceramic solids with directed bonding exhibiting structures that can be described as networks. Such solids include SiO2, Si3N4, SiC, which are of interest to applications in fusion energy production, nuclear waste storage, and device manufacture involving ion implantation or use in radiation fields. The principal investigative tools comprise a combination of experimental diffraction-based techniques, topological modeling, and molecular-dynamics simulations that have proven a rich source of information in the preceding support period. The results from the present support period fall into three task areas. The first comprises enumeration of the rigidity constraints applying to (1) more complex ceramic structures (such as rutile, corundum, spinel and olivine structures) that exhibit multiply polytopic coordination units or multiple modes of connecting such units, (2) elemental solids (such as graphite, silicon and diamond) for which a correct choice of polytope is necessary to achieve correct representation of the constraints, and (3) compounds (such as spinel and silicon carbide) that exhibit chemical disorder on one or several sublattices. With correct identification of the topological constraints, a unique correlation is shown to exist between constraint and amorphizability which demonstrates that amorphization occurs at a critical constraint loss. The second task involves the application of molecular dynamics (MD) methods to topologically-generated models
Eickholt, Jesse; Cheng, Jianlin
A number of proteins contain regions which do not adopt a stable tertiary structure in their native state. Such regions known as disordered regions have been shown to participate in many vital cell functions and are increasingly being examined as drug targets. This work presents a new sequence based approach for the prediction of protein disorder. The method uses boosted ensembles of deep networks to make predictions and participated in the CASP10 experiment. In a 10 fold cross validation procedure on a dataset of 723 proteins, the method achieved an average balanced accuracy of 0.82 and an area under the ROC curve of 0.90. These results are achieved in part by a boosting procedure which is able to steadily increase balanced accuracy and the area under the ROC curve over several rounds. The method also compared competitively when evaluated against a number of state-of-the-art disorder predictors on CASP9 and CASP10 benchmark datasets. DNdisorder is available as a web service at http://iris.rnet.missouri.edu/dndisorder/.
Shih, Patricia; Shen, Mark; Ottl, Birgit; Keehn, Brandon; Gaffrey, Michael S; Müller, Ralph-Axel
Imitation has been considered as one of the precursors for sociocommunicative development. Impairments of imitation in autism spectrum disorder (ASD) could be indicative of dysfunctional underlying neural processes. Neuroimaging studies have found reduced activation in areas associated with imitation, but a functional connectivity MRI network perspective of these regions in autism is unavailable. Functional and effective connectivity was examined in 14 male participants with ASD and 14 matched typically developing (TD) participants. We analyzed intrinsic, low-frequency blood oxygen level dependent (BOLD) fluctuations of three regions in literature found to be associated with imitation (inferior frontal gyrus [IFG], inferior parietal lobule [IPL], superior temporal sulcus [STS]). Direct group comparisons did not show significantly reduced functional connectivity within the imitation network in ASD. Conversely, we observed greater connectivity with frontal regions, particularly superior frontal and anterior cingulate gyri, in the ASD compared to TD group. Structural equation modeling of effective connectivity revealed a significantly reduced effect of IPL on IFG together with an increased influence of a region in dorsal prefrontal cortex (dPFC) on IFG in the ASD group. Our results suggest atypical connectivity of the imitation network with an enhanced role of dPFC, which may relate to behavioral impairments. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
Liebke, Lisa; Bungert, Melanie; Thome, Janine; Hauschild, Sophie; Gescher, Dorothee Maria; Schmahl, Christian; Bohus, Martin; Lis, Stefanie
Persistent loneliness is often reported by patients with borderline personality disorder (BPD). However, empirical studies investigating this aspect of BPD psychopathology are sparse. Studies from social psychology revealed that social isolation and low social functioning contribute to loneliness, that is, the subjective feeling of being alone. The aim of the present study was to contribute to the understanding of loneliness in BPD by investigating its relation to social isolation and functioning in different domains of life. Subjective experience of loneliness was measured in 80 women (40 BPD patients, 40 healthy controls) with the UCLA Loneliness Scale. Social isolation and social functioning were assessed with the Social Network Inventory and the Social Functioning Scale. In addition, we assessed global functioning with the Global Assessment of Functioning. BPD patients reported stronger feelings of loneliness compared to healthy participants. In general, the level of loneliness was linked to network size, social engagement, and prosocial behavior. Diversity of social networks and functioning in the domain of interpersonal communication were associated with the level of loneliness only in BPD. A reduced variety of roles in social life together with impairments in interpersonal communication were particularly relevant for the experience of loneliness in BPD, suggesting an indirect path to target this psychopathological feature in therapeutic interventions. However, both social isolation and social functioning were not sufficient to explain the severely increased loneliness experienced by these patients, stressing the need for further investigation of determinants of loneliness in this clinical population. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Gallea, Cecile; Ewenczyk, Claire; Degos, Bertrand; Welter, Marie-Laure; Grabli, David; Leu-Semenescu, Smaranda; Valabregue, Romain; Berroir, Pierre; Yahia-Cherif, Lydia; Bertasi, Eric; Fernandez-Vidal, Sara; Bardinet, Eric; Roze, Emmanuel; Benali, Habib; Poupon, Cyril; François, Chantal; Arnulf, Isabelle; Lehéricy, Stéphane; Vidailhet, Marie
The objective of this study was to investigate pedunculopontine nucleus network dysfunctions that mediate impaired postural control and sleep disorder in Parkinson's disease. We examined (1) Parkinson's disease patients with impaired postural control and rapid eye movement sleep behavior disorder (further abbreviated as sleep disorder), (2) Parkinson's disease patients with sleep disorder only, (3) Parkinson's disease patients with neither impaired postural control nor sleep disorder, and (4) healthy volunteers. We assessed postural control with clinical scores and biomechanical recordings during gait initiation. Participants had video polysomnography, daytime sleepiness self-evaluation, and resting-state functional MRIs. Patients with impaired postural control and sleep disorder had longer duration of anticipatory postural adjustments during gait initiation and decreased functional connectivity between the pedunculopontine nucleus and the supplementary motor area in the locomotor network that correlated negatively with the duration of anticipatory postural adjustments. Both groups of patients with sleep disorder had decreased functional connectivity between the pedunculopontine nucleus and the anterior cingulate cortex in the arousal network that correlated with daytime sleepiness. The degree of dysfunction in the arousal network was related to the degree of connectivity in the locomotor network in all patients with sleep disorder, but not in patients without sleep disorder or healthy volunteers. These results shed light on the functional neuroanatomy of pedunculopontine nucleus networks supporting the clinical manifestation and the interdependence between sleep and postural control impairments in Parkinson's disease. © 2016 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.
Wakschlag, Lauren S; Perlman, Susan B; Blair, R James; Leibenluft, Ellen; Briggs-Gowan, Margaret J; Pine, Daniel S
The arrival of the Journal's 175th anniversary occurs at a time of recent advances in research, providing an ideal opportunity to present a neurodevelopmental roadmap for understanding, preventing, and treating psychiatric disorders. Such a roadmap is particularly relevant for early-childhood-onset neurodevelopmental conditions, which emerge when experience-dependent neuroplasticity is at its peak. Employing a novel developmental specification approach, this review places recent neurodevelopmental research on early childhood disruptive behavior within the historical context of the Journal. The authors highlight irritability and callous behavior as two core exemplars of early disruptive behavior. Both phenotypes can be reliably differentiated from normative variation as early as the first years of life. Both link to discrete pathophysiology: irritability with disruptions in prefrontal regulation of emotion, and callous behavior with abnormal fear processing. Each phenotype also possesses clinical and predictive utility. Based on a nomologic net of evidence, the authors conclude that early disruptive behavior is neurodevelopmental in nature and should be reclassified as an early-childhood-onset neurodevelopmental condition in DSM-5. Rapid translation from neurodevelopmental discovery to clinical application has transformative potential for psychiatric approaches of the millennium.
London, L.; Beseler, C.; Bouchard, M.F.; Bellinger, D.C.; Colosio, C.; Grandjean, P.; Harari, R.; Kootbodien, T.; Kromhout, H.|info:eu-repo/dai/nl/074385224; Little, F.; Meijster, T.; Moretto, A.; Rohlman, D.S.; Stallones, L.
The association between pesticide exposure and neurobehavioral and neurodevelopmental effects is an area of increasing concern. This symposium brought together participants to explore the neurotoxic effects of pesticides across the lifespan. Endpoints examined included neurobehavioral, affective and
London, Leslie; Beseler, Cheryl; Bouchard, Maryse F
The association between pesticide exposure and neurobehavioral and neurodevelopmental effects is an area of increasing concern. This symposium brought together participants to explore the neurotoxic effects of pesticides across the lifespan. Endpoints examined included neurobehavioral, affective ...
Tresidder, J; Fielder, A R; Nicholson, J
Delayed visual maturation (DVM) can present as an isolated anomaly (type 1A), but can be compounded by perinatal problems (type 1B), severe neurodevelopmental delay (type 2), or ocular anomalies/nystagmus (type 3), in which group the common feature appears to be nystagmus. The neurodevelopmental and ophthalmic aspects of 26 infants with DVM were studied. Onset of visual improvement, rate of acquisition of normal vision and eventual outcome were studied quantitatively, using an adaptation of the acuity card procedure. Neurodevelopmental assessment was performed after visual improvement. The results support the long-held clinical impression that if blindness is the presenting feature, neurodevelopmental outlook is excellent. DVM could represent a defect in the extrageniculostriate visual system, and the onset of vision in all types--and the development of nystagmus in type 3--could herald the emergence of geniculostriate function.
Ruzzano, Laura; Borsboom, Denny; Geurts, Hilde M.
The association between autism and obsessive-compulsive disorder (OCD) seems largely dependent upon observed similarities in the repetitive behaviors that manifest in both disorders. The aim of this study was to use a network approach to explore the interactions between these behaviors. We constructed a network based on clinician's…
Discussion: The results are suggestive of more dispersed network communication in patients with psychotic disorder, with some evidence for trait-based network alterations in high-schizotypy individuals. Dispersed communication may contribute to the clinical phenotype in psychotic disorder. In addition, higher SMP may contribute to neuro- and social cognition, independent of psychosis risk.
Shao, Feng-jing; Sui, Yi; Zhou, Yong-hong; Sun, Ren-cheng
Investigating the underlying principles of the Treatise on Cold Damage Disorder is meaningful and interesting. In this study, we investigated the symptoms, herbal formulae, herbal drugs, and their relationships in this treatise based on a multi-subnet composited complex network model (MCCN). Syndrome subnets were constructed for the symptoms and a formula subnet for herbal drugs. By subnet compounding using MCCN, a composited network was obtained that described the treatment relationships between syndromes and formulae. The results obtained by topological analysis suggested some prescription laws that could be validated in clinics. After subnet reduction using the MCCN, six channel (Tai-yang, Yang-ming, Shao-yang, Tai-yin, Shao-yin, and Jue-yin) subnets were obtained. By analyzing the strengths of the relationships among these six channel subnets, we found that the Tai-yang channel and Yang-ming channel were related most strongly with each other, and we found symptoms that implied pathogen movements and transformations among the six channels. This study could help therapists to obtain a deeper understanding of this ancient treatise.
Arienzo, Donatello; Leow, Alex; Brown, Jesse A; Zhan, Liang; GadElkarim, Johnson; Hovav, Sarit; Feusner, Jamie D
Body dysmorphic disorder (BDD) is characterized by preoccupation with misperceived defects of appearance, causing significant distress and disability. Previous studies suggest abnormalities in information processing characterized by greater local relative to global processing. The purpose of this study was to probe whole-brain and regional white matter network organization in BDD, and to relate this to specific metrics of symptomatology. We acquired diffusion-weighted 34-direction MR images from 14 unmedicated participants with DSM-IV BDD and 16 healthy controls, from which we conducted whole-brain deterministic diffusion tensor imaging tractography. We then constructed white matter structural connectivity matrices to derive whole-brain and regional graph theory metrics, which we compared between groups. Within the BDD group, we additionally correlated these metrics with scores on psychometric measures of BDD symptom severity as well as poor insight/delusionality. The BDD group showed higher whole-brain mean clustering coefficient than controls. Global efficiency negatively correlated with BDD symptom severity. The BDD group demonstrated greater edge betweenness centrality for connections between the anterior temporal lobe and the occipital cortex, and between bilateral occipital poles. This represents the first brain network analysis in BDD. Results suggest disturbances in whole brain structural topological organization in BDD, in addition to correlations between clinical symptoms and network organization. There is also evidence of abnormal connectivity between regions involved in lower-order visual processing and higher-order visual and emotional processing, as well as interhemispheric visual information transfer. These findings may relate to disturbances in information processing found in previous studies. PMID:23322186
Valles, A.; Martens, G.J.; Weerd, P. de; Poelmans, G.J.V.; Aschrafi, A.
BACKGROUND: Schizophrenia is a highly heritable neurodevelopmental disorder. A genetic variant of microRNA-137 (miR-137) has yielded significant genome-wide association with schizophrenia, suggesting that this miRNA plays a key role in its etiology. Therefore, a molecular network of interacting
Faingold, Carl L; Blumenfeld, Hal
Improved therapy of brain disorders can be achieved by focusing on neuronal networks, utilizing combined pharmacological and stimulation paradigms guided by neuroimaging. Neuronal networks that mediate normal brain functions, such as hearing, interact with other networks, which is important but commonly neglected. Network interaction changes often underlie brain disorders, including epilepsy. "Conditional multireceptive" (CMR) brain areas (e.g., brainstem reticular formation and amygdala) are critical in mediating neuroplastic changes that facilitate network interactions. CMR neurons receive multiple inputs but exhibit extensive response variability due to milieu and behavioral state changes and are exquisitely sensitive to agents that increase or inhibit GABA-mediated inhibition. Enhanced CMR neuronal responsiveness leads to expression of emergent properties--nonlinear events--resulting from network self-organization. Determining brain disorder mechanisms requires animals that model behaviors and neuroanatomical substrates of human disorders identified by neuroimaging. However, not all sites activated during network operation are requisite for that operation. Other active sites are ancillary, because their blockade does not alter network function. Requisite network sites exhibit emergent properties that are critical targets for pharmacological and stimulation therapies. Improved treatment of brain disorders should involve combined pharmacological and stimulation therapies, guided by neuroimaging, to correct network malfunctions by targeting specific network neurons. © The Author(s) 2015.
Full Text Available The transcription repressor FOXP2 is a crucial player in nervous system evolution and development of humans and songbirds. In order to provide an additional insight into its functional role we compared target gene expression levels between human neuroblastoma cells (SH-SY5Y stably overexpressing FOXP2 cDNA of either humans or the common chimpanzee, Rhesus monkey, and marmoset, respectively. RNA-seq led to identification of 27 genes with differential regulation under the control of human FOXP2, which were previously reported to have FOXP2-driven and/or songbird song-related expression regulation. RT-qPCR and Western blotting indicated differential regulation of additional 13 new target genes in response to overexpression of human FOXP2. These genes may be directly regulated by FOXP2 considering numerous matches of established FOXP2-binding motifs as well as publicly available FOXP2-ChIP-seq reads within their putative promoters. Ontology analysis of the new and reproduced targets, along with their interactors in a network, revealed an enrichment of terms relating to cellular signaling and communication, metabolism and catabolism, cellular migration and differentiation, and expression regulation. Notably, terms including the words “neuron” or “axonogenesis” were also enriched. Complementary literature screening uncovered many connections to human developmental (autism spectrum disease, schizophrenia, Down syndrome, agenesis of corpus callosum, trismus-pseudocamptodactyly, ankyloglossia, facial dysmorphology and neurodegenerative diseases and disorders (Alzheimer’s, Parkinson’s, and Huntington’s diseases, Lewy body dementia, amyotrophic lateral sclerosis. Links to deafness and dyslexia were detected, too. Such relations existed for single proteins (e.g., DCDC2, NURR1, PHOX2B, MYH8, and MYH13 and groups of proteins which conjointly function in mRNA processing, ribosomal recruitment, cell–cell adhesion (e.g., CDH4, cytoskeleton
Talkowski, Michael E.; Rosenfeld, Jill A.; Blumenthal, Ian
Sequencing of balanced chromosomal abnormalities, combined with convergent genomic studies of gene expression, copy-number variation, and genome-wide association, identifies 22 new loci that contribute to autism and related neurodevelopmental disorders. These data support a polygenic risk model f...
Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue
This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.
Grillo, Elisa; Villard, Laurent; Clarke, Angus
Rett syndrome (RTT) is a neurodevelopmental disorder with one principal phenotype and several distinct, atypical variants (Zappella, early seizure onset and congenital variants). Mutations in MECP2 are found in most cases of classic RTT but at least two additional genes, CDKL5 and FOXG1, can...... underlie some (usually variant) cases. There is only limited correlation between genotype and phenotype. The Rett Networked Database (http://www.rettdatabasenetwork.org/) has been established to share clinical and genetic information. Through an "adaptor" process of data harmonization, a set of 293...
van Iterson, L.; de Jong, P.F.; Zijlstra, B.J.H.
Introduction: In pediatric epilepsy, comorbidities are reported to be frequent. The present study focusedon the cognitive patterns of children with isolated epilepsy, children with isolated neurodevelopmental disorders (reading disorders, math disorders, autism spectrum disorders), and children with
Full Text Available Background. Over the last few decades, an increasing number of studies have suggested a connection between neurodevelopmental problems (NDPs and body mass index (BMI. Attention deficit/hyperactivity disorder (ADHD and autism spectrum disorders (ASD both seem to carry an increased risk for developing extreme BMI. However, the results are inconsistent, and there have been only a few studies of the general population of children.Aims. We had three aims with the present study: (1 to define the prevalence of extreme (low or high BMI in the group of children with ADHD and/or ASDs compared to the group of children without these NDPs; (2 to analyze whether extreme BMI is associated with the subdomains within the diagnostic categories of ADHD or ASD; and (3 to investigate the contribution of genetic and environmental factors to BMI in boys and girls at ages 9 and 12.Method. Parents of 9- or 12-year-old twins (n = 12,496 were interviewed using the Autism—Tics, ADHD and other Comorbidities (A-TAC inventory as part of the Child and Adolescent Twin Study in Sweden (CATSS. Univariate and multivariate generalized estimated equation models were used to analyze associations between extremes in BMI and NDPs.Results. ADHD screen-positive cases followed BMI distributions similar to those of children without ADHD or ASD. Significant association was found between ADHD and BMI only among 12-year-old girls, where the inattention subdomain of ADHD was significantly associated with the high extreme BMI. ASD scores were associated with both the low and the high extremes of BMI. Compared to children without ADHD or ASD, the prevalence of ASD screen-positive cases was three times greater in the high extreme BMI group and double as much in the low extreme BMI group. Stereotyped and repetitive behaviors were significantly associated with high extreme BMIs.Conclusion. Children with ASD, with or without coexisting ADHD, are more prone to have low or high extreme BMIs than
Mogg, K; Salum, G A; Bradley, B P; Gadelha, A; Pan, P; Alvarenga, P; Rohde, L A; Pine, D S; Manfro, G G
Research with adults suggests that anxiety is associated with poor control of executive attention. However, in children, it is unclear (a) whether anxiety disorders and non-clinical anxiety are associated with deficits in executive attention, (b) whether such deficits are specific to anxiety versus other psychiatric disorders, and (c) whether there is heterogeneity among anxiety disorders (in particular, specific phobia versus other anxiety disorders). We examined executive attention in 860 children classified into three groups: anxiety disorders (n = 67), attention-deficit/hyperactivity disorder (ADHD; n = 67) and no psychiatric disorder (n = 726). Anxiety disorders were subdivided into: anxiety disorders excluding specific phobia (n = 43) and specific phobia (n = 21). The Attention Network Task was used to assess executive attention, alerting and orienting. Findings indicated heterogeneity among anxiety disorders, as children with anxiety disorders (excluding specific phobia) showed impaired executive attention, compared with disorder-free children, whereas children with specific phobia showed no executive attention deficit. Among disorder-free children, executive attention was less efficient in those with high, relative to low, levels of anxiety. There were no anxiety-related deficits in orienting or alerting. Children with ADHD not only had poorer executive attention than disorder-free children, but also higher orienting scores, less accurate responses and more variable response times. Impaired executive attention in children (reflected by difficulty inhibiting processing of task-irrelevant information) was not fully explained by general psychopathology, but instead showed specific associations with anxiety disorders (other than specific phobia) and ADHD, as well as with high levels of anxiety symptoms in disorder-free children.
Albuquerque Osório, Maria Joana; Goldman, Steven A.
The childhood disorders of glia comprise a group of diseases that include the pediatric leukodystrophies and lysosomal storage disorders, cerebral palsies and perinatal hypoxic ischemic encephalopathies, and selected neurodevelopmental disorders of glial origin. Essentially, all of these disorder...
K. Shapiro Bruce, MD
Full Text Available Academic underachievement is a common presenting symptom and has many different causes. The disorders that describe academic underachievement are based on the child’s function in cognitive, academic, or behavioral domains. The disorders that are associated with academic underachievement are final common pathways that have different etiologies and mechanisms. Multiple disorders are the rule because brain dysfunction in childhood usually affects multiple functions. Consequently, management programs must be individualized, comprehensive and address issues related to the child, school, and family. Treatment plans include parent training, academic accommodations, techniques to maintain self-esteem, and psychopharmacologic approaches. Ongoing monitoring of the management programs is necessary to detect important comorbidities that may emerge, to modify the program to meet the changing academic and social demands that occur as the child ages, and to provide current information. The outcome for children with academic underachievement is most dependent on the underlying disorder. Health providers have multiple roles to play in the prevention, detection, diagnosis and management of children with academic underachievement.
London, Leslie; Beseler, Cheryl; Bouchard, Maryse F.; Bellinger, David C.; Colosio, Claudio; Grandjean, Philippe; Harari, Raul; Kootbodien, Tahira; Kromhout, Hans; Little, Francesca; Meijster, Tim; Moretto, Angelo; Rohlman, Diane S.; Stallones, Lorann
The association between pesticide exposure and neurobehavioral and neurodevelopmental effects is an area of increasing concern. This symposium brought together participants to explore the neurotoxic effects of pesticides across the lifespan. Endpoints examined included neurobehavioral, affective and neurodevelopmental outcomes amongst occupational (both adolescent and adult workers) and non-occupational populations (children). The symposium discussion highlighted many challenges for researchers concerned with the prevention of neurotoxic illness due to pesticides and generated a number of directions for further research and policy interventions for the protection of human health, highlighting the importance of examining potential long-term effects across the lifespan arising from early adolescent, childhood or pre-natal exposure. PMID:22269431
Litt, Mark D; Kadden, Ronald M; Tennen, Howard; Kabela-Cormier, Elise
The social network of those treated for alcohol use disorder can play a significant role in subsequent drinking behavior, both for better and worse. Network Support treatment was devised to teach ways to reconstruct social networks so that they are more supportive of abstinence and less supportive of drinking. For many patients this may involve engagement with AA, but other strategies are also used. The current trial of Network Support treatment, building on our previous work, was intended to further enhance the ability of patients to construct abstinence-supportive social networks, and to test this approach against a strong control treatment. Patients were 193 men and women with alcohol use disorder recruited from the community and assigned to either 12 weeks of Network Support (NS) or Packaged Cognitive-Behavioral Treatment (PCBT), and followed for 27 months. Results of multilevel analyses indicated that NS yielded better posttreatment results in terms of both proportion of days abstinent and drinking consequences, and equivalent improvements in 90-day abstinence, heavy drinking days and drinks per drinking day. Mediation analyses revealed that NS treatment effects were mediated by pre-post changes in abstinence self-efficacy and in social network variables, especially proportion of non-drinkers in the social network and attendance at Alcoholics Anonymous. It was concluded that helping patients enhance their abstinent social network can be effective, and may provide a useful alternative or adjunctive approach to treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Mabb, Angela M.; Judson, Matthew C.; Zylka, Mark J.; Philpot, Benjamin D.
Angelman syndrome (AS) is a severe genetic disorder caused by mutations or deletions of the maternally inherited UBE3A gene. UBE3A encodes an E3 ubiquitin ligase that is expressed biallelically in most tissues but is maternally expressed in almost all neurons. In this review, we describe recent advances in understanding the expression and function of UBE3A in the brain and the etiology of AS. We highlight current AS model systems, epigenetic mechanisms of UBE3A regulation, and the identification of potential UBE3A substrates in the brain. In the process, we identify major gaps in our knowledge that, if bridged, could move us closer to identifying treatments for this debilitating neurodevelopmental disorder. PMID:21592595
Siette, Joyce; Gulea, Claudia; Priebe, Stefan
Evidence suggests that social networks of patients with psychotic disorders influence symptoms, quality of life and treatment outcomes. It is therefore important to assess social networks for which appropriate and preferably established instruments should be used. To identify instruments assessing social networks in studies of patients with psychotic disorders and explore their properties. A systematic search of electronic databases was conducted to identify studies that used a measure of social networks in patients with psychotic disorders. Eight instruments were identified, all of which had been developed before 1991. They have been used in 65 studies (total N of patients = 8,522). They assess one or more aspects of social networks such as their size, structure, dimensionality and quality. Most instruments have various shortcomings, including questionable inter-rater and test-retest reliability. The assessment of social networks in patients with psychotic disorders is characterized by a variety of approaches which may reflect the complexity of the construct. Further research on social networks in patients with psychotic disorders would benefit from advanced and more precise instruments using comparable definitions of and timescales for social networks across studies.
Dr. T.B. Hafsteinsdóttir; A Algra; M.H.F. Grypdonck; L.J. Kappelle
Background: Neurodevelopmental treatment (NDT) is a rehabilitation approach increasingly used in the care of stroke patients, although no evidence has been provided for its efficacy. Objective: To investigate the effects of NDT on the functional status and quality of life (QoL) of patients
van Wassenaer, Aleid
Fetal growth retardation is associated with postnatal growth retardation and cardio-vascular and metabolic problems later on in life. Less well described are the consequences of neurodevelopmental outcome. The term SGA is associated with mild to moderate school problems, still present in late
Conclusion: Most children with grade 2 or 3 PVL had severe neurodevelopmental delays, but attention should also be paid to the 56% of children with grade 1 PVL who presented with normal psychomotor development. Further studies of larger populations, including long-term follow-up, are necessary to evaluate the outcomes of children with PVL.
Full Text Available Abstract Background We present a statistical method of analysis of biological networks based on the exponential random graph model, namely p2-model, as opposed to previous descriptive approaches. The model is capable to capture generic and structural properties of a network as emergent from local interdependencies and uses a limited number of parameters. Here, we consider one global parameter capturing the density of edges in the network, and local parameters representing each node's contribution to the formation of edges in the network. The modelling suggests a novel definition of important nodes in the network, namely social, as revealed based on the local sociality parameters of the model. Moreover, the sociality parameters help to reveal organizational principles of the network. An inherent advantage of our approach is the possibility of hypotheses testing: a priori knowledge about biological properties of the nodes can be incorporated into the statistical model to investigate its influence on the structure of the network. Results We applied the statistical modelling to the human protein interaction network obtained with Y2H experiments. Bayesian approach for the estimation of the parameters was employed. We deduced social proteins, essential for the formation of the network, while incorporating into the model information on protein disorder. Intrinsically disordered are proteins which lack a well-defined three-dimensional structure under physiological conditions. We predicted the fold group (ordered or disordered of proteins in the network from their primary sequences. The network analysis indicated that protein disorder has a positive effect on the connectivity of proteins in the network, but do not fully explains the interactivity. Conclusions The approach opens a perspective to study effects of biological properties of individual entities on the structure of biological networks.
