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Sample records for neurodevelopmental disorder arnd

  1. Neurodevelopmental functioning in children with FAS, pFAS, and ARND.

    Science.gov (United States)

    Chasnoff, Ira J; Wells, Anne M; Telford, Erin; Schmidt, Christine; Messer, Gwendolyn

    2010-04-01

    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.

  2. ACE: Health - Neurodevelopmental Disorders

    Science.gov (United States)

    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.

  3. Sleep in Neurodevelopmental Disorders

    Science.gov (United States)

    Esbensen, Anna J; Schwichtenberg, Amy J

    2017-01-01

    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

  4. Treatments for Neurodevelopmental Disorders

    DEFF Research Database (Denmark)

    Di Pietro, Nina C; Whiteley, Louise Emma; Mizgalewicz, Ania

    2013-01-01

    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....

  5. Reversing Neurodevelopmental Disorders in Adults

    National Research Council Canada - National Science Library

    Ehninger, Dan; Li, Weidong; Fox, Kevin; Stryker, Michael P; Silva, Alcino J

    2008-01-01

    .... 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...

  6. PURA-related neurodevelopmental disorders

    OpenAIRE

    Reijnders, Margot R F; Leventer, Richard J; Lee, Boo Hon; Baralle, Diana; Selber, Paulo; Paciorkowski, Alex R; Hunt, David

    2017-01-01

    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...

  7. Drug development for neurodevelopmental disorders

    DEFF Research Database (Denmark)

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

    2018-01-01

    Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong cognitive and behavioural deficits and represent a major public health burden. FXS is the most frequent monogenic form of intellectual disability and autism, and the underlying pathophysiology linked to its causal gene...

  8. Sleep in Neurodevelopmental and Neurodegenerative Disorders.

    Science.gov (United States)

    Kotagal, Suresh

    2015-06-01

    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.

  9. Emerging pharmacotherapies for neurodevelopmental disorders.

    Science.gov (United States)

    Wetmore, Daniel Z; Garner, Craig C

    2010-09-01

    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.

  10. Amelioration of fetal alcohol-related neurodevelopmental disorders in rats: exploring pharmacological and environmental treatments.

    Science.gov (United States)

    Hannigan, J H; Berman, R F

    2000-01-01

    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.

  11. Antisocial Personality as a Neurodevelopmental Disorder.

    Science.gov (United States)

    Raine, Adrian

    2018-01-25

    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.

  12. School Neuropsychology Consultation in Neurodevelopmental Disorders

    Science.gov (United States)

    Decker, Scott L.

    2008-01-01

    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…

  13. Drosophila Modeling of Heritable Neurodevelopmental Disorders

    OpenAIRE

    Gatto, Cheryl L.; Broadie, Kendal

    2011-01-01

    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...

  14. Mental disorders, brain disorders, neurodevelopmental disorders ...

    African Journals Online (AJOL)

    . 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 ...

  15. Histone Lysine Methylation and Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Jeong-Hoon Kim

    2017-06-01

    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.

  16. The cerebellum and neurodevelopmental disorders

    Science.gov (United States)

    Stoodley, Catherine J.

    2015-01-01

    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

  17. The Cerebellum and Neurodevelopmental Disorders.

    Science.gov (United States)

    Stoodley, Catherine J

    2016-02-01

    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.

  18. Drosophila modeling of heritable neurodevelopmental disorders.

    Science.gov (United States)

    Gatto, Cheryl L; Broadie, Kendal

    2011-12-01

    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.

  19. Which neurodevelopmental disorders get researched and why?

    Science.gov (United States)

    Bishop, Dorothy V M

    2010-11-30

    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.

  20. Which neurodevelopmental disorders get researched and why?

    Directory of Open Access Journals (Sweden)

    Dorothy V M Bishop

    2010-11-01

    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.

  1. Complex Neurodevelopmental Disorders And Their Genetic Etiologies

    Directory of Open Access Journals (Sweden)

    Amna Batool

    2015-08-01

    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.

  2. Conceptualising compensation in neurodevelopmental disorders: Reflections from autism spectrum disorder.

    Science.gov (United States)

    Livingston, Lucy Anne; Happé, Francesca

    2017-06-19

    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.

  3. Yield of additional metabolic studies in neurodevelopmental disorders

    NARCIS (Netherlands)

    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

  4. Cross Talk: The Microbiota and Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    John R. Kelly

    2017-09-01

    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.

  5. Cross Talk: The Microbiota and Neurodevelopmental Disorders

    Science.gov (United States)

    Kelly, John R.; Minuto, Chiara; Cryan, John F.; Clarke, Gerard; Dinan, Timothy G.

    2017-01-01

    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

  6. Food allergy and food-based therapies in neurodevelopmental disorders

    NARCIS (Netherlands)

    De Theije, Caroline G M; Bavelaar, Bas M.; Lopes da Silva, Sofia; Korte, Sijmen Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D.

    2014-01-01

    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

  7. Management of sleep disorders in neurodevelopmental disorders and genetic syndromes.

    Science.gov (United States)

    Heussler, Helen S

    2016-03-01

    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.

  8. GABAergic circuit dysfunctions in neurodevelopmental disorders

    Directory of Open Access Journals (Sweden)

    Bidisha eChattopadhyaya

    2012-05-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Nguyen Quoc Vuong Tran

    2017-01-01

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

  10. Increased nuchal translucency thickness and risk of neurodevelopmental disorders

    DEFF Research Database (Denmark)

    Hellmuth, S G; Pedersen, L H; Miltoft, C B

    2017-01-01

    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...

  11. Neurodevelopmental disorders in children with neurofibromatosis type 1.

    Science.gov (United States)

    Vogel, Alecia C; Gutmann, David H; Morris, Stephanie M

    2017-11-01

    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.

  12. Intellectual Profiles in the Autism Spectrum and Other Neurodevelopmental Disorders

    Science.gov (United States)

    Mouga, Susana; Café, Cátia; Almeida, Joana; Marques, Carla; Duque, Frederico; Oliveira, Guiomar

    2016-01-01

    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…

  13. Adaptive Profiles in Autism and Other Neurodevelopmental Disorders

    Science.gov (United States)

    Mouga, Susana; Almeida, Joana; Café, Cátia; Duque, Frederico; Oliveira, Guiomar

    2015-01-01

    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…

  14. A compensatory role for declarative memory in neurodevelopmental disorders.

    Science.gov (United States)

    Ullman, Michael T; Pullman, Mariel Y

    2015-04-01

    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.

  15. Food allergy and food-based therapies in neurodevelopmental disorders.

    Science.gov (United States)

    de Theije, Caroline G M; Bavelaar, Bas M; Lopes da Silva, Sofia; Korte, Sijmen Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D

    2014-05-01

    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.

  16. Epigenetic and transgenerational mechanisms in infection-mediated neurodevelopmental disorders.

    Science.gov (United States)

    Weber-Stadlbauer, U

    2017-05-02

    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.

  17. Genetics and Function of Neocortical GABAergic Interneurons in Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    E. Rossignol

    2011-01-01

    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.

  18. Epigenetic Mechanisms and Therapeutic Perspectives for Neurodevelopmental Disorders

    OpenAIRE

    Kubota, Takeo; Takae, Hirasawa; Miyake, Kunio

    2012-01-01

    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...

  19. Family adjustment and interventions in neurodevelopmental disorders.

    Science.gov (United States)

    Dykens, Elisabeth M

    2015-03-01

    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.

  20. Translational animal models of autism and neurodevelopmental disorders.

    Science.gov (United States)

    Crawley, Jacqueline N

    2012-09-01

    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.

  1. Defects in autophagosome-lysosome fusion underlie Vici syndrome, a neurodevelopmental disorder with multisystem involvement

    National Research Council Canada - National Science Library

    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

    2017-01-01

    Vici syndrome (VICIS) is a rare, autosomal recessive neurodevelopmental disorder with multisystem involvement characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency...

  2. "Too Withdrawn" or "Too Friendly": Considering Social Vulnerability in Two Neuro-Developmental Disorders

    Science.gov (United States)

    Jawaid, A.; Riby, D. M.; Owens, J.; White, S. W.; Tarar, T.; Schulz, P. E.

    2012-01-01

    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…

  3. Epigenetic Mechanisms and Therapeutic Perspectives for Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Kunio Miyake

    2012-04-01

    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.

  4. Het hoofdstuk 'neurodevelopmental disorders' in de DSM-5 [DSM-5: neurodevelopmental disorders

    NARCIS (Netherlands)

    Zinkstok, J.; Buitelaar, J.

    2014-01-01

    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

  5. Paradoxical Benzodiazepine Response: A Rationale for Bumetanide in Neurodevelopmental Disorders?

    Science.gov (United States)

    Bruining, Hilgo; Passtoors, Laurien; Goriounova, Natalia; Jansen, Floor; Hakvoort, Britt; de Jonge, Maretha; Poil, Simon-Shlomo

    2015-08-01

    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.

  6. Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders

    Directory of Open Access Journals (Sweden)

    Alberto J Lopez

    2015-04-01

    Full Text Available It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, schizophrenia, and Autism Spectrum Disorder. Together, these human developmental and intellectual disability disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.

  7. Understanding autism and other neurodevelopmental disorders through experimental translational neurobehavioral models

    NARCIS (Netherlands)

    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.

    2016-01-01

    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,

  8. Neurodevelopmental disorders are highly over-represented in children with obesity: A cross-sectional study.

    Science.gov (United States)

    Wentz, Elisabet; Björk, Anna; Dahlgren, Jovanna

    2017-01-01

    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.

  9. Impact of clinical exomes in neurodevelopmental and neurometabolic disorders.

    Science.gov (United States)

    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

    2017-08-01

    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.

  10. Participation in Physical Activity for Children with Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Rubab G. Arim

    2012-01-01

    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.

  11. Rapamycin Prevents Seizures After Depletion of STRADA in a Rare Neurodevelopmental Disorder

    NARCIS (Netherlands)

    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.

    2013-01-01

    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

  12. Relationship between motor coordination, cognitive abilities, and academic achievement in Japanese children with neurodevelopmental disorders

    Directory of Open Access Journals (Sweden)

    Takuya Higashionna

    2017-12-01

    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.

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

    Science.gov (United States)

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

    2015-01-01

    The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcription factors, guidance cues and other regulatory molecules and requires the intricate and temporal orchestration of a number of developmental processes. Disturbance or failure of any of these processes causing neurodevelopmental abnormalities within the PFC may contribute to several of the cognitive deficits seen in patients with neurodevelopmental disorders. In this review, we elaborate on the specific processes underlying prefrontal development, such as induction and patterning of the prefrontal area, proliferation, migration and axonal guidance of medial prefrontal progenitors, and their eventual efferent and afferent connections. We furthermore integrate for the first time the available knowledge from genome-wide studies that have revealed genes linked to neurodevelopmental disorders with experimental molecular evidence in rodents. The integrated data suggest that the pathogenic variants in the neurodevelopmental disorder-associated genes induce prefrontal cytoarchitectonical impairments. This enhances our understanding of the molecular mechanisms of prefrontal (mis)development underlying the four major neurodevelopmental disorders in humans, that is, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder and schizophrenia, and may thus provide clues for the development of novel therapies. PMID:25450230

  14. Social neuroscience, empathy, brain integration, and neurodevelopmental disorders.

    Science.gov (United States)

    Harris, James C

    2003-08-01

    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.

  15. Influenza vaccination in children with neurologic or neurodevelopmental disorders.

    Science.gov (United States)

    Smith, Michael; Peacock, Georgina; Uyeki, Timothy M; Moore, Cynthia

    2015-05-11

    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

  16. Neurodevelopmental origins of bipolar disorder: iPSC models.

    Science.gov (United States)

    O'Shea, K Sue; McInnis, Melvin G

    2016-06-01

    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.

  17. Practitioner Review: Multilingualism and neurodevelopmental disorders - an overview of recent research and discussion of clinical implications.

    Science.gov (United States)

    Uljarević, Mirko; Katsos, Napoleon; Hudry, Kristelle; Gibson, Jenny L

    2016-11-01

    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

  18. Boys with Asperger Syndrome Grow Up: Psychiatric and Neurodevelopmental Disorders 20 Years After Initial Diagnosis.

    Science.gov (United States)

    Gillberg, I Carina; Helles, Adam; Billstedt, Eva; Gillberg, Christopher

    2016-01-01

    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.

  19. Neurodevelopmental disorders in children born to mothers with systemic lupus erythematosus.

    Science.gov (United States)

    Vinet, É; Pineau, C A; Clarke, A E; Fombonne, É; Platt, R W; Bernatsky, S

    2014-10-01

    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.

  20. Lessons Learned: Engaging Culturally Diverse Families in Neurodevelopmental Disorders Intervention Research

    Science.gov (United States)

    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.

    2017-01-01

    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…

  1. Neurobiological Circuits Regulating Attention, Cognitive Control, Motivation, and Emotion: Disruptions in Neurodevelopmental Psychiatric Disorders

    Science.gov (United States)

    Arnsten, Amy F. T.; Rubia, Katya

    2012-01-01

    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,…

  2. Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome.

    Science.gov (United States)

    Fung, Lawrence K; Quintin, Eve-Marie; Haas, Brian W; Reiss, Allan L

    2012-04-01

    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.

  3. Adaptation of the "ten questions" to screen for autism and other neurodevelopmental disorders in Uganda.

    Science.gov (United States)

    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

    2014-05-01

    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.

  4. Genes, Gender, Environment, and Novel Functions of Estrogen Receptor Beta in the Susceptibility to Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Mukesh Varshney

    2017-02-01

    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.

  5. Learning curve analyses in neurodevelopmental disorders: are children with autism spectrum disorder truly visual learners?

    Science.gov (United States)

    Erdődi, Lászlό; Lajiness-O'Neill, Renée; Schmitt, Thomas A

    2013-04-01

    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.

  6. Neurodevelopmental Disorders in Children with Severe to Profound Sensorineural Hearing Loss: A Clinical Study

    Science.gov (United States)

    Chilosi, Anna M.; Comparini, Alessandro; Scusa, Maria F.; Berrettini, Stefano; Forli, Francesca; Battini, Roberta; Cipriani, Paola; Cioni, Giovanni

    2010-01-01

    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…

  7. Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

    Directory of Open Access Journals (Sweden)

    Dichter Gabriel S

    2012-07-01

    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.

  8. Management of Sleep Disorders in Children With Neurodevelopmental Disorders: A Review.

    Science.gov (United States)

    Blackmer, Allison Beck; Feinstein, James A

    2016-01-01

    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

  9. Motor Abnormalities: From Neurodevelopmental to Neurodegenerative Through "Functional" (Neuro)Psychiatric Disorders.

    Science.gov (United States)

    Peralta, Victor; Cuesta, Manuel J

    2017-09-01

    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.

  10. Boys with Asperger Syndrome Grow Up: Psychiatric and Neurodevelopmental Disorders 20 Years after Initial Diagnosis

    Science.gov (United States)

    Gillberg, I. Carina; Helles, Adam; Billstedt, Eva; Gillberg, Christopher

    2016-01-01

    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…

  11. Neurodevelopmental disorders: theoretical approaches and its implications for education and rehabilitation

    Directory of Open Access Journals (Sweden)

    Maria Luísa Bissoto

    2011-06-01

    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.

  12. Using Sibling Designs to Understand Neurodevelopmental Disorders: From Genes and Environments to Prevention Programming

    Directory of Open Access Journals (Sweden)

    Mark Wade

    2015-01-01

    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.

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

    LENUS (Irish Health Repository)

    Merikangas, Alison K

    2012-02-01

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

  14. Paradoxical Benzodiazepine Response : A Rationale for Bumetanide in Neurodevelopmental Disorders?

    NARCIS (Netherlands)

    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

  15. Paradoxical Benzodiazepine Response: A Rationale for Bumetanide in Neurodevelopmental Disorders?

    NARCIS (Netherlands)

    Bruining, H.; Passtoors, L.; Goriounova, N.A.; Jansen, F.; Hakvoort, B.; de Jonge, M.; Poil, S.S.

    2015-01-01

    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

  16. Treatments and services for neurodevelopmental disorders on advocacy websites: Information or evaluation?

    DEFF Research Database (Denmark)

    Di Pietro, Nina C; Whiteley, Louise Emma; Illes, Judy

    2011-01-01

    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...

  17. Defects in autophagosome-lysosome fusion underlie Vici syndrome, a neurodevelopmental disorder with multisystem involvement

    OpenAIRE

    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

    2017-01-01

    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...

  18. EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy

    OpenAIRE

    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

    2016-01-01

    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...

  19. Rapamycin Prevents Seizures After Depletion of STRADA in a Rare Neurodevelopmental Disorder

    OpenAIRE

    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.

    2013-01-01

    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...

  20. Early Prevention of Severe Neurodevelopmental Behavior Disorders: An Integration

    OpenAIRE

    Schroeder, Stephen R.; Courtemanche, Andrea

    2012-01-01

    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...

  1. Disparities in Canadian indigenous health research on neurodevelopmental disorders.

    Science.gov (United States)

    Di Pietro, Nina C; Illes, Judy

    2014-01-01

    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.

  2. Is Adult ADHD a Childhood-Onset Neurodevelopmental Disorder? Evidence From a Four-Decade Longitudinal Cohort Study

    National Research Council Canada - National Science Library

    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

    2015-01-01

    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...

  3. Minor physical anomalies in schizophrenia and bipolar I disorder and the neurodevelopmental continuum of psychosis.

    Science.gov (United States)

    Akabaliev, Valentin Hristov; Sivkov, Stefan Todorov; Mantarkov, Mladen Yordanov

    2014-09-01

    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.

  4. Examining and comparing social perception abilities across childhood-onset neurodevelopmental disorders.

    Science.gov (United States)

    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

    2015-06-01

    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.

  5. Neurodevelopmental origins of abnormal cortical morphology in dissociative identity disorder.

    Science.gov (United States)

    Reinders, A A T S; Chalavi, S; Schlumpf, Y R; Vissia, E M; Nijenhuis, E R S; Jäncke, L; Veltman, D J; Ecker, C

    2018-02-01

    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.

  6. [Neurodevelopmental disorders in response to hormonally active environmental pollutants].

    Science.gov (United States)

    Kajta, Małgorzata; Wójtowicz, Anna

    2010-01-01

    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

  7. Neurodevelopmental Hypothesis about the Etiology of Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Toshio Inui

    2017-07-01

    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.

  8. Biological mechanisms associated with increased perseveration and hyperactivity in a genetic mouse model of neurodevelopmental disorder.

    Science.gov (United States)

    Trent, Simon; Dean, Rachel; Veit, Bonnie; Cassano, Tommaso; Bedse, Gaurav; Ojarikre, Obah A; Humby, Trevor; Davies, William

    2013-08-01

    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.

  9. Elevated titanium levels in Iraqi children with neurodevelopmental disorders echo findings in occupation soldiers.

    Science.gov (United States)

    Savabieasfahani, M; Alaani, S; Tafash, M; Dastgiri, S; Al-Sabbak, M

    2015-01-01

    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.

  10. Autism spectrum disorder in a community-based sample with neurodevelopmental problems in Lagos, Nigeria

    Directory of Open Access Journals (Sweden)

    Yewande O. Oshodi

    2017-01-01

    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

  11. Prevalence and comorbidities of autism among children referred to the outpatient clinics for neurodevelopmental disorders.

    Science.gov (United States)

    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

    2016-01-01

    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.

  12. Stabilizing autism: A Fleckian account of the rise of a neurodevelopmental spectrum disorder.

    Science.gov (United States)

    Verhoeff, Berend

    2014-06-01

    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.

  13. "Selfish spermatogonial selection": a novel mechanism for the association between advanced paternal age and neurodevelopmental disorders.

    Science.gov (United States)

    Goriely, Anne; McGrath, John J; Hultman, Christina M; Wilkie, Andrew O M; Malaspina, Dolores

    2013-06-01

    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.

  14. Dermatoglyphics--a possible biomarker in the neurodevelopmental model for the origin of mental disorders.

    Science.gov (United States)

    Ahmed-Popova, Ferihan M; Mantarkov, Mladen J; Sivkov, Stefan T; Akabaliev, Valentin H

    2014-01-01

    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.

  15. Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders.

    Science.gov (United States)

    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

    2017-03-01

    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

  16. Neurodevelopmental disorders: cluster 2 of the proposed meta-structure for DSM-V and ICD-11.

    Science.gov (United States)

    Andrews, G; Pine, D S; Hobbs, M J; Anderson, T M; Sunderland, M

    2009-12-01

    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.

  17. Intragenic deletion of RBFOX1 associated with neurodevelopmental/neuropsychiatric disorders and possibly other clinical presentations

    Science.gov (United States)

    2013-01-01

    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

  18. Targeted treatments for cognitive and neurodevelopmental disorders in tuberous sclerosis complex.

    Science.gov (United States)

    de Vries, Petrus J

    2010-07-01

    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.

  19. Microglial Intracellular Ca2+ Signaling in Synaptic Development and its Alterations in Neurodevelopmental Disorders.

    Science.gov (United States)

    Mizoguchi, Yoshito; Monji, Akira

    2017-01-01

    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.

  20. Neurodevelopmental marker for limbic maldevelopment in antisocial personality disorder and psychopathy.

    Science.gov (United States)

    Raine, Adrian; Lee, Lydia; Yang, Yaling; Colletti, Patrick

    2010-09-01

    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.

  1. Gluten Intolerance and Neurodevelopmental Disorders: Is Nitric Oxide the Common Biomarker Linking These Conditions?

    Science.gov (United States)

    Fluegge, Keith

    2016-01-01

    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.

  2. Neurodevelopmental hypothesis of schizophrenia

    National Research Council Canada - National Science Library

    Owen, Michael J; O'Donovan, Michael C; Thapar, Anita; Craddock, Nicholas

    2011-01-01

    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...

  3. Social cognition and neural substrates of face perception: implications for neurodevelopmental and neuropsychiatric disorders.

    Science.gov (United States)

    Lazar, Steven M; Evans, David W; Myers, Scott M; Moreno-De Luca, Andres; Moore, Gregory J

    2014-04-15

    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.

  4. Effects of methylmercury and alcohol exposure in Drosophila melanogaster: Potential risks in neurodevelopmental disorders.

    Science.gov (United States)

    Chauhan, Ved; Chauhan, Abha

    2016-06-01

    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.

  5. Rapamycin prevents seizures after depletion of STRADA in a rare neurodevelopmental disorder.

    Science.gov (United States)

    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

    2013-04-24

    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.

  6. Sensory processing and adaptive behavior deficits of children across the fetal alcohol spectrum disorder continuum.

    Science.gov (United States)

    Carr, Joshua L; Agnihotri, Sabrina; Keightley, Michelle

    2010-06-01

    Prenatal alcohol exposure can have detrimental effects on a child's development of adaptive behaviors necessary for success in the areas of academic achievement, socialization, and self-care. Sensory processing abilities have been found to affect a child's ability to successfully perform adaptive behaviors. The current study explored whether significant differences in sensory processing abilities, adaptive behavior, and neurocognitive functioning are observed between children diagnosed with partial Fetal Alcohol Syndrome (pFAS), Alcohol-Related Neurodevelopmental Disorder (ARND), or children who were prenatally exposed to alcohol (PEA), but did not meet criteria for an FASD diagnosis. The influence of IQ on adaptive behavior as well as further exploration of the relationship between sensory processing and adaptive behavior deficits among these children was also examined. A secondary analysis was conducted on some of the Short Sensory Profile (SSP) scores, Adaptive Behavior Assessment System--Second Edition (ABAS-II) scores, and Wechsler Intelligence Scale--Fourth Edition/Wechsler Preschool and Primary Scale of Intelligence--Third Edition (WISC- IV/WPPSI-III) scores of 46 children between 3 and 14 years of age with pFAS, ARND, or who were PEA. Greater sensory processing deficits were found in children with a diagnosis of pFAS and ARND compared to those in the PEA group. Children with an ARND diagnosis scored significantly worse on measures of adaptive behavior than the PEA group. Children with pFAS scored significantly lower than children with ARND or PEA on perceptual/performance IQ. No correlation was found between IQ scores and adaptive behaviors across the FASD diagnostic categories. A significant positive correlation was found between SSP and ABAS-II scores. Regardless of the diagnosis received under the FASD umbrella, functional difficulties that could not be observed using traditional measures of intelligence were found, supporting guidelines that a broad

  7. Neurodevelopmental Plasticity in Pre- and Postnatal Environmental Interactions: Implications for Psychiatric Disorders from an Evolutionary Perspective

    Directory of Open Access Journals (Sweden)

    Young-A Lee

    2015-01-01

    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.

  8. Behavioral Phenotyping Assays for Genetic Mouse Models of Neurodevelopmental, Neurodegenerative, and Psychiatric Disorders.