Pannekoek, Justine Nienke; Veer, Ilya M.; van Tol, Marie-Jose; van der Werff, Steven J. A.; Demenescu, Liliana R.; Aleman, Andre; Veltman, Dick J.; Zitman, Frans G.; Rombouts, Serge A. R. B.; van der wee, Nic J. A.
Background: Panic disorder (PD) is a prevalent and debilitating disorder but its neurobiology is still poorly understood. We investigated resting-state functional connectivity (RSFC) in PD without comorbidity in three networks that have been linked to PD before. This could provide new insights in
Hanson, Jack; Yang, Yuedong; Paliwal, Kuldip; Zhou, Yaoqi
Capturing long-range interactions between structural but not sequence neighbors of proteins is a long-standing challenging problem in bioinformatics. Recently, long short-term memory (LSTM) networks have significantly improved the accuracy of speech and image classification problems by remembering useful past information in long sequential events. Here, we have implemented deep bidirectional LSTM recurrent neural networks in the problem of protein intrinsic disorder prediction. The new method, named SPOT-Disorder, has steadily improved over a similar method using a traditional, window-based neural network (SPINE-D) in all datasets tested without separate training on short and long disordered regions. Independent tests on four other datasets including the datasets from critical assessment of structure prediction (CASP) techniques and >10 000 annotated proteins from MobiDB, confirmed SPOT-Disorder as one of the best methods in disorder prediction. Moreover, initial studies indicate that the method is more accurate in predicting functional sites in disordered regions. These results highlight the usefulness combining LSTM with deep bidirectional recurrent neural networks in capturing non-local, long-range interactions for bioinformatics applications. SPOT-disorder is available as a web server and as a standalone program at: http://sparks-lab.org/server/SPOT-disorder/index.php . email@example.com or firstname.lastname@example.org or email@example.com. Supplementary data is available at Bioinformatics online.
Acha, Joana; Pérez, Alejandro; Davidson, Doug J; Carreiras, Manuel
Dravet syndrome (DS) is an epilepsy of infantile onset, usually related to a mutation in gene sodium channel alpha 1 subunit, that leads to different typological seizures before the first year of life. Although most research has focused on the clinical description of the syndrome, some recent studies have focused on its impact on cognitive development, identifying both motor disorders and visual-processing deficits as basic factors affected in adults and children with DS. In this article, we designed a cross-sectional study to examine the cognitive phenotype of children affected by DS from a neurodevelopmental perspective. We report measures for both basic (auditory perception, visual and phonological processing, motor coordination) and higher order cognitive processes (verbal production, categorization, and executive function) in two age groups of DS children (M = 8.8 and M = 14.1) and control children of the same chronological age. Results showed an important cognitive delay in DS children with respect to controls in both basic and higher order cognitive abilities, with a better general outcome in tasks that required processing visual material (visual memory and categorization) than in tasks involving verbal material. In addition, performance of DS children in certain basic tasks (visual memory) correlated with performance on complex ones (categorization). These findings encourage promoting an early identification of not only clinical but also cognitive features in DS children from very early stages of development in order to optimize their neurodevelopmental outcome.
Micheletti, S; Palestra, F; Martelli, P; Accorsi, P; Galli, J; Giordano, L; Trebeschi, V; Fazzi, E
Angelman Syndrome (AS) is a rare neurodevelopment disorder resulting from deficient expression or function of the maternally inherited allele of UBE3A gene. The aim of the study is to attempt at providing a detailed definition of neurodevelopmental profile in AS, with particular regard to motor, cognitive, communicative, behavioural and neurovisual, features by using standardized instruments. A total of ten subjects aged from 5 to 11 years (4 males and 6 females) with molecular confirmed diagnosis of AS (7 15q11.2-q13 deletion and 3 UBE3A mutation) were enrolled in our study. All of them underwent an assessment protocol including neurological and neurovisual examination and the evaluation of motor (Gross Motor Function Measure Scale), cognitive (Griffiths Mental Development Scale and Uzgiris-Hunt Scale); adaptive (Vineland Adaptive Behavioural Scale); communication (MacArthur-Bates Communicative Development Inventory and video-recordings children's verbal expression), behavioural aspects (IPDDAG Scale) and neurovisual aspects. All children presented motor function involvement. A severe cognitive impairment was detected with different profiles according to the test applied. In all cases, communicative disability (phonemic inventory, word/gesture comprehension and production) and symptoms of inattention disorder were revealed. Neurovisual impairment was characterized by refractive errors, fundus oculi anomalies, strabismus and/or oculomotor dysfunction. AS presents a complex neurodevelopmental profile in which several aspects play a negative role in global development leading to a severe functional impairment. Intellectual disability is not the only component because neurovisual functions and behavioural disorders may worsen the global function and are needed of specific rehabilitation programs.
Kreider, Consuelo M; Bendixen, Roxanna M; Young, Mary Ellen; Prudencio, Stephanie M; McCarty, Christopher; Mann, William C
Social participation involves activities and roles providing interactions with others, including those within their social networks. This study sought to characterize social networks and participation with others for 36 youth, ages 11 to 16 years, with (n = 19) and without (n = 17) learning disability, attention disorder, or high-functioning autism. Social networks were measured using methods of personal network analysis. The Children's Assessment of Participation and Enjoyment With Whom dimension scores were used to measure participation with others. Youth from the clinical group were interviewed regarding their experiences within their social networks. Group differences were observed for six social network variables and in the proportion of overall, physical, recreational, social, and informal activities engaged with family and/or friends. Qualitative findings explicated strategies used in building, shaping, and maintaining social networks. Social network factors should be considered when seeking to understand social participation. © CAOT 2015.
Juarascio, Adrienne S; Shoaib, Amber; Timko, C Alix
The purpose of this study was to assess the number of pro-ana groups on social networking sites and to analyze their content. A general inductive approach was used to analyze the content. Two main themes emerged from the content analysis: social support and eating disorder specific content. Themes were similar across all groups; however, a linguistic analysis indicated differences between groups on the two different networking sites. There was an absence of content typically found on Internet sites. Pro-ana groups on social networking sites are focused on social interactions, and lack eating disorder specific content found on Internet sites.
Mignot, Cyril; von Stülpnagel, Celina; Nava, Caroline
OBJECTIVE: We aimed to delineate the neurodevelopmental spectrum associated with SYNGAP1 mutations and to investigate genotype-phenotype correlations. METHODS: We sequenced the exome or screened the exons of SYNGAP1 in a total of 251 patients with neurodevelopmental disorders. Molecular and clini......OBJECTIVE: We aimed to delineate the neurodevelopmental spectrum associated with SYNGAP1 mutations and to investigate genotype-phenotype correlations. METHODS: We sequenced the exome or screened the exons of SYNGAP1 in a total of 251 patients with neurodevelopmental disorders. Molecular...... and clinical data from patients with SYNGAP1 mutations from other centres were also collected, focusing on developmental aspects and the associated epilepsy phenotype. A review of SYNGAP1 mutations published in the literature was also performed. RESULTS: We describe 17 unrelated affected individuals carrying...... 13 different novel loss-of-function SYNGAP1 mutations. Developmental delay was the first manifestation of SYNGAP1-related encephalopathy; intellectual disability became progressively obvious and was associated with autistic behaviours in eight patients. Hypotonia and unstable gait were frequent...
Luke J. Norman
Full Text Available Patients with Attention-Deficit/Hyperactivity Disorder (ADHD and obsessive/compulsive disorder (OCD share problems with sustained attention, and are proposed to share deficits in switching between default mode and task positive networks. The aim of this study was to investigate shared and disorder-specific brain activation abnormalities during sustained attention in the two disorders. Twenty boys with ADHD, 20 boys with OCD and 20 age-matched healthy controls aged between 12 and 18 years completed a functional magnetic resonance imaging (fMRI version of a parametrically modulated sustained attention task with a progressively increasing sustained attention load. Performance and brain activation were compared between groups. Only ADHD patients were impaired in performance. Group by sustained attention load interaction effects showed that OCD patients had disorder-specific middle anterior cingulate underactivation relative to controls and ADHD patients, while ADHD patients showed disorder-specific underactivation in left dorsolateral prefrontal cortex/dorsal inferior frontal gyrus (IFG. ADHD and OCD patients shared left insula/ventral IFG underactivation and increased activation in posterior default mode network relative to controls, but had disorder-specific overactivation in anterior default mode regions, in dorsal anterior cingulate for ADHD and in anterior ventromedial prefrontal cortex for OCD. In sum, ADHD and OCD patients showed mostly disorder-specific patterns of brain abnormalities in both task positive salience/ventral attention networks with lateral frontal deficits in ADHD and middle ACC deficits in OCD, as well as in their deactivation patterns in medial frontal DMN regions. The findings suggest that attention performance in the two disorders is underpinned by disorder-specific activation patterns.
Knaus, Tracey A; Burns, Claire; Kamps, Jodi; Foundas, Anne L
In typical adults, fMRI studies have shown activation of primary and pre-motor regions during action word processing. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments. ASD studies have shown atypical semantic processing and motor deficits. The objective of this study was to examine semantic processing of verbs in ASD. 15 ASD adolescents and 19 typically developing adolescents, 11-16years, completed a semantic similarity judgment task during fMRI. There were no differences in task accuracy or reaction time. At the group level, both groups had activation in left language areas; controls, but not ASD, also had activation in the left pre-supplementary motor area (pre-SMA). In ASD, less left frontal activation and reduced left lateralization of activation within these regions was associated with shorter reaction times and better language skills. More left temporal activation was associated with better language abilities in ASD. Differences in pre-SMA activation may relate to motor planning deficits or differences in approach to the semantic task in ASD. Results suggest that left frontal language areas may be less efficient in ASD and those who can compensate by recruiting more right hemisphere homologues may result in better language abilities. Copyright © 2017. Published by Elsevier Inc.
Berutti, Mariangeles; Nery, Fabiano G; Sato, Rodrigo; Scippa, Angela; Kapczinski, Flavio; Lafer, Beny
To compare clinical characteristics of bipolar disorder (BD) in patients with and without a family history of mood disorders (FHMD) in a large sample from the Brazilian Research Network of Bipolar Disorders. Four-hundred eighty-eight DSM-IV BD patients participating in the Brazilian Research Network of Bipolar Disorders were included. Participants were divided between those with FHMD (n=230) and without FHMD (n=258). We compared these two groups on demographic and clinical variables and performed a logistic regression to identify which variables were most strongly associated with positive family history of mood disorders. BD patients with FHMD presented with significantly higher lifetime prevalence of any anxiety disorder, obsessive-compulsive disorder, social phobia, substance abuse, and were more likely to present history of suicide attempts, family history of suicide attempts and suicide, and more psychiatric hospitalizations than BD patients without FHMD. Logistic regression showed that the variables most strongly associated with a positive FHMD were any comorbid anxiety disorder, comorbid substance abuse, and family history of suicide. Cross-sectional study and verification of FHMD by indirect information. BD patients with FHMD differ from BD patients without FHMD in rates of comorbid anxiety disorder and substance abuse, number of hospitalizations and suicide attempts. As FHMD is routinely assessed in clinical practice, these findings may help to identify patients at risk for particular manifestations of BD and may point to a common, genetically determined neurobiological substrate that increases the risk of conditions such as comorbidities and suicidality in BD patients. Copyright © 2014 Elsevier B.V. All rights reserved.
M. Genco Usta
Full Text Available The influence of prenatal stress on psychopathology has been observed in many animal and human studies. In many studies, stress during prenatal period has been shown to result in negative feedback dysregulation and hyperactivity of hypothalamo-pituitary-adrenocortical axis. Prenatal stres also may cause increased risk of birth complications, startle or distress in response to novel and surprising stimuli during infancy; lower Full Scale IQs, language abilities and attention deficiency in period of 3-5 years; increased risk of attention deficit hyperactivity syndrome, anxiety symptoms, depressive disorder and impulsivity during adolescence. Additionally, timing of prenatal stress is also important and 12-22 weeks of gestation seems to be the most vulnerable period. The results underline the need for early prevention and intervention programs for highly anxious women during pregnancy. Administration of prenatal stress monitoring to public health programs or removing pregnant women who have been exposed to life events such as natural disaster, terror attack to secure areas that provide basic needs may be crucial.
Brandler, William M.; Paracchini, Silvia
Handedness and brain asymmetry have been linked to neurodevelopmental disorders such as dyslexia and schizophrenia. The genetic nature of this correlation is not understood. Recent discoveries have shown handedness is determined in part by the biological pathways that establish left/right (LR) body asymmetry during development. Cilia play a key role in this process, and candidate genes for dyslexia have also been recently shown to be involved in cilia formation. Defective cilia result not only in LR body asymmetry phenotypes but also brain midline phenotypes such as an absent corpus callosum. These findings suggest that the mechanisms for establishing LR asymmetry in the body are reused for brain midline development, which in turn influences traits such as handedness and reading ability. PMID:24275328
Full Text Available Intercommunication of Dopamine Receptors (DRs with their associate protein partners is crucial to maintain regular brain function in human. Majority of the brain disorders arise due to malfunctioning of such communication process. Hence, contributions of genetic factors, as well as phenotypic indications for various neurological and psychiatric disorders are often attributed as sharing in nature. In our earlier research article entitled “Human Dopamine Receptors Interaction Network (DRIN: a systems biology perspective on topology, stability and functionality of the network” (Podder et al., 2014 , we had depicted a holistic interaction map of human Dopamine Receptors. Given emphasis on the topological parameters, we had characterized the functionality along with the vulnerable properties of the network. In support of this, we hereby provide an additional data highlighting the genetic overlapping of various brain disorders in the network. The data indicates the sharing nature of disease genes for various neurological and psychiatric disorders in dopamine receptors connecting protein-protein interactions network. The data also indicates toward an alternative approach to prioritize proteins for overlapping brain disorders as valuable drug targets in the network.
Full Text Available Initial historical accounts as well as recent data suggest that emotion processing is dysfunctional in conversion disorder patients and that this alteration may be the pathomechanistic neurocognitive basis for symptoms in conversion disorder. However, to date evidence of direct interaction of altered negative emotion processing with motor control networks in conversion disorder is still lacking. To specifically study the neural correlates of emotion processing interacting with motor networks we used a task combining emotional and sensorimotor stimuli both separately as well as simultaneously during functional magnetic resonance imaging in a well characterized group of 13 conversion disorder patients with functional hemiparesis and 19 demographically matched healthy controls. We performed voxelwise statistical parametrical mapping for a priori regions of interest within emotion processing and motor control networks. Psychophysiological interaction (PPI was used to test altered functional connectivity of emotion and motor control networks. Only during simultaneous emotional stimulation and passive movement of the affected hand patients displayed left amygdala hyperactivity. PPI revealed increased functional connectivity in patients between the left amygdala and the (pre-supplemental motor area and the subthalamic nucleus, key regions within the motor control network. These findings suggest a novel mechanistic direct link between dysregulated emotion processing and motor control circuitry in conversion disorder.
Richetin, Juliette; Preti, Emanuele; Costantini, Giulio; De Panfilis, Chiara
We argue that the series of traits characterizing Borderline Personality Disorder samples do not weigh equally. In this regard, we believe that network approaches employed recently in Personality and Psychopathology research to provide information about the differential relationships among symptoms would be useful to test our claim. To our knowledge, this approach has never been applied to personality disorders. We applied network analysis to the nine Borderline Personality Disorder traits to explore their relationships in two samples drawn from university students and clinical populations (N = 1317 and N = 96, respectively). We used the Fused Graphical Lasso, a technique that allows estimating networks from different populations separately while considering their similarities and differences. Moreover, we examined centrality indices to determine the relative importance of each symptom in each network. The general structure of the two networks was very similar in the two samples, although some differences were detected. Results indicate the centrality of mainly affective instability, identity, and effort to avoid abandonment aspects in Borderline Personality Disorder. Results are consistent with the new DSM Alternative Model for Personality Disorders. We discuss them in terms of implications for therapy.
Full Text Available We argue that the series of traits characterizing Borderline Personality Disorder samples do not weigh equally. In this regard, we believe that network approaches employed recently in Personality and Psychopathology research to provide information about the differential relationships among symptoms would be useful to test our claim. To our knowledge, this approach has never been applied to personality disorders. We applied network analysis to the nine Borderline Personality Disorder traits to explore their relationships in two samples drawn from university students and clinical populations (N = 1317 and N = 96, respectively. We used the Fused Graphical Lasso, a technique that allows estimating networks from different populations separately while considering their similarities and differences. Moreover, we examined centrality indices to determine the relative importance of each symptom in each network. The general structure of the two networks was very similar in the two samples, although some differences were detected. Results indicate the centrality of mainly affective instability, identity, and effort to avoid abandonment aspects in Borderline Personality Disorder. Results are consistent with the new DSM Alternative Model for Personality Disorders. We discuss them in terms of implications for therapy.
Costantini, Giulio; De Panfilis, Chiara
We argue that the series of traits characterizing Borderline Personality Disorder samples do not weigh equally. In this regard, we believe that network approaches employed recently in Personality and Psychopathology research to provide information about the differential relationships among symptoms would be useful to test our claim. To our knowledge, this approach has never been applied to personality disorders. We applied network analysis to the nine Borderline Personality Disorder traits to explore their relationships in two samples drawn from university students and clinical populations (N = 1317 and N = 96, respectively). We used the Fused Graphical Lasso, a technique that allows estimating networks from different populations separately while considering their similarities and differences. Moreover, we examined centrality indices to determine the relative importance of each symptom in each network. The general structure of the two networks was very similar in the two samples, although some differences were detected. Results indicate the centrality of mainly affective instability, identity, and effort to avoid abandonment aspects in Borderline Personality Disorder. Results are consistent with the new DSM Alternative Model for Personality Disorders. We discuss them in terms of implications for therapy. PMID:29040324
Mason, Michael J; Light, John M; Mennis, Jeremy; Rusby, Julie C; Westling, Erika; Crewe, Stephanie; Zaharakis, Nikola; Way, Thomas; Flay, Brian R
The current study investigated the moderating effect of peer networks on neighborhood disorder's association with substance use in a sample of primarily African American urban adolescents. A convenience sample of 248 adolescents was recruited from urban health care settings and followed for two years, assessing psychological, social, and geographic risk and protective characteristics. A subset of 106 substance using participants were used for the analyses. A moderation model was tested to determine if the influence of neighborhood disorder (percent vacant housing, assault index, percent single parent headed households, percent home owner occupied, percent below poverty line) on substance use was moderated by peer network health (sum of peer risk and protective behaviors). Evidence for hypothesized peer network moderation was supported. A latent growth model found that peer network health is most strongly associated with lower baseline substance use for young adolescents residing in more disordered neighborhoods. Over the course of two years (ages approximately 14-16) this protective effect declines, and the decline is stronger for more disordered neighborhoods. Understanding the longitudinal moderating effects of peer networks within high-risk urban settings is important to the development and testing of contextually sensitive peer-based interventions. suggest that targeting the potential protective qualities of peer networks may be a promising approach for interventions seeking to reduce substance use, particularly among younger urban adolescents living in high-risk neighborhoods. Copyright © 2017 Elsevier B.V. All rights reserved.
While treating panic and agoraphobia patients with behaviour therapy, a high frequency of allergic reaction of the IgE-mediated type I was observed. Panic disorder, agoraphobia, allergic disorder, and vasomotor reactions are briefly discussed in the framework of psycho-endocrino-immunological research. A pilot study had shown a high correlation between panic disorder with and without agoraphobia and allergic reaction. A controlled study was then planned to test the hypothesized psychoimmunological relationship. 100 allergic patients, 79 panic/agoraphobic patients, and 66 controls underwent psychodiagnostic and allergic screening. 70% of the anxiety patients responded to test allergens with IgE-mediated type-I immediate reactions in comparison to 28% of the control persons. Another 15% of the panic patients reacted to nickle compound with type-IV delayed skin reactions (7% of the controls). Conversely, 10% of the allergic patients suffered from panic disorder (45% had experienced panic attacks) in contrast to 2% of the controls (24% of these reported panic attacks). The relative risk for allergic patients to develop panic disorder with and without agoraphobia is obviously five times as high as for controls. With this assumption of a psychoimmunological preparedness in mind, a behavioural medical diagnostic and therapeutic concept seems more adequate in coping both with panic/agoraphobia and allergic disorder.
Jacques, Peggy L.; Kragel, Philip A.; Rubin, David C.
Post-traumatic stress disorder (PTSD) affects the functional recruitment and connectivity between neural regions during autobiographical memory (AM) retrieval that overlap with default and control networks. Whether such univariate changes relate to potential differences in the contribution of large-scale neural networks supporting cognition in PTSD is unknown. In the current functional MRI (fMRI) study we employ independent component analysis to examine the influence the engagement of neural networks during the recall of personal memories in PTSD (15 participants) compared to non-trauma exposed, healthy controls (14 participants). We found that the PTSD group recruited similar neural networks when compared to controls during AM recall, including default network subsystems and control networks, but there were group differences in the spatial and temporal characteristics of these networks. First, there were spatial differences in the contribution of the anterior and posterior midline across the networks, and with the amygdala in particular for the medial temporal subsystem of the default network. Second, there were temporal differences in the relationship of the medial prefrontal subsystem of the default network, with less temporal coupling of this network during AM retrieval in PTSD relative to controls. These findings suggest that spatial and temporal characteristics of the default and control networks potentially differ in PTSD versus healthy controls, and contribute to altered recall of personal memory. PMID:23483523
Full Text Available Autism spectrum disorder (ASD is a developmental disorder that involves developmental delays. It has been hypothesized that aberrant neural connectivity in ASD may cause atypical brain network development. Brain graphs not only describe the differences in brain networks between clinical and control groups, but also provide information about network development within each group. In the present study, graph indices of brain networks were estimated in children with ASD and in typically developing (TD children using magnetoencephalography performed while the children viewed a cartoon video. We examined brain graphs from a developmental point of view, and compared the networks between children with ASD and TD children. Network development patterns (NDPs were assessed by examining the association between the graph indices and the raw scores on the achievement scale or the age of the children. The ASD and TD groups exhibited different NDPs at both network and nodal levels. In the left frontal areas, the nodal degree and efficiency of the ASD group were negatively correlated with the achievement scores. Reduced network connections were observed in the temporal and posterior areas of TD children. These results suggested that the atypical network developmental trajectory in children with ASD is associated with the development score rather than age.
Rief, Winfried; Burton, Chris; Frostholm, Lisbeth; Henningsen, Peter; Kleinstäuber, Maria; Kop, Willem J; Löwe, Bernd; Martin, Alexandra; Malt, Ulrik; Rosmalen, Judith; Schröder, Andreas; Shedden-Mora, Meike; Toussaint, Anne; van der Feltz-Cornelis, Christina
The harmonization of core outcome domains in clinical trials facilitates comparison and pooling of data, and simplifies the preparation and review of research projects and comparison of risks and benefits of treatments. Therefore, we provide recommendations for the core outcome domains that should be considered in clinical trials on the efficacy and effectiveness of interventions for somatic symptom disorder, bodily distress disorder, and functional somatic syndromes. The European Network on Somatic Symptom Disorders group of more than 20 experts in the field met twice in Hamburg to discuss issues of assessment and intervention research in somatic symptom disorder, bodily distress disorder, and functional somatic syndromes. The consensus meetings identified core outcome domains that should be considered in clinical trials evaluating treatments for somatic symptom disorder and associated functional somatic syndromes. The following core domains should be considered when defining ascertainment methods in clinical trials: a) classification of somatic symptom disorder/bodily distress disorder, associated functional somatic syndromes, and comorbid mental disorders (using structured clinical interviews), duration of symptoms, medical morbidity, and prior treatments; b) location, intensity, and interference of somatic symptoms; c) associated psychobehavioral features and biological markers; d) illness consequences (quality of life, disability, health care utilization, health care costs; e) global improvement and treatment satisfaction; and f) unwanted negative effects. The proposed criteria are intended to improve synergies of clinical trials and to facilitate decision making when comparing different treatment approaches. These recommendations should not result in inflexible guidelines, but increase consistency across investigations in this field.
Vince D Calhoun
Full Text Available Intrinsic functional brain networks (INs are regions showing temporal coherence with one another. These INs are present in the context of a task (as opposed to an undirected task such as rest, albeit modulated to a degree both spatially and temporally. Prominent networks include the default mode, attentional fronto-parietal, executive control, bilateral temporal lobe and motor networks. The characterization of INs has recently gained considerable momentum, however; most previous studies evaluate only a small subset of the intrinsic networks (e.g. default mode. In this paper we use independent component analysis to study INs decomposed from fMRI data collected in a large group of schizophrenia patients, healthy controls, and individuals with bipolar disorder, while performing an auditory oddball task. Schizophrenia and bipolar disorder share significant overlap in clinical symptoms, brain characteristics, and risk genes which motivates our goal of identifying whether functional imaging data can differentiate the two disorders. We tested for group differences in properties of all identified intrinsic networks including spatial maps, spectra, and functional network connectivity. A small set of default mode, temporal lobe, and frontal networks with default mode regions appearing to play a key role in all comparisons. Bipolar subjects showed more prominent changes in ventromedial and prefrontal default mode regions whereas schizophrenia patients showed changes in posterior default mode regions. Anti-correlations between left parietal areas and dorsolateral prefrontal cortical areas were different in bipolar and schizophrenia patients and amplitude was significantly different from healthy controls in both patient groups. Patients exhibited similar frequency behavior across multiple networks with decreased low frequency power. In summary, a comprehensive analysis of intrinsic networks reveals a key role for the default mode in both schizophrenia and
Jiao, Xiaodan; Ashtari, Niloufar; Rahimi-Balaei, Maryam; Chen, Qi Min; Badbezanchi, Ilnaz; Shojaei, Shahla; Marzban, Adel; Mirzaei, Nima; Chung, Seunghyuk; Guan, Teng; Li, Jiasi; Vriend, Jerry; Mehr, Shahram Ejtemaei; Kong, Jiming; Marzban, Hassan
The mevalonate cascade is a key metabolic pathway that regulates a variety of cellular functions and is thereby implicated in the pathophysiology of most brain diseases, including neurodevelopmental and neurodegenerative disorders. Emerging lines of evidence suggest that statins and Rho GTPase inhibitors are efficacious and have advantageous properties in treatment of different pathologic conditions that are relevant to the central nervous system. Beyond the original role of statins in lowering cholesterol synthesis, they have anti-inflammatory, antioxidant and modulatory effects on signaling pathways. Additionally, Rho GTPase inhibitors and statins share the mevalonate pathway as a common target of their therapeutic actions. In this review, we discuss potential mechanisms through which these drugs, via their role in the mevalonate pathway, exert their neuroprotective effects in neurodegenerative and neurodevelopmental disorders. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Mohan, Akansha; Roberto, Aaron J; Mohan, Abhishek; Lorenzo, Aileen; Jones, Kathryn; Carney, Martin J; Liogier-Weyback, Luis; Hwang, Soonjo; Lapidus, Kyle A B
The relationship of cortical structure and specific neuronal circuitry to global brain function, particularly its perturbations related to the development and progression of neuropathology, is an area of great interest in neurobehavioral science. Disruption of these neural networks can be associated with a wide range of neurological and neuropsychiatric disorders. Herein we review activity of the Default Mode Network (DMN) in neurological and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, Epilepsy (Temporal Lobe Epilepsy - TLE), attention deficit hyperactivity disorder (ADHD), and mood disorders. We discuss the implications of DMN disruptions and their relationship to the neurocognitive model of each disease entity, the utility of DMN assessment in clinical evaluation, and the changes of the DMN following treatment.
Uhlhaas, Peter J; Singer, Wolf
In recent years, numerous studies have tested the relevance of neural oscillations in neuropsychiatric conditions, highlighting the potential role of changes in temporal coordination as a pathophysiological mechanism in brain disorders. In the current review, we provide an update on this hypothesis because of the growing evidence that temporal coordination is essential for the context and goal-dependent, dynamic formation of large-scale cortical networks. We shall focus on issues that we consider particularly promising for a translational research program aimed at furthering our understanding of the origins of neuropsychiatric disorders and the development of effective therapies. We will focus on schizophrenia and autism spectrum disorders (ASDs) to highlight important issues and challenges for the implementation of such an approach. Specifically, we will argue that deficits in temporal coordination lead to a disruption of functional large-scale networks, which in turn can account for several specific dysfunctions associated with these disorders. Copyright © 2012 Elsevier Inc. All rights reserved.
McNally, R J; Mair, P; Mugno, B L; Riemann, B C
Obsessive-compulsive disorder (OCD) is often co-morbid with depression. Using the methods of network analysis, we computed two networks that disclose the potentially causal relationships among symptoms of these two disorders in 408 adult patients with primary OCD and co-morbid depression symptoms. We examined the relationship between the symptoms constituting these syndromes by computing a (regularized) partial correlation network via the graphical LASSO procedure, and a directed acyclic graph (DAG) via a Bayesian hill-climbing algorithm. The results suggest that the degree of interference and distress associated with obsessions, and the degree of interference associated with compulsions, are the chief drivers of co-morbidity. Moreover, activation of the depression cluster appears to occur solely through distress associated with obsessions activating sadness - a key symptom that 'bridges' the two syndromic clusters in the DAG. Bayesian analysis can expand the repertoire of network analytic approaches to psychopathology. We discuss clinical implications and limitations of our findings.
Walschaers, Mattia; Mulet, Roberto; Wellens, Thomas; Buchleitner, Andreas
We explain how centrosymmetry, together with a dominant doublet of energy eigenstates in the local density of states, can guarantee interference-assisted, strongly enhanced, strictly coherent quantum excitation transport between two predefined sites of a random network of two-level systems. Starting from a generalization of the chaos-assisted tunnelling mechanism, we formulate a random matrix theoretical framework for the analytical prediction of the transfer time distribution, of lower bounds of the transfer efficiency, and of the scaling behavior of characteristic statistical properties with the size of the network. We show that these analytical predictions compare well to numerical simulations, using Hamiltonians sampled from the Gaussian orthogonal ensemble.
Tasnuba Jesmin; Sajjad Waheed; Abdullah-Al-Emran,
Metabolic disorder causes the failure of metabolism process is growing concern worldwide. This research predicts a common metabolic pathway that is shared by Obesity, Type-2 Diabetes, Hypertension and Cardiovascular diseases due to metabolic disorder. A protein-protein interaction network is created to show the protein co-expression, co-regulations and interactions among gene and diseases. Genes whose are associated with metabolic diseases have been accumulated from different gene databases w...
Milovanov, A.V.; Juul Rasmussen, Jens
This paper advocates an unconventional description of charge transport processes in disordered solids, which brings together the ideas of fractal geometry, percolation theory, and topology of manifolds. We demonstrate that the basic features of ac conductivity in disordered materials as seen...... in various experiments are reproduced with remarkable accuracy by the conduction properties of percolating fractal networks near the threshold of percolation. The universal character of ac conductivity in three embedding dimensions is discussed in connection with the available experimental data. An important...
Liu, Yang; Li, Liang; Li, Baojuan; Zhang, Xi; Lu, Hongbing
The triple network model provides a common framework for understanding affective and neurocognitive dysfunctions across multiple disorders, including central executive network (CEN), default mode network (DMN), and salience network (SN). Considering the effect of traumatic experience on post-traumatic stress disorder (PTSD), this study aims to explore the alteration of triple network connectivity in a specific PTSD induced by a single prolonged trauma exposure. With arterial spin labeling sequence, three networks were identified using independent component analysis in 10 PTSD patients and 10 healthy survivors, who experienced the same coal mining flood disaster. In PTSD patients, decreased connectivity was identified in left middle frontal gyrus of CEN, left precuneus and bilateral superior frontal gyrus of DMN, and right anterior insula of SN. The decreased connectivity in left middle frontal gyrus was identified to associate with clinical severity. These results indicated the decreased triple network connectivity, which not only supported the proposal of the triple network model, but also prompted possible neurobiology mechanism of cognitive dysfunction for this kind of PTSD.
Full Text Available BACKGROUND: Autism spectrum disorders (ASD are characterized by aberrant neurodevelopment. Although the ASD brain undergoes precocious growth followed by decelerated maturation during early postnatal period of childhood, the neuroimaging approach has not been empirically applied to investigate how the ASD brain develops during adolescence. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 25 male adolescents with high functioning ASD and 25 typically developing controls for voxel-based morphometric analysis of structural magnetic resonance image. Results indicate that there is an imbalance of regional gray matter volumes and concentrations along with no global brain enlargement in adolescents with high functioning ASD relative to controls. Notably, the right inferior parietal lobule, a role in social cognition, have a significant interaction of age by groups as indicated by absence of an age-related gain of regional gray matter volume and concentration for neurodevelopmental maturation during adolescence. CONCLUSIONS/SIGNIFICANCE: The findings indicate the neural correlates of social cognition exhibits aberrant neurodevelopment during adolescence in ASD, which may cast some light on the brain growth dysregulation hypothesis. The period of abnormal brain growth during adolescence may be characteristic of ASD. Age effects must be taken into account while measures of structural neuroimaging have been clinically put forward as potential phenotypes for ASD.
Fabiano A. Gomes
Full Text Available Objective: Bipolar disorder (BD is associated with significant morbidity and mortality due to comorbid general medical conditions, particularly cardiovascular disease. This study is the first report of the Brazilian Research Network in Bipolar Disorder (BRN-BD that aims to evaluate the prevalence and clinical correlates of cardiovascular risk factors among Brazilian patients with BD. Methods: A cross-sectional study of 159 patients with DSM-IV BD, 18 years or older, consecutively recruited from the Bipolar Research Program (PROMAN in São Paulo and the Bipolar Disorder Program (PROTAHBI in Porto Alegre. Clinical, demographic, anthropometric, and metabolic variables were systematically assessed. Results: High rates of smoking (27%, physical inactivity (64.9%, alcohol use disorders (20.8%, elevated fasting glucose (26.4%, diabetes (13.2%, hypertension (38.4%, hypertriglyceridemia (25.8%, low HDL-cholesterol (27.7%, general (38.4% and abdominal obesity (59.1% were found in the sample. Male patients were more likely to have alcohol use disorders, diabetes, and hypertriglyceridemia, whereas female patients showed higher prevalence of abdominal obesity. Variables such as medication use pattern, alcohol use disorder, and physical activity were associated with selected cardiovascular risk factors in the multivariable analysis. Conclusion: This report of the BRN-BD provides new data regarding prevalence rates and associated cardiovascular risk factors in Brazilian outpatients with BD. There is a need for increasing both awareness and recognition about metabolic and cardiovascular diseases in this patient population.
Full Text Available Objective: Anxiety disorders are highly prevalent in the United States, and if untreated, result in a number of negative outcomes. This study aimed to investigate psychiatrists' current treatment practices for patients with anxiety disorders in the United States. Methods: Psychiatrist-reported data from the 1997 and 1999 American Psychiatric Institute for Research and Education Practice Research Network (PRN Study of Psychiatric Patients and Treatments (SPPT were examined, focusing on patients diagnosed with anxiety disorders. Information related to diagnostic and clinical features and treatments provided were obtained. Results: Anxiety disorders remain underdiagnosed and undertreated, since only 11.4% of the sample received a principal diagnosis of an anxiety disorder in a real world setting. Posttraumatic stress disorder was associated with particularly high comorbidity and disability, and social anxiety disorder was relatively rarely diagnosed and treated. Although combined pharmacotherapy and psychotherapy was commonly used to treat anxiety disorders, anxiolytics were more commonly prescribed than selective serotonin reuptake inhibitors (SSRIs. Conclusions: These data provide a picture of diagnosis and practice patterns across a range of psychiatric settings and suggest that anxiety disorders, despite being among the most prevalent of psychiatric disorders remain underdiagnosed and undertreated particularly in respect of the use of psychotherapeutic interventions.
Wang, Rong; Wang, Li; Yang, Yong; Li, Jiajia; Wu, Ying; Lin, Pan
Attention deficit hyperactivity disorder (ADHD) is the most common childhood neuropsychiatric disorder and affects approximately 6 -7 % of children worldwide. Here, we investigate the statistical properties of undirected and directed brain functional networks in ADHD patients based on random matrix theory (RMT), in which the undirected functional connectivity is constructed based on correlation coefficient and the directed functional connectivity is measured based on cross-correlation coefficient and mutual information. We first analyze the functional connectivity and the eigenvalues of the brain functional network. We find that ADHD patients have increased undirected functional connectivity, reflecting a higher degree of linear dependence between regions, and increased directed functional connectivity, indicating stronger causality and more transmission of information among brain regions. More importantly, we explore the randomness of the undirected and directed functional networks using RMT. We find that for ADHD patients, the undirected functional network is more orderly than that for normal subjects, which indicates an abnormal increase in undirected functional connectivity. In addition, we find that the directed functional networks are more random, which reveals greater disorder in causality and more chaotic information flow among brain regions in ADHD patients. Our results not only further confirm the efficacy of RMT in characterizing the intrinsic properties of brain functional networks but also provide insights into the possibilities RMT offers for improving clinical diagnoses and treatment evaluations for ADHD patients.
Mowbray, Orion; Quinn, Adam; Cranford, James A.
Background While some argue that social network ties of individuals with alcohol use disorders (AUD) are robust, there is evidence to suggest that individuals with AUDs have few social network ties, which are a known risk factor for health and wellness. Objectives Social network ties to friends, family, co-workers and communities of individuals are compared among individuals with a past-year diagnosis of alcohol dependence or alcohol abuse to individuals with no lifetime diagnosis of AUD. Method Respondents from Wave 2 of the National Epidemiologic Survey on Alcohol Related Conditions (NESARC) were assessed for the presence of past-year alcohol dependence or past-year alcohol abuse, social network ties, sociodemographics and clinical characteristics. Results Bivariate analyses showed that both social network size and social network diversity was significantly smaller among individuals with alcohol dependence, compared to individuals with alcohol abuse or no AUD. When social and clinical factors related to AUD status were controlled, multinomial logistic models showed that social network diversity remained a significant predictor of AUD status, while social network size did not differ among AUD groups. Conclusion Social networks of individuals with AUD may be different than individuals with no AUD, but this claim is dependent on specific AUD diagnosis and how social networks are measured. PMID:24405256
Almeida, Carolina Lopes de
Trabalho de revisão do 6º ano médico com vista à atribuição do grau de mestre (área científica de pediatria) no âmbito do ciclo de estudos de Mestrado Integrado em Medicina. Although prognosis of Congenital Hypothyroidism (CH) has been greatly modified since the introduction of newborn screening programs, persistent cognitive deficits are still reported. The aim of this study was to evaluate neurodevelopmental outcomes of children with CH and to determine whether severity of CH, age of...
Bernhardt, Boris C; Bonilha, Leonardo; Gross, Donald W
Recent years have witnessed a paradigm shift in the study and conceptualization of epilepsy, which is increasingly understood as a network-level disorder. An emblematic case is temporal lobe epilepsy (TLE), the most common drug-resistant epilepsy that is electroclinically defined as a focal epilepsy and pathologically associated with hippocampal sclerosis. In this review, we will summarize histopathological, electrophysiological, and neuroimaging evidence supporting the concept that the substrate of TLE is not limited to the hippocampus alone, but rather is broadly distributed across multiple brain regions and interconnecting white matter pathways. We will introduce basic concepts of graph theory, a formalism to quantify topological properties of complex systems that has recently been widely applied to study networks derived from brain imaging and electrophysiology. We will discuss converging graph theoretical evidence indicating that networks in TLE show marked shifts in their overall topology, providing insight into the neurobiology of TLE as a network-level disorder. Our review will conclude by discussing methodological challenges and future clinical applications of this powerful analytical approach. Copyright © 2015 Elsevier Inc. All rights reserved.
Kinast, K.; Peeters, D.; Kolk, S.M.; Schubert, D.; Homberg, J.R.
Serotonin, in its function as neurotransmitter, is well-known for its role in depression, autism and other neuropsychiatric disorders, however, less known as a neurodevelopmental factor. The serotonergic system is one of the earliest to develop during embryogenesis and early changes in serotonin
Catherine Anne Edmonson
Full Text Available Autism spectrum disorder (ASD is a neurodevelopmental disorder characterized by deficits in social interaction, difficulties with language, and repetitive/restricted behaviors. The etiology of ASD is still largely unclear, but immune dysfunction and abnormalities in synaptogenesis have repeatedly been implicated as contributing to the disease phenotype. However, an understanding of how and if these two processes are related has not firmly been established. As non-inflammatory roles of microglia become increasingly recognized as critical to normal neurodevelopment, it is important to consider how dysfunction in these process might explain the seemingly disparate findings of immune dysfunction and aberrant synaptogenesis seen in ASD. In this review, we highlight research demonstrating the importance of microglia to development of normal neural networks, review recent studies demonstrating abnormal microglia in autism, and discuss how the relationship between these processes may contribute to the development of autism and other neurodevelopmental disorders at the cellular level.
Leonidas, Carolina; Dos Santos, Manoel Antônio
This study aimed to analyze the scientific literature about social networks and social support in eating disorders (ED). By combining keywords, an integrative review was performed. It included publications from 2006-2013, retrieved from the MEDLINE, LILACS, PsycINFO, and CINAHL databases. The selection of articles was based on preestablished inclusion and exclusion criteria. A total of 24 articles were selected for data extraction. There was a predominance of studies that used nonexperimental and descriptive designs, and which were published in international journals. This review provided evidence of the fact that fully consolidated literature regarding social support and social networks in patients with ED is not available, given the small number of studies dedicated to the subject. We identified evidence that the family social network of patients with ED has been widely explored by the literature, although there is a lack of studies about other networks and sources of social support outside the family. The evidence presented in this study shows the need to include other social networks in health care. This expansion beyond family networks would include significant others - such as friends, colleagues, neighbors, people from religious groups, among others - who could help the individual coping with the disorder. The study also highlights the need for future research on this topic, as well as a need for greater investment in publications on the various dimensions of social support and social networks.
Chasnoff, Ira J; Wells, Anne M; Telford, Erin; Schmidt, Christine; Messer, Gwendolyn
The purpose of this article is to compare the neurodevelopmental profiles of 78 foster and adopted children with fetal alcohol syndrome (FAS), partial FAS (pFAS), or alcohol-related neurodevelopmental disorder (ARND). Seventy-eight foster and adopted children underwent a comprehensive diagnostic evaluation. By using criteria more stringent than those required by current guidelines, the children were placed in 1 of 3 diagnostic categories: FAS, pFAS, or ARND. Each child was evaluated across the domains of neuropsychological functioning most frequently affected by prenatal exposure to alcohol. Multivariate analyses of variance were conducted to examine differences in neuropsychological functioning between the 3 diagnostic groups. Descriptive discriminant analyses were performed in follow-up to the multivariate analyses of variance. The children in the 3 diagnostic categories were similar for descriptive and child welfare variables. Children with FAS had significantly decreased mean weight, height, and head circumference. Children with FAS exhibited the most impaired level of general intelligence, significantly worse language-based memory compared with children with ARND, and significantly poorer functional communication skills than children with pFAS. On executive functioning, the FAS group of children performed significantly worse on sequencing and shift than either the pFAS or ARND groups. Children with pFAS and ARND were similar in all neurodevelopmental domains that were tested. The children who met tightly defined physical criteria for a diagnosis of FAS demonstrated significantly poorer neurodevelopmental functioning than children with pFAS and ARND. Children in these latter 2 groups were similar in all neurodevelopmental domains that were tested.
Doll, Anselm; Sorg, Christian; Manoliu, Andrei; Wöller, Andreas; Meng, Chun; Förstl, Hans; Zimmer, Claus; Wohlschläger, Afra M.; Riedl, Valentin
Borderline personality disorder (BPD) is characterized by “stable instability” of emotions and behavior and their regulation. This emotional and behavioral instability corresponds with a neurocognitive triple network model of psychopathology, which suggests that aberrant emotional saliency and cognitive control is associated with aberrant interaction across three intrinsic connectivity networks [i.e., the salience network (SN), default mode network (DMN), and central executive network (CEN)]. The objective of the current study was to investigate whether and how such triple network intrinsic functional connectivity (iFC) is changed in patients with BPD. We acquired resting-state functional magnetic resonance imaging (rs-fMRI) data from 14 patients with BPD and 16 healthy controls. High-model order independent component analysis was used to extract spatiotemporal patterns of ongoing, coherent blood-oxygen-level-dependent signal fluctuations from rs-fMRI data. Main outcome measures were iFC within networks (intra-iFC) and between networks (i.e., network time course correlation inter-iFC). Aberrant intra-iFC was found in patients’ DMN, SN, and CEN, consistent with previous findings. While patients’ inter-iFC of the CEN was decreased, inter-iFC of the SN was increased. In particular, a balance index reflecting the relationship of CEN- and SN-inter-iFC across networks was strongly shifted from CEN to SN connectivity in patients. Results provide first preliminary evidence for aberrant triple network iFC in BPD. Our data suggest a shift of inter-network iFC from networks involved in cognitive control to those of emotion-related activity in BPD, potentially reflecting the persistent instability of emotion regulation in patients. PMID:24198777
Kamps, Debra; Mason, Rose; Thiemann-Bourque, Kathy; Feldmiller, Sarah; Turcotte, Amy; Miller, Todd
Peer networks including social groups using typical peers, scripted instruction, visual text cues, and reinforcement were examined with students with autism spectrum disorders (ASD). A multiple baseline design across four participants was used to measure students' use of communication acts with peers during free play following instruction. Peer…
Full Text Available Carolina Leonidas, Manoel Antônio dos Santos Department of Psychology, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Brazil Aims: This study aimed to analyze the scientific literature about social networks and social support in eating disorders (ED. Methods: By combining keywords, an integrative review was performed. It included publications from 2006–2013, retrieved from the MEDLINE, LILACS, PsycINFO, and CINAHL databases. The selection of articles was based on preestablished inclusion and exclusion criteria. Results: A total of 24 articles were selected for data extraction. There was a predominance of studies that used nonexperimental and descriptive designs, and which were published in international journals. This review provided evidence of the fact that fully consolidated literature regarding social support and social networks in patients with ED is not available, given the small number of studies dedicated to the subject. We identified evidence that the family social network of patients with ED has been widely explored by the literature, although there is a lack of studies about other networks and sources of social support outside the family. Conclusion: The evidence presented in this study shows the need to include other social networks in health care. This expansion beyond family networks would include significant others – such as friends, colleagues, neighbors, people from religious groups, among others – who could help the individual coping with the disorder. The study also highlights the need for future research on this topic, as well as a need for greater investment in publications on the various dimensions of social support and social networks. Keywords: eating disorders, social networks, social support, family relations, peer relations
De Vilder, Eva Y G; Hosen, Mohammad Jakir; Vanakker, Olivier M
The knowledge on the genetic etiology of complex disorders largely results from the study of rare monogenic disorders. Often these common and rare diseases show phenotypic overlap, though monogenic diseases generally have a more extreme symptomatology. ABCC6, the gene responsible for pseudoxanthoma elasticum, an autosomal recessive ectopic mineralization disorder, can be considered a paradigm gene with relevance that reaches far beyond this enigmatic orphan disease. Indeed, common traits such as chronic kidney disease or cardiovascular disorders have been linked to the ABCC6 gene. While during the last decade the awareness of the wide ramifications of ABCC6 has increased significantly, the gene itself and the transmembrane transporter it encodes have not unveiled all of the mysteries that surround them. To gain more insights, multiple approaches are being used including next-generation sequencing, computational methods, and various "omics" technologies. Much effort is made to place the vast amount of data that is gathered in an integrated system-biological network; the involvement of ABCC6 in common disorders provides a good view on the wide implications and potential of such a network. In this review, we summarize the network approaches used to study ABCC6 and the role of this gene in several complex diseases.
Full Text Available Abstract Incorporation of nanoparticles composed of surface-functionalized fumed silica (FS or native colloidal silica (CS into a nanostructured block copolymer yields hybrid nanocomposites whose mechanical properties can be tuned by nanoparticle concentration and surface chemistry. In this work, dynamic rheology is used to probe the frequency and thermal responses of nanocomposites composed of a symmetric poly(styrene-b-methyl methacrylate (SM diblock copolymer and varying in nanoparticle concentration and surface functionality. At sufficiently high loading levels, FS nanoparticle aggregates establish a load-bearing colloidal network within the copolymer matrix. Transmission electron microscopy images reveal the morphological characteristics of the nanocomposites under these conditions.
Jensen, Tina Birk; Kristensen, Anders Ringgaard; Toft, Niels
The implementation of an effective control strategy against disease in a finisher herd requires knowledge regarding the disease level in the herd. A Bayesian network was constructed that can estimate risk indexes for three cause-categories of leg disorders in a finisher herd. The cause-categories......The implementation of an effective control strategy against disease in a finisher herd requires knowledge regarding the disease level in the herd. A Bayesian network was constructed that can estimate risk indexes for three cause-categories of leg disorders in a finisher herd. The cause...... of performing systematic collection of additional information (i.e. clinical, pathological and bacteriological examination) when identifying causes of leg disorders at herd level....
Wu, Huawang; Sun, Hui; Wang, Chao; Yu, Lin; Li, Yilan; Peng, Hongjun; Lu, Xiaobing; Hu, Qingmao; Ning, Yuping; Jiang, Tianzi; Xu, Jinping; Wang, Jiaojian
Major depressive disorder (MDD) is a common psychiatric disorder that is characterized by cognitive deficits and affective symptoms. To date, an increasing number of neuroimaging studies have focused on emotion regulation and have consistently shown that emotion dysregulation is one of the central features and underlying mechanisms of MDD. Although gray matter morphological abnormalities in regions within emotion regulation networks have been identified in MDD, the interactions and relationships between these gray matter structures remain largely unknown. Thus, in this study, we adopted a structural covariance method based on gray matter volume to investigate the brain morphological abnormalities within the emotion regulation networks in a large cohort of 65 MDD patients and 65 age- and gender-matched healthy controls. A permutation test with p emotion dysregulation is an underlying mechanism of MDD by revealing disrupted structural covariance patterns in the emotion regulation network. Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Chen, Min; Yin, Xuezhi
This paper descries a new non-invasive method for diagnosis of breathing disorders based on adaptive-network-based fuzzy inference system (ANFIS). In this method, PetCO2, SpO2 and HR are chosen as inputs, and the breathing condition is selected as output ofANFIS. The inputs and output are then classified into fuzzy subsets by experts' knowledge. After, the fuzzy IF-THEN rules are built up according to the corresponding membership functions by set up of fuzzy subsets. The neural network was finally established and the membership functions and fuzzy rules were optimized by training. The results of experiment shows that ANFIS is more effective than BP Network regarding the diagnosis of breathing disorders.
Tang, Catherine So-Kum; Koh, Yvaine Yee Woen
This study aimed to determine the prevalence of addiction to social networking sites/platforms (SNS) and its comorbidity with other behavioral addiction and affective disorder among college students in Singapore. 1110 college students (age: M=21.46, SD=1.80) in Singapore completed measures assessing online social networking, unhealthy food intake and shopping addiction as well as depression, anxiety and mania. Descriptive analyses were conducted to investigate the prevalence and comorbidity of behavioral addiction and affective disorder. Chi-square tests were used to examine gender differences. The prevalence rates of SNS, food and shopping addiction were 29.5%, 4.7% and 9.3% respectively for the total sample. SNS addiction was found to co-occur with food addiction (3%), shopping addiction (5%), and both food and shopping addiction (1%). The comorbidity rates of SNS addiction and affective disorder were 21% for depression, 27.7% for anxiety, and 26.1% for mania. Compared with the total sample, students with SNS addiction reported higher comorbidity rates with other behavioral addiction and affective disorder. In general, females as compared to males reported higher comorbidity rates of SNS addiction and affective disorder. SNS addiction has a high prevalence rate among college students in Singapore. Students with SNS addiction were vulnerable to experience other behavior addiction as well as affective disorder, especially among females. Copyright © 2016. Published by Elsevier B.V.
Full Text Available Abstract Background The range of the fatty acids has been largely investigated in the plasma and erythrocytes of patients suffering from neuropsychiatric disorders. In this paper we investigate, for the first time, whether the study of the platelet fatty acids from such patients may be facilitated by means of artificial neural networks. Methods Venous blood samples were taken from 84 patients with a DSM-IV-TR diagnosis of major depressive disorder and from 60 normal control subjects without a history of clinical depression. Platelet levels of the following 11 fatty acids were analyzed using one-way analysis of variance: C14:0, C16:0, C16:1, C18:0, C18:1 n-9, C18:1 n-7, C18:2 n-6, C18:3 n-3, C20:3 n-3, C20:4 n-6 and C22:6 n-3. The results were then entered into a wide variety of different artificial neural networks. Results All the artificial neural networks tested gave essentially the same result. However, one type of artificial neural network, the self-organizing map, gave superior information by allowing the results to be described in a two-dimensional plane with potentially informative border areas. A series of repeated and independent self-organizing map simulations, with the input parameters being changed each time, led to the finding that the best discriminant map was that obtained by inclusion of just three fatty acids. Conclusion Our results confirm that artificial neural networks may be used to analyze platelet fatty acids in neuropsychiatric disorder. Furthermore, they show that the self-organizing map, an unsupervised competitive-learning network algorithm which forms a nonlinear projection of a high-dimensional data manifold on a regular, low-dimensional grid, is an optimal type of artificial neural network to use for this task.
Full Text Available Gaucher disease (GD is the most common of the lysosomal storage disorders and is caused by defects in the GBA gene encoding glucocerebrosidase (GlcCerase. The accumulation of its substrate, glucocylceramide (GlcCer is considered the main cause of GD. We found here that the expression of human mutated GlcCerase gene (hGBA that is associated with neuronopathy in GD patients causes neurodevelopmental defects in Drosophila eyes. The data indicate that endoplasmic reticulum (ER stress was elevated in Drosophila eye carrying mutated hGBAs by using of the ER stress markers dXBP1 and dBiP. We also found that Ambroxol, a potential pharmacological chaperone for mutated hGBAs, can alleviate the neuronopathic phenotype through reducing ER stress. We demonstrate a novel mechanism of neurodevelopmental defects mediated by ER stress through expression of mutants of human GBA gene in the eye of Drosophila.
Full Text Available Borderline personality disorder (BPD is characterized by stable instability of emotions and behavior and their regulation. This emotional and behavioral instability corresponds with a neurocognitive triple network model of psychopathology, which suggests that aberrant emotional saliency and cognitive control is associated with aberrant interaction across three intrinsic connectivity networks (ICN (i.e. the salience, default mode, and central executive network, SN, DMN, CEN. The objective of the current study was to investigate whether and how such triple network intrinsic functional connectivity (iFC is changed in patients with BPD. We acquired resting-state functional magnetic resonance imaging (rs-fMRI data from fourteen patients with BPD and sixteen healthy controls (HC. High-model order independent component analysis (ICA was used to extract spatiotemporal patterns of ongoing, coherent blood-oxygen-level-dependent (BOLD signal fluctuations from rs-fMRI data. Main outcome measures were iFC within networks (intra-iFC and between networks (i.e. network time course correlation inter-iFC.Aberrant intra-iFC was found in patients’ DMN, SN, and CEN, consistent with previous findings. While patients’ inter-iFC of the CEN was decreased, inter-iFC of the SN was increased. In particular, a balance index reflecting the relationship of CEN-and SN-inter-iFC across networks was strongly shifted from CEN to SN connectivity in patients. Results provide first preliminary evidence for aberrant triple network intrinsic functional connectivity in BPD. Our data suggest a shift of inter-network iFC from networks involved in cognitive control to those of emotion-related activity in BPD, potentially reflecting the persistent instability of emotion regulation in patients.