    Science.gov (United States)

    Sukoff Rizzo, Stacey J; Crawley, Jacqueline N

    2017-02-08

    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.

  9. An epigenetic framework for neurodevelopmental disorders: from pathogenesis to potential therapy.

    Science.gov (United States)

    Millan, Mark J

    2013-05-01

    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

  10. Neurocognitive habilitation therapy for children with fetal alcohol spectrum disorders: an adaptation of the Alert Program®.

    Science.gov (United States)

    Wells, Anne M; Chasnoff, Ira J; Schmidt, Christine A; Telford, Erin; Schwartz, Linda D

    2012-01-01

    This study evaluated the effectiveness of neurocognitive habilitation, a group therapy intervention for foster and adoptive caregivers and their children who were prenatally exposed to alcohol. Participants were recruited from clients seeking evaluation for fetal alcohol syndrome (FAS) and alcohol-related neurodevelopmental disorder (ARND) and were randomly assigned to treatment and no-treatment control groups. Forty children participated in the treatment program and were compared with 38 control participants using the Behavior Rating Inventory of Executive Function (BRIEF) and the Roberts Apperception Test for Children (RATC). Significant differences between the treatment and control groups were demonstrated on the BRIEF and on the RATC, suggesting that the intervention improved executive functioning and emotional problem-solving skills. These findings yield promising evidence of the effectiveness of the neurocognitive habilitation intervention in improving executive functioning and emotional problem solving in children with FAS or ARND. Copyright © 2012 by the American Occupational Therapy Association, Inc.

  11. Neurodevelopmental variability in three young girls with a rare chromosomal disorder, 48, XXXX.

    Science.gov (United States)

    Samango-Sprouse, Carole; Keen, Colleen; Mitchell, Francie; Sadeghin, Teresa; Gropman, Andrea

    2015-10-01

    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.

  12. Sleep, Plasticity and the Pathophysiology of Neurodevelopmental Disorders: The Potential Roles of Protein Synthesis and Other Cellular Processes

    Directory of Open Access Journals (Sweden)

    Dante Picchioni

    2014-03-01

    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.

  13. EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy.

    Science.gov (United States)

    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

    2016-03-01

    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

  14. The Effects of Live Music as the Discriminative Stimulus and Reinforcer on the Skill Acquisition of Learners with Neurodevelopmental Disorders

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    Harms, Melanie D.

    2013-01-01

    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…

  15. Diagnostic nomenclature for foetal alcohol spectrum disorders: the continuing challenge of causality.

    Science.gov (United States)

    Miller, A R

    2013-11-01

    Prenatal alcohol exposure is a risk factor for neurologically based cognitive and adaptive disability. Diagnostic nomenclature for prenatally exposed children with cognitive and adaptive disability who lack features for foetal alcohol syndrome (FAS) or partial FAS includes the terms alcohol-related neurodevelopmental disorder (ARND) and foetal alcohol spectrum disorder(s) (FASD). Although these terms are now widely used, this paper argues that both are problematic. ARND is flawed by unjustifiably turning a risk factor into a causal factor and shrouding the result in terminological ambiguity, while FASD is not appropriate as a clinical label, and its use as a proxy for ARND deflects critical attention from the causal inferencing that is integral to diagnosing children with an alcohol-related teratogenic condition. Existing nomenclature is at odds with logical and evidence-based diagnosing and also has implications for interpretation of epidemiological data. Diagnostic nomenclature that is not tightly linked to causal inference is preferable at the present stage of this field's development. © 2013 John Wiley & Sons Ltd.

  16. Integrating care for neurodevelopmental disorders by unpacking control: A grounded theory study

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    Gustaf Waxegård

    2016-09-01

    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.

  17. Integrating care for neurodevelopmental disorders by unpacking control: A grounded theory study

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    Waxegård, Gustaf; Thulesius, Hans

    2016-01-01

    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

  18. Development and analysis of the factor structure of parents' internalized stigma of neurodevelopmental disorder in child scale

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    Ananya Mahapatra

    2017-01-01

    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

  19. Generation of iPSC-derived Human Brain Organoids to Model Early Neurodevelopmental Disorders.

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    Gabriel, Elke; Gopalakrishnan, Jay

    2017-04-14

    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.

  20. Prenatal and postnatal animal models of immune activation: relevance to a range of neurodevelopmental disorders.

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    Harvey, Louise; Boksa, Patricia

    2012-10-01

    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.

  1. Investigating mechanisms underlying neurodevelopmental phenotypes of autistic and intellectual disability disorders: a perspective

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    Tim eKroon

    2013-10-01

    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.

  2. Insulin-Like Growth Factor 1 and Related Compounds in the Treatment of Childhood-Onset Neurodevelopmental Disorders

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    Cyrus Vahdatpour

    2016-09-01

    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.

  3. Mice lacking Brinp2 or Brinp3, or both, exhibit behaviours consistent with neurodevelopmental disorders

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    Susie Ruth Berkowicz

    2016-10-01

    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.

  4. Step-Initiation Deficits in Children with Faulty Posture Diagnosed with Neurodevelopmental Disorders during Infancy

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    Magdalena Stania

    2017-11-01

    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

  5. Psychosocial functioning in children with neurodevelopmental disorders and externalizing behavior problems.

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    Arim, Rubab G; Kohen, Dafna E; Garner, Rochelle E; Lach, Lucyna M; Brehaut, Jamie C; MacKenzie, Michael J; Rosenbaum, Peter L

    2015-01-01

    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

  6. The Endosome Localized Arf-GAP AGAP1 Modulates Dendritic Spine Morphology Downstream of the Neurodevelopmental Disorder Factor Dysbindin

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    Miranda Arnold

    2016-09-01

    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.

  7. Sleep Spindle Characteristics in Children with Neurodevelopmental Disorders and Their Relation to Cognition

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    Reut Gruber

    2016-01-01

    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.

  8. Emphasizing the Health Benefits of Vitamin D for Those with Neurodevelopmental Disorders and Intellectual Disabilities

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    William B. Grant

    2015-02-01

    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.

  9. Defects in autophagosome-lysosome fusion underlie Vici syndrome, a neurodevelopmental disorder with multisystem involvement.

    Science.gov (United States)

    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

    2017-06-14

    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.

  10. Emphasizing the health benefits of vitamin D for those with neurodevelopmental disorders and intellectual disabilities.

    Science.gov (United States)

    Grant, William B; Wimalawansa, Sunil J; Holick, Michael F; Cannell, John J; Pludowski, Pawel; Lappe, Joan M; Pittaway, Mary; May, Philip

    2015-02-27

    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.

  11. Emphasizing the Health Benefits of Vitamin D for Those with Neurodevelopmental Disorders and Intellectual Disabilities

    Science.gov (United States)

    Grant, William B.; Wimalawansa, Sunil J.; Holick, Michael F.; Cannell, John J.; Pludowski, Pawel; Lappe, Joan M.; Pittaway, Mary; May, Philip

    2015-01-01

    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

  12. The Role of Noncoding RNAs in Neurodevelopmental Disorders: The Case of Rett Syndrome.

    Science.gov (United States)

    Obiols-Guardia, Aida; Guil, Sònia

    2017-01-01

    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.

  13. Children with neurodevelopmental disorders: The burden and psychological effects on caregivers in Lagos, Nigeria

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    Andrew T Olagunju

    2017-01-01

    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

  14. Learning Curve Analyses in Neurodevelopmental Disorders: Are Children with Autism Spectrum Disorder Truly Visual Learners?

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    Erdodi, Laszlo; Lajiness-O'Neill, Renee; Schmitt, Thomas A.

    2013-01-01

    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…

  15. Computer-Aided Recognition of Facial Attributes for Fetal Alcohol Spectrum Disorders.

    Science.gov (United States)

    Valentine, Matthew; Bihm, Dustin C J; Wolf, Lior; Hoyme, H Eugene; May, Philip A; Buckley, David; Kalberg, Wendy; Abdul-Rahman, Omar A

    2017-12-01

    To compare the detection of facial attributes by computer-based facial recognition software of 2-D images against standard, manual examination in fetal alcohol spectrum disorders (FASD). Participants were gathered from the Fetal Alcohol Syndrome Epidemiology Research database. Standard frontal and oblique photographs of children were obtained during a manual, in-person dysmorphology assessment. Images were submitted for facial analysis conducted by the facial dysmorphology novel analysis technology (an automated system), which assesses ratios of measurements between various facial landmarks to determine the presence of dysmorphic features. Manual blinded dysmorphology assessments were compared with those obtained via the computer-aided system. Areas under the curve values for individual receiver-operating characteristic curves revealed the computer-aided system (0.88 ± 0.02) to be comparable to the manual method (0.86 ± 0.03) in detecting patients with FASD. Interestingly, cases of alcohol-related neurodevelopmental disorder (ARND) were identified more efficiently by the computer-aided system (0.84 ± 0.07) in comparison to the manual method (0.74 ± 0.04). A facial gestalt analysis of patients with ARND also identified more generalized facial findings compared to the cardinal facial features seen in more severe forms of FASD. We found there was an increased diagnostic accuracy for ARND via our computer-aided method. As this category has been historically difficult to diagnose, we believe our experiment demonstrates that facial dysmorphology novel analysis technology can potentially improve ARND diagnosis by introducing a standardized metric for recognizing FASD-associated facial anomalies. Earlier recognition of these patients will lead to earlier intervention with improved patient outcomes. Copyright © 2017 by the American Academy of Pediatrics.

  16. Early executive function deficit in preterm children and its association with neurodevelopmental disorders in childhood: a literature review.

    Science.gov (United States)

    Sun, Jing; Buys, Nicholas

    2012-01-01

    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.

  17. Clinical, Cognitive, and Neuroimaging Evidence of a Neurodevelopmental Continuum in Offspring of Probands With Schizophrenia and Bipolar Disorder.

    Science.gov (United States)

    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

    2017-10-21

    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.

  18. Gender Identity Disorder and Schizophrenia: Neurodevelopmental Disorders with Common Causal Mechanisms?

    Directory of Open Access Journals (Sweden)

    Ravi Philip Rajkumar

    2014-01-01

    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.

  19. Gender Identity Disorder and Schizophrenia: Neurodevelopmental Disorders with Common Causal Mechanisms?

    Science.gov (United States)

    Rajkumar, Ravi Philip

    2014-01-01

    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

  20. Gender identity disorder and schizophrenia: neurodevelopmental disorders with common causal mechanisms?

    Science.gov (United States)

    Rajkumar, Ravi Philip

    2014-01-01

    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.

  1. A Population-based Longitudinal Study of Childhood Neurodevelopmental Disorders, IQ and Subsequent Risk of Psychotic Experiences in Adolescence

    Science.gov (United States)

    Khandaker, Golam M.; Stochl, Jan; Zammit, Stanley; Lewis, Glyn; Jones, Peter B

    2014-01-01

    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

  2. Mutations of CDKL5 Cause a Severe Neurodevelopmental Disorder with Infantile Spasms and Mental Retardation

    Science.gov (United States)

    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

    2004-01-01

    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

  3. A population-based longitudinal study of childhood neurodevelopmental disorders, IQ and subsequent risk of psychotic experiences in adolescence.

    Science.gov (United States)

    Khandaker, G M; Stochl, J; Zammit, S; Lewis, G; Jones, P B

    2014-11-01

    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.

  4. Correlation between morphological MRI findings and specific diagnostic categories in fetal alcohol spectrum disorders.

    Science.gov (United States)

    Boronat, S; Sánchez-Montañez, A; Gómez-Barros, N; Jacas, C; Martínez-Ribot, L; Vázquez, E; Del Campo, M

    2017-01-01

    Fetal alcohol spectrum disorders (FASD) include physical and neurodevelopmental abnormalities related to prenatal alcohol exposure. Some neuroimaging findings have been clearly related to FASD, including corpus callosum and cerebellar anomalies. However, detailed studies correlating with specific FASD categories, that is, the fetal alcohol syndrome (FAS), partial FAS (pFAS) and alcohol related neurodevelopmental disorders (ARND), are lacking. We prospectively performed clinical assessment and brain MR imaging to 72 patients with suspected FASD, and diagnosis was confirmed in 62. The most frequent findings were hypoplasia of the corpus callosum and/or of the cerebellar vermis. Additional findings were vascular anomalies, gliosis, prominent perivascular spaces, occipito-cervical junction and cervical vertebral anomalies, pituitary hypoplasia, arachnoid cysts, and cavum septum pellucidum. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. “Selfish spermatogonial selection”: a novel mechanism for the association between advanced paternal age and neurodevelopmental disorders

    Science.gov (United States)

    Goriely, Anne; McGrath, John J.; Hultman, Christina M.; Wilkie, Andrew O.M.; Malaspina, Dolores

    2014-01-01

    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

  6. Phenotypic plasticity and the perception-action-cognition-environment paradigm in neurodevelopmental genetic disorders.

    Science.gov (United States)

    Dan, Bernard; Pelc, Karine; de Meirleir, Linda; Cheron, Guy

    2015-04-01

    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.

  7. Increased risk of neuropsychological disorders in children born preterm without major disabilities: a neurodevelopmental model

    Directory of Open Access Journals (Sweden)

    Dipasquale Filippo

    2009-06-01

    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.

  8. MECHANISMS IN ENDOCRINOLOGY: Neurodevelopmental disorders in children born to mothers with thyroid dysfunction: evidence of fetal programming?

    Science.gov (United States)

    Andersen, Stine Linding; Carlé, Allan; Karmisholt, Jesper; Pedersen, Inge Bülow; Andersen, Stig

    2017-07-01

    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.

  9. Neurodevelopmental disorders associated with dosage imbalance of ZBTB20 correlate with the morbidity spectrum of ZBTB20 candidate target genes.

    Science.gov (United States)

    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

    2014-09-01

    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.

  10. Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Amin Mottahedin

    2017-07-01

    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.

  11. Premorbid multivariate markers of neurodevelopmental instability in the prediction of adult schizophrenia-spectrum disorder

    DEFF Research Database (Denmark)

    Golembo-Smith, Shana; Schiffman, Jason; Kline, Emily

    2012-01-01

    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...

  12. A rapid chemical-genetic screen utilizing impaired movement phenotypes in C. elegans: Input into genetics of neurodevelopmental disorders.

    Science.gov (United States)

    Schmeisser, Kathrin; Fardghassemi, Yasmin; Parker, J Alex

    2017-07-01

    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.

  13. A Dose-Response Relationship between Organic Mercury Exposure from Thimerosal-Containing Vaccines and Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    David A. Geier

    2014-09-01

    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.

  14. Children with neurodevelopmental disorders and disabilities: a population-based study of healthcare service utilization using administrative data.

    Science.gov (United States)

    Arim, Rubab G; Miller, Anton R; Guèvremont, Anne; Lach, Lucyna M; Brehaut, Jamie C; Kohen, Dafna E

    2017-12-01

    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.

  15. The European Prader-Willi Syndrome Clinical Research Database: An Aid in the Investigation of a Rare Genetically Determined Neurodevelopmental Disorder

    Science.gov (United States)

    Holland, A.; Whittington, J.; Cohen, O.; Curfs, L.; Delahaye, F.; Dudley, O.; Horsthemke, B.; Lindgren, A. -C.; Nourissier, C.; Sharma, N.; Vogels, A.

    2009-01-01

    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…

  16. Responding to Requests of Families for Unproven Interventions in Neurodevelopmental Disorders: Hyperbaric Oxygen "Treatment" and Stem Cell "Therapy" in Cerebral Palsy

    Science.gov (United States)

    Bell, Emily; Wallace, Tessa; Chouinard, Isabelle; Shevell, Michael; Racine, Eric

    2011-01-01

    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…

  17. Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin-Siris syndrome

    OpenAIRE

    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.

    2016-01-01

    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...

  18. Identification and functional characterization of de novo FOXP1 variants provides novel insights into the etiology of neurodevelopmental disorder.

    Science.gov (United States)

    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

    2016-02-01

    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

  19. Further evidence that some male-based neurodevelopmental disorders are associated with high intrauterine testosterone concentrations.

    Science.gov (United States)

    James, William H

    2008-01-01

    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.

  20. [Prevalence of neurodevelopmental, behavioural and learning disorders in Pediatric Primary Care].

    Science.gov (United States)

    Carballal Mariño, Marta; Gago Ageitos, Ana; Ares Alvarez, Josefa; Del Rio Garma, Mercedes; García Cendón, Clara; Goicoechea Castaño, Ana; Pena Nieto, Josefina

    2017-11-20

    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.

  1. Synapse dysfunction in autism: a molecular medicine approach to drug discovery in neurodevelopmental disorders.

    Science.gov (United States)

    Spooren, Will; Lindemann, Lothar; Ghosh, Anirvan; Santarelli, Luca

    2012-12-01

    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.

  2. Imitation and "Theory of Mind" Competencies in Discrimination of Autism from Other Neurodevelopmental Disorders

    Science.gov (United States)

    Perra, Oliver; Williams, Justin H. G.; Whiten, Andrew; Fraser, Lesley; Benzie, Helen; Perrett, David I.

    2008-01-01

    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…

  3. Homozygous and heterozygous disruptions of ANK3: at the crossroads of neurodevelopmental and psychiatric disorders

    NARCIS (Netherlands)

    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.

    2013-01-01

    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

  4. Turing Revisited: Decoding the microRNA Messages in Brain Extracellular Vesicles for Early Detection of Neurodevelopmental Disorders.

    Science.gov (United States)

    Gillet, Virginie; Hunting, Darel John; Takser, Larissa

    2016-09-01

    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.

  5. Public health and research funding for childhood neurodevelopmental disorders in Sub-Saharan Africa: a time to balance priorities.

    Science.gov (United States)

    Bakare, Muideen O; Munir, Kerim M; Bello-Mojeed, Mashudat A

    2014-01-01

    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.

  6. Public health and research funding for childhood neurodevelopmental disorders in Sub-Saharan Africa: a time to balance priorities

    Directory of Open Access Journals (Sweden)

    Muideen O. Bakare

    2014-01-01

    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.

  7. Narrative retelling in children with neurodevelopmental disorders: is there a role for nonverbal temporal-sequencing skills?

    Science.gov (United States)

    Johnels, Jakob Åsberg; Hagberg, Bibbi; Gillberg, Christopher; Miniscalco, Carmela

    2013-10-01

    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.

  8. Modulation of GABAergic transmission in development and neurodevelopmental disorders: investigating physiology and pathology to gain therapeutic perspectives.

    Science.gov (United States)

    Deidda, Gabriele; Bozarth, Ignacio F; Cancedda, Laura

    2014-01-01

    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.

  9. Modulation of GABAergic Transmission in Development and Neurodevelopmental Disorders: Investigating Physiology and Pathology to Gain Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Gabriele eDeidda

    2014-05-01

    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.

  10. Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders

    Science.gov (United States)

    2014-07-01

    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

  11. Elevated titanium levels in Iraqi children with neurodevelopmental disorders echo findings in occupation soldiers

    OpenAIRE

    Savabieasfahani, M.; Alaani, S.; Tafash, M.; Dastgiri, S; Al-Sabbak, M.

    2014-01-01

    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...

  12. Sleep disorders in children with cerebral palsy: neurodevelopmental and behavioral correlates.

    Science.gov (United States)

    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

    2014-02-01

    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.

  13. Portal for Families Overcoming Neurodevelopmental Disorders (PFOND): Implementation of a Software Framework for Facilitated Community Website Creation by Nontechnical Volunteers.

    Science.gov (United States)

    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

    2013-08-06

    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

  14. Portal for Families Overcoming Neurodevelopmental Disorders (PFOND): Implementation of a Software Framework for Facilitated Community Website Creation by Nontechnical Volunteers

    Science.gov (United States)

    Imam, Tuhina; Lee, Cheryl E; Chen, Shirley Yu; Herman, Adam; Sharma, Balraj; Johal, Gurinder; Gu, Bobby

    2013-01-01

    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

  15. An evaluation of speech production in two boys with neurodevelopmental disorders who received communication intervention with a speech-generating device.

    Science.gov (United States)

    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

    2014-11-01

    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.

  16. Inter-rater Reliability on the Individual Music-Centered Assessment Profile forNeurodevelopmental Disorders: (IMCAP-ND) for Autism Spectrum Disorder

    DEFF Research Database (Denmark)

    Carpente, John; Manne, Stela; Gattino, Gustavo

    2018-01-01

    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...

  17. Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder.

    Science.gov (United States)

    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

    2018-03-01

    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.

  18. Attention and working memory training: A feasibility study in children with neurodevelopmental disorders.

    Science.gov (United States)

    Kerns, Kimberly A; Macoun, Sarah; MacSween, Jenny; Pei, Jacqueline; Hutchison, Marnie

    2017-01-01

    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.

  19. Child functional characteristics explain child and family outcomes better than diagnosis: Population-based study of children with autism or other neurodevelopmental disorders/disabilities.

    Science.gov (United States)

    Miller, Anton; Shen, Jane; Mâsse, Louise C

    2016-06-15

    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.

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

    Science.gov (United States)

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

    2015-01-01

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

  1. Chromosomal Microarray Analysis of Consecutive Individuals with Autism Spectrum Disorders Using an Ultra-High Resolution Chromosomal Microarray Optimized for Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Karen S. Ho

    2016-12-01

    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.

  2. The Analysis of Genetic Aberrations in Children with Inherited Neurometabolic and Neurodevelopmental Disorders

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    Krystyna Szymańska

    2014-01-01

    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.

  3. Visual sensorial impairments in neurodevelopmental disorders: evidence for a retinal phenotype in Fragile X Syndrome.

    Science.gov (United States)

    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

    2014-01-01

    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.

  4. Facilitating support groups for siblings of children with neurodevelopmental disorders using audio-conferencing: a longitudinal feasibility study.

    Science.gov (United States)

    Gettings, Sheryl; Franco, Fabia; Santosh, Paramala J

    2015-01-01

    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

  5. Induction of the GABA cell phenotype: an in vitro model for studying neurodevelopmental disorders.

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    Sivan Subburaju

    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.

  6. Mastication dyspraxia: a neurodevelopmental disorder reflecting disruption of the cerebellocerebral network involved in planned actions.

    Science.gov (United States)

    Mariën, Peter; Vidts, Annelies; Van Hecke, Wim; De Surgeloose, Didier; De Belder, Frank; Parizel, Paul M; Engelborghs, Sebastiaan; De Deyn, Peter P; Verhoeven, Jo

    2013-04-01

    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

  7. Disruption of the ASTN2 / TRIM32 locus at 9q33.1 is a risk factor in males for Autism Spectrum Disorders, ADHD and other neurodevelopmental phenotypes

    DEFF Research Database (Denmark)

    Lionel, Anath C; Tammimies, Kristiina; Vaags, Andrea K

    2014-01-01

    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...

  8. Oppositional defiant- and conduct disorder-like problems: neurodevelopmental predictors and genetic background in boys and girls, in a nationwide twin study.

    Science.gov (United States)

    Kerekes, Nóra; Lundström, Sebastian; Chang, Zheng; Tajnia, Armin; Jern, Patrick; Lichtenstein, Paul; Nilsson, Thomas; Anckarsäter, Henrik

    2014-01-01

    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.

  9. Oppositional defiant- and conduct disorder-like problems: neurodevelopmental predictors and genetic background in boys and girls, in a nationwide twin study

    Directory of Open Access Journals (Sweden)

    Nóra Kerekes

    2014-04-01

    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.

  10. Confounding diagnoses in the neurodevelopmental disabilities population: a child with hearing loss, absence epilepsy, and attention-deficit hyperactivity disorder (ADHD).

    Science.gov (United States)

    Lance, Eboni I; Shapiro, Bruce K

    2013-05-01

    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.

  11. The use of MElatonin in children with neurodevelopmental disorders and impaired sleep: a randomised, double-blind, placebo-controlled, parallel study (MENDS).

    Science.gov (United States)

    Appleton, R E; Jones, A P; Gamble, C; Williamson, P R; Wiggs, L; Montgomery, P; Sutcliffe, A; Barker, C; Gringras, P

    2012-01-01

    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

  12. Plasma Pharmacokinetic Characteristics of Risperidone and Their Relationship to Saliva Concentrations in Children with Psychiatric or Neurodevelopmental Disorders

    Science.gov (United States)

    Aman, Michael G.; Vinks, Alexander A.; Remmerie, Bart; Mannaert, Erik; Ramadan, Yaser; Masty, Jessica; Lindsay, Ronald L.; Malone, Krista

    2013-01-01

    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

  13. 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

    Directory of Open Access Journals (Sweden)

    Shu-Kun Lin

    2013-01-01

    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.

  14. Developmental neurotoxicity of inhaled ambient ultrafine particle air pollution: Parallels with neuropathological and behavioral features of autism and other neurodevelopmental disorders.

    Science.gov (United States)

    Allen, J L; Oberdorster, G; Morris-Schaffer, K; Wong, C; Klocke, C; Sobolewski, M; Conrad, K; Mayer-Proschel, M; Cory-Slechta, D A

    2017-03-01

    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.

  15. Neurodevelopmental correlates in schizophrenia

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    Ivković Maja

    2003-01-01

    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

  16. Concurrent validity of the differential ability scales, second edition with the Mullen Scales of Early Learning in young children with and without neurodevelopmental disorders.

    Science.gov (United States)

    Farmer, Cristan; Golden, Christine; Thurm, Audrey

    2016-01-01

    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.

  17. Behavioral and Neurodevelopmental Precursors to Binge-Type Eating Disorders: Support for the Role of Negative Valence Systems

    Science.gov (United States)

    Vannucci, Anna; Nelson, Eric E.; Bongiorno, Diana M.; Pine, Daniel S.; Yanovski, Jack A.; Tanofsky-Kraff, Marian

    2015-01-01

    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

  18. Identification and functional characterization of de novo FOXP1 variants provides novel insights into the etiology of neurodevelopmental disorder

    NARCIS (Netherlands)

    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.

    2016-01-01

    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

  19. Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders

    DEFF Research Database (Denmark)

    Isles, Anthony R; Ingason, Andrés; Lowther, Chelsea

    2016-01-01

    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...

  20. Assessing Parent Perceptions of Physical Activity in Families of Toddlers With Neurodevelopmental Disorders: The Parent Perceptions of Physical Activity Scale (PPPAS).

    Science.gov (United States)

    Lakes, Kimberley D; Abdullah, Maryam M; Youssef, Julie; Donnelly, Joseph H; Taylor-Lucas, Candice; Goldberg, Wendy A; Cooper, Dan; Aizik, Shlomit

    2017-08-01

    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.

  1. Genetic predictors of celiac disease, lactose intolerance, and vitamin D function and presence of peptide morphins in urine of children with neurodevelopmental disorders.

    Science.gov (United States)

    Bojović, Katarina; Stanković, Biljana; Kotur, Nikola; Krstić-Milošević, Dijana; Gašić, Vladimir; Pavlović, Sonja; Zukić, Branka; Ignjatović, Đurđica

    2017-07-24

    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.

  2. Febrile Seizures and Epilepsy: Association With Autism and Other Neurodevelopmental Disorders in the Child and Adolescent Twin Study in Sweden.

    Science.gov (United States)

    Gillberg, Christopher; Lundström, Sebastian; Fernell, Elisabeth; Nilsson, Gill; Neville, Brian

    2017-09-01

    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.

  3. Translational Approaches for Studying Neurodevelopmental Disorders Utilizing in Vivo Proton (+H) Magnetic Resonance Spectroscopic Imaging in Rats

    Science.gov (United States)

    Ronca, April E.

    2014-01-01

    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

  4. Behavioral alterations in rat offspring following maternal immune activation and ELR-CXC chemokine receptor antagonism during pregnancy: implications for neurodevelopmental psychiatric disorders.

    Science.gov (United States)

    Ballendine, Stephanie A; Greba, Quentin; Dawicki, Wojciech; Zhang, Xiaobei; Gordon, John R; Howland, John G

    2015-03-03

    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.

  5. Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin-Siris syndrome.

    Science.gov (United States)

    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

    2016-03-01

    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/

  6. A neurodevelopmental approach to understanding memory processes among intellectually gifted youth with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Whitaker, Ashley M; Bell, Terece S; Houskamp, Beth M; O'Callaghan, Erin T

    2015-01-01

    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.

  7. Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders.

    Directory of Open Access Journals (Sweden)

    Anthony R Isles

    2016-05-01

    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

  8. Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders

    Science.gov (United States)

    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

    2016-01-01

    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

  9. Screening for fetal alcohol spectrum disorders by nonmedical community workers.

    Science.gov (United States)

    O'Connor, Mary J; Rotheram-Borus, Mary Jane; Tomlinson, Mark; Bill, Claudine; LeRoux, Ingrid M; Stewart, Jackie

    2014-01-01

    South Africa has the highest prevalence of Fetal Alcohol Spectrum Disorders (FASD) in the world yet many women have no access to clinic care or to physicians in their communities. The shortage of physicians trained in the diagnosis of FASD is even more severe. Thus there is a need to train community workers to assist in the delivery of health care. This study reports on the effectiveness of training community workers to screen for a possible diagnosis of a FASD. Community workers in Cape Town, South Africa were trained to screen for FASD in 139, 18-month-old toddlers with prenatal alcohol exposure (PAE). Children were assessed according to the salient characteristics of individuals with PAE using height, weight, head circumference (OFC), philtrum, and lip measurements according to criteria set forth by the Institute of Medicine. Screen-positive children were referred for diagnostic assessment to a pediatrician reliably trained in the diagnosis of FASD. Of the screen-positive children, 93% received an FASD diagnosis suggesting that the screening procedure was highly sensitive. Diagnoses included 15% with fetal alcohol syndrome (FAS), 23% with Partial FAS, and 62% with Alcohol Related Neurodevelopmental Disorder (ARND, provisional). The use of community workers to screen for FASD represents a promising approach to effective diagnosis of children affected by PAE in areas lacking adequate medical resources.

  10. Neurodevelopmental delay in children exposed in utero to hyperemesis gravidarum.

    Science.gov (United States)

    Fejzo, Marlena S; Magtira, Aromalyn; Schoenberg, Frederic Paik; Macgibbon, Kimber; Mullin, Patrick M

    2015-06-01

    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.

  11. Pediatric Neurodevelopmental Treatment

    Science.gov (United States)

    Camacho, Ricardo; McCauley, Brandon; Szczech Moser, Christy

    2016-01-01

    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.

  12. 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

    OpenAIRE

    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.

    2017-01-01

    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, ...

  13. Sleep in children with neurodevelopmental disabilities.

    Science.gov (United States)

    Angriman, Marco; Caravale, Barbara; Novelli, Luana; Ferri, Raffaele; Bruni, Oliviero

    2015-06-01

    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.

  14. International telemedicine consultations for neurodevelopmental disabilities.

    Science.gov (United States)

    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

    2014-06-01

    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

  15. Age- and sex-dependent laterality of rat hippocampal cholinergic system in relation to animal models of neurodevelopmental and neurodegenerative disorders.

    Science.gov (United States)

    Kristofiková, Zdena; Stástný, Frantisek; Bubeniková, Vera; Druga, Rastislav; Klaschka, Jan; Spaniel, Filip

    2004-04-01

    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

  16. Nocturnal incontinence in children with fetal alcohol spectrum disorders (FASD) in a South African cohort.

    Science.gov (United States)

    Roozen, Sylvia; Olivier, Leana; Niemczyk, Justine; von Gontard, Alexander; Peters, Gjalt-Jorn Y; Kok, Gerjo; Viljoen, Denis; Curfs, Leopold

    2017-10-01

    Fetal alcohol spectrum disorders (FASD) are one of the leading preventable causes of intellectual disabilities (ID). Not much is known about the topic of pediatric incontinence related to FASD, for example nocturnal enuresis (NE), daytime urinary incontinence (DUI), and fecal incontinence (FI). So far, incontinence problems have been examined among children with other specific syndromes. The aim of the present study is to investigate the possible presence of incontinence among children with FASD in a South African cohort. The South African version of the combined questionnaire including the "Parental Questionnaire: Enuresis/Urinary Incontinence" and "Encopresis Questionnaire - Screening Version"; and lower urinary tract symptoms (LUTS) were assessed by the "International-Consultation-on-Incontinence-Questionnaire - Pediatric Lower Urinary Tract Symptom" (ICIQ-CLUTS) among 99 interviewees (e.g. mothers, grandparents) of children with FASD. Moreover, scores on the "Griffiths Mental Development Scales - Extended Revised" (GMDS-ER) were obtained of all included children for further statistical analysis. The overall incontinence rate was 20% (n = 20), in children diagnosed within the FASD spectrum (fetal alcohol syndrome or FAS n = 17, partial fetal alcohol syndrome or pFAS, n = 1, alcohol related neurodevelopmental disorder or ARND n = 2). NE affected 16% (n = 16) of children with a FASD (FAS n = 13, pFAS n = 1, and ARND n = 2). DUI was reported in one child (FAS), and FI in 4% (n = 4) of children (again, only FAS). No indication of lower urinary tract symptoms (LUTS) in the clinical range was reported (sample mean score = 5.17). Based on the GMDS-ER, 88% of the children scored lower than 10th percentile. This is a first study to examine the problems of incontinence among children diagnosed within the spectrum of FASD. The rates for children with a FASD are lower than the rates for many children with special needs, but much higher than for typically

  17. 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.

    Science.gov (United States)

    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

    2017-05-01

    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.

  18. Neurodevelopmental disorder associated with prenatal exposure to alcohol (ND-PAE): A proposed diagnostic method of capturing the neurocognitive phenotype of FASD.

    Science.gov (United States)

    Kable, Julie A; Mukherjee, Raja A S

    2017-01-01

    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.

  19. Neurodevelopmental Treatment (NDT): Therapeutic Intervention and Its Efficacy.

    Science.gov (United States)

    Stern, Francine Martin; Gorga, Delia

    1988-01-01

    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…

  20. Approaching the prevalence of the full spectrum of fetal alcohol spectrum disorders in a South African population-based study.

    Science.gov (United States)

    May, Philip A; Blankenship, Jason; Marais, Anna-Susan; Gossage, J Phillip; Kalberg, Wendy O; Barnard, Ronel; De Vries, Marlene; Robinson, Luther K; Adnams, Colleen M; Buckley, David; Manning, Melanie; Jones, Kenneth L; Parry, Charles; Hoyme, H Eugene; Seedat, Soraya

    2013-05-01

    The prevalence and characteristics of fetal alcohol spectrum disorders (FASD) were determined in this fourth study of first-grade children in a South African community. Active case ascertainment methods were employed among 747 first-grade pupils. The detailed characteristics of children within the continuum of FASD are contrasted with randomly selected, normal controls on (i) physical growth and dysmorphology; (ii) cognitive/behavioral characteristics; and (iii) maternal risk factors. The rates of specific diagnoses within the FASD spectrum continue to be among the highest reported in any community in the world. The prevalence (per 1,000) is as follows: fetal alcohol syndrome (FAS)-59.3 to 91.0; partial fetal alcohol syndrome (PFAS)-45.3 to 69.6; and alcohol-related neurodevelopmental disorder (ARND)-30.5 to 46.8. The overall rate of FASD is therefore 135.1 to 207.5 per 1,000 (or 13.6 to 20.9%). Clinical profiles of the physical and cognitive/behavioral traits of children with a specific FASD diagnosis and controls are provided for understanding the full spectrum of FASD in a community. The spectral effect is evident in the characteristics of the diagnostic groups and summarized by the total (mean) dysmorphology scores of the children: FAS = 18.9; PFAS = 14.3; ARND = 12.2; and normal controls, alcohol exposed = 8.2 and unexposed = 7.1. Documented drinking during pregnancy is significantly correlated with verbal (r = -0.253) and nonverbal ability (r = -0.265), negative behaviors (r = 0.203), and total dysmorphology score (r = 0.431). Other measures of drinking during pregnancy are significantly associated with FASD, including binge drinking as low as 3 drinks per episode on 2 days of the week. High rates of specific diagnoses within FASD were well documented in this new cohort of children. FASD persists in this community. The data reflect an increased ability to provide accurate and discriminating diagnoses throughout the continuum of FASD. Copyright © 2012 by the

  1. Prevalence and characteristics of fetal alcohol spectrum disorders.

    Science.gov (United States)

    May, Philip A; Baete, Amy; Russo, Jaymi; Elliott, Amy J; Blankenship, Jason; Kalberg, Wendy O; Buckley, David; Brooks, Marita; Hasken, Julie; Abdul-Rahman, Omar; Adam, Margaret P; Robinson, Luther K; Manning, Melanie; Hoyme, H Eugene

    2014-11-01

    To determine the prevalence and characteristics of fetal alcohol spectrum disorders (FASD) among first grade students (6- to 7-year-olds) in a representative Midwestern US community. From a consented sample of 70.5% of all first graders enrolled in public and private schools, an oversample of small children (≤ 25th percentile on height, weight, and head circumference) and randomly selected control candidates were examined for physical growth, development, dysmorphology, cognition, and behavior. The children's mothers were interviewed for maternal risk. Total dysmorphology scores differentiate significantly fetal alcohol syndrome (FAS) and partial FAS (PFAS) from one another and from unexposed controls. Alcohol-related neurodevelopmental disorder (ARND) is not as clearly differentiated from controls. Children who had FASD performed, on average, significantly worse on 7 cognitive and behavioral tests and measures. The most predictive maternal risk variables in this community are late recognition of pregnancy, quantity of alcoholic drinks consumed 3 months before pregnancy, and quantity of drinking reported for the index child's father. From the final multidisciplinary case findings, 3 techniques were used to estimate prevalence. FAS in this community likely ranges from 6 to 9 per 1000 children (midpoint, 7.5), PFAS from 11 to 17 per 1000 children (midpoint, 14), and the total rate of FASD is estimated at 24 to 48 per 1000 children, or 2.4% to 4.8% (midpoint, 3.6%). Children who have FASD are more prevalent among first graders in this Midwestern city than predicted by previous, popular estimates. Copyright © 2014 by the American Academy of Pediatrics.

  2. Neurodevelopmental processes and psychological functioning in autism.

    Science.gov (United States)

    Gillberg, C

    1999-01-01

    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.

  3. Why and how to assess the aetiological diagnosis of children with intellectual disability/mental retardation and other neurodevelopmental disorders: description of the Finnish approach.

    Science.gov (United States)

    Wilska, M L; Kaski, M K

    2001-01-01

    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.

  4. [Neurodevelopmental theories of schizophrenia--preclinical studies].

    Science.gov (United States)

    Lehner, Małgorzata; Taracha, Ewa; Wisłowska, Aleksandra; Zienowicz, Małgorzata; Maciejak, Piotr; Skórzewska, Anna; Płaźnik, Adam

    2003-01-01

    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.

  5. Stochastic Signatures of Involuntary Head Micro-movements Can Be Used to Classify Females of ABIDE into Different Subtypes of Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Elizabeth B. Torres

    2017-06-01

    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

  6. Perspectives from neuro-developmental disorders affecting ...

    Indian Academy of Sciences (India)

    Unknown

    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.

  7. Central tetrahydrobiopterin concentration in neurodevelopmental disorders

    Directory of Open Access Journals (Sweden)

    Richard E Frye

    2010-07-01

    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.

  8. Early Care in Children with Neurodevelopmental Disorders

    Science.gov (United States)

    Ponce-Meza, Jacqueline

    2017-01-01

    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…

  9. Early care in children with neurodevelopmental disorders

    Directory of Open Access Journals (Sweden)

    Jacqueline Ponce-Meza

    2017-04-01

    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.

  10. Neurodevelopmental model of schizophrenia: update 2012

    National Research Council Canada - National Science Library

    Rapoport, J L; Giedd, J N; Gogtay, N

    2012-01-01

    ... greatest potential to modify or extend, the neurodevelopmental model of schizophrenia. Longitudinal whole-population studies support a dimensional, rather than categorical, concept of psychosis...

  11. Assisted reproduction and child neurodevelopmental outcomes: a systematic review.

    Science.gov (United States)

    Bay, Bjørn; Mortensen, Erik Lykke; Kesmodel, Ulrik Schiøler

    2013-09-01

    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.

  12. Subjective Experience of Episodic Memory and Metacognition: A Neurodevelopmental Approach

    Directory of Open Access Journals (Sweden)

    Celine eSouchay

    2013-12-01

    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.

  13. Assisted reproduction and child neurodevelopmental outcomes

    DEFF Research Database (Denmark)

    Bay, Bjørn; Mortensen, Erik Lykke; Kesmodel, Ulrik Schiøler

    2013-01-01

    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....

  14. Molecular Basis of Neurodegeneration and Neurodevelopmental Defects in Menkes Disease

    Science.gov (United States)

    Zlatic, Stephanie; Comstra, Heather Skye; Gokhale, Avanti; Petris, Michael J.; Faundez, Victor

    2015-01-01

    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

  15. Communication Intervention for Young Children with Severe Neurodevelopmental Disabilities via Telehealth

    Science.gov (United States)

    Simacek, Jessica; Dimian, Adele F.; McComas, Jennifer J.

    2017-01-01

    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…

  16. The continuum of fetal alcohol spectrum disorders in four rural communities in South Africa: Prevalence and characteristics.

    Science.gov (United States)

    May, Philip A; de Vries, Marlene M; Marais, Anna-Susan; Kalberg, Wendy O; Adnams, Colleen M; Hasken, Julie M; Tabachnick, Barbara; Robinson, Luther K; Manning, Melanie A; Jones, Kenneth Lyons; Hoyme, Derek; Seedat, Soraya; Parry, Charles D H; Hoyme, H Eugene

    2016-02-01

    Prevalence and characteristics of the continuum of diagnoses within fetal alcohol spectrum disorders (FASD) were researched in previously unstudied rural, agricultural, lower socioeconomic populations in South Africa (ZA). Using an active case ascertainment approach among first grade learners, 1354 (72.6%) were consented into the study via: height, weight, and/or head circumference ≤ 25th centile and/or random selection as normal control candidates. Final diagnoses were made following: examination by pediatric dysmorphologists/geneticists, cognitive/behavioral testing, and maternal risk factor interviews. FASD children were significantly growth deficient and dysmorphic: physical measurements, cardinal facial features of FAS, and total dysmorphology scores clearly differentiated diagnostic categories from severe to mild to normal in a consistent, linear fashion. Neurodevelopmental delays were also significantly worse for each of the FASD diagnostic categories, although not as consistently linear across groups. Alcohol use is well documented as the proximal maternal risk factor for each diagnostic group. Significant distal maternal risk factors in this population are: low body weight, body mass, education, and income; and high gravidity, parity, and age at birth of the index child. In this low SES, highly rural region, FAS occurs in 93-128 per 1000 children, PFAS in 58-86, and, ARND in 32-46 per 1000. Total FASD affect 182-259 per 1000 children or 18-26%. Very high rates of FASD exist in these rural areas and isolated towns where entrenched practices of regular binge drinking co-exist with challenging conditions for childbearing and child development. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. The Neurodevelopmental Basis of Early Childhood Disruptive Behavior: Irritable and Callous Phenotypes as Exemplars.

    Science.gov (United States)

    Wakschlag, Lauren S; Perlman, Susan B; Blair, R James; Leibenluft, Ellen; Briggs-Gowan, Margaret J; Pine, Daniel S

    2017-11-17

    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.

  18. Neurobehavioral and neurodevelopmental effects of pesticide exposures

    NARCIS (Netherlands)

    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.

    2012-01-01

    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

  19. Neurobehavioral and neurodevelopmental effects of pesticide exposures

    DEFF Research Database (Denmark)

    London, Leslie; Beseler, Cheryl; Bouchard, Maryse F

    2012-01-01

    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 ...

  20. Delayed visual maturation: ophthalmic and neurodevelopmental aspects.

    Science.gov (United States)

    Tresidder, J; Fielder, A R; Nicholson, J

    1990-10-01

    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.

  1. Sequencing Chromosomal Abnormalities Reveals Neurodevelopmental Loci that Confer Risk across Diagnostic Boundaries

    DEFF Research Database (Denmark)

    Talkowski, Michael E.; Rosenfeld, Jill A.; Blumenthal, Ian

    2012-01-01

    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...

  2. Fetal Alcohol Exposure

    Science.gov (United States)

    ... categories: 4 » Fetal Alcohol Syndrome (FAS) » Partial FAS (pFAS) » Alcohol-Related Neurodevelopmental Disorder (ARND) » Alcohol-Related Birth ... either prenatally, after birth, or both Partial FAS (pFAS) Partial FAS (pFAS) involves prenatal alcohol exposure, and ...

  3. Comparison of spatial working memory in children with prenatal alcohol exposure and those diagnosed with ADHD; A functional magnetic resonance imaging study

    Directory of Open Access Journals (Sweden)

    Malisza Krisztina L

    2012-05-01

    Full Text Available Abstract Background Alcohol related neurodevelopmental disorder (ARND falls under the umbrella of fetal alcohol spectrum disorder (FASD, but individuals do not demonstrate the facial characteristics associated with fetal alcohol syndrome (FAS, making diagnosis difficult. While attentional problems in ARND are similar to those found in attention-deficit/hyperactivity disorder (ADHD, the underlying impairment in attention pathways may be different. Methods Functional magnetic resonance imaging (fMRI of a working memory (1-back task of 63 children, 10 to 14 years old, diagnosed with ARND and ADHD, as well as typically developing (TD controls, was conducted at 3 T. Diffusion tensor imaging (DTI data were also acquired. Results Activations were observed in posterior parietal and occipital regions in the TD group and in dorsolateral prefrontal and posterior parietal regions in the ARND group, whereas the ADHD group activated only dorsolateral prefrontal regions, during the working memory component of the task (1-back minus 0-back contrast. The increases in frontal and parietal activity were significantly greater in the ARND group compared to the other groups. This increased activity was associated with reduced accuracy and increased response time variability, suggesting that ARND subjects exert greater effort to manage short-term memory load. Significantly greater intra-subject variability, demonstrated by fMRI region-of-interest analysis, in the ADHD and ARND groups compared to the TD group suggests that moment-to-moment lapses in attention contributed to their poorer task performance. Differences in functional activity in ARND subjects with and without a diagnosis of ADHD resulted primarily from reduced activation by the ARND/ADHD + group during the 0-back task. In contrast, children with ADHD alone clearly showed reduced activations during the 1-back task. DTI analysis revealed that the TD group had significantly higher total tract volume

  4. Pediatric epilepsy and comorbid reading disorders, math disorders, or autism spectrum disorders: Impact of epilepsy on cognitive patterns

    NARCIS (Netherlands)

    van Iterson, L.; de Jong, P.F.; Zijlstra, B.J.H.

    2015-01-01

    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

  5. Neurodevelopmental problems and extremes in BMI

    Directory of Open Access Journals (Sweden)

    Nóra Kerekes

    2015-07-01

    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

  6. Fetal alcohol spectrum disorders in Finland: clinical delineation of 77 older children and adolescents.

    Science.gov (United States)

    Autti-Rämö, Ilona; Fagerlund, Ase; Ervalahti, Nina; Loimu, Leena; Korkman, Marit; Hoyme, H Eugene

    2006-01-15

    The adverse effects of alcohol on the developing human comprise a spectrum of structural anomalies and behavioral and neurocognitive disabilities, most accurately termed fetal alcohol spectrum disorders (FASD). We previously have proposed revisions to the 1996 Institute of Medicine Diagnostic Criteria for diagnoses in the FASD continuum [fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (PFAS), alcohol related birth defects (ARBD), and alcohol related neurodevelopmental disorder (ARND)], allowing for more reproducible and accurate FASD diagnosis in a clinical setting [Hoyme et al., 2005]. The NIAAA recently has coordinated and funded an international consortium of projects aimed at more complete characterization of the teratogenic spectrum of alcohol. One of the projects sites is in Finland. The aims of this project are: (1) to completely clinically characterize the structural and learning/behavioral phenotypes of a large cohort of older children and adolescents with moderate to severe disability within the FASD continuum; (2) to correlate FASD dysmorphology and behavioral phenotypes with CNS structure and function (i.e., MRS, MRI correlations); (3) to compare the phenotype of a genetically homogeneous population of Finnish children with FASD to that observed in other populations. We have recently completed dysmorphology examination and parent/guardian interviews of the 77 children in the Finnish cohort. The purpose of this report is to present historical and morphometric data on these patients, thereby more completely delineating the clinical spectrum of FASD in older children and adolescents, contrasting the phenotype with that described in other populations and examining whether a weighted dysmorphology score could be used as a clinical and research adjunct when fetal alcohol exposure is being suspected. All children were previously diagnosed with FASD by an experienced pediatric specialist in Finland, and all were exposed to significant maternal

  7. Cell therapy for pediatric disorders of glia

    DEFF Research Database (Denmark)

    Albuquerque Osório, Maria Joana; Goldman, Steven A.

    2016-01-01

    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...

  8. Academic underachievement: A neurodevelopmental perspective

    Directory of Open Access Journals (Sweden)

    K. Shapiro Bruce, MD

    2011-03-01

    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.