Zhao Xiaohu [Imaging Department of Tong Ji Hospital of Tong Ji University, Shanghai 200065 (China) and Bio-X lab, Department of Physics, Zhe Jiang University, Hangzhou 310027 (China)], E-mail: email@example.com; Wang Peijun [Imaging Department of Tong Ji Hospital of Tong Ji University, Shanghai 200065 (China)], E-mail: firstname.lastname@example.org; Li Chunbo [Department of Psychiatry, Tong Ji Hospital of Tong Ji University, Shanghai 200065 (China)], E-mail: email@example.com; Hu Zhenghui [Department of Electrical and Engineering, Hong Kong University of Science and Technology, Hong Kong (China)], E-mail: firstname.lastname@example.org; Xi Qian [Imaging Department of Tong Ji Hospital of Tong Ji University, Shanghai 200065 (China)], E-mail: email@example.com; Wu Wenyuan [Department of Psychiatry, Tong Ji Hospital of Tong Ji University, Shanghai 200065 (China)], E-mail: firstname.lastname@example.org; Tang Xiaowei [Bio-X lab, Department of Physics, Zhe Jiang University, Hangzhou 310027 (China)], E-mail: email@example.com
Anxiety disorder, a common mental disorder in our clinical practice, is characterized by unprovoked anxiety. Medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC), which closely involved in emotional processing, are critical regions in the default mode network. We used functional magnetic resonance imaging (fMRI) to investigate whether default mode network activity is altered in patients with anxiety disorder. Ten anxiety patients and 10 healthy controls underwent fMRI while listening to emotionally neutral words alternating with rest (Experiment 1) and threat-related words alternating with emotionally neutral words (Experiment 2). In Experiment 1, regions of deactivation were observed in patients and controls. In Experiment 2, regions of deactivation were observed only in patients. The observed deactivation patterns in the two experiments, which included MPFC, PCC, and inferior parietal cortex, were similar and consistent with the default model network. Less deactivation in MPFC and greater deactivation in PCC were observed for patients group comparing to controls in Experiment 1. Our observations suggest that the default model network is altered in anxiety patients and dysfunction in MPFC and PCC may play an important role in anxiety psychopathology.
Sun, Delin; Peverill, Matthew R; Swanson, Chelsea S; McLaughlin, Katie A; Morey, Rajendra A
Childhood maltreatment is associated with posttraumatic stress disorder (PTSD) and elevated rates of adolescent and adult psychopathology including major depression, bipolar disorder, substance use disorders, and other medical comorbidities. Gray matter volume changes have been found in maltreated youth with (versus without) PTSD. However, little is known about the alterations of brain structural covariance network topology derived from cortical thickness in maltreated youth with PTSD. High-resolution T1-weighted magnetic resonance imaging scans were from demographically matched maltreated youth with PTSD (N = 24), without PTSD (N = 64), and non-maltreated healthy controls (n = 67). Cortical thickness data from 148 cortical regions was entered into interregional partial correlation analyses across participants. The supra-threshold correlations constituted connections in a structural brain network derived from four types of centrality measures (degree, betweenness, closeness, and eigenvector) estimated network topology and the importance of nodes. Between-group differences were determined by permutation testing. Maltreated youth with PTSD exhibited larger centrality in left anterior cingulate cortex than the other two groups, suggesting cortical network topology specific to maltreated youth with PTSD. Moreover, maltreated youth with versus without PTSD showed smaller centrality in right orbitofrontal cortex, suggesting that this may represent a vulnerability factor to PTSD following maltreatment. Longitudinal follow-up of the present results will help characterize the role that altered centrality plays in vulnerability and resilience to PTSD following childhood maltreatment. Copyright © 2017. Published by Elsevier Ltd.
Hogue, Aaron; Evans, Steven W.; Levin, Frances R.
This article introduces neurodevelopmental and clinical considerations for treating adolescents with co-occurring attention deficit hyperactivity disorder (ADHD) and adolescent substance use (ASU) in outpatient settings. We first describe neurobiological impairments common to ADHD and ASU, including comorbidity with conduct disorder, that evoke a…
Lima-Ojeda, Juan M; Rupprecht, Rainer; Baghai, Thomas C
The main aims of this paper are to review and evaluate the neurobiology of the depressive syndrome from a neurodevelopmental perspective. An English language literature search was performed using PubMed. Depression is a complex syndrome that involves anatomical and functional changes that have an early origin in brain development. In subjects with genetic risk for depression, early stress factors are able to mediate not only the genetic risk but also gene expression. There is evidence that endocrine and immune interactions have an important impact on monoamine function and that the altered monoamine signalling observed in the depressive syndrome has a neuro-endocrino-immunological origin early in the development. Neurodevelopment is a key aspect to understand the whole neurobiology of depression.
Anker, Justin J; Forbes, Miriam K; Almquist, Zack W; Menk, Jeremiah S; Thuras, Paul; Unruh, Amanda S; Kushner, Matt G
Internalizing disorders co-occur with alcohol use disorder (AUD) at a rate that exceeds chance and compromise conventional AUD treatment. The "vicious cycle" model of comorbidity specifies drinking to cope (DTC) as a link between these disorders that, when not directly addressed, undermines the effectiveness of conventional treatments. Interventions based on this model have proven successful but there is no direct evidence for how and to what extent DTC contributes to the maintenance of comorbidity. In the present study, we used network analysis to depict associations between syndrome-specific groupings of internalizing symptoms, alcohol craving, and drinking behavior, as well as DTC and other extradiagnostic variables specified in the vicious cycle model (e.g., perceived stress and coping self-efficacy). Network analyses of 362 individuals with comorbid anxiety and AUD assessed at the beginning of residential AUD treatment indicated that while internalizing conditions and drinking elements had only weak direct associations, they were strongly connected with DTC and perceived stress. Consistent with this, centrality indices showed that DTC ranked as the most central/important element in the network in terms of its "connectedness" to all other network elements. A series of model simulations-in which individual elements were statistically controlled for-demonstrated that DTC accounted for all the relationships between the drinking-related elements and internalizing elements in the network; no other variable had this effect. Taken together, our findings suggest that DTC may serve as a "keystone" process in maintaining comorbidity between internalizing disorders and AUD. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Smith, Rachel V; Young, April M; Mullins, Ursula L; Havens, Jennifer R
Examination of the association of antisocial personality disorder (ASPD) with substance use and HIV risk behaviors within the social networks of rural people who use drugs. Interviewer-administered questionnaires were used to assess substance use, HIV risk behavior, and social network characteristics of drug users (n = 503) living in rural Appalachia. The MINI International Psychiatric Interview was used to determine whether participants met DSM-IV criteria for ASPD and Axis-I psychological comorbidities (eg, major depressive disorder, posttraumatic stress disorder, generalized anxiety disorder). Participants were also tested for herpes simplex 2, hepatitis C, and HIV. Multivariate generalized linear mixed modeling was used to determine the association between ASPD and risk behaviors, substance use, and social network characteristics. Approximately one-third (31%) of participants met DSM-IV criteria for ASPD. In multivariate analysis, distrust and conflict within an individual's social networks, as well as past 30-day use of heroin and crack, male gender, younger age, lesser education, heterosexual orientation, and comorbid MDD were associated with meeting diagnostic criteria for ASPD. Participants meeting criteria for ASPD were more likely to report recent heroin and crack use, which are far less common drugs of abuse in this population in which the predominant drug of abuse is prescription opioids. Greater discord within relationships was also identified among those with ASPD symptomatology. Given the elevated risk for blood-borne infection (eg, HIV) and other negative social and health consequences conferred by this high-risk subgroup, exploration of tailored network-based interventions with mental health assessment is recommended. © 2016 National Rural Health Association.
Ghibellini, Giulia; Brancati, Francesco; Castori, Marco
In the last decade, increasing attention has been devoted to the extra-articular and extra-cutaneous manifestations of joint hypermobility syndrome, also termed Ehlers-Danlos syndrome, hypermobility type (i.e., JHS/EDS-HT). Despite the fact that the current diagnostic criteria for both disorders remain focused on joint hypermobility, musculoskeletal pain and skin changes, medical practice and research have started investigating a wide spectrum of visceral, neurological and developmental complications, which represent major burdens for affected individuals. In particular, children with generalized joint hypermobility often present with various neurodevelopmental issues and can be referred for neurological consultation. It is common that investigations in these patients yield negative or inconsistent results, eventually leading to the exclusion of any structural neurological or muscle disorder. In the context of specialized clinics for connective tissue disorders, a clear relationship between generalized joint hypermobility and a characteristic neurodevelopmental profile affecting coordination is emerging. The clinical features of these patients tend to overlap with those of developmental coordination disorder and can be associated with learning and other disabilities. Physical and psychological consequences of these additional difficulties add to the chief manifestations of the pre-existing connective tissue disorder, affecting the well-being and development of children and their families. In this review, particular attention is devoted to the nature of the link between joint hypermobility, coordination difficulties and neurodevelopmental issues in children. Presumed pathogenesis and management issues are explored in order to attract more attention on this association and nurture future clinical research. © 2015 Wiley Periodicals, Inc.
Jin, Seung-Hyun; Jeong, Woorim; Chung, Chun Kee
Electrophysiologic hubs within the large-scale functional networks in mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS) have not been investigated. We hypothesized that mTLE with HS has different resting-state network hubs in their large-scale functional networks compared to the hubs in healthy controls (HC). We also hypothesized that the hippocampus would be a functional hub in mTLE patients with HS. Resting-state functional networks, identified by using magnetoencephalography (MEG) signals in the theta, alpha, beta, and gamma frequency bands, were evaluated. Networks in 44 mTLE patients with HS (left mTLE = 22; right mTLE = 22) were compared with those in 46 age-matched HC. We investigated betweenness centrality at the source-level MEG network. The main network hubs were at the pole of the left superior temporal gyrus in the beta band, the pole of the left middle temporal gyrus in the beta and gamma bands, left hippocampus in the theta and alpha bands, and right posterior cingulate gyrus in all four frequency bands in mTLE patients; all of which were different from the main network hubs in HC. Only patients with left mTLE showed profound differences from HC at the left hippocampus in the alpha band. Our analysis of resting-state MEG signals shows that altered electrophysiologic functional hubs in mTLE patients reflect pathophysiologic brain network reorganization. Because we detected network hubs in both hippocampal and extrahippocampal areas, it is probable that mTLE is a large-scale network disorder rather than a focal disorder. The hippocampus was a network hub in left mTLE but not in right mTLE patients, which may be due to intrinsic functional and structural asymmetries between left and right mTLE patients. The evaluation of cortical hubs, even in the spike-free resting-state, could be a clinical diagnostic marker of mTLE with HS. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
Beeney, Joseph E; Hallquist, Michael N; Clifton, Allan D; Lazarus, Sophie A; Pilkonis, Paul A
Examining differences in social integration, social support, and relationship characteristics in social networks may be critical for understanding the character and costs of the social difficulties experienced of borderline personality disorder (BPD). We conducted an ego-based (self-reported, individual) social network analysis of 142 participants recruited from clinical and community sources. Each participant listed the 30 most significant people (called alters) in their social network, then rated each alter in terms of amount of contact, social support, attachment strength and negative interactions. In addition, measures of social integration were determined using participant's report of the connection between people in their networks. BPD was associated with poorer social support, more frequent negative interactions, and less social integration. Examination of alter-by-BPD interactions indicated that whereas participants with low BPD symptoms had close relationships with people with high centrality within their networks, participants with high BPD symptoms had their closest relationships with people less central to their networks. The results suggest that individuals with BPD are at a social disadvantage: Those with whom they are most closely linked (including romantic partners) are less socially connected (i.e., less central) within their social network. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Full Text Available Understanding the organizational architecture of human brain function and its alteration patterns in diseased brains such as Autism Spectrum Disorder (ASD patients are of great interests. In-vivo functional magnetic resonance imaging (fMRI offers a unique window to investigate the mechanism of brain function and to identify functional network components of the human brain. Previously, we have shown that multiple concurrent functional networks can be derived from fMRI signals using whole-brain sparse representation. Yet it is still an open question to derive group-wise consistent networks featured in ASD patients and controls. Here we proposed an effective volumetric network descriptor, named connectivity map, to compactly describe spatial patterns of brain network maps and implemented a fast framework in Apache Spark environment that can effectively identify group-wise consistent networks in big fMRI dataset. Our experiment results identified 144 group-wisely common intrinsic connectivity networks (ICNs shared between ASD patients and healthy control subjects, where some ICNs are substantially different between the two groups. Moreover, further analysis on the functional connectivity and spatial overlap between these 144 common ICNs reveals connectomics signatures characterizing ASD patients and controls. In particular, the computing time of our Spark-enabled functional connectomics framework is significantly reduced from 240 hours (C++ code, single core to 20 hours, exhibiting a great potential to handle fMRI big data in the future.
Full Text Available P300 Auditory Event-Related Potentials (P3AERPs were recorded in nine school-age children with auditory processing disorders and nine age- and gender-matched controls in response to tone burst stimuli presented at varying rates (1/second or 3/second under varying levels of competing noise (0 dB, 40 dB, or 60 dB SPL. Neural network modeling results indicated that speed of information processing and task-related demands significantly influenced P3AERP latency in children with auditory processing disorders. Competing noise and rapid stimulus rates influenced P3AERP amplitude in both groups.
Weigel, Angelika; Gumz, Antje; Kästner, Denise; Romer, Georg; Wegscheider, Karl; Löwe, Bernd
The "Health care network anorexia and bulimia nervosa", a subproject of psychenet - the Hamburg network for mental health - aims to decrease the incidence of eating disorders as well as the risk for chronic illness courses. One focal project, therefore, evaluates a school-based prevention manual in a randomized controlled trial. The other one examines the impact of a systemic public health intervention on early treatment initiation in anorexia nervosa. The present article provides an overview about study design and interventions in both focal projects as well as preliminary results. © Georg Thieme Verlag KG Stuttgart · New York.
van Asselt-Goverts, A. E.; Embregts, P. J. C. M.; Hendriks, A. H. C.; Wegman, K. M.; Teunisse, J. P.
The aim of this study was to determine the similarities and differences in social network characteristics, satisfaction and wishes with respect to the social network between people with mild or borderline intellectual disabilities (ID), people with autism spectrum disorders (ASD) and a reference group. Data were gathered from 105 young adults…
Wessa, Michèle; Kanske, Philipp; Linke, Julia
Bipolar disorder (BD) is a severe, chronic disease with a heritability of 60-80%. BD is frequently misdiagnosed due to phenomenological overlap with other psychopathologies, an important issue that calls for the identification of biological and psychological vulnerability and disease markers. Altered structural and functional connectivity, mainly between limbic and prefrontal brain areas, have been proposed to underlie emotional and motivational dysregulation in BD and might represent relevant vulnerability and disease markers. In the present laboratory review we discuss functional and structural neuroimaging findings on emotional and motivational dysregulation from our research group in BD patients and healthy individuals at risk to develop BD. As a main result of our studies, we observed altered orbitofrontal and limbic activity and reduced connectivity between dorsal prefrontal and limbic brain regions, as well as reduced integrity of fiber tracts connecting prefrontal and subcortical brain structures in BD patients and high-risk individuals. Our results provide novel insights into pathophysiological mechanisms of bipolar disorder. The current laboratory review provides a specific view of our group on altered brain connectivity and underlying psychological processes in bipolar disorder based on our own work, integrating relevant findings from others. Thereby we attempt to advance neuropsychobiological models of BD.
Cardiovascular considerations of attention deficit hyperactivity disorder medications: a report of the European Network on Hyperactivity Disorders work group, European Attention Deficit Hyperactivity Disorder Guidelines Group on attention deficit hyperactivity disorder drug safety meeting.
Hamilton, Robert M; Rosenthal, Eric; Hulpke-Wette, Martin; Graham, John G I; Sergeant, Joseph
Regulatory decisions regarding attention deficit hyperactivity disorder drug licensing and labelling, along with recent statements from professional associations, raise questions of practice regarding the evaluation and treatment of patients with attention deficit hyperactivity disorder. To address these issues for the European community, the European Network for Hyperkinetic Disorders, through its European Attention Deficit Hyperactivity Disorder Guidelines Group, organised a meeting between attention deficit hyperactivity disorder specialists, paediatric cardiovascular specialists, and representatives of the major market authorisation holders for attention deficit hyperactivity disorder medications. This manuscript represents their consensus on cardiovascular aspects of attention deficit hyperactivity disorder medications. Although sudden death has been identified in multiple young individuals on attention deficit hyperactivity disorder medication causing regulatory concern, when analysed for exposure using currently available data, sudden death does not appear to exceed that of the general population. There is no current evidence to suggest an incremental benefit to electrocardiography assessment of the general attention deficit hyperactivity disorder patient. Congenital heart disease patients have an increased prevalence of attention deficit hyperactivity disorder, and can benefit from attention deficit hyperactivity disorder therapies, including medication. The attention deficit hyperactivity disorder specialist is the appropriate individual to evaluate benefit and risk and recommend therapy in all patients, although discussion with a heart specialist is reasonable for congenital heart disease patients. For attention deficit hyperactivity disorder patients with suspected heart disease or risk factor/s for sudden death, assessment by a heart specialist is recommended, as would also be the case for a non-attention deficit hyperactivity disorder patient. The
Bikic, Aida; Leckman, James F; Lindschou, Jane; Christensen, Torben Ø; Dalsgaard, Søren
Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by symptoms of inattention and impulsivity and/or hyperactivity and a range of cognitive dysfunctions...
David J Mellert
Full Text Available Interindividual differences in neuronal wiring may contribute to behavioral individuality and affect susceptibility to neurological disorders. To investigate the causes and potential consequences of wiring variation in Drosophila melanogaster, we focused on a hemilineage of ventral nerve cord interneurons that exhibits morphological variability. We find that late-born subclasses of the 12A hemilineage are highly sensitive to genetic and environmental variation. Neurons in the second thoracic segment are particularly variable with regard to two developmental decisions, whereas its segmental homologs are more robust. This variability "hotspot" depends on Ultrabithorax expression in the 12A neurons, indicating variability is cell-intrinsic and under genetic control. 12A development is more variable and sensitive to temperature in long-established laboratory strains than in strains recently derived from the wild. Strains with a high frequency of one of the 12A variants also showed a high frequency of animals with delayed spontaneous flight initiation, whereas other wing-related behaviors did not show such a correlation and were thus not overtly affected by 12A variation. These results show that neurodevelopmental robustness is variable and under genetic control in Drosophila and suggest that the fly may serve as a model for identifying conserved gene pathways that stabilize wiring in stressful developmental environments. Moreover, some neuronal lineages are variation hotspots and thus may be more amenable to evolutionary change.
Mertz, Line Granild Bie; Thaulov, Per; Trillingsgaard, Anegen; Christensen, Rikke; Vogel, Ida; Hertz, Jens Michael; Ostergaard, John R
Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability, developmental delay, lack of speech, and epileptic seizures. Previous studies have indicated that children with AS due to 15q11.2-q13 deletions have a more severe developmental delay and present more often autistic features than those with AS caused by other genetic etiologies. The present study investigated the neurodevelopmental profiles of the different genetic etiologies of AS, and examined the evolution of mental development and autistic features over a 12-year period in children with a 15q11.2-q13 deletion. This study included 42 children with AS. Twelve had a Class I deletion, 18 had Class II deletions, three showed atypical large deletions, five had paternal uniparental disomy (pUPD) and four had UBE3A mutations. Children with a deletion (Class I and Class II) showed significantly reduced developmental age in terms of visual perception, receptive language, and expressive language when compared to those with a UBE3A mutation and pUPD. Within all subgroups, expressive language performance was significantly reduced when compared to the receptive performance. A follow-up study of seven AS cases with 15q11.2-q13 deletions revealed that over 12 years, the level of autistic features did not change, but both receptive and expressive language skills improved. Copyright © 2014 Elsevier Ltd. All rights reserved.
Sanne C T Peeters
Full Text Available Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN, is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder.Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk, group × environmental exposure (to cannabis, developmental trauma and urbanicity and symptomatology.There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL, the precuneus (PCu and the medial prefrontal cortex (MPFC. Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity.Increased functional connectivity in individuals with (increased risk for psychotic disorder may reflect trait-related network alterations. The within-network "connectivity at rest" intermediate phenotype was not associated with (subclinical psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure.
Kaplan, C. Nadir; Hinczewski, Michael; Berker, A. Nihat
For a variety of quenched random spin systems on an Apollonian network, including ferromagnetic and antiferromagnetic bond percolation and the Ising spin glass, we find the persistence of ordered phases up to infinite temperature over the entire range of disorder. We develop a renormalization-group technique that yields highly detailed information, including the exact distributions of local magnetizations and local spin-glass order parameters, which turn out to exhibit, as function of temperature, complex and distinctive tulip patterns.
Rosana Carla do Nascimento Givigi
Full Text Available This study follows the epistemological assumptions of the Brazilian Interactionism, articulated with the Discourse Analysis and Meaning Network. The main purpose was to analyze the effects of the intervention work with children, their families and schools. The intervention aimed at the construction of language and the modification of the meanings attached to these subjects. The methodological device used clinical-qualitative and action research. Five children with language disorders aged 0 to 5 years, their families and schools participated in this two-year study. The procedures were distinct for the different networks: child, family, school. The speech therapy sessions were performed weekly and were based on the Interactionist approach. Interviews with the families were conducted, as well as meetings with the group of parents. At school, the weekly visits used the collaborative action research perspective. The main results were modifications in the children’s behaviour; modification of the meanings given to language disorders; more communicative attempts; more efficient interactions; and collaborative work in schools. The idea of human development based on a historical and cultural process of significations was the guideline of the study. It was possible to verify that, after the network activity, there was a gradual modification of the meanings of language disorders in parents, educational agents and children. Actual life conditions and discursive practices are interwoven throughout time, enabling to reflect on the dynamics of relationships and developing processes.
Full Text Available Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient–host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control and hippocampus (cognitive processing from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine.
Meng, Qingying; Ying, Zhe; Noble, Emily; Zhao, Yuqi; Agrawal, Rahul; Mikhail, Andrew; Zhuang, Yumei; Tyagi, Ethika; Zhang, Qing; Lee, Jae-Hyung; Morselli, Marco; Orozco, Luz; Guo, Weilong; Kilts, Tina M; Zhu, Jun; Zhang, Bin; Pellegrini, Matteo; Xiao, Xinshu; Young, Marian F; Gomez-Pinilla, Fernando; Yang, Xia
Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Claire M Koenig
Full Text Available Misoprostol is a synthetic analogue of prostaglandin E1 that is administered to women at high doses to induce uterine contractions for early pregnancy termination and at low doses to aid in cervical priming during labor. Because of the known teratogenic effects of misoprostol when given during gestation and its effects on axonal growth in vitro, we examined misoprostol for its potential as a neurodevelopmental toxicant when administered to neonatal C57BL6/J mice. Mice were injected subcutaneously (s.c. with 0.4, 4 or 40 µg/kg misoprostol on postnatal day 7, the approximate developmental stage in mice of human birth, after which neonatal somatic growth, and sensory and motor system development were assessed. These doses were selected to span the range of human exposure used to induce labor. In addition, adult mice underwent a battery of behavioral tests relevant to neurodevelopmental disorders such as autism including tests for anxiety, stereotyped behaviors, social communication and interactions, and learning and memory. No significant effects of exposure were found for any measure of development or behavioral endpoints. In conclusion, the results of the present study in C57BL/6J mice do not provide support for neurodevelopmental toxicity after misoprostol administration approximating human doses and timed to coincide with the developmental stage of human birth.
Dunkley, Benjamin T; Doesburg, Sam M; Jetly, Rakesh; Sedge, Paul A; Pang, Elizabeth W; Taylor, Margot J
Soldiers with post-traumatic stress disorder (PTSD) exhibit elevated gamma-band synchrony in left fronto-temporal cortex, and connectivity measures in these regions correlate with comorbidities and PTSD severity, which suggests increased gamma synchrony is related to symptomology. However, little is known about the role of intrinsic, phase-synchronised networks in the disorder. Using magnetoencephalography (MEG), we characterised spectral connectivity in the default-mode, salience, visual, and attention networks during resting-state in a PTSD population and a trauma-exposed control group. Intrinsic network connectivity was examined in canonical frequency bands. We observed increased inter-network synchronisation in the PTSD group compared with controls in the gamma (30-80 Hz) and high-gamma range (80-150 Hz). Analyses of connectivity and symptomology revealed that PTSD severity was positively associated with beta synchrony in the ventral-attention-to-salience networks, and gamma synchrony within the salience network, but also negatively correlated with beta synchrony within the visual network. These novel results show that frequency-specific, network-level atypicalities may reflect trauma-related alterations of ongoing functional connectivity, and correlations of beta synchrony in attentional-to-salience and visual networks with PTSD severity suggest complicated network interactions mediate symptoms. These results contribute to accumulating evidence that PTSD is a complicated network-based disorder expressed as altered neural interactions. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.
Full Text Available Depression, Major Depression or mental disorder creates severe diseases. Mental illness such as Unipolar Major Depression, Bipolar Disorder, Dysthymia, Schizophrenia, Cardiovascular Diseases (Hypertension, Coronary Heart Disease, Stroke etc., are known as Major Depression. Several studies have revealed the possibilities about the association among Bipolar Disorder, Schizophrenia, Coronary Heart Diseases and Stroke with each other. The current study aimed to investigate the relationships between genetic variants in the above four diseases and to create a common pathway or PPI network. The associated genes of each disease are collected from different gene database with verification using R. After performing some preprocessing, mining and operations using R on collected genes, seven (7 common associated genes are discovered on selected four diseases (SZ, BD, CHD and Stroke. In each of the iteration, the numbers of collected genes are reduced up to 51%, 36%, 10%, 2% and finally less than 1% respectively. Moreover, common pathway on selected diseases has been investigated in this research.
Glans, Martin; Bejerot, Susanne; Humble, Mats B
Generalised joint hypermobility (GJH) is reportedly overrepresented among clinical cases of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and developmental coordination disorder (DCD). It is unknown if these associations are dimensional and, therefore, also relevant among non-clinical populations. To investigate if GJH correlates with sub-syndromal neurodevelopmental symptoms in a normal population. Hakim-Grahame's 5-part questionnaire (5PQ) on GJH, neuropsychiatric screening scales measuring ADHD and ASD traits, and a DCD-related question concerning clumsiness were distributed to a non-clinical, adult, Swedish population ( n =1039). In total, 887 individuals met our entry criteria. We found no associations between GJH and sub-syndromal symptoms of ADHD, ASD or DCD. Although GJH is overrepresented in clinical cases with neurodevelopmental disorders, such an association seems absent in a normal population. Thus, if GJH serves as a biomarker cutting across diagnostic boundaries, this association is presumably limited to clinical populations. None. © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.