  9. Neurobehavioural and neurodevelopmental effects of pesticide exposures

    Science.gov (United States)

    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

    2012-01-01

    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

  10. Angelman Syndrome: Insights into Genomic Imprinting and Neurodevelopmental Phenotypes

    Science.gov (United States)

    Mabb, Angela M.; Judson, Matthew C.; Zylka, Mark J.; Philpot, Benjamin D.

    2011-01-01

    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

  11. Neurodevelopmental treatment after stroke : a comparative study

    NARCIS (Netherlands)

    Dr. T.B. Hafsteinsdóttir; A Algra; M.H.F. Grypdonck; L.J. Kappelle

    2005-01-01

    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

  12. Neurodevelopmental consequences of being born SGA

    NARCIS (Netherlands)

    van Wassenaer, Aleid

    2005-01-01

    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

  13. Neurodevelopmental Outcomes of Children with Periventricular Leukomalacia

    Directory of Open Access Journals (Sweden)

    Takashi Imamura

    2013-12-01

    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.

  14. Cognitive characterization of children with Dravet syndrome: A neurodevelopmental perspective.

    Science.gov (United States)

    Acha, Joana; Pérez, Alejandro; Davidson, Doug J; Carreiras, Manuel

    2015-01-01

    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.

  15. Neurodevelopmental profile in Angelman syndrome: more than low intelligence quotient.

    Science.gov (United States)

    Micheletti, S; Palestra, F; Martelli, P; Accorsi, P; Galli, J; Giordano, L; Trebeschi, V; Fazzi, E

    2016-10-21

    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.

  16. Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy

    DEFF Research Database (Denmark)

    Mignot, Cyril; von Stülpnagel, Celina; Nava, Caroline

    2016-01-01

    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...

  17. Neurodevelopmental Outcomes of Prenatal Stress

    Directory of Open Access Journals (Sweden)

    M. Genco Usta

    2012-03-01

    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.

  18. The genetic relationship between handedness and neurodevelopmental disorders☆

    Science.gov (United States)

    Brandler, William M.; Paracchini, Silvia

    2014-01-01

    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

  19. Mevalonate Cascade and Neurodevelopmental and Neurodegenerative Diseases: Future Targets for Therapeutic Application.

    Science.gov (United States)

    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

    2017-01-01

    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 epub@benthamscience.org.

  20. Neurodevelopmental outcomes in children with congenital hypothyroidism

    OpenAIRE

    Almeida, Carolina Lopes de

    2016-01-01

    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...

  1. Genetic and pharmacological manipulations of the serotonergic system in early life: neurodevelopmental underpinnings of autism-related behavior

    NARCIS (Netherlands)

    Kinast, K.; Peeters, D.; Kolk, S.M.; Schubert, D.; Homberg, J.R.

    2013-01-01

    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

  2. Mutation of Semaphorin-6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology.

    LENUS (Irish Health Repository)

    2011-01-01

    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.

  3. Expression of human Gaucher disease gene GBA generates neurodevelopmental defects and ER stress in Drosophila eye.

    Directory of Open Access Journals (Sweden)

    Takahiro Suzuki

    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.

  4. A Clinician's Guide to Co-Occurring ADHD among Adolescent Substance Users: Comorbidity, Neurodevelopmental Risk, and Evidence-Based Treatment Options

    Science.gov (United States)

    Hogue, Aaron; Evans, Steven W.; Levin, Frances R.

    2017-01-01

    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…

  5. Neurobiology of depression: A neurodevelopmental approach.

    Science.gov (United States)

    Lima-Ojeda, Juan M; Rupprecht, Rainer; Baghai, Thomas C

    2017-03-03

    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.

  6. Neurodevelopmental attributes of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type: Update and perspectives.

    Science.gov (United States)

    Ghibellini, Giulia; Brancati, Francesco; Castori, Marco

    2015-03-01

    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.

  7. Cognitive computer training in children with attention deficit hyperactivity disorder (ADHD) versus no intervention: study protocol for a randomized controlled trial

    National Research Council Canada - National Science Library

    Bikic, Aida; Leckman, James F; Lindschou, Jane; Christensen, Torben Ø; Dalsgaard, Søren

    2015-01-01

    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...

  8. Genetic and Environmental Control of Neurodevelopmental Robustness in Drosophila.

    Directory of Open Access Journals (Sweden)

    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.

  9. Neurodevelopmental outcome in Angelman syndrome: genotype-phenotype correlations.

    Science.gov (United States)

    Mertz, Line Granild Bie; Thaulov, Per; Trillingsgaard, Anegen; Christensen, Rikke; Vogel, Ida; Hertz, Jens Michael; Ostergaard, John R

    2014-07-01

    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.

  10. Lack of evidence for neonatal misoprostol neurodevelopmental toxicity in C57BL6/J mice.

    Directory of Open Access Journals (Sweden)

    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.

  11. Generalised joint hypermobility and neurodevelopmental traits in a non-clinical adult population.

    Science.gov (United States)

    Glans, Martin; Bejerot, Susanne; Humble, Mats B

    2017-09-01

    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.

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

    National Research Council Canada - National Science Library

    Nguyen Quoc Vuong Tran; Kunio Miyake

    2017-01-01

    .... 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...

  13. Immunization Safety Review: Thimerosal - Containing Vaccines and Neurodevelopmental Disorders

    National Research Council Canada - National Science Library

    Stratton, Kathleen; Gable, Alicia; McCormick, Marie C

    2001-01-01

    ..., and Marie C.McCormick, Editors Immunization Safety Review Committee Board on Health Promotion and Disease Prevention INSTITUTE OF MEDICINE NATIONAL ACADEMY PRESS Washington, D.C. Copyrightoriginal retained, the be not from cannot book, paper original however, for version formatting, authoritative the typesetting-specific created from the as publ...

  14. Eyeblink Conditioning: A Non-Invasive Biomarker for Neurodevelopmental Disorders

    Science.gov (United States)

    Reeb-Sutherland, Bethany C.; Fox, Nathan A.

    2015-01-01

    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,…

  15. Pediatric neuroenhancement: ethical, legal, social, and neurodevelopmental implications.

    Science.gov (United States)

    Graf, William D; Nagel, Saskia K; Epstein, Leon G; Miller, Geoffrey; Nass, Ruth; Larriviere, Dan

    2013-03-26

    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.

  16. The neurodevelopmental basis of math anxiety.

    Science.gov (United States)

    Young, Christina B; Wu, Sarah S; Menon, Vinod

    2012-05-01

    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.

  17. Models of Neurodevelopmental Abnormalities in Schizophrenia

    Science.gov (United States)

    Powell, Susan B.

    2013-01-01

    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

  18. Neurodevelopmental Outcomes After Neonatal Surgery for Major Noncardiac Anomalies

    NARCIS (Netherlands)

    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

    2016-01-01

    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

  19. Novel roles for immune molecules in neural development: Implications for neurodevelopmental disoders

    Directory of Open Access Journals (Sweden)

    Paula A Garay

    2010-09-01

    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.

  20. Postnatal Phencyclidine (PCP) as a Neurodevelopmental Animal Model of Schizophrenia Pathophysiology and Symptomatology: A Review.

    Science.gov (United States)

    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).

  1. Disorders of visual perception

    NARCIS (Netherlands)

    Ffytche, Dominic H.; Blom, J. D.; Catani, M.

    2010-01-01

    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

  2. Macrophage migration inhibitory factor and autism spectrum disorders

    NARCIS (Netherlands)

    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

  3. Structural Brain Abnormalities in Adolescents with Autism Spectrum Disorder and Patients with Attention Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Brieber, Sarah; Neufang, Susanne; Bruning, Nicole; Kamp-Becker, Inge; Remschmidt, Helmut; Herpertz-Dahlmann, Beate; Fink, Gereon R.; Konrad, Kerstin

    2007-01-01

    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…

  4. Beyond survival: 5-year neurodevelopmental follow-up of a cohort of preterm infants in Colombo, Sri Lanka.

    Science.gov (United States)

    Sumanasena, S P; Vipulaguna, D V; Mendis, M M; Gunawardena, N S

    2017-10-18

    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.

  5. Animal-Assisted Therapy on Children with Autism Spectrum Disorder

    OpenAIRE

    Méndez Moreno, Alba

    2017-01-01

    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...

  6. Neurodevelopmental Biology Associated with Childhood Sexual Abuse

    Science.gov (United States)

    De Bellis, Michael D.; Spratt, Eve G.; Hooper, Stephen R.

    2011-01-01

    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…

  7. Communication Intervention for Young Children with Severe Neurodevelopmental Disabilities Via Telehealth.

    Science.gov (United States)

    Simacek, Jessica; Dimian, Adele F; McComas, Jennifer J

    2017-03-01

    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.

  8. The Neuroanatomy of Autism Spectrum Disorder: An Overview of Structural Neuroimaging Findings and Their Translatability to the Clinical Setting

    Science.gov (United States)

    Ecker, Christine

    2017-01-01

    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…

  9. Long-term neurodevelopmental outcome after fetal arrhythmia

    NARCIS (Netherlands)

    Lopriore, Enrico; Aziz, Muhammed I.; Nagel, Helene T.; Blom, Nico A.; Rozendaal, Lieke; Kanhai, Humphrey H. H.; Vandenbussche, Frank P. H. A.

    2009-01-01

    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

  10. Neurodevelopmental Problems in Maltreated Children Referred with Indiscriminate Friendliness

    Science.gov (United States)

    Kocovska, Eva; Puckering, Christine; Follan, Michael; Smillie, Maureen; Gorski, Charlotta; Barnes, James; Wilson, Philip; Young, David; Lidstone, Emma; Pritchett, Rachel; Hockaday, Harriet; Minnis, Helen

    2012-01-01

    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…

  11. Update on the Role of Environmental Toxins in Neurodevelopmental Disabilities

    Science.gov (United States)

    Kouris, Steven

    2007-01-01

    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…

  12. Pharmacogenetics of the Neurodevelopmental Impact of Anticancer Chemotherapy

    Science.gov (United States)

    Robaey, Philippe; Krajinovic, Maja; Marcoux, Sophie; Moghrabi, Albert

    2008-01-01

    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…

  13. Neurodevelopmental Effects of Early Deprivation in Postinstitutionalized Children

    Science.gov (United States)

    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.

    2010-01-01

    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…

  14. Neurodevelopmental status of HIV-exposed but uninfected children ...

    African Journals Online (AJOL)

    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.

  15. Extreme hyperbilirubinaemia in Zimbabwean neonates: neurodevelopmental outcome at 4 months

    NARCIS (Netherlands)

    Wolf, M. J.; Beunen, G.; Casaer, P.; Wolf, B.

    1997-01-01

    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

  16. Das Parteiverbot gem. Art. 21 II GG / Arnd Uhle

    Index Scriptorium Estoniae

    Uhle, Arnd

    2017-01-01

    Parteide tegevuse keelustamisest või piiramisest põhiseaduse artikli 21 tähenduses; Saksa konstitutsioonikohtu 17.01.2017 lahendist ja selle õiguslikest tagajärgedest. Samal teemal ka artikkel lk. 590-597

  17. Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

    NARCIS (Netherlands)

    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

  18. Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD

    NARCIS (Netherlands)

    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.

    2015-01-01

    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

  19. Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

    NARCIS (Netherlands)

    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

  20. Neurodevelopmental outcome after cardiac surgery utilizing cardiopulmonary bypass in children

    Directory of Open Access Journals (Sweden)

    Aymen N Naguib

    2015-01-01

    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

  1. Effect of co-twin gender on neurodevelopmental symptoms: a twin register study.

    Science.gov (United States)

    Eriksson, Jonna Maria; Lundström, Sebastian; Lichtenstein, Paul; Bejerot, Susanne; Eriksson, Elias

    2016-01-01

    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.

  2. Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder

    NARCIS (Netherlands)

    Rommelse, N.N.J.; Franke, B.; Geurts, H.M.; Hartman, C.A.; Buitelaar, J.K.

    2010-01-01

    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

  3. Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder.

    NARCIS (Netherlands)

    Rommelse, N.N.J.; Franke, B.; Geurts, H.M.; Hartman, C.A.; Buitelaar, J.K.

    2010-01-01

    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

  4. Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder

    NARCIS (Netherlands)

    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

  5. The effect of musical attention control training (MACT) on attention skills of adolescents with neurodevelopmental delays: a pilot study.

    Science.gov (United States)

    Pasiali, Varvara; LaGasse, A Blythe; Penn, Saundra L

    2014-01-01

    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

  6. Adult Learning Disorders: Contemporary Issues

    Science.gov (United States)

    Wolf, Lorraine E., Ed.; Schreiber, Hope E., Ed.; Wasserstein, Jeanette, Ed.

    2008-01-01

    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…

  7. Thyroid hormone for preventing of neurodevelopmental impairment in preterm infants.

    Science.gov (United States)

    Osborn, D A

    2000-01-01

    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

  8. Neurodevelopmental problems in maltreated children referred with indiscriminate friendliness

    OpenAIRE

    Kocovska, E.; Puckering, C; Follan, M.; Smillie, M.; Gorski, C.; Lidstone, E; Pritchett, R.; Hockaday, H.; Minnis, H.

    2012-01-01

    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...

  9. Targeting neural synchrony deficits is sufficient to improve cognition in a schizophrenia-related neurodevelopmental model

    Directory of Open Access Journals (Sweden)

    Heekyung eLee

    2014-02-01

    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.

  10. Critical appraisal of omega-3 fatty acids in attention-deficit/hyperactivity disorder treatment

    NARCIS (Netherlands)

    Konigs, A.; Kiliaan, A.J.

    2016-01-01

    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

  11. "With concord of sweet sounds...": new perspectives on the diversity of musical experience in autism and other neurodevelopmental conditions.

    Science.gov (United States)

    Heaton, Pamela; Allen, Rory

    2009-07-01

    Questions about music's evolution and functions have long excited interest among scholars. More recent theoretical accounts have stressed the importance of music's social origins and functions. Autism and Williams syndrome, neurodevelopmental disorders supposedly characterized by contrasting social and musical phenotypes, have been invoked as evidence for these. However, empirical data on social skills and deficits in autism and Williams syndrome do not support the notion of contrasting social phenotypes: research findings suggest that the social deficits characteristic of both disorders may increase rather than reduce the importance of music. Current data do not allow for a direct comparison of musical phenotypes in autism and Williams syndrome, although it is noted that deficits in music cognition have been observed in Williams syndrome, but not in autism. In considering broader questions about musical understanding in neurodevelopmental disorders, we conclude that intellectual impairment is likely to result in qualitative differences between handicapped and typical listeners, but this does not appear to limit the extent to which individuals can derive benefits from the experience of listening to music.

  12. STRENGTHENING THE REFLECTIVE FUNCTIONING CAPACITIES OF PARENTS WHO HAVE A CHILD WITH A NEURODEVELOPMENTAL DISABILITY THROUGH A BRIEF, RELATIONSHIP-FOCUSED INTERVENTION.

    Science.gov (United States)

    Sealy, Julie; Glovinsky, Ira P

    2016-01-01

    This randomized controlled trial examined the reflective functioning capacities of caregivers who have a child with a neurodevelopmental disorder between the ages of 2 years 0 months and 6 years 11 months. Children with a neurodevelopmental disorder receive a range of diagnoses, including sutism; however, they all exhibit social communication challenges that can derail social relationships. Forty parent-child dyads in Barbados were randomly assigned to either a developmental individual-difference, relationship-based/floortime(DIR/FT) group (n = 20), or a psychoeducational (wait-list) group (n = 20) with parental reflective functioning measured before and after a 12-week DIR/FT treatment intervention. Results revealed significant gains in parental reflective functioning in the treatment group, as compared to the psychoeducational (wait-list) group, after the 12-week relationship-focused intervention. © 2016 Michigan Association for Infant Mental Health.

  13. The changing nervous system: neurobehavioral consequences of early brain disorders

    National Research Council Canada - National Science Library

    Broman, Sarah H; Fletcher, Jack

    1999-01-01

    ..., and Behavioral Sparing, 114 Bertram R. Payne xvxvi Contents PART III NEURODEVELOPMENTAL COURSE OF EARLY BRAIN DISORDERS 7. Role of the Corpus Callosum in the Cognitive Development of Children with C...

  14. Long-term neurodevelopmental outcome of monochorionic and matched dichorionic twins.

    Directory of Open Access Journals (Sweden)

    Karien E A Hack

    Full Text Available BACKGROUND: Monochorionic (MC twins are at increased risk for perinatal mortality and serious morbidity due to the presence of placental vascular anastomoses. Cerebral injury can be secondary to haemodynamic and hematological disorders during pregnancy (especially twin-to-twin transfusion syndrome (TTTS or intrauterine co-twin death or from postnatal injury associated with prematurity and low birth weight, common complications in twin pregnancies. We investigated neurodevelopmental outcome in MC and dichorionic (DC twins at the age of two years. METHODS: This was a prospective cohort study. Cerebral palsy (CP was studied in 182 MC infants and 189 DC infants matched for weight and age at delivery, gender, ethnicity of the mother and study center. After losses to follow-up, 282 of the 366 infants without CP were available to be tested with the Griffiths Mental Developmental Scales at 22 months corrected age, all born between January 2005 and January 2006 in nine perinatal centers in The Netherlands. Due to phenotypic (unalikeness in mono-or dizygosity, the principal investigator was not blinded to chorionic status; perinatal outcome, with exception of co-twin death, was not known to the examiner. FINDINGS: Four out of 182 MC infants had CP (2.2% - two of the four CP-cases were due to complications specific to MC twin pregnancies (TTTS and co-twin death and the other two cases of CP were the result of cystic PVL after preterm birth - compared to one sibling of a DC twin (0.5%; OR 4.2, 95% CI 0.5-38.2 of unknown origin. Follow-up rate of neurodevelopmental outcome by Griffith's test was 76%. The majority of 2-year-old twins had normal developmental status. There were no significant differences between MC and DC twins. One MC infant (0.7% had a developmental delay compared to 6 DC infants (4.2%; OR 0.2, 95% 0.0-1.4. Birth weight discordancy did not influence long-term outcome, though the smaller twin had slightly lower developmental scores than its

  15. The incidence of unprovoked seizures and occurrence of neurodevelopmental comorbidities in children at the time of their first epileptic seizure and during the subsequent six months.

    Science.gov (United States)

    Åndell, Eva; Tomson, Torbjörn; Carlsson, Sofia; Hellebro, Eva; Andersson, Tomas; Adelöw, Cecilia; Åmark, Per

    2015-07-01

    To evaluate the incidence of unprovoked seizures in children and the prevalence of related neurodevelopmental comorbidities at the time of the presumed first seizure and six months thereafter. The medical records of all children (0-18 years of age) seeking medical attention as the result of a first unprovoked seizure between September 1, 2001 and December 31, 2006, and registered in the population-based Stockholm Incidence Registry of Epilepsy (SIRE) were reviewed. Neurodevelopmental comorbidities were evaluated on the basis of the medical records from this first visit and from other healthcare during the following six months. The incidence of unprovoked seizures was between 30 and 204/100,000 person years (n=766) in the different age groups. It was highest among the youngest children and lowest among the 18-year-olds with small gender differences. The most common neurodevelopment comorbidities were developmental delay (22%, CI: 19-25%), speech/language and learning difficulties (23%, CI: 20-26%) and intellectual disability (16%, CI: 13-18%). The types of neurodevelopmental comorbidity varied by age at the time of seizure onset, with cerebral palsy being more common among the 0-5-year-olds, attention deficits among the 6-16-year-olds, and autism and psychiatric diagnosis among the older children. An associated neurodevelopmental comorbidity was more common among those experiencing recurrent than single seizures during follow-up six months from the index seizure (42% versus 66%). In 68% (CI: 64-71%) of the children there was no known or suspected neurodevelopmental comorbidity. The incidence of unprovoked, non-febrile seizures among 0-18-year-olds included in the SIRE was 67/100,000 person-years. Neurodevelopmental comorbidities were common already at the time of onset of the seizure disorder, indicating that neither seizure treatment nor seizures were the underlying cause of other neurodevelopmental symptoms in these patients during the period studied. Copyright

  16. Neurodevelopmental pathways to preterm children's specific and general mathematic abilities.

    Science.gov (United States)

    Jaekel, Julia; Bartmann, Peter; Schneider, Wolfgang; Wolke, Dieter

    2014-10-01

    Preterm children have problems with mathematics but knowledge about the predictors of specific mathematic abilities in preterm populations is scarce. This study investigated neurodevelopmental pathways to children's general and specific mathematic abilities across the full gestational age range. Prospective geographically defined longitudinal investigation in Germany. 947 children across the full gestational age range (23-41 weeks). Outcome measures. At 8 years, children's cognitive and mathematic abilities were measured and residuals of a regression predicting mathematic scores by IQ were used to identify specific mathematic abilities. Neurodevelopmental cascade models revealed that adverse effects of preterm birth on mathematic abilities were mediated by neonatal risk. Specific mathematic abilities were uniquely predicted by the duration of hospitalization and ventilation. Prolonged neonatal medical treatment and, in particular, mechanical ventilation may lead to specific impairments in mathematic tasks. These findings have implications for the mode of respiratory support in neonates, routine follow-up and intervention planning as well as research about brain reorganization after preterm birth. Copyright © 2014. Published by Elsevier Ireland Ltd.

  17. Thyroid hormones for preventing neurodevelopmental impairment in preterm infants.

    Science.gov (United States)

    Osborn, D A

    2001-01-01

    Observational studies have shown an association between transiently low thyroid hormone levels in preterm infants in the first weeks of life (transient hypothyroxinemia) and 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 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 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. Nine studies were identified that compared thyroid hormone treatment to control. Four randomized and one quasi-randomized study met inclusion criteria. All studies enrolled preterm infants thyroid hormones. Four studies used thyroxine, whereas Amato 1989 used triiodothyronine. Only two studies with neurodevelopmental follow-up were of good methodology. All studies were of small size with the largest, van Wassenaer 1997, enrolling 200 infants. Meta-analysis of five studies found no significant difference in mortality to discharge (typical RR 0.70, 95% CI 0.42, 1.17) in infants who received thyroid hormone treatment compared to controls. Meta-analysis of two studies found no significant

  18. Neurodevelopmental correlates of proneness to guilt and shame in adolescence and early adulthood

    Directory of Open Access Journals (Sweden)

    Sarah Whittle

    2016-06-01

    Full Text Available Investigating how brain development during adolescence and early adulthood underlies guilt- and shame-proneness may be important for understanding risk processes for mental disorders. The aim of this study was to investigate the neurodevelopmental correlates of interpersonal guilt- and shame-proneness in healthy adolescents and young adults using structural magnetic resonance imaging (sMRI. Sixty participants (age range: 15–25 completed sMRI and self-report measures of interpersonal guilt- and shame-proneness. Independent of interpersonal guilt, higher levels of shame-proneness were associated with thinner posterior cingulate cortex (PCC thickness and smaller amygdala volume. Higher levels of shame-proneness were also associated with attenuated age-related reductions in thickness of lateral orbitofrontal cortex (lOFC. Our findings highlight the complexities in understanding brain–behavior relationships during the adolescent/young adult period. Results were consistent with growing evidence that accelerated cortical thinning during adolescence may be associated with superior socioemotional functioning. Further research is required to understand the implications of these findings for mental disorders characterized by higher levels of guilt and shame.

  19. Melatonin treatment for sleep disorders in children with neurodevelopmental disorders: an observational study.

    Science.gov (United States)

    Ross, Caroline; Davies, Paul; Whitehouse, William

    2002-05-01

    The study aim was to quantify melatonin-associated improvement in sleep by means of a parent-completed sleep diary during routine outpatient activity. An investigation into sleep disturbance was made at neurology outpatient appointments. Those parents who identified a problem were asked to complete a sleep diary, after which treatment was initiated. The first week of the diary was completed before treatment, the second when established on the maximum dose of melatonin required. Forty-nine patients (26 males, 23 females) aged from one to 13 years, were treated between 1997 and 1998: 28 of these returned interpretable diaries. In a further 18 patients, an assessment could be made of the usefulness of the treatment. Patients were fairly typical of those attending a tertiary centre, the most common primary diagnosis being epilepsy (n=26). Only seven patients were visually impaired. Of the 46 patients who were assessed, 34 showed an improvement. No adverse effects were attributed to the treatment.

  20. Schatzki's Ring in Angelman Syndrome: A Diagnostic Dilemma in Neurodevelopmentally Disabled Patients

    OpenAIRE

    Choi, Young Sammy; Sachar, David Scott

    2009-01-01

    Angelman Syndrome is a neurodevelopmental condition with a characteristic phenotype that includes epilepsy and lack of communication. We describe its first reported association with Schatzki's ring that presented as a life-long history of intermittent retching. Because of associated cognitive dysfunction, careful diagnostic consideration is required to detect this underlying condition. Keywords Schatzki's ring; Angelman Syndrome; Esophageal "B" ring; Barium esophagogram; Neurodevelopmental de...