Shepherd, E G; Knupp, A M; Welty, S E; Susey, K M; Gardner, W P; Gest, A L
Bronchopulmonary dysplasia (BPD) is a pulmonary disease associated with poor neurodevelopmental and medical outcomes. Patients with BPD are medically fragile, at high risk for complications and require interdisciplinary care. We tested the hypothesis that a chronic care approach for BPD would improve neurodevelopmental outcomes relative to the National Institute of Child and Human Development Neonatal Research Network (NICHD NRN) and reduce medical complications. Infants were followed as inpatients and outpatients. Bayley developmental exams were carried out at 18-24 months of age and compared with the NICHD NRN report. Finally, rates of readmission (a proxy for medical complications) were compared before and after implementation of the Comprehensive Center for BPD (CCBPD). Developmental scores obtained in 2007 and 2008 show that 12 and 10% of patients with moderate BPD (n=61) had Bayley Scores <70 for mental and motor indices respectively, whereas corresponding national rates were 35 and 26%. For patients with severe BPD (n=46), 15 and 11% of patients within the CCBPD vs 50 and 42% of national patients scored <70 for mental and motor indices, respectively. Finally, readmission rates dropped from 29% in the year before the implementation of the CCPD (n=269) to 5% thereafter (n=866, P<0.0001). The encouraging neurodevelopmental outcomes and readmission rates associated with a chronic care approach to BPD suggest these infants may be best served by a comprehensive interdisciplinary approach to care that focuses on neurodevelopment throughout the hospital stay.
Full Text Available Metabolic disorder causes the failure of metabolism process is growing concern worldwide. This research predicts a common metabolic pathway that is shared by Obesity, Type-2 Diabetes, Hypertension and Cardiovascular diseases due to metabolic disorder. A protein-protein interaction network is created to show the protein co-expression, co-regulations and interactions among gene and diseases. Genes whose are associated with metabolic diseases have been accumulated from different gene databases with verification and 'mined' them to establish gene interaction network models for expressing the molecular linkages among genes and diseases which affect disease progression. The number of associated genes identified for Type 2 Diabetes (T2D is 250, Hypertension (HT is 156, Obesity (OB is 185 and cardiovascular disease (CVD is 178. Among the sorted candidate gene 10 common genes are identified whose are directly or indirectly associated with four diseases by doing linkage filtering. By analysing the gene network model and PPI network a common metabolic pathway among metabolic diseases has been investigated.
McDonald, Leah J; Griffin, Margaret L; Kolodziej, Monika E; Fitzmaurice, Garrett M; Weiss, Roger D
In this exploratory analysis, we assessed the effect of drug use among social-network members on recovery from drug dependence in patients with co-occurring bipolar disorder. Patients (n = 57) enrolled in a group therapy study completed assessments over 15 months. Patients with zero to one drug users in their social networks at intake had few days of drug use during treatment and follow-up, whereas those with ≥ 2 drug users had significantly more days of drug use. Multivariate analysis showed that patients who consistently named multiple drug users in their social networks had a marked increase in drug use over 15 months, while those who never or occasionally named multiple drug users had a small decline in drug use over time. Multiple drug users in social networks of treatment-seeking drug-dependent patients with co-occurring bipolar disorder may indicate poor drug use outcomes; efforts to reduce the association with drug users may be useful. This clinical trial has been registered in a public trials registry at clinicaltrials.gov (identifier is NCT00227838). © American Academy of Addiction Psychiatry.
McNally, Richard J; Heeren, Alexandre; Robinaugh, Donald J
Background: The network approach to mental disorders offers a novel framework for conceptualizing posttraumatic stress disorder (PTSD) as a causal system of interacting symptoms. Objective: In this study, we extended this work by estimating the structure of relations among PTSD symptoms in adults reporting personal histories of childhood sexual abuse (CSA; N = 179). Method: We employed two complementary methods. First, using the graphical LASSO, we computed a sparse, regularized partial correlation network revealing associations (edges) between pairs of PTSD symptoms (nodes). Next, using a Bayesian approach, we computed a directed acyclic graph (DAG) to estimate a directed, potentially causal model of the relations among symptoms. Results: For the first network, we found that physiological reactivity to reminders of trauma, dreams about the trauma, and lost of interest in previously enjoyed activities were highly central nodes. However, stability analyses suggest that these findings were unstable across subsets of our sample. The DAG suggests that becoming physiologically reactive and upset in response to reminders of the trauma may be key drivers of other symptoms in adult survivors of CSA. Conclusions: Our study illustrates the strengths and limitations of these network analytic approaches to PTSD.
Nguyen Quoc Vuong Tran; Kunio Miyake
.... Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis...
Stratton, Kathleen; Gable, Alicia; McCormick, Marie C
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Reeb-Sutherland, Bethany C.; Fox, Nathan A.
Eyeblink conditioning (EBC) is a classical conditioning paradigm typically used to study the underlying neural processes of learning and memory. EBC has a well-defined neural circuitry, is non-invasive, and can be employed in human infants shortly after birth making it an ideal tool to use in both developing and special populations. In addition,…
Graf, William D; Nagel, Saskia K; Epstein, Leon G; Miller, Geoffrey; Nass, Ruth; Larriviere, Dan
The use of prescription medication to augment cognitive or affective function in healthy persons-or neuroenhancement-is increasing in adult and pediatric populations. In children and adolescents, neuroenhancement appears to be increasing in parallel to the rising rates of attention-deficit disorder diagnoses and stimulant medication prescriptions, and the opportunities for medication diversion. Pediatric neuroenhancement remains a particularly unsettled and value-laden practice, often without appropriate goals or justification. Pediatric neuroenhancement presents its own ethical, social, legal, and developmental issues, including the fiduciary responsibility of physicians caring for children, the special integrity of the doctor-child-parent relationship, the vulnerability of children to various forms of coercion, distributive justice in school settings, and the moral obligation of physicians to prevent misuse of medication. Neurodevelopmental issues include the importance of evolving personal authenticity during childhood and adolescence, the emergence of individual decision-making capacities, and the process of developing autonomy. This Ethics, Law, and Humanities Committee position paper, endorsed by the American Academy of Neurology, Child Neurology Society, and American Neurological Association, focuses on various implications of pediatric neuroenhancement and outlines discussion points in responding to neuroenhancement requests from parents or adolescents. Based on currently available data and the balance of ethics issues reviewed in this position paper, neuroenhancement in legally and developmentally nonautonomous children and adolescents without a diagnosis of a neurologic disorder is not justifiable. In nearly autonomous adolescents, the fiduciary obligation of the physician may be weaker, but the prescription of neuroenhancements is inadvisable because of numerous social, developmental, and professional integrity issues.
Sacchet, Matthew D; Ho, Tiffany C; Connolly, Colm G; Tymofiyeva, Olga; Lewinn, Kaja Z; Han, Laura Km; Blom, Eva H; Tapert, Susan F; Max, Jeffrey E; Frank, Guido Kw; Paulus, Martin P; Simmons, Alan N; Gotlib, Ian H; Yang, Tony T
Major depressive disorder (MDD) often emerges during adolescence, a critical period of brain development. Recent resting-state fMRI studies of adults suggest that MDD is associated with abnormalities within and between resting-state networks (RSNs). Here we tested whether adolescent MDD is characterized by abnormalities in interactions among RSNs. Participants were 55 unmedicated adolescents diagnosed with MDD and 56 matched healthy controls. Functional connectivity was mapped using resting-state fMRI. We used the network-based statistic (NBS) to compare large-scale connectivity between groups and also compared the groups on graph metrics. We further assessed whether group differences identified using nodes defined from functionally defined RSNs were also evident when using anatomically defined nodes. In addition, we examined relations between network abnormalities and depression severity and duration. Finally, we compared intranetwork connectivity between groups and assessed the replication of previously reported MDD-related abnormalities in connectivity. The NBS indicated that, compared with controls, depressed adolescents exhibited reduced connectivity (pdepression was significantly correlated with reduced connectivity in this set of network interactions (p=0.020, corrected), specifically with reduced connectivity between components of the dorsal attention network. The dorsal attention network was also characterized by reduced intranetwork connectivity in the MDD group. Finally, we replicated previously reported abnormal connectivity in individuals with MDD. In summary, adolescents with MDD show hypoconnectivity between large-scale brain networks compared with healthy controls. Given that connectivity among these networks typically increases during adolescent neurodevelopment, these results suggest that adolescent depression is associated with abnormalities in neural systems that are still developing during this critical period.
Young, Christina B; Wu, Sarah S; Menon, Vinod
Math anxiety is a negative emotional reaction to situations involving mathematical problem solving. Math anxiety has a detrimental impact on an individual's long-term professional success, but its neurodevelopmental origins are unknown. In a functional MRI study on 7- to 9-year-old children, we showed that math anxiety was associated with hyperactivity in right amygdala regions that are important for processing negative emotions. In addition, we found that math anxiety was associated with reduced activity in posterior parietal and dorsolateral prefrontal cortex regions involved in mathematical reasoning. Multivariate classification analysis revealed distinct multivoxel activity patterns, which were independent of overall activation levels in the right amygdala. Furthermore, effective connectivity between the amygdala and ventromedial prefrontal cortex regions that regulate negative emotions was elevated in children with math anxiety. These effects were specific to math anxiety and unrelated to general anxiety, intelligence, working memory, or reading ability. Our study identified the neural correlates of math anxiety for the first time, and our findings have significant implications for its early identification and treatment.
Powell, Susan B.
The neurodevelopmental hypothesis of schizophrenia asserts that the underlying pathology of schizophrenia has its roots in brain development and that these brain abnormalities do not manifest themselves until adolescence or early adulthood. Animal models based on developmental manipulations have provided insight into the vulnerability of the developing fetus and the importance of the early environment for normal maturation. These models have provided a wide range of validated approaches to answer questions regarding environmental influences on both neural and behavioral development. In an effort to better understand the developmental hypothesis of schizophrenia, animal models have been developed, which seek to model the etiology and/or the pathophysiology of schizophrenia or specific behaviors associated with the disease. Developmental models specific to schizophrenia have focused on epidemiological risk factors (e.g., prenatal viral insult, birth complications) or more heuristic models aimed at understanding the developmental neuropathology of the disease (e.g., ventral hippocampal lesions). The combined approach of behavioral and neuroanatomical evaluation of these models strengthens their utility in improving our understanding of the pathophysiology of schizophrenia and developing new treatment strategies. PMID:21312409
Stolwijk, Lisanne J.; Lemmers, P. M A; Harmsen, Marissa; Groenendaal, Floris; De Vries, Linda S.; Van Der Zee, David C.; Benders, Manon J N; Van Herwaarden-Lindeboom, M. Y A
CONTEXT: Increasing concerns have been raised about the incidence of neurodevelopmental delay in children with noncardiac congenital anomalies (NCCA) requiring neonatal surgery. OBJECTIVE: This study aimed to determine the incidence and potential risk factors for developmental delay after neonatal
Ruth A. Lanius
Full Text Available Background: Three intrinsic connectivity networks in the brain, namely the central executive, salience, and default mode networks, have been identified as crucial to the understanding of higher cognitive functioning, and the functioning of these networks has been suggested to be impaired in psychopathology, including posttraumatic stress disorder (PTSD. Objective: 1 To describe three main large-scale networks of the human brain; 2 to discuss the functioning of these neural networks in PTSD and related symptoms; and 3 to offer hypotheses for neuroscientifically-informed interventions based on treating the abnormalities observed in these neural networks in PTSD and related disorders. Method: Literature relevant to this commentary was reviewed. Results: Increasing evidence for altered functioning of the central executive, salience, and default mode networks in PTSD has been demonstrated. We suggest that each network is associated with specific clinical symptoms observed in PTSD, including cognitive dysfunction (central executive network, increased and decreased arousal/interoception (salience network, and an altered sense of self (default mode network. Specific testable neuroscientifically-informed treatments aimed to restore each of these neural networks and related clinical dysfunction are proposed. Conclusions: Neuroscientifically-informed treatment interventions will be essential to future research agendas aimed at targeting specific PTSD and related symptoms.
Debate, Rita Digioacchino; Tedesco, Lisa A
The incidence of eating disorders has increased substantially over the last forty years. Primary care physicians and dentists share a parallel challenge for secondary prevention of anorexia nervosa and bulimia nervosa. The dentist, in particular, has a uniquely important and valuable role with respect to assessment of oral and physical manifestations, patient communication, referral, case management, and restorative care. Despite this crucial role, few dentists are engaged in eating disorder-specific secondary prevention. The purpose of this study was to explore beliefs, attitudes, and experiences of general dentists regarding eating disorder-specific secondary prevention behaviors using focus group methodology. Three ninety-minute focus groups were conducted with twenty-one general dentists (seventeen male, four female) recruited from the 2004 Academy of General Dentistry Leadership Conference. Data from the focus groups were analyzed to identify two over-arching themes and associated subthemes with regard to supports and barriers to eating disorder-specific secondary prevention practices. Analysis of data revealed that training, network, and dental professional contingencies emerged as places of influence for increasing capacity among dentists with regard to secondary prevention of eating disorders. This exploratory assessment identifies leverage points where strategic interventions including curriculum development, policies, and practices can be developed to support and sustain secondary preventive clinical behaviors among dentists.
Basu, Sankar; Mukharjee, Debasish
There has been considerable debate about the contribution of salt bridges to the stabilization of protein folds, in spite of their participation in crucial protein functions. Salt bridges appear to contribute to the activity-stability trade-off within proteins by bringing high-entropy charged amino acids into close contacts during the course of their functions. The current study analyzes the modes of association of salt bridges (in terms of networks) within globular proteins and at protein-protein interfaces. While the most common and trivial type of salt bridge is the isolated salt bridge, bifurcated salt bridge appears to be a distinct salt-bridge motif having a special topology and geometry. Bifurcated salt bridges are found ubiquitously in proteins and interprotein complexes. Interesting and attractive examples presenting different modes of interaction are highlighted. Bifurcated salt bridges appear to function as molecular clips that are used to stitch together large surface contours at interacting protein interfaces. The present work also emphasizes the key role of salt-bridge-mediated interactions in the partial folding of proteins containing long stretches of disordered regions. Salt-bridge-mediated interactions seem to be pivotal to the promotion of "disorder-to-order" transitions in small disordered protein fragments and their stabilization upon binding. The results obtained in this work should help to guide efforts to elucidate the modus operandi of these partially disordered proteins, and to conceptualize how these proteins manage to maintain the required amount of disorder even in their bound forms. This work could also potentially facilitate explorations of geometrically specific designable salt bridges through the characterization of composite salt-bridge networks. Graphical abstract ᅟ.
Mayo-Wilson, Evan; Dias, Sofia; Mavranezouli, Ifigeneia; Kew, Kayleigh; Clark, David M; Ades, A E; Pilling, Stephen
Summary Background Social anxiety disorder?a chronic and naturally unremitting disease that causes substantial impairment?can be treated with pharmacological, psychological, and self-help interventions. We aimed to compare these interventions and to identify which are most effective for the acute treatment of social anxiety disorder in adults. Methods We did a systematic review and network meta-analysis of interventions for adults with social anxiety disorder, identified from published and un...
Tessitore, Alessandro; Santangelo, Gabriella; De Micco, Rosa; Giordano, Alfonso; Raimo, Simona; Amboni, Marianna; Esposito, Fabrizio; Barone, Paolo; Tedeschi, Gioacchino; Vitale, Carmine
To investigate intrinsic neural networks connectivity changes in Parkinson's disease (PD) patients with and without impulse control disorders (ICD). Fifteen patients with PD with ICD (ICD+), 15 patients with PD without ICD (ICD-) and 24 age and sex-matched healthy controls (HC) were enrolled in the study. To identify patients with and without ICD and/or punding, we used the Minnesota Impulsive Disorders Interview (MIDI) and a clinical interview based on diagnostic criteria for each symptom. All patients underwent a detailed neuropsychological evaluation. Whole brain structural and functional imaging was performed on a 3T GE MR scanner. Statistical analysis of functional data was completed using BrainVoyager QX software. Voxel-based morphometry (VBM) was used to test whether between-group differences in resting-state connectivity were related to structural abnormalities. The presence of ICD symptoms was associated with an increased connectivity within the salience and default-mode networks, as well as with a decreased connectivity within the central executive network (p < .05 corrected). ICD severity was correlated with both salience and default mode networks connectivity changes only in the ICD+ group. VBM analysis did not reveal any statistically significant differences in local grey matter volume between ICD+ and ICD- patients and between all patients and HC (p < .05. FWE). The presence of a disrupted connectivity within the three core neurocognitive networks may be considered as a potential neural correlate of ICD presence in patients with PD. Our findings provide additional insights into the mechanisms underlying ICD in PD, confirming the crucial role of an abnormal prefrontal-limbic-striatal homeostasis in their development. Copyright © 2017 Elsevier Ltd. All rights reserved.
Paula A Garay
Full Text Available Although the brain has classically been considered "immune-privileged," current research suggests extensive communication between the nervous and the immune systems in both health and disease. Recent studies demonstrate that immune molecules are present at the right place and time to modulate the development and function of the healthy and diseased CNS. Indeed, immune molecules play integral roles in the CNS throughout neural development, including affecting neurogenesis, neuronal migration, axon guidance, synapse formation, activity-dependent refinement of circuits, and synaptic plasticity. Moreover, the roles of individual immune molecules in the nervous system may change over development. This review focuses on the effects of immune molecules on neuronal connections in the mammalian central nervous system—specifically the roles for MHCI and its receptors, complement, and cytokines on the function, refinement, and plasticity of cortical and hippocampal synapses and their relationship to neurodevelopmental disorders. These functions for immune molecules during neural development suggest that they could also mediate pathological responses to chronic elevations of cytokines in neurodevelopmental disorders, including autism spectrum disorders (ASD and schizophrenia.
Coutinho, Joana; Goncalves, Oscar Filipe; Soares, José Miguel; Marques, Paulo; Sampaio, Adriana
Obsessive-compulsive personality (OCPD) disorder is characterized by a pattern of excessive self-control, perfectionism and behavioral and cognitive rigidity. Despite the fact that OCPD is the most common personality disorder in the general population, published studies looking at the brain correlates of this disorder are practically nonexistent. The main goal of this study was to analyze the presence of brain alterations in OCPD when compared to healthy controls, specifically at the level of the Default Mode Network (DMN). The DMN is a well-established resting state network which was found to be associated with psychological processes that may play a key role in OCPD (e.g., self-awareness, episodic future thinking and mental simulation). Ten individuals diagnosed with OCPD and ten healthy controls underwent a clinical assessment interview and a resting-state functional magnetic resonance imaging (fMRI) acquisition. The results show that OCPD patients presented an increased functional connectivity in the precuneus (i.e., a posterior node of the DMN), known to be involved in the retrieval manipulation of past events in order to solve current problems and develop plans for the future. These results suggest that this key node of the DMN may play an important role in the pathophysiology of OCPD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Ruocco, Anthony C.; Reilly, James L.; Rubin, Leah H.; Daros, Alex R.; Gershon, Elliot S.; Tamminga, Carol A.; Pearlson, Godfrey D.; Hill, S. Kristian; Keshavan, Matcheri S.; Gur, Ruben C.; Sweeney, John A.
Background Difficulty recognizing facial emotions is an important social-cognitive deficit associated with psychotic disorders. It also may reflect a familial risk for psychosis in schizophrenia-spectrum disorders and bipolar disorder. Objective The objectives of this study from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium were to: 1) compare emotion recognition deficits in schizophrenia, schizoaffective disorder and bipolar disorder with psychosis, 2) determine the familiality of emotion recognition deficits across these disorders, and 3) evaluate emotion recognition deficits in nonpsychotic relatives with and without elevated Cluster A and Cluster B personality disorder traits. Method Participants included probands with schizophrenia (n=297), schizoaffective disorder (depressed type, n=61; bipolar type, n=69), bipolar disorder with psychosis (n=248), their first-degree relatives (n=332, n=69, n=154, and n=286, respectively) and healthy controls (n=380). All participants completed the Penn Emotion Recognition Test, a standardized measure of facial emotion recognition assessing four basic emotions (happiness, sadness, anger and fear) and neutral expressions (no emotion). Results Compared to controls, emotion recognition deficits among probands increased progressively from bipolar disorder to schizoaffective disorder to schizophrenia. Proband and relative groups showed similar deficits perceiving angry and neutral faces, whereas deficits on fearful, happy and sad faces were primarily isolated to schizophrenia probands. Even non-psychotic relatives without elevated Cluster A or Cluster B personality disorder traits showed deficits on neutral and angry faces. Emotion recognition ability was moderately familial only in schizophrenia families. Conclusions Emotion recognition deficits are prominent but somewhat different across psychotic disorders. These deficits are reflected to a lesser extent in relatives, particularly on angry and
Ruocco, Anthony C; Reilly, James L; Rubin, Leah H; Daros, Alex R; Gershon, Elliot S; Tamminga, Carol A; Pearlson, Godfrey D; Hill, S Kristian; Keshavan, Matcheri S; Gur, Ruben C; Sweeney, John A
Difficulty recognizing facial emotions is an important social-cognitive deficit associated with psychotic disorders. It also may reflect a familial risk for psychosis in schizophrenia-spectrum disorders and bipolar disorder. The objectives of this study from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium were to: 1) compare emotion recognition deficits in schizophrenia, schizoaffective disorder and bipolar disorder with psychosis, 2) determine the familiality of emotion recognition deficits across these disorders, and 3) evaluate emotion recognition deficits in nonpsychotic relatives with and without elevated Cluster A and Cluster B personality disorder traits. Participants included probands with schizophrenia (n=297), schizoaffective disorder (depressed type, n=61; bipolar type, n=69), bipolar disorder with psychosis (n=248), their first-degree relatives (n=332, n=69, n=154, and n=286, respectively) and healthy controls (n=380). All participants completed the Penn Emotion Recognition Test, a standardized measure of facial emotion recognition assessing four basic emotions (happiness, sadness, anger and fear) and neutral expressions (no emotion). Compared to controls, emotion recognition deficits among probands increased progressively from bipolar disorder to schizoaffective disorder to schizophrenia. Proband and relative groups showed similar deficits perceiving angry and neutral faces, whereas deficits on fearful, happy and sad faces were primarily isolated to schizophrenia probands. Even non-psychotic relatives without elevated Cluster A or Cluster B personality disorder traits showed deficits on neutral and angry faces. Emotion recognition ability was moderately familial only in schizophrenia families. Emotion recognition deficits are prominent but somewhat different across psychotic disorders. These deficits are reflected to a lesser extent in relatives, particularly on angry and neutral faces. Deficits were evident in non
Dong, Guangheng; Lin, Xiao; Hu, Yanbo; Xie, Chunming; Du, Xiaoxia
Literatures have shown that Internet gaming disorder (IGD) subjects show impaired executive control and enhanced reward sensitivities than healthy controls. However, how these two networks jointly affect the valuation process and drive IGD subjects' online-game-seeking behaviors remains unknown. Thirty-five IGD and 36 healthy controls underwent a resting-states scan in the MRI scanner. Functional connectivity (FC) was examined within control and reward network seeds regions, respectively. Nucleus accumbens (NAcc) was selected as the node to find the interactions between these two networks. IGD subjects show decreased FC in the executive control network and increased FC in the reward network when comparing with the healthy controls. When examining the correlations between the NAcc and the executive control/reward networks, the link between the NAcc - executive control network is negatively related with the link between NAcc - reward network. The changes (decrease/increase) in IGD subjects' brain synchrony in control/reward networks suggest the inefficient/overly processing within neural circuitry underlying these processes. The inverse proportion between control network and reward network in IGD suggest that impairments in executive control lead to inefficient inhibition of enhanced cravings to excessive online game playing. This might shed light on the mechanistic understanding of IGD.
Lee, Deokjong; Lee, Junghan; Lee, Jung Eun; Jung, Young-Chul
Internet gaming disorder (IGD) is a type of behavioral addiction characterized by abnormal executive control, leading to loss of control over excessive gaming. Attention deficit and hyperactivity disorder (ADHD) is one of the most common comorbid disorders in IGD, involving delayed development of the executive control system, which could predispose individuals to gaming addiction. We investigated the influence of childhood ADHD on neural network features of IGD. Resting-state functional magnetic resonance imaging analysis was performed on 44 young, male IGD subjects with and without childhood ADHD and 19 age-matched, healthy male controls. Posterior cingulate cortex (PCC)-seeded connectivity was evaluated to assess abnormalities in default mode network (DMN) connectivity, which is associated with deficits in executive control. IGD subjects without childhood ADHD showed expanded functional connectivity (FC) between DMN-related regions (PCC, medial prefrontal cortex, thalamus) compared with controls. These subjects also exhibited expanded FC between the PCC and brain regions implicated in salience processing (anterior insula, orbitofrontal cortex) compared with IGD subjects with childhood ADHD. IGD subjects with childhood ADHD showed expanded FC between the PCC and cerebellum (crus II), a region involved in executive control. The strength of connectivity between the PCC and cerebellum (crus II) was positively correlated with self-reporting scales reflecting impulsiveness. Individuals with IGD showed altered PCC-based FC, the characteristics of which might be dependent upon history of childhood ADHD. Our findings suggest that altered neural networks for executive control in ADHD would be a predisposition for developing IGD. Copyright © 2017 Elsevier Inc. All rights reserved.
Peat, Christine M; Berkman, Nancy D; Lohr, Kathleen N; Brownley, Kimberly A; Bann, Carla M; Cullen, Katherine; Quattlebaum, Mary J; Bulik, Cynthia M
Psychological and pharmacological interventions for binge-eating disorder have previously demonstrated efficacy (compared with placebo or waitlist control); thus, we aimed to expand that literature with a review of comparative effectiveness. We searched MEDLINE,® EMBASE,® Cochrane Library, Academic OneFile, CINAHL® for binge-eating disorder treatment articles and selected studies using predetermined inclusion and exclusion criteria. Data were sufficient for network meta-analysis comparing two pharmacological interventions; psychological interventions were analysed qualitatively. In all, 28 treatment comparisons were included in this review: one pharmacological comparison (second-generation antidepressants versus lisdexamfetamine) and 26 psychological comparisons. Only three statistically significant differences emerged: lisdexamfetamine was better at increasing binge abstinence than second-generation antidepressants; therapist-led cognitive behavioural therapy was better at reducing binge-eating frequency than behavioural weight loss, but behavioural weight loss was better at reducing weight. The majority of other treatment comparisons revealed few significant differences between groups. Thus, patients and clinicians can choose from several effective treatment options. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
Robert J Thoma
Full Text Available Functional MRI studies have identified a distributed set of brain activations to be associated with auditory verbal hallucinations (AVH. However, very little is known about how activated brain regions may be linked together into AVH-generating networks. Fifteen volunteers with schizophrenia or schizoaffective disorder pressed buttons to indicate on-set and off-set of AVH during fMRI scanning. When a general linear model (GLM was used to compare BOLD signals during periods in which subjects indicated that they were versus were not experiencing AVH (‘AVH-on’ versus ‘AVH-off’, it revealed AVH-related activity in bilateral inferior frontal and superior temporal regions; the right middle temporal gyrus; and the left insula, supramarginal gyrus, inferior parietal lobule and extra-nuclear white matter. In an effort to identify AVH-related networks, the raw data were also processed using independent component analyses (ICA. Four ICA components were spatially consistent with an a priori network framework based upon published meta-analyses of imaging correlates of AVH. Of these four components, only a network involving bilateral auditory cortices and posterior receptive language areas was significantly and positively correlated with the pattern of AVH-on versus AVH-off. The ICA also identified two additional networks (occipital-temporal and medial pre-frontal, not fully matching the meta-analysis framework, but nevertheless containing nodes reported as active in some studies of AVH. Both networks showed significant AVH-related profiles, but both were most active during AVH-off periods. Overall, the data suggest that AVH generation requires specific and selective activation of auditory cortical and posterior language regions, perhaps coupled to a release of indirect influence by occipital and medial frontal structures.
Grayson, B; Barnes, S A; Markou, A; Piercy, C; Podda, G; Neill, J C
that it will provide a useful neurodevelopmental model to complement other models such as maternal immune activation, particularly when combined with other manipulations to produce dual or triple hit models. However, the developmental trajectory of behavioural and neuropathological changes induced by postnatal PCP and their relevance to schizophrenia must be carefully mapped out. Overall, we support further development of dual (or triple) hit models incorporating genetic, neurodevelopmental and appropriate environmental elements in the search for more aetiologically valid animal models of schizophrenia and neurodevelopmental disorders (NDDs).
Hansen, Kasper Lage; Mølgård, Kjeld; Greenway, Steven
Aberrant organ development is associated with a wide spectrum of disorders, from schizophrenia to congenital heart disease, but systems-level insight into the underlying processes is very limited. Using heart morphogenesis as general model for dissecting the functional architecture of organ...... of a developing organ identifying several novel signaling modules. Our results show that organ development relies on surprisingly few, extensively recycled, protein modules that integrate into complex higher-order networks. This design allows the formation of a complicated organ using simple building blocks...
Wilcox, Claire E; Mayer, Andrew R; Bogenschutz, Michael P; Ling, Josef; Dekonenko, Charlene; Cumbo, Heather
Individuals with alcohol use disorders (AUDs) have deficits in cognitive control, but how they change with treatment is unclear. Seven patients with AUD and anxiety from an open-label trial of disulfiram plus lorazepam performed a multisensory Stroop task during fMRI (both pre and post initiation of treatment), and were compared to nine healthy controls (HCs) (n = 16; Albuquerque, NM; years 2009-2012). Evoked BOLD signal and resting state functional connectivity were compared (HC vs. AUD; Scan 1 vs. Scan 2). AUD demonstrated hyperactivity and altered connectivity in the cognitive control network compared to HC, but treatment did not normalize function.
Krishna, Nithin; Fischer, Bernard A; Miller, Moshe; Register-Brown, Kelly; Patchan, Kathleen; Hackman, Ann
We report the case of a young man diagnosed with schizophrenia who presented with stalking behaviors that may have been caused by problematic use or participation in social media networks (SMN). We review the possible role of SMN in the formation of his romantic delusion and offer suggestions for clinicians around incorporation of SMN questions into assessments. It is imperative to identify populations at risk of SMN-related stalking behaviors to stratify mental health resources and interventions. Additional studies are needed to further clarify the role of SMN in psychotic disorders. Copyright © 2013 Elsevier Inc. All rights reserved.
Stevens, Ed; Jason, Leonard A; Ram, Daphna; Light, John
Social support and characteristics of one's social network have been shown to be beneficial for abstinence and substance use disorder recovery. The current study explores how specific sources of social support relate to general feelings of social support and abstinence-specific self-efficacy. Data were collected from 31 of 33 individuals residing in 5 recovery houses. Participants were asked to complete social support and social network measures, along with measures assessing abstinence from substance use, abstinence self-efficacy, and involvement in 12-step groups. A significant positive relationship was found between general social support and abstinence-specific self-efficacy. General social support was also significantly associated with the specific social support measures of sense of community and Alcoholics Anonymous (AA) affiliation. Social network size predicted abstinence-related factors such as AA affiliation and perceived stress. These results provide insight regarding individual feelings of social support and abstinence-specific self-efficacy by showing that one's social network-level characteristics are related to one's perceptions of social support. We also found preliminary evidence that individual Oxford Houses influence one's feelings of social support.
Ffytche, Dominic H.; Blom, J. D.; Catani, M.
Visual perceptual disorders are often presented as a disparate group of neurological deficits with little consideration given to the wide range of visual symptoms found in psychiatric and neurodevelopmental disease. Here, the authors attempt a functional anatomical classification of all disorders
Hackius, Marc; Werth, Esther; Sürücü, Oguzkan; Baumann, Christian R; Imbach, Lukas L
Patients with Parkinson's disease (PD) and REM sleep behavior disorder (RBD) show mostly unimpaired motor behavior during REM sleep, which contrasts strongly to coexistent nocturnal bradykinesia. The reason for this sudden amelioration of motor control in REM sleep is unknown, however. We set out to determine whether movements during REM sleep are processed by different motor networks than movements in the waking state. We recorded local field potentials in the subthalamic nucleus (STN) and scalp EEG (modified 10/20 montage) during sleep in humans with PD and RBD. Time-locked event-related β band oscillations were calculated during movements in REM sleep compared with movements in the waking state and during NREM sleep. Spectral analysis of STN local field potentials revealed elevated β power during REM sleep compared with NREM sleep and β power in REM sleep reached levels similar as in the waking state. Event-related analysis showed time-locked β desynchronization during WAKE movements. In contrast, we found significantly elevated β activity before and during movements in REM sleep and NREM sleep. Corticosubthalamic coherence was reduced during REM and NREM movements. We conclude that sleep-related movements are not processed by the same corticobasal ganglia network as movements in the waking state. Therefore, the well-known seemingly normal motor performance during RBD in PD patients might be generated by activating alternative motor networks for movement initiation. These findings support the hypothesis that pathological movement-inhibiting basal ganglia networks in PD patients are bypassed during sleep. This study provides evidence that nocturnal movements during REM sleep in Parkinson's disease (PD) patients are not processed by the same corticobasal ganglia network as movements in the waking state. This implicates the existence of an alternative motor network that does not depend directly on the availability of l-Dopa in the basal ganglia. These findings
Grigorenko, Elena L.; Han, Summer S.; Yrigollen, Carolyn M.; Leng, Lin; Mizue, Yuka; Anderson, George M.; Mulder, Erik J.; de Bildt, Annelies; Minderaa, Ruud B.; Volkmar, Fred R.; Chang, Joseph T.; Bucala, Richard
OBJECTIVE. Autistic spectrum disorders are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes
Ramakrishnan, Navneeth; Lai, Ying Tong; Lara, Silvia; Parish, Meera M.; Adam, Shaffique
A linear unsaturating magnetoresistance at high perpendicular magnetic fields, together with a quadratic positive magnetoresistance at low fields, has been seen in many different experimental materials, ranging from silver chalcogenides and thin films of InSb to topological materials like graphene and Dirac semimetals. In the literature, two very different theoretical approaches have been used to explain this classical magnetoresistance as a consequence of sample disorder. The phenomenological random resistor network model constructs a grid of four terminal resistors, each with a varying random resistance. The effective medium theory model imagines a smoothly varying disorder potential that causes a continuous variation of the local conductivity. Here, we demonstrate numerically that both models belong to the same universality class and that a restricted class of the random resistor network is actually equivalent to the effective medium theory. Both models are also in good agreement with experiments on a diverse range of materials. Moreover, we show that in both cases, a single parameter, i.e., the ratio of the fluctuations in the carrier density to the average carrier density, completely determines the magnetoresistance profile.
Song, Z; Zhang, M; Huang, P
Major depressive disorder (MDD) is a serious mental disorder that negatively affects the quality of life of many individuals, and is a heavy economic burden to society. In recent years it was thought that depression is a 'disconnection syndrome'. Disorganized brain activity and un-modulated emotion responses were considered the key neuropathologies underlying depression. In the present study, we investigated the alteration of whole brain network connectivity in 28 first-episode, drug-naive patients, using resting-state functional magnetic resonance imaging and a new analytical method called voxel-based eigenvector centrality mapping. We found that compared with normal controls, MDD patients had lower functional connectivity in the bilateral middle frontal gyrus, insula, hippocampus, amygdala and cerebellum, and higher functional connectivity in the medial prefrontal cortex. The functional connectivity strength at the right hippocampus (r=-0.413, P=0.032) and the right insula (r=-0.372, P=0.041) negatively correlated with the severity of the disease. We further examined coordination among these regions, and found that frontal-subcortical connection was reduced and insula-medial prefrontal cortex (mPFC) connection was increased. These results are consistent with previous hypotheses on the neural mechanism of MDD, and provide further evidence that emotion networks are already interrupted in early stages of depression.
Daniels, Judith K.; McFarlane, Alexander C.; Bluhm, Robyn L.; Moores, Kathryn A.; Clark, C. Richard; Shaw, Marnie E.; Williamson, Peter C.; Densmore, Maria; Lanius, Ruth A.
Background Working memory processing and resting-state connectivity in the default mode network are altered in patients with post-traumatic stress disorder (PTSD). Because the ability to effortlessly switch between concentration on a task and an idling state during rest is implicated in both these alterations, we undertook a functional magnetic resonance imaging study with a block design to analyze task-induced modulations in connectivity. Methods We performed a working memory task and psychophysiologic interaction analyses with the posterior cingulate cortex and the medial prefrontal cortex as seed regions during fixation in 12 patients with severe, chronic PTSD and 12 healthy controls. Results During the working memory task, the control group showed significantly stronger connectivity with areas implicated in the salience and executive networks, including the right inferior frontal gyrus and the right inferior parietal lobule. The PTSD group showed stronger connectivity with areas implicated in the default mode network, namely enhanced connectivity between the posterior cingulate cortex and the right superior frontal gyrus and between the medial prefrontal cortex and the left parahip-pocampal gyrus. Limitations Because we were studying alterations in patients with severe, chronic PTSD, we could not exclude patients taking medication. The small sample size may have limited the power of our analyses. To avoid multiple testing in a small sample, we only used 2 seed regions for our analyses. Conclusion The different patterns of connectivity imply significant group differences with task-induced switches (i.e., engaging and disengaging the default mode network and the central-executive network). PMID:20569651
Brieber, Sarah; Neufang, Susanne; Bruning, Nicole; Kamp-Becker, Inge; Remschmidt, Helmut; Herpertz-Dahlmann, Beate; Fink, Gereon R.; Konrad, Kerstin
Background: Although autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are two distinct neurodevelopmental diseases, they share behavioural, neuropsychological and neurobiological characteristics. For the identification of endophenotypes across diagnostic categories, further investigations of phenotypic overlap…
Sumanasena, S P; Vipulaguna, D V; Mendis, M M; Gunawardena, N S
There is a lack of information on long-term neurodevelopmental outcome in preterm neonates in low- and middle-income countries. To describe the developmental attainments of preterm neonates followed up for 5 years and to identify the risk factors for impairment. A prospective descriptive cohort study was undertaken in neonates of 34 weeks gestation born within a period of 12 months at a single tertiary maternity and neonatal unit in Colombo, Sri Lanka. Infants were assessed for neurodevelopment using the Bayley Infant and Toddler III® Assessments at 6, 12 and 24 months of corrected age and school readiness assessment at 5 years. Fifty-one infants were assessed at least once, 45 were assessed at 2 years and 39 had a final assessment at 5 years. Neurodevelopmental attainment deteriorated significantly in the cognitive and motor composite scores from 6 to 24 months (p < 0.05). By 5 years the number of children with delay in cognitive, language and motor domains had reduced significantly from 24 months (p < 0.05) but the cognitive skills remained most affected (10/39). At 5 years, 13 of 39 children had a confirmed diagnosis of a neurodevelopmental disorder: eight had attention deficit hyperactivity disorder, three autism spectrum disorder, one cerebral palsy and one visual impairment. Surfactant administration and retinopathy of prematurity were the most significant risks for delayed development at 5 years (p < 0.05). Deterioration of cognitive and motor composite scores over the first 24 months highlights the need for regular surveillance of premature infants. There was a discrepancy between the diagnosis of neurodevelopmental delay at 24 months and at 5 years. But the notable impact on school readiness skills requires public health initiatives to cater for the needs of these children.
McGinty, Emma E; Busch, Susan H; Stuart, Elizabeth A; Huskamp, Haiden A; Gibson, Teresa B; Goldman, Howard H; Barry, Colleen L
The Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008 requires commercial insurers providing group coverage for substance use disorder services to offer benefits for those services at a level equal to those for medical or surgical benefits. Unlike previous parity policies instituted for federal employees and in individual states, the law extends parity to out-of-network services. We conducted an interrupted time-series analysis using insurance claims from large self-insured employers to evaluate whether federal parity was associated with changes in out-of-network treatment for 525,620 users of substance use disorder services. Federal parity was associated with an increased probability of using out-of-network services, an increased average number of out-of-network outpatient visits, and increased average total spending on out-of-network services among users of those services. Our findings were broadly consistent with the contention of federal parity proponents that extending parity to out-of-network services would broaden access to substance use disorder care obtained outside of plan networks. Project HOPE—The People-to-People Health Foundation, Inc.
Full Text Available Functional brain network (FBN has been becoming an increasingly important way to model the statistical dependence among neural time courses of brain, and provides effective imaging biomarkers for diagnosis of some neurological or psychological disorders. Currently, Pearson's Correlation (PC is the simplest and most widely-used method in constructing FBNs. Despite its advantages in statistical meaning and calculated performance, the PC tends to result in a FBN with dense connections. Therefore, in practice, the PC-based FBN needs to be sparsified by removing weak (potential noisy connections. However, such a scheme depends on a hard-threshold without enough flexibility. Different from this traditional strategy, in this paper, we propose a new approach for estimating FBNs by remodeling PC as an optimization problem, which provides a way to incorporate biological/physical priors into the FBNs. In particular, we introduce an L1-norm regularizer into the optimization model for obtaining a sparse solution. Compared with the hard-threshold scheme, the proposed framework gives an elegant mathematical formulation for sparsifying PC-based networks. More importantly, it provides a platform to encode other biological/physical priors into the PC-based FBNs. To further illustrate the flexibility of the proposed method, we extend the model to a weighted counterpart for learning both sparse and scale-free networks, and then conduct experiments to identify autism spectrum disorders (ASD from normal controls (NC based on the constructed FBNs. Consequently, we achieved an 81.52% classification accuracy which outperforms the baseline and state-of-the-art methods.
Ford, Kristen A; Théberge, Jean; Neufeld, Richard J; Williamson, Peter C; Osuch, Elizabeth A
Major Depressive Disorder (MDD) and Bipolar Disorder (BD) can be difficult to differentiate, as both feature depressive episodes. Here we have utilized fMRI and a measure of trait bipolarity to examine resting-state functional connectivity of brain activation in the default mode network in youth with MDD and BD to isolate trait-specific patterns. We collected resting-state fMRI scans from thirty youth (15 MDD; 15 BD, Type 1). The Bipolarity Index (BI) was completed by each patient's treating psychiatrist. Independent components analysis was used to extract a default mode network component from each participant, and then multiple regression was used to identify correlations between bipolarity and network activation. Activation in putamen/claustrum/insula correlated positively with BI; activation in the postcentral gyrus/posterior cingulate gyrus correlated negatively with BI. These correlations did not appear to be driven by movement in the scanner, state depression, gender or lithium use. There were group differences in state depression and sex that needed to be statistically covaried; differences in medication use existed between the groups; sample size was not large. The identification of the putamen/claustrum in our positive correlation may indicate a potential trait marker for the psychomotor activation unique to bipolar mania. The negative correlation in the postcentral gyrus/posterior cingulate suggests that this functional inactivation is more specific to MDD and is consistent with previous research. Ultimately, this approach may help to develop techniques to minimize the current clinical dilemma by facilitating the classification between BD and MDD. © 2013 Elsevier B.V. All rights reserved.
Full Text Available Background: Antipsychotic monotherapy or polypharmacy (concurrent use of two or more antipsychotics are used for treating patients with psychiatric disorders (PDs. Usually, antipsychotic monotherapy has a lower cost than polypharmacy. This study aimed to predict the cost of antipsychotic medications (AM of psychiatric patients in Iran. Materials and Methods: For this purpose, 790 patients with PDs who were discharged between June and September 2010 were selected from Razi Psychiatric Hospital, Tehran, Iran. For cost prediction of AM of PD, neural network (NN and multiple linear regression (MLR models were used. Analysis of data was performed with R 2.15.1 software. Results: Mean ± standard deviation (SD of the duration of hospitalization (days in patients who were on monotherapy and polypharmacy was 31.19 ± 15.55 and 36.69 ± 15.93, respectively (P < 0.001. Mean and median costs of medication for monotherapy (n = 507 were $8.25 and $6.23 and for polypharmacy (n =192 were $13.30 and $9.48, respectively (P = 0.001. The important variables for cost prediction of AM were duration of hospitalization, type of treatment, and type of psychiatric ward in the MLR model, and duration of hospitalization, type of diagnosed disorder, type of treatment, age, Chlorpromazine dosage, and duration of disorder in the NN model. Conclusion: Our findings showed that the artificial NN (ANN model can be used as a flexible model for cost prediction of AM.
Méndez Moreno, Alba
Autism Spectrum Disorder (ASD) is a common, incurable neurodevelopmental disorder impairing the individual’s capacity of social communication and interaction. There is not any pharmacological treatment available for this disorder affecting about 1% of children worldwide, which creates a need for complementary therapeutic interventions for ASD management. Animal-assisted therapy (AAT) has been proved as effective for the management of other neurodevelopmental and psychiatric disorders – such a...
Jhung, Kyungun; Ku, Jeonghun; Kim, Se Joo; Lee, Hyeongrae; Kim, Kyung Ran; An, Suk Kyoon; Kim, Sun I; Yoon, Kang-Jun; Lee, Eun
Neurobiological models of obsessive-compulsive disorder (OCD) emphasize disturbances of the corticostriatal circuit, but it remains unclear as to how these complex network dysfunctions correspond to heterogeneous OCD phenotypes. We aimed to investigate corticostriatal functional connectivity alterations distinct to OCD characterized predominantly by contamination/washing symptoms. Functional connectivity strengths of the striatal seed regions with remaining brain regions during the resting condition and the contamination symptom provocation condition were compared among 13 OCD patients with predominant contamination/washing symptoms (CON), 13 OCD patients without these symptoms (NCON), and 18 healthy controls. The CON group showed distinctively altered functional connectivity between the ventral striatum and the insula during both the resting and symptom-provoking conditions. Also, the connectivity strength between the ventral striatum and the insula significantly correlated with contamination/washing symptom severity. As common connectivity alterations of the whole OCD subjects, corticostriatal circuits involving the orbitofrontal and temporal cortices were again confirmed. To our knowledge, this is the first study that examined specific abnormalities in functional connectivity of contamination/washing symptom dimension OCD. The findings suggest limbic network dysfunctions to play a pivotal role in contamination/washing symptoms, possibly associated with emotionally salient error awareness. Our study sample allowed us to evaluate the corticostriatal network dysfunction underlying the contamination/washing symptom dimension, which leaves other major symptom dimensions to be explored in the future. Copyright © 2014 Elsevier Inc. All rights reserved.
De Bellis, Michael D.; Spratt, Eve G.; Hooper, Stephen R.
Child maltreatment appears to be the single most preventable cause of mental illness and behavioral dysfunction in the United States. Few published studies examine the developmental and the psychobiological consequences of sexual abuse. There are multiple mechanisms through which sexual abuse can cause post-traumatic stress disorder, activate…
O'Donoghue, Stefani; Holleran, Laurena; Cannon, Dara M; McDonald, Colm
The dysconnectivity hypothesis suggests that psychotic illnesses arise not from regionally specific focal pathophysiology, but rather from impaired neuroanatomical integration across networks of brain regions. Decreased white matter organization has been hypothesized to be a feature of psychotic illnesses in general, which is supported by meta-analyses of DTI studies in bipolar disorder and schizophrenia. Although many diffusion MRI studies investigate bipolar disorder and schizophrenia alone, relatively few studies directly compare structural features in these psychotic illnesses. Recently, the application of graph theory analyses to DTI data has supported the dysconnectivity hypothesis in bipolar disorder and schizophrenia, employing topological properties to assess neuroanatomical dysconnectivity. This selective review evaluates white matter alterations using Diffusion Tensor Imaging (DTI) in bipolar disorder and schizophrenia, with a focus upon direct comparison DTI studies in both psychotic illnesses. We then expand in more detail on the development of network analyses and the application of these techniques in bipolar disorder and schizophrenia. Converging evidence indicates that frontal connectivity alterations are common to both disorders, with prominent fronto-temporal deficits identified in schizophrenia and inter-hemispheric and limbic alterations reported in bipolar disorder. In bipolar disorder, most connectome reports use cortical maps alone, which given the importance of the limbic system in emotional regulation may limit the scope of network approaches in mood disorders. Further direct connectivity comparisons between these psychotic illnesses may assist in unravelling the neuroanatomical deviations underpinning the overlapping features of psychosis and cognitive impairment, and the more diagnostically distinctive features of affective disturbance in bipolar disorder and deficit syndrome in schizophrenia. Copyright © 2016 Elsevier B.V. All rights
Simacek, Jessica; Dimian, Adele F; McComas, Jennifer J
Young children with neurodevelopmental disorders such as autism spectrum disorders (ASD) and Rett syndrome often experience severe communication impairments. This study examined the efficacy of parent-implemented communication assessment and intervention with remote coaching via telehealth on the acquisition of early communication skills of three young children with ASD (2) and Rett syndrome (1). Efficacy of the intervention was evaluated using single-case experimental designs. First, functional assessment was used to identify idiosyncratic/potentially communicative responses and contexts for each child. Next, parents implemented functional communication training (FCT). All of the children acquired the targeted communication responses. The findings support the efficacy of telehealth as a service delivery model to coach parents on intervention strategies for their children's early communication skills.
Nargiso, Jessica E; Kuo, Caroline C; Zlotnick, Caron; Johnson, Jennifer E
The nature of social support available to incarcerated women is not well-understood, particularly among women at high risk of negative outcomes, including women dually diagnosed with Major Depressive Disorder and a Substance Use Disorder (MDD-SUD). Descriptive statistics and paired-tests were conducted on 60 incarcerated MDD-SUD women receiving in-prison substance use and depression treatments to characterize the women's social networks, including the strength of support, network characteristics, and types of support provided as well as to determine what aspects of social support may be amenable to change during incarceration and post-release. Study results showed that, on average, women perceived they had moderately supportive individuals in their lives, although more than a quarter of the sample could not identify any regular supporters in their network at baseline. During incarceration, women's social networks significantly increased in general supportiveness, and decreased in network size and percentage of substance users in their networks. Participants maintained positive social support gains post-release in most areas while also significantly increasing the size of their support network post-release. Findings suggest that there are aspects of incarcerated MDD-SUD women's social networks that are amenable to change during incarceration and post-release and provide insight into treatment targets for this vulnerable population.
Autism spectrum disorder is a complex neurodevelopmental disorder, which is accompanied by differences in brain anatomy, functioning and brain connectivity. Due to its neurodevelopmental character, and the large phenotypic heterogeneity among individuals on the autism spectrum, the neurobiology of autism spectrum disorder is inherently difficult…
Lopriore, Enrico; Aziz, Muhammed I.; Nagel, Helene T.; Blom, Nico A.; Rozendaal, Lieke; Kanhai, Humphrey H. H.; Vandenbussche, Frank P. H. A.
OBJECTIVE: The purpose of this study was to determine the long-term neurodevelopmental outcome in fetuses with severe tachy- or bradyarrhythmia. STUDY DESIGN: This was a follow-up study to assess the neurologic, mental, and psychomotor development in cases with fetal cardiac arrhythmia. RESULTS: A
Kocovska, Eva; Puckering, Christine; Follan, Michael; Smillie, Maureen; Gorski, Charlotta; Barnes, James; Wilson, Philip; Young, David; Lidstone, Emma; Pritchett, Rachel; Hockaday, Harriet; Minnis, Helen
We aimed to explore the extent of neurodevelopmental difficulties in severely maltreated adopted children. We recruited 34 adopted children, referred with symptoms of indiscriminate friendliness and a history of severe maltreatment in their early childhood and 32 typically developing comparison children without such a history, living in biological…
Toxic exposures during pregnancy and early childhood continue to play an important role as a preventable cause of neurodevelopmental disabilities in the U.S. and around the world. Identifying and eliminating these toxins should be a priority, but the task is made exceedingly difficult due to the severe limits of scientific knowledge in this area…
Robaey, Philippe; Krajinovic, Maja; Marcoux, Sophie; Moghrabi, Albert
Pharmacogenetics holds the promise of minimizing adverse neurodevelopmental outcomes of cancer patients by identifying patients at risk, enabling the individualization of treatment and the planning of close follow-up and early remediation. This review focuses first on methotrexate, a drug often implicated in neurotoxicity, especially when used in…
Pollak, Seth D.; Nelson, Charles A.; Schlaak, Mary F.; Roeber, Barbara J.; Wewerka, Sandi S.; Wiik, Kristen L.; Frenn, Kristin A.; Loman, Michelle M.; Gunnar, Megan R.
The neurodevelopmental sequelae of early deprivation were examined by testing (N = 132) 8- and 9-year-old children who had endured prolonged versus brief institutionalized rearing or rearing in the natal family. Behavioral tasks included measures that permit inferences about underlying neural circuitry. Children raised in institutionalized…
Neurodevelopmental status of HIV-exposed but uninfected children: A pilot study. P Springer, B Laughton, M Tomlinson, J Harvey, M Esser. Abstract. Introduction. HIV affects children both directly and indirectly, with evidence of increased infectious mortality and morbidity in the HIV-exposed but uninfected (HEU) infant.
Wolf, M. J.; Beunen, G.; Casaer, P.; Wolf, B.
As part of a prospective study of severely jaundiced Zimbabwean infants, the relationship between maximum total serum bilirubin (TSB) concentration in the neonatal period and neurodevelopmental outcome at the corrected age of 4 months was studied. Fifty infants with a TSB of > 400 micromol/l (23.4
Boersma, M.; Kemner, C.; Reus, M.A. de; Collin, G; Snijders, T.M.; Hofman, D.; Buitelaar, J.K.; Stam, C.J.; Heuvel, M.P. van den
Communication and integration of information between brain regions plays a key role in healthy brain function. Conversely, disruption in brain communication may lead to cognitive and behavioral problems. Autism is a neurodevelopmental disorder that is characterized by impaired social interactions
Higgins, Gerald A; Allyn-Feuer, Ari; Barbour, Edward; Athey, Brian D
A regulatory network in the human brain mediating lithium response in bipolar patients was revealed by analysis of functional SNPs from genome-wide association studies (GWAS) and published gene association studies, followed by epigenome mapping. An initial set of 23,312 SNPs in linkage disequilibrium with lead SNPs, and sub-threshold GWAS SNPs rescued by pathway analysis, were studied in the same populations. These were assessed using our workflow and annotation by the epigenome roadmap consortium. Twenty-seven percent of 802 SNPs that were associated with lithium response (13 published studies gene association studies and two GWAS) were shared in common with 1281 SNPs from 18 GWAS examining psychiatric disorders and adverse events associated with lithium treatment. Nineteen SNPs were annotated as active regulatory elements such as enhancers and promoters in a tissue-specific manner. They were located within noncoding regions of ten genes: ANK3, ARNTL, CACNA1C, CACNG2, CDKN1A, CREB1, GRIA2, GSK3B, NR1D1 and SLC1A2. Following gene set enrichment and pathway analysis, these genes were found to be significantly associated (p = 10(-27); Fisher exact test) with an AMPA2 glutamate receptor network in human brain. Our workflow results showed concordance with annotation of regulatory elements from the epigenome roadmap. Analysis of cognate mRNA and enhancer RNA exhibited patterns consistent with an integrated pathway in human brain. This pharmacoepigenomic regulatory pathway is located in the same brain regions that exhibit tissue volume loss in bipolar disorder. Although in silico analysis requires biological validation, the approach provides value for identification of candidate variants that may be used in pharmacogenomic testing to identify bipolar patients likely to respond to lithium.