  1. Piece Work: Fabric Collage as a Neurodevelopmental Approach to Trauma Treatment

    Science.gov (United States)

    Homer, Eliza S.

    2015-01-01

    This article describes the use of collaborative fabric collage based on a neurodevelopmental adaptation for an adult who was being treated for trauma. The case demonstrates the value of thinking about neurodevelopmental factors when creating art therapy interventions. A biologically respectful treatment that offers relational, relevant,…

  2. The Functional Evaluation of Eating Difficulties Scale: Study Protocol and Validation in Infants with Neurodevelopmental Impairments and Disabilities

    Directory of Open Access Journals (Sweden)

    Anna Cavallini

    2017-12-01

    Full Text Available IntroductionA reliable and accurate evaluation of oral-motor skills in newborns at risk for swallowing and feeding disorders is key to set the goals of effective early interventions. Although many tools are available to assess oral-motor skills in newborns, limited evidence exists for what pertains their reliability and their effectivity in predicting short- and long-term developmental outcomes in at-risk infants. The aim of the present study is to develop and provide a preliminary validation of a new clinically grounded tool [i.e., the Functional Evaluation of Eating Difficulties Scale (FEEDS] specifically designed to be used with at-risk newborns and infants. The paper describes the steps of tool development and information on the reliability of the tool are provided.Methods/analysisThe FEEDS has been developed according to clinical evidence and expertise by a multidisciplinary team of professionals dealing with feeding problems in at-risk infants diagnosed with neurodevelopmental impairments and disabilities. The steps of FEEDS development are reported, together with a detailed description of items, scoring procedure, and clinical cutoff. The FEEDS has been applied to a relatively large sample of 0- to 12-month-old infants (N = 136 with neurodevelopmental disability, enrolled consecutively between 2004 and 2016 at the Scientific Institute IRCCS Eugenio Medea (Bosisio Parini, Italy, which is the main rehabilitation hospital for children with neurodevelopmental disabilities in Italy. Internal consistency (Cronbach’s alpha and reliability (inter-rater agreement have been assessed.Ethics and disseminationAll the procedures are consistent with the World Medical Association Declaration of Helsinki (2013 and the FEEDS has been approved by the clinical committee of the Scientific Institute IRCCS Eugenio Medea. Further psychometric characteristics and evidence of the predictive validity of the FEEDS will be obtained on a larger sample and they

  3. The Functional Evaluation of Eating Difficulties Scale: Study Protocol and Validation in Infants with Neurodevelopmental Impairments and Disabilities.

    Science.gov (United States)

    Cavallini, Anna; Provenzi, Livio; Sacchi, Daniela; Longoni, Laura; Borgatti, Renato

    2017-01-01

    A reliable and accurate evaluation of oral-motor skills in newborns at risk for swallowing and feeding disorders is key to set the goals of effective early interventions. Although many tools are available to assess oral-motor skills in newborns, limited evidence exists for what pertains their reliability and their effectivity in predicting short- and long-term developmental outcomes in at-risk infants. The aim of the present study is to develop and provide a preliminary validation of a new clinically grounded tool [i.e., the Functional Evaluation of Eating Difficulties Scale (FEEDS)] specifically designed to be used with at-risk newborns and infants. The paper describes the steps of tool development and information on the reliability of the tool are provided. The FEEDS has been developed according to clinical evidence and expertise by a multidisciplinary team of professionals dealing with feeding problems in at-risk infants diagnosed with neurodevelopmental impairments and disabilities. The steps of FEEDS development are reported, together with a detailed description of items, scoring procedure, and clinical cutoff. The FEEDS has been applied to a relatively large sample of 0- to 12-month-old infants ( N  = 136) with neurodevelopmental disability, enrolled consecutively between 2004 and 2016 at the Scientific Institute IRCCS Eugenio Medea (Bosisio Parini, Italy), which is the main rehabilitation hospital for children with neurodevelopmental disabilities in Italy. Internal consistency (Cronbach's alpha) and reliability (inter-rater agreement) have been assessed. All the procedures are consistent with the World Medical Association Declaration of Helsinki (2013) and the FEEDS has been approved by the clinical committee of the Scientific Institute IRCCS Eugenio Medea. Further psychometric characteristics and evidence of the predictive validity of the FEEDS will be obtained on a larger sample and they will be reported in future publications from this group.

  4. Executive functioning deficits in preschool children with Fetal Alcohol Spectrum Disorders.

    Science.gov (United States)

    Fuglestad, Anita J; Whitley, Marisa L; Carlson, Stephanie M; Boys, Christopher J; Eckerle, Judith K; Fink, Birgit A; Wozniak, Jeffrey R

    2015-01-01

    Executive function (EF) deficit is a hallmark of Fetal Alcohol Spectrum Disorders (FASD), but the vast majority of available evidence comes from school-age children and adolescents. Very little is known about EF during the critical developmental period prior to 6 years of age in FASD. We evaluated EF in 39 children with FASD (3.0-5.5 years) and a comparison group of 50 age-matched, nonexposed controls. Measures included the EF Scale for Early Childhood and a Delay of Gratification task. Compared to age-matched controls, preschool children with FASD had impairments on the EF Scale and showed more impulsivity on the Delay of Gratification task. To confirm the EF Scale finding, FASD group performance was compared to a separate normative dataset (N = 1,400). Those with FASD performed below normal (M = -0.57, SD = 0.92). Within the FASD group, IQ was correlated with the EF Scale (partial r = .60, p = .001) and Delay of Gratification (partial r = .58, p = .005). EF Scale performance did not differ significantly across levels of FASD severity (fetal alcohol syndrome [FAS], partial FAS, or alcohol-related neurobehavioral disorder [ARND]). However, compared to normative data, those with FAS had the largest deficits (M = -0.91 SD from the mean, SE = 0.23), followed by partial FAS (M = -0.66 SD from the mean, SE = 0.26), then ARND (M = -0.36 SD from the mean, SE = 0.20). These novel data show that EF deficits manifest well before the age of 6 years in children with FASD, that they occur across the spectrum, and that EF may be most impaired in children with more severe forms of FASD and/or lower IQs.

  5. Gestational Age and Autism Spectrum Disorder

    DEFF Research Database (Denmark)

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

    2016-01-01

    Autism Spectrum Disorder (ASD) is a serious neurodevelopmental disorder. Several previous studies have identified pre-term birth as a risk factor for ASD but none has studied whether the association between gestational age and ASD has changed over time. This is a Danish population-based follow...

  6. Immune dysregulation in autism spectrum disorder

    NARCIS (Netherlands)

    Briceno Noriega, D.; Savelkoul, H.F.J.

    2014-01-01

    Autism spectrum disorder (ASD) is a common and severe neuro-developmental disorder in early childhood which is defined by social and communication deficits and repetitive and stereotypic behaviours. The aetiology of ASD remains poorly understood. Susceptibility to development of ASD has significant

  7. Twin-twin transfusion syndrome: neurodevelopmental screening test

    Directory of Open Access Journals (Sweden)

    Amabile Vessoni Arias

    2015-03-01

    Full Text Available Objective To assess the neurodevelopmental functions (cognition, language and motor function of survivors of twin-twin transfusion syndrome (TTTS. Method Observational cross-sectional study of a total of 67 monochorionic diamniotic twins who underwent fetoscopic laser coagulation (FLC for treatment of TTTS. The study was conducted at the Center for Investigation in Pediatrics (CIPED, Universidade Estadual de Campinas. Ages ranged from one month and four days to two years four months. Bayley Scales of Infant and Toddler Development Screening Test-III, were used for evaluation. Results Most children reached the competent category and were classified as having appropriate performance. The preterm children scored worse than term infants for gross motor subtest (p = 0.036. Conclusion The majority of children reached the expected development according to their age. Despite the good neurodevelopment, children classified at risk should be monitored for development throughout childhood.

  8. Prenatal exposure to organophosphorus pesticides and childhood neurodevelopmental phenotypes.

    Science.gov (United States)

    Furlong, Melissa A; Herring, Amy; Buckley, Jessie P; Goldman, Barbara D; Daniels, Julie L; Engel, Lawrence S; Wolff, Mary S; Chen, Jia; Wetmur, Jim; Barr, Dana Boyd; Engel, Stephanie M

    2017-10-01

    Prenatal exposure to organophosphorus pesticides (OPs) has been associated with different neurodevelopmental outcomes across different cohorts. A phenotypic approach may address some of these differences by incorporating information across scales and accounting for the complex correlational structure of neurodevelopmental outcomes. Additionally, Bayesian hierarchical modeling can account for confounding by collinear co-exposures. We use this framework to examine associations between prenatal exposure to OPs and behavior, executive functioning, and IQ assessed at age 6-9 years in a cohort of 404 mother/infant pairs recruited during pregnancy. We derived phenotypes of neurodevelopment with a factor analysis, and estimated associations between OP metabolites and these phenotypes in Bayesian hierarchical models for exposure mixtures. We report seven factors: 1) Impulsivity and Externalizing, 2) Executive Functioning, 3) Internalizing, 4) Perceptual Reasoning, 5) Adaptability, 6) Processing Speed, and 7) Verbal Intelligence. These, along with the Working Memory Index, were standardized and scaled so that positive values reflected positive attributes and negative values represented adverse outcomes. Standardized dimethylphosphate metabolites were negatively associated with Internalizing factor scores (β^ - 0.13, 95% CI - 0.26, 0.00) but positively associated with Executive Functioning factor scores (β^ 0.18, 95% CI 0.04, 0.31). Standardized diethylphosphate metabolites were negatively associated with the Working Memory Index (β^ - 0.17, 95% CI - 0.33, - 0.03). Associations with factor scores were generally stronger and more precise than associations with individual instrument-specific items. Factor analysis of outcomes may provide some advantages in etiological studies of childhood neurodevelopment by incorporating information across scales to reduce dimensionality and improve precision. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Neurodevelopmental outcome of 31 patients with borderline fetal ventriculomegaly.

    Science.gov (United States)

    Tatlı, Burak; Özer, Irmak; Ekici, Barış; Kalelioğlu, Ibrahim; Has, Recep; Eraslan, Emine; Yüksel, Atıl

    2012-09-01

    We present the neurodevelopmental outcome of patients with isolated borderline fetal ventriculomegaly. The present study was carried out at the Department of Pediatric Neurology, Istanbul Medical Faculty, Istanbul University in July-December 2010. Prenatal second trimester detailed ultrasound examinations were performed by obstetricians at the Prenatal Diagnosis Department of Istanbul Medical School, and 31 consecutive patients aged 8-33 months have been included in the study. Four patients with atrial diameters of over 15 mm and three patients with central nervous system development anomalies were excluded from the study. In order to assess the neuromotor development of patients, neurologic examinations and the Bayley Scales of Infant Development (BSID-III) were used. Nine patients were female (29%) and 22 were male (71%). In the postnatal period, tuberous sclerosis was found in one patient, Down syndrome in one, and equinovarus foot deformity in one. Atrial diameter was patients and >12 mm in 13. Cranial ultrasounds done in the first postnatal month revealed persisting ventriculomegaly in nine patients. The two patients who scored significantly low in all areas on the Bayley Scales of Infant Development were the patients with Down syndrome and tuberous sclerosis. The one scoring low in the motor area was the patient with the equinovarus foot deformity. The BSID-III scores of the patients whose prenatal ventricle diameter was patients showing slight developmental delay were the ones whose cranial ultrasound in the first postnatal month showed persisting ventriculomegaly. In patients with borderline fetal ventriculomegaly, atrial diameter being more than 12 mm, the condition persisting in the first postnatal month and the presence of accompanying syndromes and malformations all constitute clear risk factors for neurodevelopmental outcome. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Markers of neurodevelopmental impairments in early-onset psychosis

    Directory of Open Access Journals (Sweden)

    Petruzzelli MG

    2015-07-01

    Full Text Available Maria Giuseppina Petruzzelli,1 Lucia Margari,1 Francesco Craig,1 Maria Gloria Campa,1 Domenico Martinelli,2 Adriana Pastore,3 Marta Simone,1 Francesco Margari3 1Child and Adolescence Neuropsychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University “Aldo Moro” of Bari, 2Department of Medical and Surgical Sciences; University of Foggia, Foggia, 3Psychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organ, University “Aldo Moro” of Bari, Bari, Italy Background: The aim of this study was to assess the association between the clinical and neurobiological markers of neurodevelopmental impairments and early-onset schizophrenia spectrum psychosis. Methods: A sample of 36 patients with early-onset schizophrenia spectrum psychosis was compared to a control sample of 36 patients with migraine. We assessed early childhood neurodevelopmental milestones using a modified version of the General Developmental Scale, general intellectual ability using the Wechsler Intelligence Scale for Children–Revised or Leiter International Performance Scale–Revised for patients with speech and language abnormalities, and neurological soft signs with specific regard to subtle motor impairment. Results: Subjects with early-onset psychosis had a higher rate of impaired social development (P=0.001, learning difficulties (P=0.04, enuresis (P=0.0008, a lower intelligence quotient (P<0.001, and subtle motor impairments (P=0.005 than control subjects. Conclusion: We suggest that neurodevelopment in early-onset psychosis is characterized by a global impairment of functional and adaptive skills that manifests from early childhood, rather than a delay or limitation in language and motor development. The current evidence is based on a small sample and should be investigated in larger samples in future research. Keywords: early-onset psychosis, early-onset schizophrenia, neurodevelopment, social cognition

  11. SLC2A3 single-nucleotide polymorphism and duplication influence cognitive processing and population-specific risk for attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    Merker, S.; Reif, A.; Ziegler, G.C.; Weber, H.; Mayer, U.; Ehlis, A.C.; Conzelmann, A.; Johansson, S.; Muller-Reible, C.; Nanda, I.; Haaf, T.; Ullmann, R.; Romanos, M.; Fallgatter, A.J.; Pauli, P.; Strekalova, T.; Jansch, C.; Arias Vasquez, A.; Haavik, J.; Ribases, M.; Ramos-Quiroga, J.A.; Buitelaar, J.K.; Franke, B.; Lesch, K.P.

    2017-01-01

    BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs)

  12. Adult attention-deficit hyperactivity disorder: Why should we pay ...

    African Journals Online (AJOL)

    Background: Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, with a chronic, costly and debilitating course if untreated. Limited access to diagnosis and treatment for adults with ADHD contributes to the cost of the disorder and the burden of disease. Aim: This study aims to identify ...

  13. Late Identification of Autistic Disorder in Nigeria: An Illustration with ...

    African Journals Online (AJOL)

    Background: Autistic disorder is a severe neuro-developmental disorder. In recent years, there has been an increased concern about the upsurge in the prevalence of autism. Psychiatrists and other clinicians have a pivotal role in its identification. Methods: This is a report of 2 cases of autistic disorder seen at a child and

  14. Microdeletions of ELP4 Are Associated with Language Impairment, Autism Spectrum Disorder, and Mental Retardation

    DEFF Research Database (Denmark)

    Addis, Laura; Ahn, Joo Wook; Dobson, Richard

    2015-01-01

    Copy-number variations (CNVs) are important in the aetiology of neurodevelopmental disorders and show broad phenotypic manifestations. We compared the presence of small CNVs disrupting the ELP4-PAX6 locus in 4,092 UK individuals with a range of neurodevelopmental conditions, clinically referred f...

  15. Association between Severity of Behavioral Phenotype and Comorbid Attention Deficit Hyperactivity Disorder Symptoms in Children with Autism Spectrum Disorders

    Science.gov (United States)

    Rao, Patricia A.; Landa, Rebecca J.

    2014-01-01

    Autism spectrum disorder and attention deficit hyperactivity disorder are neurodevelopmental disorders that cannot be codiagnosed under existing diagnostic guidelines ("Diagnostic and Statistical Manual of the American Psychiatric Association," 4th ed., text rev.). However, reports are emerging that attention deficit hyperactivity…

  16. Executive Functioning Differences between Adults with Attention Deficit Hyperactivity Disorder and Autistic Spectrum Disorder in Initiation, Planning and Strategy Formation

    Science.gov (United States)

    Bramham, Jessica; Ambery, Fiona; Young, Susan; Morris, Robin; Russell, Ailsa; Xenitidis, Kiriakos; Asherson, Philip; Murphy, Declan

    2009-01-01

    Executive functioning deficits characterize the neuropsychological profiles of the childhood neurodevelopmental disorders of attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD). This study sought to determine whether similar impairments exist in adults with ADHD (N = 53) and ASD (N = 45) in comparison with a…

  17. Co-morbidity in Attention-Deficit Hyperactivity Disorder: A Clinical Study from India.

    Science.gov (United States)

    Jacob, P; Srinath, S; Girimaji, S; Seshadri, S; Sagar, J V

    2016-12-01

    To assess the prevalence of neurodevelopmental and psychiatric co-morbidities in children and adolescents diagnosed with attention-deficit hyperactivity disorder at a tertiary care child and adolescent psychiatry centre. A total of 63 children and adolescents who were diagnosed with attention-deficit hyperactivity disorder and fulfilled the inclusion criteria were comprehensively assessed for neurodevelopmental and psychiatric co-morbidities. The tools used included the Mini-International Neuropsychiatric Interview for Children and Adolescents, Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHD-RS), Children's Global Assessment Scale, Clinical Global Impression Scale, Vineland Social Maturity Scale, and Childhood Autism Rating Scale. All except 1 subject had neurodevelopmental and / or psychiatric disorder co-morbid with attention-deficit hyperactivity disorder; 66.7% had both neurodevelopmental and psychiatric disorders. Specific learning disability was the most common co-existing neurodevelopmental disorder and oppositional defiant disorder was the most common psychiatric co-morbidity. The mean baseline ADHD-RS scores were significantly higher in the group with psychiatric co-morbidities, especially in the group with oppositional defiant disorder. Co-morbidity is present at a very high frequency in clinic-referred children diagnosed with attention-deficit hyperactivity disorder. Psychiatric co-morbidity, specifically oppositional defiant disorder, has an impact on the severity of attention-deficit hyperactivity disorder. Co-morbidity needs to be explicitly looked for during evaluation and managed appropriately.

  18. PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.

    Science.gov (United States)

    Zollo, Massimo; Ahmed, Mustafa; Ferrucci, Veronica; Salpietro, Vincenzo; Asadzadeh, Fatemeh; Carotenuto, Marianeve; Maroofian, Reza; Al-Amri, Ahmed; Singh, Royana; Scognamiglio, Iolanda; Mojarrad, Majid; Musella, Luca; Duilio, Angela; Di Somma, Angela; Karaca, Ender; Rajab, Anna; Al-Khayat, Aisha; Mohan Mohapatra, Tribhuvan; Eslahi, Atieh; Ashrafzadeh, Farah; Rawlins, Lettie E; Prasad, Rajniti; Gupta, Rashmi; Kumari, Preeti; Srivastava, Mona; Cozzolino, Flora; Kumar Rai, Sunil; Monti, Maria; Harlalka, Gaurav V; Simpson, Michael A; Rich, Philip; Al-Salmi, Fatema; Patton, Michael A; Chioza, Barry A; Efthymiou, Stephanie; Granata, Francesca; Di Rosa, Gabriella; Wiethoff, Sarah; Borgione, Eugenia; Scuderi, Carmela; Mankad, Kshitij; Hanna, Michael G; Pucci, Piero; Houlden, Henry; Lupski, James R; Crosby, Andrew H; Baple, Emma L

    2017-04-01

    PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  19. Neuroprogression in bipolar disorder.

    Science.gov (United States)

    Schneider, Marguerite Reid; DelBello, Melissa P; McNamara, Robert K; Strakowski, Stephen M; Adler, Caleb M

    2012-06-01

    Recent theories regarding the neuropathology of bipolar disorder suggest that both neurodevelopmental and neurodegenerative processes may play a role. While magnetic resonance imaging has provided significant insight into the structural, functional, and connectivity abnormalities associated with bipolar disorder, research assessing longitudinal changes has been more limited. However, such research is essential to elucidate the pathophysiology of the disorder. The aim of our review is to examine the extant literature for developmental and progressive structural and functional changes in individuals with and at risk for bipolar disorder. We conducted a literature review using MEDLINE and the following search terms: bipolar disorder, risk, child, adolescent, bipolar offspring, MRI, fMRI, DTI, PET, SPECT, cross-sectional, longitudinal, progressive, and developmental. Further relevant articles were identified by cross-referencing with identified manuscripts. There is some evidence for developmental and progressive neurophysiological alterations in bipolar disorder, but the interpretation of correlations between neuroimaging findings and measures of illness exposure or age in cross-sectional studies must be performed with care. Prospective longitudinal studies placed in the context of normative developmental and atrophic changes in neural structures and pathways thought to be involved in bipolar disorder are needed to improve our understanding of the neurodevelopmental underpinnings and progressive changes associated with bipolar disorder. © 2012 John Wiley and Sons A/S.

  20. Copy number variation in obsessive-compulsive disorder and tourette syndrome: A cross-disorder study

    NARCIS (Netherlands)

    L.M. McGrath; D. Yu (D.); C.R. Marshall (Christian); L.K. Davis (Lea); B. Thiruvahindrapuram (Bhooma); B. Li (Bingbin); C. Cappi (Carolina); G. Gerber (Gloria); A. de Wolf (Anneke); F.A. Schroeder (Frederick); L. Osiecki (Lisa); C. O'Dushlaine (Colm); A. Kirby (Andrew); C. Illmann (Cornelia); S. Haddad (Stephen); P. Gallagher (Patience); J. Fagerness (Jesen); C.L. Barr (Cathy); L. Bellodi (Laura); F. Benarroch (Fortu); O.J. Bienvenu (Oscar); D.W. Black (Donald W); J. Bloch (Jocelyne); R.D. Bruun (Ruth); C.L. Budman (Cathy); B. Camarena (Beatriz); D. Cath (Daniëlle); M.C. Cavallini (Maria); S. Chouinard; V. Coric (Vladimir); C. Cullen; R. Delorme (Richard); D.A.J.P. Denys (Damiaan); E.M. Derks (Eske); Y. Dion (Yves); M.C. Rosário (Maria); C.E. Eapen (Chundamannil Eapen); P. Evans; P. Falkai (Peter); T.V. Fernandez (Thomas); H. Garrido (Helena); D. Geller (Daniel); H.J. Grabe (Hans Jörgen); M. Grados (Marco); B.D. Greenberg (Benjamin); V. Gross-Tsur (Varda); E. Grünblatt (Edna); M.L. Heiman (Mark); S.M.J. Hemmings (Sian); L.D. Herrera (Luis); A.G. Hounie (Ana); J. Jankovic (Joseph); J.L. Kennedy; R.A. King; R. Kurlan; N. Lanzagorta (Nuria); M. Leboyer (Marion); J.F. Leckman; L. Lennertz (Leonhard); C. Lochner (Christine); T.L. Lowe (Thomas); H.N. Lyon (Helen); F. MacCiardi (Fabio); W. Maier (Wolfgang); J.T. McCracken (James); W.M. McMahon (William); D.L. Murphy (Dennis); A.L. Naarden (Allan); E. Nurmi (Erika); A.J. Pakstis; C. Pato (Carlos); C. Pato (Carlos); J. Piacentini (John); C. Pittenger (Christopher); M.N. Pollak (Michael); V.I. Reus (Victor); M.A. Richter (Margaret); M. Riddle (Mark); M.M. Robertson; D. Rosenberg (David); G.A. Rouleau; S. Ruhrmann (Stephan); A.S. Sampaio (Aline); J. Samuels (Jonathan); P. Sandor (Paul); B. Sheppard (Brooke); H.S. Singer (Harvey); J.H. Smit (Jan); D.J. Stein (Dan); J.A. Tischfield (Jay); H. Vallada (Homero); J. Veenstra-Vanderweele (Jeremy); S. Walitza (Susanne); Y. Wang (Ying); A. Wendland (Annika); Y.Y. Shugart; E.C. Miguel (Euripedes); H. Nicolini (Humberto); B.A. Oostra (Ben); R. Moessner (Rainald); M. Wagner (Michael); A. Ruiz-Linares (Andres); P. Heutink (Peter); G. Nestadt (Gerald); N.B. Freimer (Nelson); T.L. Petryshen (Tracey); D. Posthuma (Danielle); M.A. Jenike (Michael); N.J. Cox (Nancy); G.L. Hanna (Gregory); H. Brentani (Helena); S.W. Scherer (Stephen); P.D. Arnold (Paul); S.E. Stewart; C. Mathews; J.A. Knowles (James A); E.H. Cook (Edwin); D.L. Pauls (David); K. Wang (Kai); J.M. Scharf; B.M. Neale (Benjamin)

    2014-01-01

    textabstractObjective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and

  1. Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study.