Yu, Dongmei; Mathews, Carol A.; Scharf, Jeremiah M.; Neale, Benjamin M.; Davis, Lea K.; Gamazon, Eric R.; Derks, Eske M.; Evans, Patrick; Edlund, Christopher K.; Crane, Jacquelyn; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M.; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Berrio, Gabriel Bedoya; Bienvenu, O. Joseph; Black, Donald W.; Bloch, Michael H.; Brentani, Helena; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Campbell, Desmond D.; Cappi, Carolina; Silgado, Julio C. Cardona; Cavallini, Maria C.; Chavira, Denise A.; Chouinard, Sylvain; Cook, Edwin H.; Cookson, M. R.; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniete; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald L.; Girard, Simon L.; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Gruenblatt, Edna; Hardy, John; Heiman, Gary A.; Hemmings, Sian M. J.; Herrera, Luis D.; Hezel, Dianne M.; Hoekstra, Pieter J.; Jankovic, Joseph; Kennedy, James L.; King, Robert A.; Konkashbaev, Anuar I.; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L.; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T.; Restrepo, Sandra C. Mesa; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L.; Naarden, Allan L.; Nurmi, Erika; Ochoa, William Cornejo; Ophoff, Roel A.; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlo N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L.; Renner, Tobias; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark A.; Robertson, Mary M.; Romero, Roxana; Rosario, Maria C.; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Service, Susan K.; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Strengman, Eric; Tischfield, Jay A.; Turiel, Maurizio; Duarte, Ana V. Valencia; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R.; Westenberg, Herman G. M.; Shugart, Yin Yao; Hounie, Ana G.; Miguel, Euripedes C.; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C.; McMahon, William; Posthuma, Danielle; Oostra, Ben A.; Nestadt, Gerald; Routeau, Guy A.; Purcell, Shaun; Jenike, Michael A.; Heutink, Peter; Hanna, Gregory L.; Conti, David V.; Arnold, Paul D.; Freimer, Nelson B.; Stewart, Evelyn; Knowles, James A.; Cox, Nancy J.; Pauls, David L.
Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The
Yu, Dongmei; Mathews, Carol A.; Scharf, Jeremiah M.; Neale, Benjamin M.; Davis, Lea K.; Gamazon, Eric R.; Derks, Eske M.; Evans, Patrick; Edlund, Christopher K.; Crane, Jacquelyn; Fagerness, Jesen A.; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M.; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, O. Joseph; Black, Donald W.; Bloch, Michael H.; Brentani, Helena; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Campbell, Desmond D.; Cappi, Carolina; Silgado, Julio C. Cardona; Cavallini, Maria C.; Chavira, Denise A.; Chouinard, Sylvain; Cook, Edwin H.; Cookson, M. R.; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniele; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald L.; Girard, Simon L.; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Grünblatt, Edna; Hardy, John; Heiman, Gary A.; Hemmings, Sian M. J.; Herrera, Luis D.; Hezel, Dianne M.; Hoekstra, Pieter J.; Jankovic, Joseph; Kennedy, James L.; King, Robert A.; Konkashbaev, Anuar I.; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L.; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T.; Mesa Restrepo, Sandra C.; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L.; Naarden, Allan L.; Nurmi, Erika; Ochoa, William Cornejo; Ophoff, Roel A.; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L.; Renner, Tobias; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark A.; Robertson, Mary M.; Romero, Roxana; Rosário, Maria C.; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Service, Susan K.; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Strengman, Eric; Tischfield, Jay A.; Turiel, Maurizio; Valencia Duarte, Ana V.; Vallada, Homero; Veenstra-Vanderweele, Jeremy; Walitza, Susanne; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R.; Westenberg, Herman G. M.; Shugart, Yin Yao; Hounie, Ana G.; Miguel, Euripedes C.; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C.; McMahon, William; Posthuma, Danielle; Oostra, Ben A.; Nestadt, Gerald; Rouleau, Guy A.; Purcell, Shaun; Jenike, Michael A.; Heutink, Peter; Hanna, Gregory L.; Conti, David V.; Arnold, Paul D.; Freimer, Nelson B.; Stewart, S. Evelyn; Knowles, James A.; Cox, Nancy J.; Pauls, David L.
Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a
Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M; Neale, Benjamin M; Davis, Lea K; Gamazon, Eric R; Derks, Eske M; Evans, Patrick; Edlund, Christopher K; Crane, Jacquelyn; Fagerness, Jesen A; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, O Joseph; Black, Donald W; Bloch, Michael H; Brentani, Helena; Bruun, Ruth D; Budman, Cathy L; Camarena, Beatriz; Campbell, Desmond D; Cappi, Carolina; Silgado, Julio C Cardona; Cavallini, Maria C; Chavira, Denise A; Chouinard, Sylvain; Cook, Edwin H; Cookson, M R; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniele; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald L; Girard, Simon L; Grabe, Hans J; Grados, Marco A; Greenberg, Benjamin D; Gross-Tsur, Varda; Grünblatt, Edna; Hardy, John; Heiman, Gary A; Hemmings, Sian M J; Herrera, Luis D; Hezel, Dianne M; Hoekstra, Pieter J; Jankovic, Joseph; Kennedy, James L; King, Robert A; Konkashbaev, Anuar I; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T; Mesa Restrepo, Sandra C; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L; Naarden, Allan L; Nurmi, Erika; Ochoa, William Cornejo; Ophoff, Roel A; Pakstis, Andrew J; Pato, Michele T; Pato, Carlos N; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L; Renner, Tobias; Reus, Victor I; Richter, Margaret A; Riddle, Mark A; Robertson, Mary M; Romero, Roxana; Rosário, Maria C; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S; Samuels, Jack; Sandor, Paul; Service, Susan K; Sheppard, Brooke; Singer, Harvey S; Smit, Jan H|info:eu-repo/dai/nl/113700644; Stein, Dan J; Strengman, Eric; Tischfield, Jay A; Turiel, Maurizio; Valencia Duarte, Ana V; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R; Westenberg, Herman G M; Shugart, Yin Yao; Hounie, Ana G; Miguel, Euripedes C; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C|info:eu-repo/dai/nl/194111423; McMahon, William; Posthuma, Danielle; Oostra, Ben A; Nestadt, Gerald; Rouleau, Guy A; Purcell, Shaun; Jenike, Michael A; Heutink, Peter; Hanna, Gregory L; Conti, David V; Arnold, Paul D; Freimer, Nelson B; Stewart, S Evelyn; Knowles, James A; Cox, Nancy J; Pauls, David L
OBJECTIVE: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The
Aymen N Naguib
Full Text Available Introduction: Modulating the stress response and perioperative factors can have a paramount impact on the neurodevelopmental outcome of infants who undergo cardiac surgery utilizing cardiopulmonary bypass. Materials and Methods: In this single center prospective follow-up study, we evaluated the impact of three different anesthetic techniques on the neurodevelopmental outcomes of 19 children who previously underwent congenital cardiac surgery within their 1 st year of life. Cases were done from May 2011 to December 2013. Children were assessed using the Stanford-Binet Intelligence Scales (5 th edition. Multiple regression analysis was used to test different parental and perioperative factors that could significantly predict the different neurodevelopmental outcomes in the entire cohort of patients. Results: When comparing the three groups regarding the major cognitive scores, a high-dose fentanyl (HDF patients scored significantly higher than the low-dose fentanyl (LDF + dexmedetomidine (DEX (LDF + DEX group in the quantitative reasoning scores (106 ± 22 vs. 82 ± 15 P = 0.046. The bispectral index (BIS value at the end of surgery for the -LDF group was significantly higher than that in LDF + DEX group (P = 0.011. For the entire cohort, a strong correlation was seen between the standard verbal intelligence quotient (IQ score and the baseline adrenocorticotropic hormone level, the interleukin-6 level at the end of surgery and the BIS value at the end of the procedure with an R 2 value of 0.67 and P < 0.04. There was an inverse correlation between the cardiac Intensive Care Unit length of stay and the full-scale IQ score (R = 0.4675 and P 0.027. Conclusions: Patients in the HDF group demonstrated overall higher neurodevelopmental scores, although it did not reach statistical significance except in fluid reasoning scores. Our results may point to a possible correlation between blunting the stress response and improvement of the neurodevelopmental
George, Joanne M; Boyd, Roslyn N; Colditz, Paul B; Rose, Stephen E; Pannek, Kerstin; Fripp, Jurgen; Lingwood, Barbara E; Lai, Melissa M; Kong, Annice H T; Ware, Robert S; Coulthard, Alan; Finn, Christine M; Bandaranayake, Sasaka E
More than 50 percent of all infants born very preterm will experience significant motor and cognitive impairment. Provision of early intervention is dependent upon accurate, early identification of infants at risk of adverse outcomes. Magnetic resonance imaging at term equivalent age combined with General Movements assessment at 12 weeks corrected age is currently the most accurate method for early prediction of cerebral palsy at 12 months corrected age. To date no studies have compared the use of earlier magnetic resonance imaging combined with neuromotor and neurobehavioural assessments (at 30 weeks postmenstrual age) to predict later motor and neurodevelopmental outcomes including cerebral palsy (at 12-24 months corrected age). This study aims to investigate i) the relationship between earlier brain imaging and neuromotor/neurobehavioural assessments at 30 and 40 weeks postmenstrual age, and ii) their ability to predict motor and neurodevelopmental outcomes at 3 and 12 months corrected age. This prospective cohort study will recruit 80 preterm infants born ≤ 30 week's gestation and a reference group of 20 healthy term born infants from the Royal Brisbane & Women's Hospital in Brisbane, Australia. Infants will undergo brain magnetic resonance imaging at approximately 30 and 40 weeks postmenstrual age to develop our understanding of very early brain structure at 30 weeks and maturation that occurs between 30 and 40 weeks postmenstrual age. A combination of neurological (Hammersmith Neonatal Neurologic Examination), neuromotor (General Movements, Test of Infant Motor Performance), neurobehavioural (NICU Network Neurobehavioural Scale, Premie-Neuro) and visual assessments will be performed at 30 and 40 weeks postmenstrual age to improve our understanding of the relationship between brain structure and function. These data will be compared to motor assessments at 12 weeks corrected age and motor and neurodevelopmental outcomes at 12 months corrected age
Pontes, Halley M
Background and aims Previous studies focused on examining the interrelationships between social networking site (SNS) addiction and Internet gaming disorder (IGD) in isolation. Moreover, little is known about the potential simultaneous differential effects of SNS addiction and IGD on psychological health. This study investigated the interplay between these two technological addictions and ascertained how they can uniquely and distinctively contribute to increasing psychiatric distress when accounting for potential effects stemming from sociodemographic and technology-related variables. Methods A sample of 509 adolescents (53.5% males) aged 10-18 years (mean = 13.02, SD = 1.64) were recruited. Results It was found that key demographic variables can play a distinct role in explaining SNS addiction and IGD. Furthermore, it was found that SNS addiction and IGD can augment the symptoms of each other, and simultaneously contribute to deterioration of overall psychological health in a similar fashion, further highlighting potentially common etiological and clinical course between these two phenomena. Finally, the detrimental effects of IGD on psychological health were found to be slightly more pronounced than those produced by SNS addiction, a finding that warrants additional scientific scrutiny. Discussion and conclusion The implications of these results are further discussed in light of the existing evidence and debates regarding the status of technological addictions as primary and secondary disorders.
Chatterton, Mary Lou; Stockings, Emily; Berk, Michael; Barendregt, Jan J; Carter, Rob; Mihalopoulos, Cathrine
BackgroundFew trials have compared psychosocial therapies for people with bipolar affective disorder, and conventional meta-analyses provided limited comparisons between therapies.AimsTo combine evidence for the efficacy of psychosocial interventions used as adjunctive treatment of bipolar disorder in adults, using network meta-analysis (NMA).MethodSystematic review identified studies and NMA was used to pool data on relapse to mania or depression, medication adherence, and symptom scales for mania, depression and Global Assessment of Functioning (GAF).ResultsCarer-focused interventions significantly reduced the risk of depressive or manic relapse. Psychoeducation alone and in combination with cognitive-behavioural therapy (CBT) significantly reduced medication non-adherence. Psychoeducation plus CBT significantly reduced manic symptoms and increased GAF. No intervention was associated with a significant reduction in depression symptom scale scores.ConclusionsOnly interventions for family members affected relapse rates. Psychoeducation plus CBT reduced medication non-adherence, improved mania symptoms and GAF. Novel methods for addressing depressive symptoms are required. © The Royal College of Psychiatrists 2017.
Uebelacker, Lisa; Dufour, Steven C; Dinerman, Jacob G; Walsh, Samantha L; Hearing, Casey; Gillette, Lee T; Deckersbach, Thilo; Nierenberg, Andrew A; Weinstock, Lauren; Sylvia, Louisa G
Despite ongoing advances in the treatment of mood disorders, a substantial proportion of people diagnosed with major depression or bipolar disorder remain symptomatic over time. Yoga, which has been shown to reduce stress and depressive symptoms, as well as to improve overall quality of life, shows promise as an adjunctive treatment. However, dissemination of yoga for clinical populations remains challenging. The purpose of this pilot study was to test the feasibility and acceptability of an online yoga intervention for individuals with mood disorders. In total, 56 adults who reported being diagnosed with a mood disorder (bipolar disorder, major depressive disorder, cyclothymia, or schizoaffective disorder) were recruited from MoodNetwork, an online community of individuals with mood disorders. A feedback survey and a measure of positive and negative affect were administered before and after a 30-minute online Hatha yoga class. In total, 44 individuals (78.6%) completed all components of the yoga class. The mean score on a 10-point Likert scale rating how much participants liked the online yoga class was 7.24 (SD=2.40). Most participants (67.9%) reported that they would be "somewhat likely" or "very likely" to participate in an online yoga program again. There was a statistically significant decrease in negative affect after completing the class (t=-6.05; P0.10). These preliminary data support the utility of online yoga tailored specifically for people with mood disorders as a possible adjunctive intervention that warrants further investigation.
Erguzel, Turker Tekin; Ozekes, Serhat; Gultekin, Selahattin; Tarhan, Nevzat; Hizli Sayar, Gokben; Bayram, Ali
The combination of repetitive transcranial magnetic stimulation (rTMS), a non-pharmacological form of therapy for treating major depressive disorder (MDD), and electroencephalogram (EEG) is a valuable tool for investigating the functional connectivity in the brain. This study aims to explore whether pre-treating frontal quantitative EEG (QEEG) cordance is associated with response to rTMS treatment among MDD patients by using an artificial intelligence approach, artificial neural network (ANN). The artificial neural network using pre-treatment cordance of frontal QEEG classification was carried out to identify responder or non-responder to rTMS treatment among 55 MDD subjects. The classification performance was evaluated using k-fold cross-validation. The ANN classification identified responders to rTMS treatment with a sensitivity of 93.33%, and its overall accuracy reached to 89.09%. Area under Receiver Operating Characteristic (ROC) curve (AUC) value for responder detection using 6, 8 and 10 fold cross validation were 0.917, 0.823 and 0.894 respectively. Potential utility of ANN approach method can be used as a clinical tool in administering rTMS therapy to a targeted group of subjects suffering from MDD. This methodology is more potentially useful to the clinician as prediction is possible using EEG data collected before this treatment process is initiated. It is worth using feature selection algorithms to raise the sensitivity and accuracy values.
Himle, Joseph A; Taylor, Robert Joseph; Nguyen, Ann W; Williams, Monnica T; Lincoln, Karen D; Taylor, Harry Owen; Chatters, Linda M
Although there is a large literature on the influence of social support on mental health there is limited research on social support and OCD. This is especially the case for African Americans and Black Caribbeans. This study examines the relationship between family and friendship networks and the prevalence of OCD. The analysis is based on the National Survey of American Life a nationally representative sample of African Americans and Black Caribbeans. Variables included frequency of contact with family and friends, subjective closeness with family and friends, and negative interactions (conflict, criticisms) with family members. The results indicated that only negative interaction with family members was significantly associated with OCD prevalence. African Americans and Black Caribbeans with more frequent negative interactions with family members had a higher likelihood of having OCD. Subjective closeness and frequency of contact with family and friends was not protective of OCD. Overall the findings are consistent with previous work which finds that social support is an inconsistent protective factor of psychiatric disorders, but negative interactions with support network members is more consistently associated with mental health problems.
Pedrosa, Erika; Shah, Abhishek; Tenore, Christopher; Capogna, Michael; Villa, Catalina; Guo, Xingyi; Zheng, Deyou; Lachman, Herbert M
Therapeutic concentrations of lithium salts inhibit glycogen synthase kinase 3 beta (GSK3β) and phosphoinositide (PI) signaling suggesting that abnormal activation of these pathways could be a factor in the pathophysiology of bipolar disorder (BD). Involvement of these pathways is also supported by recent genome-wide association studies (GWASs). One way investigators have investigated the molecular basis of BD and the therapeutic action of lithium is by microarray expression studies, since both GSK3β- and PI-mediated signal transduction pathways are coupled to transcriptional activation and inhibition. However, expression profiling has some limitations and investigators cannot use the approach to analyze fetal brain tissue, arguably the most relevant biological structure related to the development of genetically based psychiatric disorders. To address these shortcomings, the authors have taken a novel approach using chromatin immunoprecipitation-enriched material annealed to microarrays (ChIP-chip) targeting genes in fetal brain tissue bound by β-catenin, a transcription factor that is directly regulated by GSK3β. The promoters for 640 genes were found to be bound by β-catenin, many of which are known schizophrenia (SZ), autism spectrum disorder (ASD), and BD candidates, including CACNA1B, NRNG, SNAP29, FGFR1, PCDH9, and nine others identified in recently published GWASs and genome-wide searches for copy number variants (CNVs). The findings suggest that seemingly disparate candidate genes for SZ and BD can be incorporated into a common molecular network revolving around GSK3β/β-catenin signaling. In addition, the finding that a putative lithium-responsive pathway may influence a subgroup of SZ and ASD candidate genes could have therapeutic implications.
van den Brink, R H S; Schutter, N; Hanssen, D. J. C.; Elzinga, B. M.; Rabeling-Keus, I M; Stek, M L; Comijs, H C; Penninx, B W J H; Oude Voshaar, R C
AIMS: Poor recovery from depressive disorder has been shown to be related to low perceived social support and loneliness, but not to social network size or frequency of social interactions. Some studies suggest that the significance of social relationships for depression course may be greater in
Anderson, Ariana; Locke, Jill; Kretzmann, Mark; Kasari, Connie
Although children with autism spectrum disorder are frequently included in mainstream classrooms, it is not known how their social networks change compared to typically developing children and whether the factors predictive of this change may be unique. This study identified and compared predictors of social connectivity of children with and…
Hochman, Julia M.; Carter, Erik W.; Bottema-Beutel, Kristen; Harvey, Michelle N.; Gustafson, Jenny R.
Although peer interaction takes on increased salience during adolescence, such social connections remain elusive for many high school students with autism spectrum disorder (ASD). This social isolation can be particularly prevalent within unstructured school contexts. In this study, we examined the effects of a lunchtime peer network intervention…
Waller, Jessica A; Tamm, Joseph A; Abdourahman, Aicha; Pehrson, Alan L; Li, Yan; Cajina, Manuel; Sánchez, Connie
The multimodal antidepressant vortioxetine displays an antidepressant profile distinct from those of conventional selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and possesses cognitive-enhancing properties in preclinical and clinical studies. Recent studies have begun to investigate molecular mechanisms that may differentiate vortioxetine from other antidepressants. Acute studies in adult rats and chronic studies in a middle-aged mouse model reveal upregulation of several markers that play a central role in synaptic plasticity. However, the effect of chronic vortioxetine treatment on expression of neuroplasticity and neurodevelopmental biomarkers in naïve rats has not been evaluated. In the present study, we demonstrate that vortioxetine at a range of doses regulates expression of genes associated with plasticity in the frontal cortex, hippocampus, region encompassing the amygdala, as well as in blood, and displays similar effects relative to the SSRI fluoxetine in adult naïve rats. These genes encode immediate early genes (IEGs), translational regulators, and the neurodevelopmental marker Sema4g. Similar findings detected in brain regions and in blood provide a potential translational impact, and vortioxetine appears to consistently regulate signaling in these networks of neuroplasticity and developmental markers. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.
Full Text Available BACKGROUND: Numerous studies have demonstrated the higher-order functions of the cerebellum, including emotion regulation and cognitive processing, and have indicated that the cerebellum should therefore be included in the pathophysiological models of major depressive disorder. The aim of this study was to compare the resting-state functional connectivity of the cerebellum in adults with major depression and healthy controls. METHODS: Twenty adults with major depression and 20 gender-, age-, and education-matched controls were investigated using seed-based resting-state functional connectivity magnetic resonance imaging. RESULTS: Compared with the controls, depressed patients showed significantly increased functional connectivity between the cerebellum and the temporal poles. However, significantly reduced cerebellar functional connectivity was observed in the patient group in relation to both the default-mode network, mainly including the ventromedial prefrontal cortex and the posterior cingulate cortex/precuneus, and the executive control network, mainly including the superior frontal cortex and orbitofrontal cortex. Moreover, the Hamilton Depression Rating Scale score was negatively correlated with the functional connectivity between the bilateral Lobule VIIb and the right superior frontal gyrus in depressed patients. CONCLUSIONS: This study demonstrated increased cerebellar coupling with the temporal poles and reduced coupling with the regions in the default-mode and executive control networks in adults with major depression. These differences between patients and controls could be associated with the emotional disturbances and cognitive control function deficits that accompany major depression. Aberrant cerebellar connectivity during major depression may also imply a substantial role for the cerebellum in the pathophysiological models of depression.
Stange, Jonathan P; Jenkins, Lisanne M; Hamlat, Elissa J; Bessette, Katie L; DelDonno, Sophie R; Kling, Leah R; Passarotti, Alessandra M; Phan, K Luan; Klumpp, Heide; Ryan, Kelly A; Langenecker, Scott A
Major depressive disorder (MDD) is characterized by dysfunction in cognitive and emotional systems. However, the neural network correlates of cognitive control (cold cognition) and emotion processing (hot cognition) during the remitted state of MDD (rMDD) remain unclear and not fully probed, which has important implications for identifying intermediate phenotypes of depression risk. 43 young adults with rMDD and 33 healthy controls (HCs) underwent fMRI while completing separate tasks of cold cognition (Parametric Go/No-Go test) and hot cognition (Facial Emotion Processing Test). Two 2 group (rMDD, HC) × 2 event (sad/fearful faces, correct rejections) factorial models of activation were calculated in SPM8. Functional activation was evaluated in the salience and emotional network (SEN) and the cognitive control network (CCN), including hypothesized interaction between group and task within the CCN. Individuals with rMDD demonstrated greater spatial extent of suprathreshold activation within the SEN during sad faces relative to HCs. There were several regions within the CCN in which HCs showed greater activation than rMDD during correct rejections of lures, whereas individuals with rMDD showed greater activation than HCs during sad or fearful faces. Results were not directly compared with active MDD. These results provide evidence of deficient CCN engagement during cognitive control in rMDD (dysfunctional cold cognition). Elevated SEN activation during sad faces could represent heightened salience of negative emotional faces in rMDD; elevated CCN activation during emotional faces in rMDD could represent compensatory regulatory control. These group differences may represent vulnerability factors, scars of prior depressive episodes, or processes maintaining wellness. Copyright © 2017 Elsevier B.V. All rights reserved.
Sanvisens, Arantza; Zuluaga, Paola; Rivas, Inmaculada; Rubio, Gabriel; Gual, Antoni; Torrens, Marta; Short, Antoni; Álvarez, Francisco Javier; Tor, Jordi; Farré, Magí; Rodríguez de Fonseca, Fernando; Muga, Roberto
The Alcohol Program of the Spanish Network on Addictive Disorders-RTA requires a longitudinal study to address different research questions related to alcoholism. The cohort study (CohRTA) focuses on patients seeking treatment for alcohol use disorder, as a multicentre, collaborative research project aimed to improve secondary prevention and early diagnosis of pathological processes associated with the disorder. multicentre cohort study in adults (>18 years) seeking their first treatment of the disorder. Patients sign an informed consent and data is collected in an online platform specifically designed for the study; patients are also requested to provide biological samples that are stored in a biobank. Baseline and prospective, socio-demographic, epidemiological, clinical and treatment data are collected. Currently there are 10 participating centres that expect to recruit more than 1,000 patients. As of December 2015, 344 patients (77% men) were included. Median age at admission was 50 years (IQR: 43-55 years). Median age at the start of alcohol consumption was 15 years (IQR: 14-18 years) and 61% of cases reported antecedents of alcohol use disorder in the family. During the 30 days prior to admission, alcohol consumption amounted to 12.5 SDU/day (IQR: 7.1-20 SDU/day), 72% of the patients were tobacco smokers and 30% currently used cocaine. Organising an open cohort of patients with alcohol use disorder may be crucial to better understand the clinical consequences of alcoholism in Spain. This cohort may potentiate quantitative and qualitative research within the Spanish Network on Addictive Disorders-RTA/RETICS. Having a well-established, representative cohort of patients will increase translational research on consequences of alcoholism in our country.
Eriksson, Jonna Maria; Lundström, Sebastian; Lichtenstein, Paul; Bejerot, Susanne; Eriksson, Elias
Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders thought to have both genetic and environmental causes. It has been hypothesized that exposure to elevated levels of prenatal testosterone is associated with elevated traits of ASD and ADHD. Assuming that testosterone levels from a dizygotic male twin fetus may lead to enhanced testosterone exposure of its co-twins, we aimed to test the prenatal testosterone hypothesis by comparing same-sex with opposite-sex dizygotic twins with respect to neurodevelopmental symptoms. Neuropsychiatric traits were assessed in a population-based twin cohort from the Child and Adolescent Twin Study in Sweden (CATSS). Parental interviews were conducted for 16,312 dizygotic twins, 9 and 12 years old, with the Autism-Tics, ADHD, and other Comorbidities inventory (A-TAC). Girls with a female co-twin had an increased risk of reaching the cut-off score for ADHD compared with girls with a male co-twin. Both boys and girls with a female co-twin displayed a larger number of traits related to attention deficit and repetitive and stereotyped behaviors than those with a male twin. In girls, this also extended to social interaction and the combined measures for ASD and ADHD, however, with small effect sizes. Our results are reverse to what would have been expected from the prenatal testosterone hypothesis but consistent with a previous study of ASD and ADHD traits in dizygotic twins. The seemingly protective effect for girls of having a twin brother may be an effect of parent report bias, but may also be an unexpected effect of sharing the intrauterine environment with a male co-twin.
Oh, Sechang; Kwon, Hyeokjun; Varadan, Vijay K.
Good sleep is critical for one's overall physical and mental health but more than 50 million Americans have experienced or are suffering from sleep disorders. Nevertheless, 85% of them remain undiagnosed or untreated. They can lead to chronic diseases. Sleep disorders are diagnosed through polysomnography, also known as sleep study, performed in a sleep laboratory overnight. This perturbs his/her daily sleep routine, and consequently, an accurate diagnosis cannot be made. Many companies have been developing home sleep test systems to reduce the cost of sleep studies and provide a more convenience solution to patients. The category of the system varies as type II, type III and type IV according to the type of sleep study. Current systems cannot be easily extended from one type to include a higher type. A patient who has a type III system to diagnose sleep apnea should additionally purchase a type II system which has functions that overlap with a type III system, to evaluate sleep stages. In this paper, we propose a wireless telemedicine system for easy extension of channels using the start network topology of the Zigbee protocol. The HST system consists of two wireless HST devices with a Zigbee module, a wireless HST receiver with both a Zigbee and a Wi-Fi module, and a sever which monitors/saves the physiological signals. One transmitter provides 5 channels for 2x EOG, 2x EEG and EMG to evaluate sleep stages. The other transmitter provides 5 additional channels for ECG, nasal air flow, body position, abdominal/chest efforts and oxygen saturation to diagnose sleep apnea. These two transmitters, acting as routers, and the receiver as a coordinator form a Zigbee star network. The data from each transmitter in the receiver are retransmitted to the monitoring unit through Wi-Fi. By building a star network with Zigbee, channels can be easily extended so that low level systems can be upgraded to higher level systems by simply adding the necessary channels. In addition
Latkin, Carl A; Tseng, Tuo-Yen; Davey-Rothwell, Melissa; Kennedy, Ryan D; Moran, Meghan Bridgid; Czaplicki, Lauren; Edwards, Catie; Falade-Nwulia, Oluwaseun; Chander, Geetanjali; Knowlton, Amy R
Impoverished urban neighborhoods tend to have higher rates of smoking and higher rates of exposure to secondhand smoke as compared to more affluent neighborhoods. Contextual factors of neighborhood disorder and social network and household composition may have an impact on indoor smoking behaviors. The TIDE study examined psychosocial factors associated with smoking behaviors among impoverished inner-city smokers in Baltimore, Maryland. Among a community-recruited sample of 413 smokers who lived with others, most (73%) reported that they or others smoked in their residence. Cohabitation with children, elderly, and those with asthma and other respiratory condition was not associated with indoor smoking. Neighborhood disorder, the proportion of social network members who smoked with the study participant, and the proportion of household members who smoked were all independently associated with smoking indoors. The study findings suggest the importance of addressing neighborhood and social network factors when developing programs for promoting indoor smoking bans as well as cessation and prevention programs.
Pompoli, Alessandro; Furukawa, Toshi A; Imai, Hissei; Tajika, Aran; Efthimiou, Orestis; Salanti, Georgia
Panic disorder is characterised by the presence of recurrent unexpected panic attacks, discrete periods of fear or anxiety that have a rapid onset and include symptoms such as racing heart, chest pain, sweating and shaking. Panic disorder is common in the general population, with a lifetime prevalence of 1% to 4%. A previous Cochrane meta-analysis suggested that psychological therapy (either alone or combined with pharmacotherapy) can be chosen as a first-line treatment for panic disorder with or without agoraphobia. However, it is not yet clear whether certain psychological therapies can be considered superior to others. In order to answer this question, in this review we performed a network meta-analysis (NMA), in which we compared eight different forms of psychological therapy and three forms of a control condition. To assess the comparative efficacy and acceptability of different psychological therapies and different control conditions for panic disorder, with or without agoraphobia, in adults. We conducted the main searches in the CCDANCTR electronic databases (studies and references registers), all years to 16 March 2015. We conducted complementary searches in PubMed and trials registries. Supplementary searches included reference lists of included studies, citation indexes, personal communication to the authors of all included studies and grey literature searches in OpenSIGLE. We applied no restrictions on date, language or publication status. We included all relevant randomised controlled trials (RCTs) focusing on adults with a formal diagnosis of panic disorder with or without agoraphobia. We considered the following psychological therapies: psychoeducation (PE), supportive psychotherapy (SP), physiological therapies (PT), behaviour therapy (BT), cognitive therapy (CT), cognitive behaviour therapy (CBT), third-wave CBT (3W) and psychodynamic therapies (PD). We included both individual and group formats. Therapies had to be administered face-to-face. The
Bareš, Martin; Apps, Richard; Kikinis, Zora; Timmann, Dagmar; Oz, Gulin; Ashe, James J; Loft, Michaela; Koutsikou, Stella; Cerminara, Nadia; Bushara, Khalaf O; Kašpárek, Tomáš
The proceedings of the workshop synthesize the experimental, preclinical, and clinical data suggesting that the cerebellum, basal ganglia (BG), and their connections play an important role in pathophysiology of various movement disorders (like Parkinson's disease and atypical parkinsonian syndromes) or neurodevelopmental disorders (like autism). The contributions from individual distinguished speakers cover the neuroanatomical research of complex networks, neuroimaging data showing that the cerebellum and BG are connected to a wide range of other central nervous system structures involved in movement control. Especially, the cerebellum plays a more complex role in how the brain functions than previously thought.
Goch, Caspar J; Stieltjes, Bram; Henze, Romy; Hering, Jan; Poustka, Luise; Meinzer, Hans-Peter; Maier-Hein, Klaus H
Diagnosis of autism spectrum disorders (ASD) is difficult, as symptoms vary greatly and are difficult to quantify objectively. Recent work has focused on the assessment of non-invasive diffusion tensor imaging-based biomarkers that reflect the microstructural characteristics of neuronal pathways in the brain. While tractography-based approaches typically analyze specific structures of interest, a graph-based large-scale network analysis of the connectome can yield comprehensive measures of larger-scale architectural patterns in the brain. Commonly applied global network indices, however, do not provide any specificity with respect to functional areas or anatomical structures. Aim of this work was to assess the concept of network centrality as a tool to perform locally specific analysis without disregarding the global network architecture and compare it to other popular network indices. We create connectome networks from fiber tractographies and parcellations of the human brain and compute global network indices as well as local indices for Wernicke's Area, Broca's Area and the Motor Cortex. Our approach was evaluated on 18 children suffering from ASD and 18 typically developed controls using magnetic resonance imaging-based cortical parcellations in combination with diffusion tensor imaging tractography. We show that the network centrality of Wernicke's area is significantly (palterations. This could reflect the reduced capacity for comprehension of language in ASD. The betweenness centrality could potentially be an important metric in the development of future diagnostic tools in the clinical context of ASD diagnosis. Our results further demonstrate the applicability of large-scale network analysis tools in the domain of region-specific analysis with a potential application in many different psychological disorders.
Rommelse, N.N.J.; Franke, B.; Geurts, H.M.; Hartman, C.A.; Buitelaar, J.K.
Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates both disorders co-occur with a high frequency, in 20-50% of children with ADHD meeting criteria for ASD and in 30-80% of ASD children meeting
Rommelse, N.N.J.; Franke, B.; Geurts, H.M.; Hartman, C.A.; Buitelaar, J.K.
Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates both disorders co-occur with a high frequency, in 20-50% of children with ADHD meeting criteria for ASD and in 30-80% of ASD children meeting
Rommelse, Nanda N. J.; Franke, Barbara; Geurts, Hilde M.; Hartman, Catharina A.; Buitelaar, Jan K.
Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders. Evidence indicates both disorders co-occur with a high frequency, in 20-50% of children with ADHD meeting criteria for ASD and in 30-80% of ASD children meeting
Vaibhav A. Diwadkar
Full Text Available Abnormalities in the brain’s attention network may represent early identifiable neurobiological impairments in individuals at increased risk for schizophrenia or bipolar disorder. Here we provide evidence of dysfunctional regional and network function in adolescents at higher genetic risk for schizophrenia or bipolar disorder (henceforth HGR. During fMRI, participants engaged in a sustained attention task with variable demands. The task alternated between attention (120 s, visual control (passive viewing; 120 s and rest (20 s epochs. Low and high demand attention conditions were created using the rapid presentation of 2- or 3-digit numbers. Subjects were required to detect repeated presentation of numbers. We demonstrate that the recruitment of cortical and striatal regions are disordered in HGR: Relative to typical controls (TC, HGR showed lower recruitment of the dorsal prefrontal cortex, but higher recruitment of the superior parietal cortex. This imbalance was more dramatic in the basal ganglia. There, a group by task demand interaction was observed, such that increased attention demand led to increased engagement in TC, but disengagement in HGR. These activation studies were complemented by network analyses using Dynamic Causal Modeling. Competing model architectures were assessed across a network of cortical-striatal regions, distinguished at a second level using random effects Bayesian model selection. In the winning architecture, HGR were characterized by significant reductions in coupling across both frontal-striatal and frontal-parietal pathways. The effective connectivity analyses indicate emergent network dysconnection, consistent with findings in patients with schizophrenia. Emergent patterns of regional dysfunction and disconnection in cortical-striatal pathways may provide functional biological signatures in the adolescent risk state for psychiatric illness.
Pasiali, Varvara; LaGasse, A Blythe; Penn, Saundra L
Given the effect of musical training on the rate and accuracy of processing auditory information, therapeutic uses of music may potentially have remedial benefits for individuals with neurodevelopmental deficits. However, additional studies are needed to establish efficacy of music therapy interventions for attention skills in children/adolescents with neurodevelopmental disabilities including those with Autism Spectrum Disorders (ASD). To establish feasibility and preliminary efficacy of a group music therapy protocol to improve attention skills (sustained, selective, attentional control/switching) in adolescents diagnosed with autism and/or developmental delays. This single group pretest/posttest study took place in a private school for high functioning adolescents with neurodevelopmental delays. Nine students (4 males, 5 females), ages 13 to 20, participated in the study. Autism severity was assessed using the CARS2-HF and indicated the following distribution for study participants: severe (n = 3), mild (n = 4), or minimal/no (n = 2) symptoms. We assessed feasibility of implementing a 45-min Musical Attention Control Training (MACT) intervention delivered by a board-certified music therapist eight times over 6 weeks in a school setting. We also examined preliminary efficacy of the MACT to improve attention skills using the Test of Everyday Attention for Children (TEA-Ch). Parental consent rate was 100%. All nine participants successfully completed testing measures and 6 weeks of the intervention. Average participation rate was 97%. Data analysis showed positive trends and improvements on measures of attentional control/switching and selective attention. The results showed that the intervention and testing measures were feasible to implement and acceptable to the participants who all completed the protocol. Data analysis demonstrated positive trends indicating that more research on the use of music therapy attention training in high-functioning adolescents with
Wolf, Lorraine E., Ed.; Schreiber, Hope E., Ed.; Wasserstein, Jeanette, Ed.
Recent advances in neuroimaging and genetics technologies have enhanced our understanding of neurodevelopmental disorders in adults. The authors in this volume not only discuss such advances as they apply to adults with learning disorders, but also address their translation into clinical practice. One cluster of chapters addresses developmental…
Osborn, D A
Observational studies have shown an association between transiently low thyroid hormone levels in preterm infants in the first weeks of life (transient hypothyroxemia) and an abnormal neurodevelopmental outcome. Thyroid hormone therapy might prevent this morbidity. To assess whether thyroid hormone therapy in preterm infants without congenital hypothyroidism results in clinically important changes in neonatal and long term outcomes in terms of both benefits and harms. The standard search strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register, MEDLINE, previous reviews including cross references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching in the English language. All trials using random or quasi-random patient allocation, in which thyroid hormone therapy (either treatment or prophylaxis) was compared to a control in premature infants. Primary clinical outcomes included measures of neurodevelopmental outcome and mortality. Assessment of trial quality, data extraction and synthesis of data, using relative risk (RR) and weighted mean difference (WMD), were performed using standard methods of the Cochrane Collaboration and its Neonatal Review Group. Eight studies were identified that compared thyroid hormone treatment to control. Four randomized or quasi-randomized studies met inclusion criteria (Chowdhry 1984, Amato 1989, van Wassenaer 1997 and Vanhole 1997). All studies enrolled preterm infants thyroid hormones. Three studies used thyroxine, whereas Amato 1989 used triiodothyronine. Only two studies with neurodevelopmental follow-up were of good methodology (van Wassenaer 1997 and Vanhole 1997). All studies were of small size with the largest, van Wassenaer 1997, enrolling 200 infants. A lack of comparability of data (neurodevelopmental test or timing of follow-up) prevented meta-analytic pooling of the studies for
Ma, Xinpei; Sayama, Hiroki
Recent research has established both a theoretical basis and strong empirical evidence that effective social behavior plays a beneficial role in the maintenance of physical and psychological well-being of people. To test whether social behavior and well-being are also associated in online communities, we studied the correlations between the recovery of patients with mental disorders and their behaviors in online social media. As the source of the data related to the social behavior and progress of mental recovery, we used PatientsLikeMe (PLM), the world's first open-participation research platform for the development of patient-centered health outcome measures. We first constructed an online social network structure based on patient-to-patient ties among 200 patients obtained from PLM. We then characterized patients' online social activities by measuring the numbers of "posts and views" and "helpful marks" each patient obtained. The patients' recovery data were obtained from their self-reported status information that was also available on PLM. We found that some node properties (in-degree, eigenvector centrality and PageRank) and the two online social activity measures were significantly correlated with patients' recovery. Furthermore, we re-collected the patients' recovery data two months after the first data collection. We found significant correlations between the patients' social behaviors and the second recovery data, which were collected two months apart. Our results indicated that social interactions in online communities such as PLM were significantly associated with the current and future recoveries of patients with mental disorders.
Full Text Available Recent research has established both a theoretical basis and strong empirical evidence that effective social behavior plays a beneficial role in the maintenance of physical and psychological well-being of people. To test whether social behavior and well-being are also associated in online communities, we studied the correlations between the recovery of patients with mental disorders and their behaviors in online social media. As the source of the data related to the social behavior and progress of mental recovery, we used PatientsLikeMe (PLM, the world’s first open-participation research platform for the development of patient-centered health outcome measures. We first constructed an online social network structure based on patient-to-patient ties among 200 patients obtained from PLM. We then characterized patients’ online social activities by measuring the numbers of “posts and views” and “helpful marks” each patient obtained. The patients’ recovery data were obtained from their self-reported status information that was also available on PLM. We found that some node properties (in-degree, eigenvector centrality and PageRank and the two online social activity measures were significantly correlated with patients’ recovery. Furthermore, we re-collected the patients’ recovery data two months after the first data collection. We found significant correlations between the patients’ social behaviors and the second recovery data, which were collected two months apart. Our results indicated that social interactions in online communities such as PLM were significantly associated with the current and future recoveries of patients with mental disorders.
Fang, Jiliang; Rong, Peijing; Hong, Yang; Fan, Yangyang; Liu, Jun; Wang, Honghong; Zhang, Guolei; Chen, Xiaoyan; Shi, Shan; Wang, Liping; Liu, Rupeng; Hwang, Jiwon; Li, Zhengjie; Tao, Jing; Wang, Yang; Zhu, Bing; Kong, Jian
Depression is the most common form of mental disorder in community and health care settings and current treatments are far from satisfactory. Vagus nerve stimulation (VNS) is a Food and Drug Administration approved somatic treatment for treatment-resistant depression. However, the involvement of surgery has limited VNS only to patients who have failed to respond to multiple treatment options. Transcutaneous VNS (tVNS) is a relatively new, noninvasive VNS method based on the rationale that there is afferent/efferent vagus nerve distribution on the surface of the ear. The safe and low-cost characteristics of tVNS have the potential to significantly expand the clinical application of VNS. In this study, we investigated how tVNS can modulate the default mode network (DMN) functional connectivity (FC) in mild or moderate major depressive disorder (MDD) patients. Forty-nine MDD patients were recruited and received tVNS or sham tVNS (stVNS) treatments. Thirty-four patients completed the study and were included in data analysis. After 1 month of tVNS treatment, the 24-item Hamilton Depression Rating Scale score reduced significantly in the tVNS group as compared with the stVNS group. The FC between the DMN and anterior insula and parahippocampus decreased; the FC between the DMN and precuneus and orbital prefrontal cortex increased compared with stVNS. All these FC increases are also associated with 24-item Hamilton Depression Rating Scale reduction. tVNS can significantly modulate the DMN FC of MDD patients; our results provide insights to elucidate the brain mechanism of tVNS treatment for MDD patients. Copyright © 2016. Published by Elsevier Inc.
Evaluation of a methodology for a collaborative multiple source surveillance network for autism spectrum disorders--Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2002.
Van Naarden Braun, Kim; Pettygrove, Sydney; Daniels, Julie; Miller, Lisa; Nicholas, Joyce; Baio, Jon; Schieve, Laura; Kirby, Russell S; Washington, Anita; Brocksen, Sally; Rahbar, Hossein; Rice, Catherine
Autism spectrum disorders (ASDs) encompass a spectrum of conditions, including autistic disorder; pervasive developmental disorders, not otherwise specified (PDD-NOS); and Asperger disorder. Impairments associated with ASDs can range from mild to severe. In 2000, in response to increasing public heath concern regarding ASDs, CDC established the Autism and Developmental Disabilities Monitoring (ADDM) Network. The primary objective of this ongoing surveillance system is to track the prevalence and characteristics of ASDs in the United States. ADDM data are useful to understand the prevalence of ASDs and have implications for improved identification, health and education service planning, and intervention for children with ASDs. Because complete, valid, timely, and representative prevalence estimates are essential to inform public health responses to ASDs, evaluating the effectiveness and efficiency of the ADDM methodology is needed to determine how well these methods meet the network's objective. 2002. The ADDM Network is a multiple-source, population-based, active system for monitoring ASDs and other developmental disabilities. In 2002, data were collected from 14 collaborative sites. This report describes an evaluation conducted using guidelines established by CDC for evaluating public health surveillance systems and is based on examination of the following characteristics of the ADDM Network surveillance system: simplicity, flexibility, data quality, acceptability, representativeness, sensitivity, predictive value positive (PVP), timeliness, stability, data confidentiality and security, and sources of variability. Using multiple sources for case ascertainment strengthens the system's representativeness, sensitivity, and flexibility, and the clinician review process aims to bolster PVP. Sensitivity and PVP are difficult to measure, but the ADDM methodology provides the best possible estimate currently available of prevalence of ASDs without conducting complete
This study investigated the applicability of a Bayesian belief network (BBN) to MR images to diagnose temporomandibular disorders (TMDs). Our aim was to determine the progression of TMDs, focusing on how each finding affects the other. We selected 1.5-T MRI findings (33 variables) and diagnoses (bone changes and disc displacement) of patients with TMD from 2007 to 2008. There were a total of 295 cases with 590 sides of temporomandibular joints (TMJs). The data were modified according to the research diagnostic criteria of TMD. We compared the accuracy of the BBN using 11 algorithms (necessary path condition, path condition, greedy search-and-score with Bayesian information criterion, Chow-Liu tree, Rebane-Pearl poly tree, tree augmented naïve Bayes model, maximum log likelihood, Akaike information criterion, minimum description length, K2 and C4.5), a multiple regression analysis and an artificial neural network using resubstitution validation and 10-fold cross-validation. There were 191 TMJs (32.4%) with bone changes and 340 (57.6%) with articular disc displacement. The BBN path condition algorithm using resubstitution validation and 10-fold cross-validation was >99% accurate. However, the main advantage of a BBN is that it can represent the causal relationships between different findings and assign conditional probabilities, which can then be used to interpret the progression of TMD. Osteoarthritic bone changes progressed from condyle to articular fossa and finally to mandibular bone contours. Disc displacement was directly related to severe bone changes. Early bone changes were not directly related to disc displacement. TMJ functional factors (condylar translation, bony space and disc form) and age mediated between bone changes and disc displacement.
Armour, Cherie; Fried, Eiko I; Deserno, Marie K; Tsai, Jack; Pietrzak, Robert H
Recent developments in psychometrics enable the application of network models to analyze psychological disorders, such as PTSD. Instead of understanding symptoms as indicators of an underlying common cause, this approach suggests symptoms co-occur in syndromes due to causal interactions. The current study has two goals: (1) examine the network structure among the 20 DSM-5 PTSD symptoms, and (2) incorporate clinically relevant variables to the network to investigate whether PTSD symptoms exhibit differential relationships with suicidal ideation, depression, anxiety, physical functioning/quality of life (QoL), mental functioning/QoL, age, and sex. We utilized a nationally representative U.S. military veteran's sample; and analyzed the data from a subsample of 221 veterans who reported clinically significant DSM-5 PTSD symptoms. Networks were estimated using state-of-the-art regularized partial correlation models. Data and code are published along with the paper. The 20-item DSM-5 PTSD network revealed that symptoms were positively connected within the network. Especially strong connections emerged between nightmares and flashbacks; blame of self or others and negative trauma-related emotions, detachment and restricted affect; and hypervigilance and exaggerated startle response. The most central symptoms were negative trauma-related emotions, flashbacks, detachment, and physiological cue reactivity. Incorporation of clinically relevant covariates into the network revealed paths between self-destructive behavior and suicidal ideation; concentration difficulties and anxiety, depression, and mental QoL; and depression and restricted affect. These results demonstrate the utility of a network approach in modeling the structure of DSM-5 PTSD symptoms, and suggest differential associations between specific DSM-5 PTSD symptoms and clinical outcomes in trauma survivors. Implications of these results for informing the assessment and treatment of this disorder, are discussed
Kocovska, E.; Puckering, C; Follan, M.; Smillie, M.; Gorski, C.; Lidstone, E; Pritchett, R.; Hockaday, H.; Minnis, H.
We aimed to explore the extent of neurodevelopmental difficulties in severely maltreated adopted children. We recruited 34 adopted children, referred with symptoms of indiscriminate friendliness and a history of severe maltreatment in their early childhood and 32 typically developing comparison children without such a history, living in biological families. All 66 children, aged 5–12 years, underwent a detailed neuropsychiatric assessment. The overwhelming majority of the adopted/indiscrimina...
Full Text Available Cognitive symptoms are core features of mental disorders but procognitive treatments are limited. We have proposed a ‘discoordination’ hypothesis that cognitive impairment results from aberrant coordination of neural activity. We reported that neonatal ventral hippocampus lesion (NVHL rats, an established neurodevelopmental model of schizophrenia, have abnormal neural synchrony and cognitive deficits in the active place avoidance task. During stillness, we observed that cortical local field potentials sometimes resembled epileptiform spike-wave discharges with higher prevalence in NVHL rats, indicating abnormal neural synchrony due perhaps to imbalanced excitation-inhibition coupling. Here, within the context of the hypothesis, we investigated whether attenuating abnormal neural synchrony will improve cognition in NVHL rats. We report that 1 interhippocampal synchrony in the theta and beta bands is correlated with active place avoidance performance; 2 the anticonvulsant ethosuximide attenuated the abnormal spike-wave activity, improved cognitive control, and reduced hyperlocomotion; 3 ethosuximide normalized the task-associated theta and beta synchrony between the two hippocampi but also increased synchrony between the medial prefrontal cortex and hippocampus above control levels; 4 the antipsychotic olanzapine was less effective at improving cognitive control and normalizing place avoidance-related inter-hippocampal neural synchrony, although it reduced hyperactivity; and 5 olanzapine caused an abnormal pattern of frequency-independent increases in neural synchrony, in both NVHL and control rats. These data suggest that normalizing aberrant neural synchrony can be beneficial and that drugs targeting the pathophysiology of abnormally coordinated neural activities may be a promising theoretical framework and strategy for developing treatments that improve cognition in neurodevelopmental disorders such as schizophrenia.
Full Text Available The neurological complications of AIDS (neuroAIDS during the infection of human immunodeficiency virus (HIV are symptomized by non-specific, multifaceted neurological conditions and therefore, defining a specific diagnosis/treatment mechanism(s for this neuro-complexity at the molecular level remains elusive. Using an in silico based integrated gene network analysis we discovered that HIV infection shares convergent gene networks with each of twelve neurological disorders selected in this study. Importantly, a common gene network was identified among HIV infection, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and age macular degeneration. An mRNA microarray analysis in HIV-infected monocytes showed significant changes in the expression of several genes of this in silico derived common pathway which suggests the possible physiological relevance of this gene-circuit in driving neuroAIDS condition. Further, this unique gene network was compared with another in silico derived novel, convergent gene network which is shared by seven major neurological disorders (Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Age Macular Degeneration, Amyotrophic Lateral Sclerosis, Vascular Dementia, and Restless Leg Syndrome. These networks differed in their gene circuits; however, in large, they involved innate immunity signaling pathways, which suggests commonalities in the immunological basis of different neuropathogenesis. The common gene circuits reported here can provide a prospective platform to understand how gene-circuits belonging to other neuro-disorders may be convoluted during real-time neuroAIDS condition and it may elucidate the underlying-and so far unknown-genetic overlap between HIV infection and neuroAIDS risk. Also, it may lead to a new paradigm in understanding disease progression, identifying biomarkers, and developing therapies.
Zhu, Hongru; Qiu, Changjian; Meng, Yajing; Yuan, Minlan; Zhang, Yan; Ren, Zhengjia; Li, Yuchen; Huang, Xiaoqi; Gong, Qiyong; Lui, Su; Zhang, Wei
Recent studies involving connectome analysis including graph theory have yielded potential biomarkers for mental disorders. In this study, we aimed to investigate the differences of resting-state network between patients with social anxiety disorder (SAD) and healthy controls (HCs), as well as to distinguish between individual subjects using topological properties. In total, 42 SAD patients and the same number of HCs underwent resting functional MRI, and the topological organization of the whole-brain functional network was calculated using graph theory. Compared with the controls, the patients showed a decrease in 49 positive connections. In the topological analysis, the patients showed an increase in the area under the curve (AUC) of the global shortest path length of the network (Lp) and a decrease in the AUC of the global clustering coefficient of the network (Cp). Furthermore, the AUCs of Lp and Cp were used to effectively discriminate the individual SAD patients from the HCs with high accuracy. This study revealed that the neural networks of the SAD patients showed changes in topological characteristics, and these changes were prominent not only in both groups but also at the individual level. This study provides a new perspective for the identification of patients with SAD. PMID:28266518
Konigs, A.; Kiliaan, A.J.
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. The classical treatment of ADHD where stimulant medication is used has revealed severe side effects and intolerance. Consequently, the demand to search for alternative treatment has increased rapidly. When
Li, Yanwei; Yu, Dongchuan
Functional near infrared spectroscopy (fNIRS) is particularly suited for the young population and ecological measurement. However, thus far, not enough effort has been given to the clinical diagnosis of young children with Autism Spectrum Disorder (ASD) by using fNIRS. The current study provided some insights into the quantitative analysis of functional networks in young children (ages 4.8-8.0years old) with and without ASD and, in particular, investigated the network efficiency and lobe-level connectivity of their functional networks while watching a cartoon. The main results included that: (i) Weak network efficiency was observed in young children with ASD, even for a wide range of threshold for the binarization of functional networks; (ii) A maximum classification accuracy rate of 83.3% was obtained for all participants by using the k-means clustering method with network efficiencies as the feature parameters; and (iii) Weak lobe-level inter-region connections were uncovered in the right prefrontal cortex, including its linkages with the left prefrontal cortex and the bilateral temporal cortex. Such results indicate that the right prefrontal cortex might make a major contribution to the psychopathology of young children with ASD at the functional network architecture level, and at the functional lobe-connectivity level, respectively. Copyright © 2016 Elsevier Inc. All rights reserved.
Yerys, Benjamin E; Gordon, Evan M; Abrams, Danielle N; Satterthwaite, Theodore D; Weinblatt, Rachel; Jankowski, Kathryn F; Strang, John; Kenworthy, Lauren; Gaillard, William D; Vaidya, Chandan J
Functional pathology of the default mode network is posited to be central to social-cognitive impairment in autism spectrum disorders (ASD). Altered functional connectivity of the default mode network's midline core may be a potential endophenotype for social deficits in ASD. Generalizability from prior studies is limited by inclusion of medicated participants and by methods favoring restricted examination of network function. This study measured resting-state functional connectivity in 22 8-13 year-old non-medicated children with ASD and 22 typically developing controls using seed-based and network segregation functional connectivity methods. Relative to controls the ASD group showed both under- and over-functional connectivity within default mode and non-default mode regions, respectively. ASD symptoms correlated negatively with the connection strength of the default mode midline core-medial prefrontal cortex-posterior cingulate cortex. Network segregation analysis with the participation coefficient showed a higher area under the curve for the ASD group. Our findings demonstrate that the default mode network in ASD shows a pattern of poor segregation with both functional connectivity metrics. This study confirms the potential for the functional connection of the midline core as an endophenotype for social deficits. Poor segregation of the default mode network is consistent with an excitation/inhibition imbalance model of ASD.
Shedden-Mora, Meike; Lau, Katharina; Kuby, Amina; Groß, Beatrice; Gladigau, Maria; Fabisch, Alexandra; Löwe, Bernd
The management of somatoform disorders in primary care is often limited due to low diagnostic accuracy, delayed referral to psychotherapy and overuse of health care. To address these difficulties, this study aimed to establish a collaborative stepped health care network (Sofu-Net). Sofu-Net was established among 41 primary care physicians, 35 psychotherapists and 8 mental health clinics. Baseline assessment in primary care showed elevated psychopathology and deficits in health care among patients with somatoform symptoms. Network partners provided positive evaluations of Sofu-Net. © Georg Thieme Verlag KG Stuttgart · New York.