    NARCIS (Netherlands)

    McGrath, L.M.; Yu, D.; Marshall, C.; Davis, L.K.; Thiruvahindrapuram, B.; Li, B.; Cappi, C.; Gerber, G.; Wolf, A.; Schroeder, F.A.; Osiecki, L.; O'Dushlaine, C.; Kirby, A.; Illmann, C.; Haddad, S.; Gallagher, P.; Fagerness, J.A.; Barr, C.L.; Bellodi, L.; Benarroch, F.; Bienvenu, O.J.; Black, D. W.; Bloch, M.H.; Bruun, R.D.; Budman, C.L.; Camarena, B.; Cath, D.C.; Cavallini, M.C.; Chouinard, S.; Coric, V.; Cullen, B.; Delorme, R.; Denys, D.; Derks, E.M.; Dion, Y.; Rosário, M.C.; Eapen, V.; Evans, P.; Falkai, P.; Fernandez, T.V.; Garrido, H.; Geller, D.; Grabe, H.J.; Grados, M.A.; Greenberg, B.D.; Gross-Tsur, V.; Grünblatt, E.; Heiman, G.A.; Hemmings, S.M.; Herrera, L.D.; Hounie, A.G.; Jankovic, J.; Kennedy, J.L.; King, R.A.; Kurlan, R.; Lanzagorta, N.; Leboyer, M.; Leckman, J.F.; Lennertz, L.; Lochner, C.; Lowe, T.L.; Lyon, G.J.; Macciardi, F.; Maier, W.; McCracken, J.T.; McMahon, W.; Murphy, D.L.; Naarden, A.L.; Neale, B. M.; Nurmi, E.; Pakstis, A.J.; Pato, M. T.; Piacentini, J.; Pittenger, C.; Pollak, Y.; Reus, V.I.; Richter, M.A.; Riddle, M.; Robertson, M.M.; Rosenberg, D.; Rouleau, G.A.; Ruhrmann, S.; Sampaio, A.S.; Samuels, J.; Sandor, P.; Sheppard, B.; Singer, H.S.; Smit, J.H.; Stein, D.J.; Tischfield, J.A.; Vallada, H.; Veenstra-Vanderweele, J.; Walitza, S.; Wang, Y.; Wendland, J.R.; Shugart, Y.Y.; Miguel, E.C.; Nicolini, H.; Oostra, B.A.; Moessner, R.; Wagner, M.; Ruiz-Linares, A.; Heutink, P.; Nestadt, G.; Freimer, N.; Petryshen, T.; Posthuma, D.; Jenike, M.A.; Cox, N.J.; Hanna, G.L.; Brentani, H.; Scherer, S.W.; Arnold, P.D.; Stewart, S.E.; Mathews, C.A.; Knowles, J.A.; Cook, E.H.; Pauls, D.L.; Wang, K.; Scharf, J.M.

    2014-01-01

    Objective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest

  2. Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study

    NARCIS (Netherlands)

    McGrath, Lauren M.; Yu, Dongmei; Marshall, Christian; Davis, Lea K.; Thiruvahindrapuram, Bhooma; Li, Bingbin; Cappi, Carolina; Gerber, Gloria; Wolf, Aaron; Schroeder, Frederick A.; Osiecki, Lisa; O'Dushlaine, Colm; Kirby, Andrew; Illmann, Cornelia; Haddad, Stephen; Gallagher, Patience; Fagerness, Jesen A.; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Bienvenu, O. Joseph; Black, Donald W.; Bloch, Michael H.; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Cath, Danielle C.; Cavallini, Maria C.; Chouinard, Sylvain; Coric, Vladimir; Cullen, Bernadette; Delorme, Richard; Denys, Damiaan; Derks, Eske M.; Dion, Yves; Rosário, Maria C.; Eapen, Valsama; Evans, Patrick; Falkai, Peter; Fernandez, Thomas V.; Garrido, Helena; Geller, Daniel; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Grünblatt, Edna; Heiman, Gary A.; Hemmings, Sian M. J.; Herrera, Luis D.; Hounie, Ana G.; Jankovic, Joseph; Kennedy, James L.; King, Robert A.; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Lochner, Christine; Lowe, Thomas L.; Lyon, Gholson J.; Macciardi, Fabio; Maier, Wolfgang; McCracken, James T.; McMahon, William; Murphy, Dennis L.; Naarden, Allan L.; Neale, Benjamin M.; Nurmi, Erika; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark; Robertson, Mary M.; Rosenberg, David; Rouleau, Guy A.; Ruhrmann, Stephan; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Tischfield, Jay A.; Vallada, Homero; Veenstra-Vanderweele, Jeremy; Walitza, Susanne; Wang, Ying; Wendland, Jens R.; Shugart, Yin Yao; Miguel, Euripedes C.; Nicolini, Humberto; Oostra, Ben A.; Moessner, Rainald; Wagner, Michael; Ruiz-Linares, Andres; Heutink, Peter; Nestadt, Gerald; Freimer, Nelson; Petryshen, Tracey; Posthuma, Danielle; Jenike, Michael A.; Cox, Nancy J.; Hanna, Gregory L.; Brentani, Helena; Scherer, Stephen W.; Arnold, Paul D.; Stewart, S. Evelyn; Mathews, Carol A.; Knowles, James A.; Cook, Edwin H.; Pauls, David L.; Wang, Kai; Scharf, Jeremiah M.

    2014-01-01

    Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare ( <1%) copy number variants (CNVs) in OCD and the largest genome-wide

  3. Copy number variation in obsessive-compulsive disorder and tourette syndrome : a cross-disorder study

    NARCIS (Netherlands)

    McGrath, Lauren M; Yu, Dongmei; Marshall, Christian; Davis, Lea K; Thiruvahindrapuram, Bhooma; Li, Bingbin; Cappi, Carolina; Gerber, Gloria; Wolf, Aaron; Schroeder, Frederick A; Osiecki, Lisa; O'Dushlaine, Colm; Kirby, Andrew; Illmann, Cornelia; Haddad, Stephen; Gallagher, Patience; Fagerness, Jesen A; Barr, Cathy L; Bellodi, Laura; Benarroch, Fortu; Bienvenu, O Joseph; Black, Donald W; Bloch, Michael H; Bruun, Ruth D; Budman, Cathy L; Camarena, Beatriz; Cath, Danielle C|info:eu-repo/dai/nl/194111423; Cavallini, Maria C; Chouinard, Sylvain; Coric, Vladimir; Cullen, Bernadette; Delorme, Richard; Denys, Damiaan; Derks, Eske M; Dion, Yves; Rosário, Maria C; Eapen, Valsama; Evans, Patrick; Falkai, Peter; Fernandez, Thomas V; Garrido, Helena; Geller, Daniel; Grabe, Hans J; Grados, Marco A; Greenberg, Benjamin D; Gross-Tsur, Varda; Grünblatt, Edna; Heiman, Gary A; Hemmings, Sian M J; Herrera, Luis D; Hounie, Ana G; Jankovic, Joseph; Kennedy, James L; King, Robert A; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F; Lennertz, Leonhard; Lochner, Christine; Lowe, Thomas L; Lyon, Gholson J; Macciardi, Fabio; Maier, Wolfgang; McCracken, James T; McMahon, William; Murphy, Dennis L; Naarden, Allan L; Neale, Benjamin M; Nurmi, Erika; Pakstis, Andrew J; Pato, Michele T; Pato, Carlos N; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Reus, Victor I; Richter, Margaret A; Riddle, Mark; Robertson, Mary M; Rosenberg, David; Rouleau, Guy A; Ruhrmann, Stephan; Sampaio, Aline S; Samuels, Jack; Sandor, Paul; Sheppard, Brooke; Singer, Harvey S; Smit, Jan H|info:eu-repo/dai/nl/113700644; Stein, Dan J; Tischfield, Jay A; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Wendland, Jens R; Shugart, Yin Yao; Miguel, Euripedes C; Nicolini, Humberto; Oostra, Ben A; Moessner, Rainald; Wagner, Michael; Ruiz-Linares, Andres; Heutink, Peter; Nestadt, Gerald; Freimer, Nelson; Petryshen, Tracey; Posthuma, Danielle; Jenike, Michael A; Cox, Nancy J; Hanna, Gregory L; Brentani, Helena; Scherer, Stephen W; Arnold, Paul D; Stewart, S Evelyn; Mathews, Carol A; Knowles, James A; Cook, Edwin H; Pauls, David L; Wang, Kai; Scharf, Jeremiah M

    OBJECTIVE: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest

  4. Elimination diets' efficacy and mechanisms in attention deficit hyperactivity disorder and autism spectrum disorder

    NARCIS (Netherlands)

    Ly, Verena; Bottelier, Marco; Hoekstra, Pieter J.; Vasquez, Alejandro Arias; Buitelaar, Jan K.; Rommelse, Nanda N.

    Nutrition plays an important role in neurodevelopment. This insight has led to increasing research into the efficacy of nutrition-related interventions for treating neurodevelopmental disorders. This review discusses an elimination diet as a treatment for attention deficit hyperactivity disorder and

  5. One-year infant outcome in women with early-onset hypertensive disorders of pregnancy

    NARCIS (Netherlands)

    Rep, A.; Ganzevoort, W.; van Wassenaer, A. G.; Bonsel, G. J.; Wolf, H.; de Vries, J. I. P.

    2008-01-01

    Objectives To evaluate the role of plasma volume expansion on 1-year infant outcome after severe hypertensive disorders of pregnancy and to determine prognostic factors for adverse neurodevelopmental infant outcome. Design Randomised controlled trial, observational prognostic study. Setting Two

  6. One-year infant outcome in women with early-onset hypertensive disorders of pregnancy

    NARCIS (Netherlands)

    Rep, A.; Ganzevoort, W.; van Wassenaer, A.G.; Bonsel, G.J.; de Wolf, H.; de Vries, J.I.

    2008-01-01

    Objectives: To evaluate the role of plasma volume expansion on 1-year infant outcome after severe hypertensive disorders of pregnancy and to determine prognostic factors for adverse neurodevelopmental infant outcome. Design: Randomised controlled trial, observational prognostic study. Setting: Two

  7. Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders

    NARCIS (Netherlands)

    Ramsey, J.M.; Guest, P.C.; Broek, J.A.C.; Glennon, J.C.; Rommelse, N.N.; Franke, B.; Rahmoune, H.; Buitelaar, J.K.; Bahn, S.

    2013-01-01

    BACKGROUND: Autism spectrum disorders (ASDs) are neurodevelopmental conditions with symptoms manifesting before the age of 3, generally persisting throughout life and affecting social development and communication. Here, we have investigated changes in protein biomarkers in blood during childhood

  8. Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders

    NARCIS (Netherlands)

    J.M. Ramsey (Jordan); P.C. Guest (Paul); J.A.C. Broek (Jantine A.); J.C. Glennon (Jeffrey C); N. Rommelse (Nanda); B. Franke (Barbara); H. Rahmoune (Hassan); J.K. Buitelaar (Jan); S. Bahn (Sabine)

    2013-01-01

    textabstractBackground: Autism spectrum disorders (ASDs) are neurodevelopmental conditions with symptoms manifesting before the age of 3, generally persisting throughout life and affecting social development and communication. Here, we have investigated changes in protein biomarkers in blood during

  9. Blood lead concentrations in Jamaican children with and without autism spectrum disorder

    National Research Council Canada - National Science Library

    Rahbar, Mohammad H; Samms-Vaughan, Maureen; Dickerson, Aisha S; Loveland, Katherine A; Ardjomand-Hessabi, Manouchehr; Bressler, Jan; Shakespeare-Pellington, Sydonnie; Grove, Megan L; Pearson, Deborah A; Boerwinkle, Eric

    .... Lead is a toxic metal shown to cause neurodevelopmental disorders in children. Several studies have investigated the possible association between exposure to lead and ASD, but their findings are conflicting...

  10. Understanding the Comorbidity between Dyslexia and Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Boada, Richard; Willcutt, Erik G.; Pennington, Bruce F.

    2012-01-01

    Dyslexia and attention-deficit/hyperactivity disorder (ADHD) are 2 of the most prevalent complex neurodevelopmental disorders of childhood, each affecting approximately 5% of the population in the United States. These disorders are also each comorbid with speech sound disorder and language impairment. Understanding the nature of the comorbidity…

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

    NARCIS (Netherlands)

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

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

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

    Science.gov (United States)

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

    2015-01-01

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

  13. NEURODEVELOPMENTAL CARE OF PRETERM BABIES AND ITS KEY ELEMENTS

    Directory of Open Access Journals (Sweden)

    I. M. Sarapuk

    2017-07-01

    Full Text Available Over the past few decades, the advancements in the perinatal and neonatal intensive care have led to a significant survival of premature infants. However neurodevelopmental outcome still remains the topical issues of concern. Developmental care is an approach that is aimed to reduce the mismatches between extra- and intra-uterine environments, decrease the stress of preterm newborns in neonative intensive care units, and thus promote optimal neurobehavioral development of the infant. The Newborn Individualized Developmental Care and Assessment Program (NIDCAP model was developed as a clinical framework for the implementation of developmental care. The model focuses on detailed reading of each individual infant’s behavioral cues. By observing the child during the routine manipulation performance (before, during and after and a detailed description of his/her behavioral responses, a professional can assess the ability of the infant’s immature nervous system to tolerate the environment and care manipulations. Such evaluation will enable to determine the adequacy of environmental conditions and care manipulations to baby’s opportunities and needs, with their subsequent correction and adaptation. NIDCAP’s aim is to support the child in its increasing tolerance to stimuli and to minimize stressful events and manipulation. With the help of NIDCAP approaches in neonatal care, medical staff study how to read infants’ behavior, hear their voice and understand them.

  14. Neurodevelopmental profile of Down syndrome in Chinese children.

    Science.gov (United States)

    Kwong, K L; Wong, V

    1996-04-01

    To give an overall appraisal of the clinical features of Down syndrome (DS) in Chinese children with emphasis on the neurodevelopmental outcome, and to compare the related complications with that of other races. The records of 124 Chinese children with DS assessed at the Child Assessment Centre of the University Department of Paediatrics in the Duchess of Kent Children's Hospital from 1985 to 1993 were reviewed. Thirty-one per cent of patients had microcephaly. Eighty-five percent (33/39) when assessed in the first year of life had a developmental quotient (DQ) above 50 but only 29% (2/7) had DQ above 50 when assessed after the age of 5. Only two patients (1.6%) had epilepsy: infantile spasms (1) and Lennox-Gastaut syndrome (1). Hearing impairment was found in 45% of children with mild conductive hearing impairment being the most common. Chinese children with DS, when compared with other races, were similarly intellectually disabled, but were less likely to develop epilepsy.

  15. Differential susceptibility to the environment: an evolutionary--neurodevelopmental theory.

    Science.gov (United States)

    Ellis, Bruce J; Boyce, W Thomas; Belsky, Jay; Bakermans-Kranenburg, Marian J; van Ijzendoorn, Marinus H

    2011-02-01

    Two extant evolutionary models, biological sensitivity to context theory (BSCT) and differential susceptibility theory (DST), converge on the hypothesis that some individuals are more susceptible than others to both negative (risk-promoting) and positive (development-enhancing) environmental conditions. These models contrast with the currently dominant perspective on personal vulnerability and environmental risk: diathesis stress/dual risk. We review challenges to this perspective based on emerging theory and data from the evolutionary, developmental, and health sciences. These challenges signify the need for a paradigm shift in conceptualizing Person x Environment interactions in development. In this context we advance an evolutionary--neurodevelopmental theory, based on DST and BSCT, of the role of neurobiological susceptibility to the environment in regulating environmental effects on adaptation, development, and health. We then outline current thinking about neurogenomic and endophenotypic mechanisms that may underpin neurobiological susceptibility, summarize extant empirical research on differential susceptibility, and evaluate the evolutionary bases and implications of BSCT and DST. Finally, we discuss applied issues including methodological and statistical considerations in conducting differential susceptibility research; issues of ecological, cultural, and racial--ethnic variation in neurobiological susceptibility; and implications of differential susceptibility for designing social programs. We conclude that the differential susceptibility paradigm has far-reaching implications for understanding whether and how much child and adult development responds, for better and for worse, to the gamut of species-typical environmental conditions.

  16. Prader-Willi Syndrome and Schaaf-Yang Syndrome: Neurodevelopmental Diseases Intersecting at the MAGEL2 Gene

    Science.gov (United States)

    Fountain, Michael D.; Schaaf, Christian P.

    2016-01-01

    Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by neonatal hypotonia, developmental delay/intellectual disability, and characteristic feeding behaviors with failure to thrive during infancy; followed by hyperphagia and excessive weight gain later in childhood. Individuals with PWS also manifest complex behavioral phenotypes. Approximately 25% meet criteria for autism spectrum disorder (ASD). PWS is caused by the absence of paternally expressed, maternally silenced genes at chromosome 15q11-q13. MAGEL2 is one of five protein-coding genes in the PWS-critical domain. Truncating point mutations of the paternal allele of MAGEL2 cause Schaaf-Yang syndrome, which has significant phenotypic overlap with PWS, but is also clinically distinct; based on the presence of joint contractures, and a particularly high prevalence of autism spectrum disorder (up to 75% of affected individuals). The clinical and molecular overlap between PWS and Schaaf-Yang syndrome, but also their distinguishing features provide insight into the pathogenetic mechanisms underlying both disorders. PMID:28933382

  17. Prader-Willi Syndrome and Schaaf-Yang Syndrome: Neurodevelopmental Diseases Intersecting at the MAGEL2 Gene

    Directory of Open Access Journals (Sweden)

    Michael D. Fountain

    2016-01-01

    Full Text Available Prader-Willi syndrome (PWS is a neurodevelopmental disorder characterized by neonatal hypotonia, developmental delay/intellectual disability, and characteristic feeding behaviors with failure to thrive during infancy; followed by hyperphagia and excessive weight gain later in childhood. Individuals with PWS also manifest complex behavioral phenotypes. Approximately 25% meet criteria for autism spectrum disorder (ASD. PWS is caused by the absence of paternally expressed, maternally silenced genes at chromosome 15q11-q13. MAGEL2 is one of five protein-coding genes in the PWS-critical domain. Truncating point mutations of the paternal allele of MAGEL2 cause Schaaf-Yang syndrome, which has significant phenotypic overlap with PWS, but is also clinically distinct; based on the presence of joint contractures, and a particularly high prevalence of autism spectrum disorder (up to 75% of affected individuals. The clinical and molecular overlap between PWS and Schaaf-Yang syndrome, but also their distinguishing features provide insight into the pathogenetic mechanisms underlying both disorders.

  18. Prognosis and long-term neurodevelopmental outcome in conservatively treated twin-to-twin transfusion syndrome

    Directory of Open Access Journals (Sweden)

    Ochiai Masayuki

    2011-04-01

    Full Text Available Abstract Background Amnioreduction remains a treatment option for pregnancies with twin-to-twin transfusion syndrome (TTTS not meeting criteria for laser surgery or those in which it is not feasible. Amnioreduction is a relatively simple treatment which does not require sophisticated technical equipment. Previous reports of conservative management have indicated that major neurodevelopmental impairment occurs in 14.3-26% of survivors. The purpose of this study was to investigate long-term neurodevelopmental outcome in conservatively treated TTTS. Methods During the nine-year study period from January 1996 to December 2004, all pregnancies with TTTS who were admitted to our center were investigated. TTTS was diagnosed by using standard prenatal ultrasound criteria, and staged according to the criteria of Quintero et al. We reviewed gestational age at diagnosis, gestational age at delivery, the stage of TTTS at diagnosis, and diagnosis to delivery interval. Neonatal cranial ultrasound findings were reviewed and the neurodevelopmental outcomes were evaluated. Results Twenty-one pregnancies with TTTS were included. Thirteen pregnancies (62% were treated with serial amnioreduction. The mean gestational age at delivery was 28 weeks (22 - 34 weeks. The perinatal mortality rate was 42.9%. Twenty survivors were followed up until at least 3 years of age. The mean age at follow-up was 6.3 years (3 - 12 years. Six children (30% had neurodevelopmental impairment. Four children (20% had major neurodevelopmental impairment and two children (10% had minor neurodevelopmental impairment. Children with neurodevelopmental impairment were delivered before 29 weeks of gestation. Conclusions Our study showed a high rate of perinatal mortality and a high rate of major neurodevelopmental impairment in conservatively treated TTTS. The long-term outcomes for the survivors with TTTS were good when survivors were delivered after 29 weeks of gestation.

  19. Review of Prevalence Studies of Tic Disorders: Methodological Caveats

    OpenAIRE

    Cubo, Esther

    2012-01-01

    Introduction Tic disorders are neurodevelopmental disorders of childhood associated with psychiatric comorbidity and academic problems. Estimating the prevalence and understanding the epidemiology of tic disorders is more complex than was once thought. Until fairly recently, tic disorders were thought to be rare, but today tics are believed to be the most common movement disorder, with 0.2?46.3% of schoolchildren experiencing tics during their lifetime. Tentative explanations for differing pr...

  20. Association between severity of behavioral phenotype and comorbid attention deficit hyperactivity disorder symptoms in children with autism spectrum disorders

    OpenAIRE

    Rao, Patricia A; Landa, Rebecca J

    2013-01-01

    Autism spectrum disorder and attention deficit hyperactivity disorder are neurodevelopmental disorders that cannot be codiagnosed under existing diagnostic guidelines (Diagnostic and Statistical Manual of the American Psychiatric Association, 4th ed., text rev.). However, reports are emerging that attention deficit hyperactivity disorder is sometimes comorbid with autism spectrum disorder. In the current study, we examined rates of parent-reported clinically significant symptoms of attention ...

  1. Neurodevelopmental origins of lifespan changes in brain and cognition.

    Science.gov (United States)

    Walhovd, Kristine B; Krogsrud, Stine K; Amlien, Inge K; Bartsch, Hauke; Bjørnerud, Atle; Due-Tønnessen, Paulina; Grydeland, Håkon; Hagler, Donald J; Håberg, Asta K; Kremen, William S; Ferschmann, Lia; Nyberg, Lars; Panizzon, Matthew S; Rohani, Darius A; Skranes, Jon; Storsve, Andreas B; Sølsnes, Anne Elisabeth; Tamnes, Christian K; Thompson, Wesley K; Reuter, Chase; Dale, Anders M; Fjell, Anders M

    2016-08-16

    Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4-88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother-Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain-cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course.

  2. Infant and childhood neurodevelopmental outcomes following prenatal exposure to selective serotonin reuptake inhibitors: overview and design of a Finnish Register-Based Study (FinESSI

    Directory of Open Access Journals (Sweden)

    Malm Heli

    2012-12-01

    Full Text Available Abstract Background Experimental animal studies and one population-based study have suggested an increased risk for adverse neurodevelopmental outcome after prenatal exposure to SSRIs. We describe the methods and design of a population-based study examining the association between prenatal SSRI exposure and neurodevelopment until age 14. Methods and design This is a cohort study of national registers in Finland: the Medical Birth Register, the Register of Congenital Malformations, the Hospital Discharge Register including inpatient and outpatient data, the Drug Reimbursement Register, and the Population Register. The total study population includes 845,345 women and their live-born, singleton offspring aged 14 or younger and born during Jan 1st 1996-Dec 31st 2010. We will compare the prevalence of psychiatric and neurodevelopmental outcomes in offspring exposed prenatally to SSRIs to offspring exposed to prenatal depression and unexposed to SSRIs. Associations between exposure and outcome are assessed by statistical methods including specific modeling to account for correlated outcomes within families and differences in duration of follow-up between the exposure groups. Descriptive results. Of all pregnant women with pregnancy ending in delivery (n = 859,359, 1.9% used SSRIs. The prevalence of diagnosed depression and depression-related psychiatric disorders within one year before or during pregnancy was 1.7%. The cumulative incidence of registered psychiatric or neurodevelopmental disorders was 6.9% in 2010 among all offspring born during the study period (age range 0–14 years. Discussion The study has the potential for significant public health importance in providing information on prenatal exposure to SSRIs and long-term neurodevelopment.

  3. A neurodevelopmental survey of Angelman syndrome with genotype-phenotype correlations

    Science.gov (United States)

    Gentile, Jennifer K.; Tan, Wen-Hann; Horowitz, Lucia T.; Bacino, Carlos A.; Skinner, Steven A.; Barbieri-Welge, Rene; Bauer-Carlin, Astrid; Beaudet, Arthur L.; Bichell, Terry Jo; Lee, Hye-Seung; Sahoo, Trilochan; Waisbren, Susan E.; Bird, Lynne M.; Peters, Sarika U.

    2010-01-01

    Objective Angelman syndrome (AS) is a neurodevelopmental disorder caused by a deletion on chromosome 15, uniparental disomy (UPD), imprinting defect, or UBE3A mutation. It is characterized by intellectual disability with minimal speech and certain behavioral characteristics. We used standardized measures to characterize the developmental profile and to analyze genotype-phenotype correlations in AS. Method The study population consisted of 92 children, between 5 months and 5 years of age, enrolled in a Natural History Study. Each participant was evaluated using the Bayley Scales of Infant and Toddler Development (Third Edition) (BSID-III), the Vineland Adaptive Behavior Scales (Second Edition) (VABS-II), and the Aberrant Behavior Checklist. Results 74% had a deletion and 26% had UPD, an imprinting defect or a UBE3A mutation (“non-deletion”). The mean±standard deviation (SD) BSID-III cognitive scale developmental quotient (DQ) was 40.5±15.5. Participants with deletions were more developmentally delayed than the non-deletion participants in all BSID-III domains except in expressive language skills. The cognitive DQ was higher than the DQ in each of the other domains, and the receptive language DQ was higher than the expressive language DQ. In the VABS-II, deletion participants had weaker motor and language skills than the non-deletion participants. Conclusion Children with AS have a distinct developmental and behavioral profile; their cognitive skills are stronger than their language and motor skills, and their receptive language skills are stronger than expressive language skills. Developmental outcomes are associated with genotype, with deletion patients having worse outcomes than non-deletion patients. PMID:20729760

  4. Towards a Neurodevelopmental Model of Clinical Case Formulation

    OpenAIRE

    Solomon, Marjorie; Hessl, David; Chiu, Sufen; Olsen, Emily; Hendren, Robert

    2009-01-01

    Rapid advances in molecular genetics and neuroimaging over the last 10-20 years have been a catalyst for research in neurobiology, developmental psychopathology, and translational neuroscience. Methods of study in psychiatry, previously described as “slow maturing,” now are becoming sufficiently sophisticated to more effectively investigate the biology of higher mental processes. Despite these technological advances, the recognition that psychiatric disorders are disorders of neurodevelopment...

  5. Chromosomal Abnormalities and Putative Susceptibility Genes in Autism Spectrum Disorders

    DEFF Research Database (Denmark)

    Nielsen, Mette Gilling

    Autism spectrum disorders (ASDs) is a heterogeneous group of neurodevelopmental disorders with a significant genetic component as shown by family and twin studies. However, only a few genes have repeatedly been shown to be involved in the development of ASDs. The aim of this study has been...

  6. De Novo Coding Variants Are Strongly Associated with Tourette Disorder

    NARCIS (Netherlands)

    Willsey, A. Jeremy; Fernandez, Thomas V.; Yu, Dongmei; King, Robert A.; Dietrich, Andrea; Xing, Jinchuan; Sanders, Stephan J.; Mandell, Jeffrey D.; Huang, Alden Y.; Richer, Petra; Smith, Louw; Dong, Shan; Samocha, Kaitlin E.; Neale, Benjamin M.; Coppola, Giovanni; Mathews, Carol A.; Tischfield, Jay A.; Scharf, Jeremiah M.; State, Matthew W.; Heiman, Gary A.

    2017-01-01

    Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186

  7. Attention deficit hyperactivity symptoms and disorder (ADHD) among ...

    African Journals Online (AJOL)

    Attention deficit hyperactivity symptoms and disorder (ADHD) among African children: a review of epidemiology and co-morbidities. ... from Africa is limited. For effective healthcare policy further studies are needed to define the magnitude and burden of ADHD and other childhood neurodevelopmental disorders in Africa.

  8. Interleukin-18 modulation in autism spectrum disorders

    NARCIS (Netherlands)

    Businaro, R.; Corsi, M.; Azzara, G.; Di Raimo, T.; Laviola, G.; Romano, E.; Ricci, L.; Maccarrone, M.; Aronica, E.; Fuso, A.; Ricci, S.

    2016-01-01

    BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disease which affects 1 in 88 children. Its etiology remains basically unknown, but it is apparent that neuroinflammation is involved in disease development. Great attention has been focused on pro-inflammatory cytokines, and several

  9. Comorbidity of Autism Spectrum Disorders and Emotional/behavioral Disorders: Towards Improved Diagnostic Procedures, Instructional Programming, and Personnel Preparation

    Science.gov (United States)

    Clinton, Elias

    2016-01-01

    An emotional/behavioral disorder is a mental health disability characterized by intensive internalized behaviors (e.g., anxiety, depression) and/or externalized behaviors (e.g., physical aggression, verbal aggression). Autism is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behaviors (i.e., stereo…

  10. Attention deficit hyperactivity disorder and autism spectrum disorder symptoms in school-age children born very preterm

    NARCIS (Netherlands)

    Bröring, Tinka; Oostrom, Kim J.; van Dijk-Lokkart, Elisabeth M.; Lafeber, Harrie N.; Brugman, Anniek; Oosterlaan, Jaap

    2018-01-01

    Very preterm (VP) children face a broad range of neurodevelopmental sequelae, including behavioral problems. To investigate prevalence, pervasiveness and co-occurrence of symptoms of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in school-age children born very

  11. Postnatal dexamethasone, respiratory and neurodevelopmental outcomes at two years in babies born extremely preterm.

    Science.gov (United States)

    Qin, Gordon; Lo, Jessica W; Marlow, Neil; Calvert, Sandy A; Greenough, Anne; Peacock, Janet L

    2017-01-01

    Postnatal dexamethasone is associated with reduction in bronchopulmonary dysplasia. There remains, however, concern that its short-term benefits are accompanied by long-term adverse effects e.g. poorer neurodevelopmental outcomes. Our aim was to determine the effects of administration of postnatal dexamethasone on respiratory and neurodevelopmental outcome at two years of age after adjusting for neonatal and infant risk factors. The study included 412 infants born at 23-28 weeks of gestation, 29% had received postnatal dexamethasone. Two outcomes were examined, respiratory hospital admissions in the past 12 months and neurodevelopmental impairment. Logistic regression, adjusted for sex, birthweight z-score, gestation, maternal smoking, oxygen dependency at 36 weeks, airleak, patent ductus arteriosus, pulmonary haemorrhage, major ultrasound abnormality, mode of ventilation and age at assessment, was undertaken. After adjustment, postnatal dexamethasone was associated with significantly increased proportions of both respiratory hospital readmission: (0.35 vs 0.15, difference = 0.20; 95% CI: 0.08, 0.31) and neurodevelopmental impairment (0.59 vs 0.45, difference = 0.14; 95% CI: 0.02, 0.26). Postnatal dexamethasone use in extremely preterm infants is associated with increased risks of respiratory hospital admissions and neurodevelopmental impairment. These associations were not explained by excess neonatal morbidities.

  12. Pediatric epilepsy and comorbid reading disorders, math disorders, or autism spectrum disorders: Impact of epilepsy on cognitive patterns.

    Science.gov (United States)

    van Iterson, Loretta; de Jong, Peter F; Zijlstra, Bonne J H

    2015-03-01

    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 epilepsy and these neurodevelopmental disorders as comorbidities. Based on two samples of referred children, one with epilepsy, reading disorders, math disorders, or ASDs occurring in "isolation" (n=117) and one with reading disorders, math disorders, and ASDs occurring comorbid with epilepsy (n=171), cognitive patterns were compared. The patterns displayed by verbal and nonverbal abilities from the WISC series were studied with repeated measures ANOVA. Thereafter, an exploratory 2∗3∗2 factorial analysis was done to study the independent contribution of the type of comorbidity and of the presence or absence of epilepsy to the VIQ-PIQ pattern. In isolated epilepsy, a VIQ>PIQ pattern was found, which was not seen in the other disorders. When epilepsy and another disorder co-occurred, patterns were altered. They resembled partly the pattern seen in isolated epilepsy and partly the pattern seen in the isolated neurodevelopmental disorder. In comorbid reading disorders, the VIQ>PIQ pattern was mitigated; in comorbid math disorders, it was exacerbated. In comorbid ASDs, no clear pattern emerged. In the presence of epilepsy, patterns characteristic of isolated disorders appeared systematically shifted toward relatively lowered performance abilities or relatively spared verbal abilities. The similar "impact" exerted by epilepsy on the patterns of the various conditions suggested shared mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Neurodevelopmental effects of chronic exposure to elevated levels of pro-inflammatory cytokines in a developing visual system

    Directory of Open Access Journals (Sweden)

    Ruthazer Edward S

    2010-01-01

    Full Text Available Abstract Background Imbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with a number of severe and prevalent neurodevelopmental disorders, including autism spectrum disorder, schizophrenia and Down syndrome. Although several studies have shown that cytokines have potent effects on neural function, their role in neural development is still poorly understood. In this study, we investigated the link between abnormal cytokine levels and neural development using the Xenopus laevis tadpole visual system, a model frequently used to examine the anatomical and functional development of neural circuits. Results Using a test for a visually guided behavior that requires normal visual system development, we examined the long-term effects of prolonged developmental exposure to three pro-inflammatory cytokines with known neural functions: interleukin (IL-1β, IL-6 and tumor necrosis factor (TNF-α. We found that all cytokines affected the development of normal visually guided behavior. Neuroanatomical imaging of the visual projection showed that none of the cytokines caused any gross abnormalities in the anatomical organization of this projection, suggesting that they may be acting at the level of neuronal microcircuits. We further tested the effects of TNF-α on the electrophysiological properties of the retinotectal circuit and found that long-term developmental exposure to TNF-α resulted in enhanced spontaneous excitatory synaptic transmission in tectal neurons, increased AMPA/NMDA ratios of retinotectal synapses, and a decrease in the number of immature synapses containing only NMDA receptors, consistent with premature maturation and stabilization of these synapses. Local interconnectivity within the tectum also appeared to remain widespread, as shown by increased recurrent polysynaptic activity, and was similar to what is seen in more immature, less refined tectal circuits. TNF-α treatment also enhanced the

  14. The Effects of Physical Activity on Children Diagnosed with Attention Deficit Hyperactivity Disorder: A Review

    Science.gov (United States)

    Reeves, Matthew Jonathan; Bailey, Richard P.

    2016-01-01

    Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental psychiatric disorder among children. Despite the noted positive aspects of the disorder, it is often associated with a range of negative outcomes for that are detrimental to children's education and wider well-being. This comprehensive scoping review examined…

  15. The predictive validity of neonatal MRI for neurodevelopmental outcome in very preterm children.

    Science.gov (United States)

    Anderson, Peter J; Cheong, Jeanie L Y; Thompson, Deanne K

    2015-03-01

    Very preterm children are at a high risk for neurodevelopmental impairments, but there is variability in the pattern and severity of outcome. Neonatal magnetic resonance imaging (MRI) enhances the capacity to detect brain injury and altered brain development and assists in the prediction of high-risk children who warrant surveillance and early intervention. This review describes the application of conventional and advanced MRI with very preterm neonates, specifically focusing on the relationship between neonatal MRI findings and later neurodevelopmental outcome. Research demonstrates that conventional MRI is strongly associated with neurodevelopmental outcome in childhood. Further studies are needed to examine the role of advanced MRI techniques in predicting outcome in very preterm children, but early research findings are promising. In conclusion, neonatal MRI is predictive of later neurodevelopment but is dependent on appropriately trained specialists and should be interpreted in conjunction with other clinical and social information. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Neurodevelopmental outcome in Angelman syndrome: Genotype-phenotype correlations

    DEFF Research Database (Denmark)

    Mertz, Line Granild Bie; Thaulov, Per; Trillingsgaard, Anegen

    2014-01-01

    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...

  17. Two-year neurodevelopmental outcomes of ventilated preterm infants treated with inhaled nitric oxide.

    Science.gov (United States)

    Walsh, Michele C; Hibbs, Anna Maria; Martin, Camilia R; Cnaan, Avital; Keller, Roberta L; Vittinghoff, Eric; Martin, Richard J; Truog, William E; Ballard, Philip L; Zadell, Arlene; Wadlinger, Sandra R; Coburn, Christine E; Ballard, Roberta A

    2010-04-01

    In a randomized multi-center trial, we demonstrated that inhaled nitric oxide begun between 7 and 21 days and given for 24 days significantly increased survival without bronchopulmonary dysplasia (BPD) in ventilated premature infants weighing score <70 on the Bayley Scales II), compared with 114 of 234 (49%) in the placebo group (relative risk, 0.92; 95% CI, 0.75-1.12; P = .39). No differences on any subcomponent of neurodevelopmental impairment or growth variables were found between inhaled nitric oxide or placebo. Inhaled nitric oxide improved survival free of BPD, with no adverse neurodevelopmental effects at 2 years of age. Copyright 2010 Mosby, Inc. All rights reserved.

  18. Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association.

    Science.gov (United States)

    Marino, Bradley S; Lipkin, Paul H; Newburger, Jane W; Peacock, Georgina; Gerdes, Marsha; Gaynor, J William; Mussatto, Kathleen A; Uzark, Karen; Goldberg, Caren S; Johnson, Walter H; Li, Jennifer; Smith, Sabrina E; Bellinger, David C; Mahle, William T

    2012-08-28

    The goal of this statement was to review the available literature on surveillance, screening, evaluation, and management strategies and put forward a scientific statement that would comprehensively review the literature and create recommendations to optimize neurodevelopmental outcome in the pediatric congenital heart disease (CHD) population. A writing group appointed by the American Heart Association and American Academy of Pediatrics reviewed the available literature addressing developmental disorder and disability and developmental delay in the CHD population, with specific attention given to surveillance, screening, evaluation, and management strategies. MEDLINE and Google Scholar database searches from 1966 to 2011 were performed for English-language articles cross-referencing CHD with pertinent search terms. The reference lists of identified articles were also searched. The American College of Cardiology/American Heart Association classification of recommendations and levels of evidence for practice guidelines were used. A management algorithm was devised that stratified children with CHD on the basis of established risk factors. For those deemed to be at high risk for developmental disorder or disabilities or for developmental delay, formal, periodic developmental and medical evaluations are recommended. A CHD algorithm for surveillance, screening, evaluation, reevaluation, and management of developmental disorder or disability has been constructed to serve as a supplement to the 2006 American Academy of Pediatrics statement on developmental surveillance and screening. The proposed algorithm is designed to be carried out within the context of the medical home. This scientific statement is meant for medical providers within the medical home who care for patients with CHD. Children with CHD are at increased risk of developmental disorder or disabilities or developmental delay. Periodic developmental surveillance, screening, evaluation, and reevaluation

  19. Copy Number Variation in Obsessive-Compulsive Disorder and Tourette Syndrome: A Cross-Disorder Study

    Science.gov (United States)

    McGrath, Lauren M.; Yu, Dongmei; Marshall, Christian; Davis, Lea K.; Thiruvahindrapuram, Bhooma; Li, Bingbin; Cappi, Carolina; Gerber, Gloria; Wolf, Aaron; Schroeder, Frederick A.; Osiecki, Lisa; O’Dushlaine, Colm; Kirby, Andrew; Illmann, Cornelia; Haddad, Stephen; Gallagher, Patience; Fagerness, Jesen A.; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Bienvenu, O. Joseph; Black, Donald W.; Bloch, Michael H.; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Cath, Danielle C.; Cavallini, Maria C.; Chouinard, Sylvain; Coric, Vladimir; Cullen, Bernadette; Delorme, Richard; Denys, Damiaan; Derks, Eske M.; Dion, Yves; Rosário, Maria C.; Eapen, Valsama; Evans, Patrick; Falkai, Peter; Fernandez, Thomas; Garrido, Helena; Geller, Daniel; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Grünblatt, Edna; Heiman, Gary A.; Hemmings, Sian M.J.; Herrera, Luis D.; Hounie, Ana G.; Jankovic, Joseph; Kennedy, James L; King, Robert A.; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Lochner, Christine; Lowe, Thomas L.; Lyon, Gholson J.; Macciardi, Fabio; Maier, Wolfgang; McCracken, James T.; McMahon, William; Murphy, Dennis L.; Naarden, Allan L; Neale, Benjamin M; Nurmi, Erika; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark; Robertson, Mary M.; Rosenberg, David; Rouleau, Guy A.; Ruhrmann, Stephan; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Tischfield, Jay A.; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Wendland, Jens R.; Shugart, Yin Yao; Miguel, Euripedes C.; Nicolini, Humberto; Oostra, Ben A.; Moessner, Rainald; Wagner, Michael; Ruiz-Linares, Andres; Heutink, Peter; Nestadt, Gerald; Freimer, Nelson; Petryshen, Tracey; Posthuma, Danielle; Jenike, Michael A.; Cox, Nancy J.; Hanna, Gregory L.; Brentani, Helena; Scherer, Stephen W.; Arnold, Paul D.; Stewart, S. Evelyn; Mathews, Carol A.; Knowles, James A.; Cook, Edwin H.; Pauls, David L.; Wang, Kai; Scharf, Jeremiah M.

    2014-01-01

    Objective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable, neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. Method The primary analyses utilized a cross-disorder design for 2,699 patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Results Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p=.09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 patient deletions: 0 control deletions, p=0.08 in current study, p=0.025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support to the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in autism or schizophrenia (2–4%). Conclusion Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes. PMID:25062598

  20. Genome-wide expression studies in autism spectrum disorder, Rett syndrome, and Down syndrome.

    Science.gov (United States)

    Lintas, Carla; Sacco, Roberto; Persico, Antonio M

    2012-01-01

    Though different in their aetiology, autism spectrum disorder (ASD), Rett syndrome (RTT) and Down syndrome (DS) are three neurodevelopmental disorders sharing significant clinical and neuropathological overlaps. Genome-wide expression studies are reviewed and available datasets from post-mortem brains reanalyzed to identify genes and gene pathways dysregulated in all three disorders. Our results surprisingly converge upon immune, and not neurodevelopmental genes, as the most consistently shared abnormality in genome-wide expression patterns. A dysregulated immune response, accompanied by enhanced oxidative stress and abnormal mitochondrial metabolism seemingly represents the common molecular underpinning of these neurodevelopmental disorders. This conclusion may be important for the definition of pharmacological therapies able to ameliorate clinical symptoms across these disorders. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Neurodevelopmental and neurobehavioural effects of polybrominated and perfluorinated chemicals: a systematic review of the epidemiological literature using a quality assessment scheme.

    Science.gov (United States)

    Roth, N; Wilks, M F

    2014-10-15

    Concerns over effects of halogenated persistent environmental contaminants on the developing brain have been expressed for many years, and human biomonitoring has confirmed that low-level, prenatal and/or postnatal exposure of children to these chemicals is ubiquitous. Over the last decade there have been increasing reports in the epidemiological literature of the potential association of exposure to polybromo diphenylethers (PBDEs) and perfluorinated chemicals (PFCs) with neurodevelopmental and/or neurobehavioural effects in infants and children, such as adverse birth outcomes, cognitive deficits, developmental delay and attention deficit hyperactivity disorders (ADHD). However, direct evidence from epidemiology studies has been limited and contradictory. Given the general lack of comparability across studies in terms of design, conduct, methodology and reporting, we developed a checklist-type quality assessment scheme based on the STROBE guidelines and the proposed HONEES criteria, and conducted a systematic review of the epidemiological peer-reviewed literature published since 2006 on neurodevelopmental and/or neurobehavioural effects following prenatal and postnatal exposure to PBDEs and PFCs. We rated 7 of the 18 studies that met our inclusion criteria as being of high quality, 7 of moderate quality and 4 of low quality. Frequently observed shortcomings were the lack of consideration of confounding factors; uncertainties regarding exposure characterization; inadequate sample size; the lack of a clear dose-response; and the representativeness/generalizability of the results. Collectively, the epidemiological evidence does currently not support a strong causal association between PBDEs and PFCs and adverse neurodevelopmental and neurobehavioural outcomes in infants and children. However, despite their limitations, the studies raise questions that require further investigation through hypothesis-driven studies using more harmonized study designs and methodologies

  2. Neurodevelopmental and psychiatric issues in Down's syndrome: assessment and intervention.

    Science.gov (United States)

    Vicari, Stefano; Pontillo, Maria; Armando, Marco

    2013-06-01

    Down's syndrome (DS) is the most frequent genetic cause of intellectual disability and patients with DS show significant psychopathology (18-23%). Moreover, individuals with DS often show a cognitive decline associated with ageing characterized by a deterioration in memory, language and cognitive functioning. According to these relevant findings, an overview is presented of state-of-the-art knowledge of the neurocognitive, neurobiological and psychopathological profile, assessment and treatment of patients with DS. The linguistic characteristics of DS develop differently along distinct developmental trajectories. Thus, for example, morphosyntax deficit, especially in production, is more evident in adolescence than in early childhood and lexicon is usually better preserved in all ages (at least in comprehension). So far, rehabilitation is the only effective approach for improving cognitive and linguistic abilities. However, ongoing preliminary reports on other approaches such as transmagnetic stimulation or drugs suggest alternative or integrative treatment for the future. Individuals with DS show typical organization of brain structures related to some cognitive abilities, such as reduced volume in frontal and prefrontal areas, which is related to poor executive and linguistic abilities. They also frequently show psychiatric disorders such as externalizing disorders as well as depression, anxiety and obsessive-compulsive disorder. Nevertheless, as for other genetic syndrome with intellectual disability, there is a significant lack of research specifically focused on treatments of psychiatric and behavioural problems in DS. This is true both for psychosocial and for pharmacological interventions.

  3. Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders

    Science.gov (United States)

    2015-07-01

    ultrapure water at a flow rate of 450 µL/minute. Unless otherwise noted, all reagents were purchased from Sigma-Aldrich. 5 Problems encountered in...M. Brezun, A. Daszuta, Serotonin mediates oestrogen stimulation of cell proliferation in the adult dentate gyrus. Eur. J. Neurosci. 14, 1417–24...phosphate dibasic, 7% methanol (JT Baker, cat. no. 9093-03), and 5 mg EDTA in ultrapure water at a flow rate of 450 µL/minute. For measures of biogenic

  4. Food additives, essential nutrients and neurodevelopmental behavioural disorders in children: A brief review.

    Science.gov (United States)

    Buka, Irena; Osornio-Vargas, Alvaro; Clark, Brenda

    2011-08-01

    In recent decades, changing lifestyles in Canadian homes has led to demand for foods with long shelf lives that are cosmetically appealing, palatable, easy to prepare and to consume. Food additives, especially preservatives and artificial colours as well as suboptimal intake of essential nutrients, have been linked to hyperactive behaviours and poor attention in a subgroup of children. Although other risk factors (ie, genetic, etc) for these conditions have received more attention in the scientific literature, the authors believe that there is enough evidence to consider dietary influences as a modifiable risk factor. This would involve raising awareness among clinicians and, subsequently, reviewing food regulatory processes to better protect children in Canada - similar to the regulations recently undertaken by the British Food Standards Agency. Conflicts of interest due to food and medication industry support for organizations advocating for children would need to be resolved by open communication between government regulatory agencies, academia and industry. Canadian parents and children need to be advised to limit unnecessary food additives and consume a diet rich in essential nutrients while more complete relationships are being explored further.

  5. Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders

    Science.gov (United States)

    2016-09-01

    Medline Patterson PH (2002) Maternal infection: window on neuroimmune inter- actions in fetal brain development and mental illness. Curr Opin Neuro- biol...or absence of labor. Am J Obstet Gynecol 199:375.e1–375.e5. CrossRef Medline Shayda H, Mahmood JT, Ebrahim T, Jamileh G, Golnaz Ensieh KS, Parivash D

  6. Neurodevelopmental Disorders Caused by De Novo Variants in KCNB1 Genotypes and Phenotypes

    DEFF Research Database (Denmark)

    de Kovel, Carolien G F; Syrbe, Steffen; Brilstra, Eva H

    2017-01-01

    Importance: Knowing the range of symptoms seen in patients with a missense or loss-of-function variant in KCNB1 and how these symptoms correlate with the type of variant will help clinicians with diagnosis and prognosis when treating new patients. Objectives: To investigate the clinical spectrum ...

  7. Intragenic deletion of RBFOX1 associated with neurodevelopmental/neuropsychiatric disorders and possibly other clinical presentations

    OpenAIRE

    Zhao, Wei-Wei

    2013-01-01

    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 signif...

  8. Assessing quality of nursing care as a confounding variable in an outcome study on Neurodevelopmental treatment

    NARCIS (Netherlands)

    L. van der Weide; M.H.F. Grypdonck; Dr. T.B. Hafsteinsdóttir; K. Strijker; C. Kruitwagen

    2007-01-01

    When planning a study measuring the effects of a neurodevelopmental treatment (NDT), we were confronted with the methodological problem that while measuring the effects of NDT, a rival hypothesis is that the decision to implement the NDT might be related to the quality of nursing care. Therefore, we

  9. Child neurodevelopmental outcomes following preterm and term birth: What can the placenta tell us?

    Science.gov (United States)

    Hodyl, Nicolette A; Aboustate, Natalie; Bianco-Miotto, Tina; Roberts, Claire T; Clifton, Vicki L; Stark, Michael J

    2017-09-01

    A significant proportion of children born preterm will experience some level of neurodevelopmental impairment. Changes in placental function have been observed with many antenatal conditions that are risk factors for preterm birth and/or poor neurodevelopment including fetal growth restriction and in-utero inflammation. This review will highlight placental factors that have been studied to understand the underlying mechanisms and identify biomarkers that lead to poor child neurodevelopmental outcomes. These include changes in gross morphological and histopathological structure and the placental inflammatory response to prenatal infection. Further, we will describe the placenta's role as both a barrier to maternally-derived bioactive substances critical for normal fetal brain development, such as cortisol, and a source of neuroactive steroids and neurotrophins known to have critical functions in neuronal proliferation, axonal growth, myelination and the regulation of apoptosis. Finally, emerging data supporting the potential utility of novel placental biomarkers in the early prediction of poor neurodevelopmental outcome in infants born both preterm and term will be discussed. These include the assessment of genetic variants (e.g. single nucleotide polymorphisms in placental tissue) and epigenetic biomarkers (e.g. placental microRNAs and placental DNA methylation). With the placenta the key tissue regulating the fetal environment, integration of observed changes in placental function with genetic and epigenetic variations may advance our ability to predict future infant health. Ultimately, this may facilitate targeted allocation of health resources with the aim of improving lifelong neurodevelopmental capability. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Neurodevelopmental Status and Adaptive Behaviors in Preschool Children with Chronic Kidney Disease

    Science.gov (United States)

    Duquette, Peter J.; Hooper, Stephen R.; Icard, Phil F.; Hower, Sarah J.; Mamak, Eva G.; Wetherington, Crista E.; Gipson, Debbie S.

    2009-01-01

    This study examines the early neurodevelopmental function of infants and preschool children who have chronic kidney disease (CKD). Fifteen patients with CKD are compared to a healthy control group using the "Mullen Scales of Early Learning" (MSEL) and the "Vineland Adaptive Behavior Scale" (VABS). Multivariate analysis reveals…

  11. Severe influenza among children and young adults with neurologic and neurodevelopmental conditions - Ohio, 2011.

    Science.gov (United States)

    2012-01-06

    Children with neurologic and neurodevelopmental conditions are at increased risk for severe outcomes from influenza, including death. In April 2011, the Ohio Department of Health and CDC investigated an influenza outbreak that began in February 2011 in a residential facility for 130 children and young adults with neurologic and neurodevelopmental conditions. This report summarizes the characteristics and clinical courses of 13 severely ill residents with suspected or confirmed influenza; 10 were hospitalized, and seven died. Diagnosis is challenging in this population, and clinicians should consider influenza in patients with neurologic and neurodevelopmental conditions who have respiratory illness or a decline in baseline medical status when influenza is circulating in the community. Prompt testing, early and aggressive antiviral treatment, and antiviral chemoprophylaxis are important for these patients. When influenza is suspected, antiviral treatment should be given as soon as possible after symptom onset, ideally within 48 hours. Treatment should not wait for laboratory confirmation of influenza. During outbreaks, antiviral chemoprophylaxis should be provided to all residents of institutional facilities (e.g., nursing homes and long-term- care facilities), regardless of vaccination status. Residential facilities for patients with neurologic and neurodevelopmental conditions are encouraged to vaccinate all eligible residents and staff members against influenza.

  12. No association between transient hypothyroxinaemia of prematurity and neurodevelopmental outcome in young adulthood

    NARCIS (Netherlands)

    Hollanders, J.J.; Israëls, J.; Pal, S.M. van der; Verkerk, P.H.; Rotteveel, J.; Finken, M.J.J.; Hille, E.T.M.; Groot, C.H. de; Kloosterboer-Boerrigter, H.; Ouden, A.L. den; Rijpstra, A.; Verloove-Vanhorick, S.P.; Vogelaar, J.A.; Kok, J.H.; Ilsen, A.; Lans, M. van der; Boelen-Van Der Loo, W.J.C.; Lundqvist, T.; Heymans, H.S.A.; Duiverman, E.J.; Geven, W.B.; Duiverman, M.L.; Geven, L.I.; Vrijlandt, E.J.L.E.; Mulder, A.L.M.; Gerver, A.; Kollée, L.A.A.; Reijmers, L.; Sonnemans, R.; Wit, J.M.; Dekker, F.W.; Weisglas-Kuperus, N.; Heijden, A.J. van der; Goudoever, J.B. van; Weissenbruch, M.M. van; Cranendonk, A.; Delemarre-Van De Waal, H.A.; Groot, L. de; Samsom, J.F.; Vries, L.S. de; Rademaker, K.J.; Moerman, E.; Voogsgeerd, M.; Kleine, M.J.K. de; Andriessen, P.; Dielissen-Van Helvoirt, C.C.M.; Mohamed, I.; Straaten, H.L.M. van; Baerts, W.; Veneklaas Slots-Kloosterboer, G.W.; Tuller-Pikkemaat, E.M.J.; Ens-Dokkum, M.H.; Steenbrugge, G.J. van

    2015-01-01

    Context: Transient hypothyroxinaemia of prematurity (THoP) has been associated with neurodevelopmental impairment in infancy and childhood. It is not known whether these relations persist into adulthood. Objective: To examine whether there is an effect of THoP on intelligence quotient (IQ) score and

  13. Brain Injury and Neurodevelopmental Outcome in Congenital Heart Disease : A Systematic Review

    NARCIS (Netherlands)

    Mebius, Mirthe J.; Kool, Elisabeth M. W.; Bilardo, Catherina M.; Bos, Arend F.

    2017-01-01

    CONTEXT: Brain injury during prenatal and preoperative postnatal life might play a major role in neurodevelopmental impairment in infants with congenital heart disease (CIID) who require corrective or palliative surgery during infancy. A systematic review of cerebral findings during this period in

  14. Brain Injury and Neurodevelopmental Outcome in Congenital Heart Disease: A Systematic Review.

    Science.gov (United States)

    Mebius, Mirthe J; Kooi, Elisabeth M W; Bilardo, Catherina M; Bos, Arend F

    2017-07-01

    Brain injury during prenatal and preoperative postnatal life might play a major role in neurodevelopmental impairment in infants with congenital heart disease (CHD) who require corrective or palliative surgery during infancy. A systematic review of cerebral findings during this period in relation to neurodevelopmental outcome (NDO), however, is lacking. To assess the association between prenatal and postnatal preoperative cerebral findings and NDO in infants with CHD who require corrective or palliative surgery during infancy. PubMed, Embase, reference lists. We conducted 3 different searches for English literature between 2000 and 2016; 1 for prenatal cerebral findings, 1 for postnatal preoperative cerebral findings, and 1 for the association between brain injury and NDO. Two reviewers independently screened sources and extracted data on cerebral findings and neurodevelopmental outcome. Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Abnormal cerebral findings are common during the prenatal and postnatal preoperative periods. Prenatally, a delay of cerebral development was most common; postnatally, white matter injury, periventricular leukomalacia, and stroke were frequently observed. Abnormal Doppler measurements, brain immaturity, cerebral oxygenation, and abnormal EEG or amplitude-integrated EEG were all associated with NDO. Observational studies, different types of CHD with different pathophysiological effects, and different reference values. Prenatal and postnatal preoperative abnormal cerebral findings might play an important role in neurodevelopmental impairment in infants with CHD. Increased awareness of the vulnerability of the young developing brain of an infant with CHD among caregivers is essential. Copyright © 2017 by the American Academy of Pediatrics.

  15. Neurodevelopmental Outcomes in Very Low Birth Weight Infants Using Aminophylline for the Treatment of Apnea

    Directory of Open Access Journals (Sweden)

    Shu-Leei Tey

    2016-02-01

    Conclusion: Aminophylline therapy for apnea of prematurity had no apparent and additional risk on the neurodevelopmental outcomes of VLBW infants at a corrected age of 18 months. Further studies with a larger sample size are needed to confirm the adverse neurological effects of aminophylline treatment.

  16. Early neurodevelopmental screening in tuberous sclerosis complex: a potential window of opportunity.

    Science.gov (United States)

    Gipson, Tanjala T; Gerner, Gwendolyn; Srivastava, Siddharth; Poretti, Andrea; Vaurio, Rebecca; Hartman, Adam; Johnston, Michael V

    2014-09-01

    Infants born with tuberous sclerosis complex, a genetic condition resulting from a mutation in TSC1 or TSC2, are at increased risk for intellectual disability and/or autism. Features of epilepsy, neuropathology, genetics, as well as timing and type of mechanism-based medications have been proposed as risk factors. Neurodevelopmental outcomes have been reported among these studies; however, few include data about the individuals' early neurodevelopmental profile, a factor that may contribute significantly to these outcomes. Further, there is no clinical standard for the neurodevelopmental assessment of these infants. The paucity of data regarding the natural history of neurodevelopment in infants with tuberous sclerosis complex and the lack of a gold standard for neurodevelopmental evaluation present a significant challenge for clinicians and researchers. During the first year of life, we tracked the onset of infantile spasms, the type and timing of antiepileptic treatments, and the associated response of two age-matched infants with tuberous sclerosis complex. We also employed Capute Scales as a part of a structured neurodevelopmental evaluation to characterize and compare their neurodevelopmental profiles. Infant 1 developed infantile spasms with confirmed hypsarrhythmia at 4 months of age. Treatment with vigabatrin was initiated within 24 hours with near immediate cessation of seizures and no further seizures to date. Expressive language delay was detected at 12 months and treated with speech and/or language therapy. Infant 2 developed complex partial seizures at 1 month. Treatment included levetiracetam, oxcarbazepine, and the ketogenic diet. Vigabatrin was initiated on detection of hypsarrhythmia after 4 months. Intractable epilepsy persists to date. Global developmental delay was evident by 8 months and treated with physical, occupational, and speech and/or language therapy. Many risk factors have been associated with intellectual disability and/or autism in

  17. Rare CNVs in Suicide Attempt include Schizophrenia-Associated Loci and Neurodevelopmental Genes: A Pilot Genome-Wide and Family-Based Study.

    Directory of Open Access Journals (Sweden)

    Marcus Sokolowski

    Full Text Available Suicidal behavior (SB has a complex etiology involving genes and environment. One of the genetic components in SB could be copy number variations (CNVs, as CNVs are implicated in neurodevelopmental disorders. However, a recently published genome-wide and case-control study did not observe any significant role of CNVs in SB. Here we complemented these initial observations by instead using a family-based trio-sample that is robust to control biases, having severe suicide attempt (SA in offspring as main outcome (n = 660 trios. We first tested for CNV associations on the genome-wide Illumina 1M SNP-array by using FBAT-CNV methodology, which allows for evaluating CNVs without reliance on CNV calling algorithms, analogous to a common SNP-based GWAS. We observed association of certain T-cell receptor markers, but this likely reflected inter-individual variation in somatic rearrangements rather than association with SA outcome. Next, we used the PennCNV software to call 385 putative rare (100 kb CNVs, observed in n = 225 SA offspring. Nine SA offspring had rare CNV calls in a set of previously schizophrenia-associated loci, indicating the importance of such CNVs in certain SA subjects. Several additional, very large (>1MB sized CNV calls in 15 other SA offspring also spanned pathogenic regions or other neural genes of interest. Overall, 45 SA had CNVs enriched for 65 medically relevant genes previously shown to be affected by CNVs, which were characterized by a neurodevelopmental biology. A neurodevelopmental implication was partly congruent with our previous SNP-based GWAS, but follow-up analysis here indicated that carriers of rare CNVs had a decreased burden of common SNP risk-alleles compared to non-carriers. In conclusion, while CNVs did not show genome-wide association by the FBAT-CNV methodology, our preliminary observations indicate rare pathogenic CNVs affecting neurodevelopmental functions in a subset of SA, who were distinct from SA having

  18. Pesticide Exposure and Neurodevelopmental Outcomes: Review of the Epidemiologic and Animal Studies

    Science.gov (United States)

    Burns, Carol J.; McIntosh, Laura J.; Mink, Pamela J.; Jurek, Anne M.; Li, Abby A.

    2013-01-01

    Assessment of whether pesticide exposure is associated with neurodevelopmental outcomes in children can best be addressed with a systematic review of both the human and animal peer-reviewed literature. This review analyzed epidemiologic studies testing the hypothesis that exposure to pesticides during pregnancy and/or early childhood is associated with neurodevelopmental outcomes in children. Studies that directly queried pesticide exposure (e.g., via questionnaire or interview) or measured pesticide or metabolite levels in biological specimens from study participants (e.g., blood, urine, etc.) or their immediate environment (e.g., personal air monitoring, home dust samples, etc.) were eligible for inclusion. Consistency, strength of association, and dose response were key elements of the framework utilized for evaluating epidemiologic studies. As a whole, the epidemiologic studies did not strongly implicate any particular pesticide as being causally related to adverse neurodevelopmental outcomes in infants and children. A few associations were unique for a health outcome and specific pesticide, and alternative hypotheses could not be ruled out. Our survey of the in vivo peer-reviewed published mammalian literature focused on effects of the specific active ingredient of pesticides on functional neurodevelopmental endpoints (i.e., behavior, neuropharmacology and neuropathology). In most cases, effects were noted at dose levels within the same order of magnitude or higher compared to the point of departure used for chronic risk assessments in the United States. Thus, although the published animal studies may have characterized potential neurodevelopmental outcomes using endpoints not required by guideline studies, the effects were generally observed at or above effect levels measured in repeated-dose toxicology studies submitted to the U.S. Environmental Protection Agency (EPA). Suggestions for improved exposure assessment in epidemiology studies and more effective

  19. Telephone interviews and online questionnaires can be used to improve neurodevelopmental follow-up rates.

    Science.gov (United States)

    Johnson, Samantha; Seaton, Sarah E; Manktelow, Bradley N; Smith, Lucy K; Field, David; Draper, Elizabeth S; Marlow, Neil; Boyle, Elaine M

    2014-04-08

    Maximising response rates to neurodevelopmental follow-up is a key challenge for paediatric researchers. We have investigated the use of telephone interviews and online questionnaires to improve response rates, reduce non-response bias, maintain data completeness and produce unbiased outcomes compared with postal questionnaires when assessing neurodevelopmental outcomes at 2 years. A prospective cohort study of babies born ≥32 weeks gestation. Neurodevelopmental outcomes were assessed at 2 years of age using a parent questionnaire completed via post, telephone or online. Relative Risks with 95% confidence intervals (RR; 95% CI) were calculated to identify participant characteristics associated with non-response and questionnaire response mode (postal vs. telephone/online). The proportion of missing data and prevalence of adverse outcomes was compared between response modes using generalized linear models. Offering telephone/online questionnaires increased the study response rate from 55% to 60%. Telephone/online responders were more likely to be non-white (RR 1.6; [95% CI 1.1, 2.4]), non-English speaking (1.6; [1.0, 2.6]) or have a multiple birth (1.6; [1.1, 2.3]) than postal responders. There were no significant differences in the prevalence of adverse neurodevelopmental outcomes between those who responded via post vs. telephone/online (1.1; [0.9, 1.4]). Where parents attempted all questionnaire sections, there were no significant differences in the proportion of missing data between response modes. Where there is sufficient technology and resources, offering telephone interviews and online questionnaires can enhance response rates and improve sample representation to neurodevelopmental follow-up, whilst maintaining data completeness and unbiased outcomes.

  20. Automated electroencephalographic discontinuity in cooled newborns predicts cerebral MRI and neurodevelopmental outcome.

    Science.gov (United States)

    Dunne, Jonathan M; Wertheim, David; Clarke, Paul; Kapellou, Olga; Chisholm, Philippa; Boardman, James P; Shah, Divyen K

    2017-01-01

    Prolonged electroencephalographic (EEG) discontinuity has been associated with poor neurodevelopmental outcomes after perinatal asphyxia but its predictive value in the era of therapeutic hypothermia (TH) is unknown. In infants undergoing TH for hypoxic-ischaemic encephalopathy (HIE) prolonged EEG discontinuity is associated with cerebral tissue injury on MRI and adverse neurodevelopmental outcome. Retrospective study of term neonates from three UK centres who received TH for perinatal asphyxia, had continuous two channel amplitude-integrated EEG with EEG for a minimum of 48 h, brain MRI within 6 weeks of birth and neurodevelopmental outcome data at a median age of 24 months. Mean discontinuity was calculated using a novel automated algorithm designed for analysis of the raw EEG signal. Of 49 eligible infants, 17 (35%) had MR images predictive of death or severe neurodisability (unfavourable outcome) and 29 (59%) infants had electrographic seizures. In multivariable logistic regression, mean discontinuity at 24 h and 48 h (both p=0.01), and high seizure burden (p=0.05) were associated with severe cerebral tissue injury on MRI. A mean discontinuity >30 s/min-long epoch, had a specificity and positive predictive value of 100%, sensitivity of 71% and a negative predictive value of 88% for unfavourable neurodevelopmental outcome at a 10 µV threshold. In addition to seizure burden, excessive EEG discontinuity is associated with increased cerebral tissue injury on MRI and is predictive of abnormal neurodevelopmental outcome in infants treated with TH. The high positive predictive value of EEG discontinuity at 24 h may be valuable in selecting newborns with HIE for adjunctive treatments. 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/.

  1. Pesticide exposure and neurodevelopmental outcomes: review of the epidemiologic and animal studies.

    Science.gov (United States)

    Burns, Carol J; McIntosh, Laura J; Mink, Pamela J; Jurek, Anne M; Li, Abby A

    2013-01-01

    Assessment of whether pesticide exposure is associated with neurodevelopmental outcomes in children can best be addressed with a systematic review of both the human and animal peer-reviewed literature. This review analyzed epidemiologic studies testing the hypothesis that exposure to pesticides during pregnancy and/or early childhood is associated with neurodevelopmental outcomes in children. Studies that directly queried pesticide exposure (e.g., via questionnaire or interview) or measured pesticide or metabolite levels in biological specimens from study participants (e.g., blood, urine, etc.) or their immediate environment (e.g., personal air monitoring, home dust samples, etc.) were eligible for inclusion. Consistency, strength of association, and dose response were key elements of the framework utilized for evaluating epidemiologic studies. As a whole, the epidemiologic studies did not strongly implicate any particular pesticide as being causally related to adverse neurodevelopmental outcomes in infants and children. A few associations were unique for a health outcome and specific pesticide, and alternative hypotheses could not be ruled out. Our survey of the in vivo peer-reviewed published mammalian literature focused on effects of the specific active ingredient of pesticides on functional neurodevelopmental endpoints (i.e., behavior, neuropharmacology and neuropathology). In most cases, effects were noted at dose levels within the same order of magnitude or higher compared to the point of departure used for chronic risk assessments in the United States. Thus, although the published animal studies may have characterized potential neurodevelopmental outcomes using endpoints not required by guideline studies, the effects were generally observed at or above effect levels measured in repeated-dose toxicology studies submitted to the U.S. Environmental Protection Agency (EPA). Suggestions for improved exposure assessment in epidemiology studies and more effective

  2. Neurodevelopmental effects in children associated with exposure to organophosphate pesticides: A systematic review

    Science.gov (United States)

    Muñoz-Quezada, María Teresa; Lucero, Boris A.; Barr, Dana B.; Steenland, Kyle; Levy, Karen; Ryan, P. Barry; Iglesias, Veronica; Alvarado, Sergio; Concha, Carlos; Rojas, Evelyn; Vega, Catalina

    2013-01-01

    Many studies have investigated the neurodevelopmental effects of prenatal and early childhood exposures to organophosphate (OP) pesticides among children, but they have not been collectively evaluated. The aim of the present article is to synthesize reported evidence over the last decade on OP exposure and neurodevelopmental effects in children. The Data Sources were PubMed, Web of Science, EBSCO, SciVerse Scopus, SpringerLink, SciELO and DOAJ. The eligibility criteria considered were studies assessing exposure to OP pesticides and neurodevelopmental effects in children from birth to 18 years of age, published between 2002 and 2012 in English or Spanish. Twenty-seven articles met the eligibility criteria. Studies were rated for evidential consideration as high, intermediate, or low based upon the study design, number of participants, exposure measurement, and neurodevelopmental measures. All but one of the 27 studies evaluated showed some negative effects of pesticides on neurobehavioral development. A positive dose–response relationship between OP exposure and neurodevelopmental outcomes was found in all but one of the 12 studies that assessed dose–response. In the ten longitudinal studies that assessed prenatal exposure to OPs, cognitive deficits (related to working memory) were found in children at age 7 years, behavioral deficits (related to attention) seen mainly in toddlers, and motor deficits (abnormal reflexes) seen mainly in neonates. No meta-analysis was possible due to different measurements of exposure assessment and outcomes. Eleven studies (all longitudinal) were rated high, 14 studies were rated intermediate, and two studies were rated low. Evidence of neurological deficits associated with exposure to OP pesticides in children is growing. The studies reviewed collectively support the hypothesis that exposure to OP pesticides induces neurotoxic effects. Further research is needed to understand effects associated with exposure in critical windows

  3. Cytokines and the neurodevelopmental basis of mental illness

    Directory of Open Access Journals (Sweden)

    Udani eRatnayake

    2013-10-01

    Full Text Available Epidemiological studies suggest that prenatal exposure to different types of viral or bacterial infections may be associated with similar outcomes; i.e., an increased risk of mental illness disorders in the offspring. Infections arising from various causes have similar debilitating effects in later life, suggesting that the exact pathogen may not be the critical factor in determining the neurological and cognitive outcome in the offspring. Instead, it is thought that response of the innate immune system, specifically the increased production of inflammatory cytokines, may be the critical mediator in altering fetal brain development pre-disposing the offspring to mental illness disorders later in life. Inflammatory cytokines are essential for normal brain development. Factors such as the site of cytokine production, a change in balance between anti- and pro- inflammatory cytokines, placental transfer of cytokines, the effects of cytokines on glial cells, and the effects of glucocorticoids are important when evaluating the impact of maternal infection on fetal brain development. Although it is clear that cytokines are altered in the fetal brain following maternal infection, further evidence is required to determine if cytokines are the critical factor that alters the trajectory of brain development, subsequently leading to postnatal behavioural and neurological abnormalities.

  4. Principles and Practices of Neurodevelopmental Assessment in Children: Lessons Learned from the Centers for Children’s Environmental Health and Disease Prevention Research

    Science.gov (United States)

    Dietrich, Kim N.; Eskenazi, Brenda; Schantz, Susan; Yolton, Kimberly; Rauh, Virginia A.; Johnson, Caroline B.; Alkon, Abbey; Canfield, Richard L.; Pessah, Isaac N.; Berman, Robert F.

    2005-01-01

    Principles and practices of pediatric neurotoxicology are reviewed here with the purpose of guiding the design and execution of the planned National Children’s Study. The developing human central nervous system is the target organ most vulnerable to environmental chemicals. An investigation of the effects of environmental exposures on child development is a complex endeavor that requires consideration of numerous critical factors pertinent to a study’s concept, design, and execution. These include the timing of neurodevelopmental assessment, matters of biologic plausibility, site, child and population factors, data quality assurance and control, the selection of appropriate domains and measures of neurobehavior, and data safety and monitoring. Here we summarize instruments for the assessment of the neonate, infant, and child that are being employed in the Centers for Children’s Environmental Health and Disease Prevention Research, sponsored by the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency, discuss neural and neurobiologic measures of development, and consider the promises of gene–environment studies. The vulnerability of the human central nervous system to environmental chemicals has been well established, but the contribution these exposures may make to problems such as attention deficit disorder, conduct problems, pervasive developmental disorder, or autism spectrum disorder remain uncertain. Large-scale studies such as the National Children’s Study may provide some important clues. The human neurodevelopmental phenotype will be most clearly represented in models that include environmental chemical exposures, the social milieu, and complex human genetic characteristics that we are just beginning to understand. PMID:16203260

  5. The Perfect Storm: Preterm Birth, Neurodevelopmental Mechanisms, and Autism Causation.

    Science.gov (United States)

    Erdei, Carmina; Dammann, Olaf

    2014-01-01

    A unifying model of autism causation remains elusive, and thus well-designed explanatory models are needed to develop appropriate therapeutic and preventive interventions. This essay argues that autism is not a static disorder, but rather an ongoing process. We discuss the link between preterm birth and autism and briefly review the evidence supporting the link between immune system characteristics and both prematurity and autism. We then propose a causation process model of autism etiology and pathogenesis, in which both neurodevelopment and ongoing/prolonged neuroinflammation are necessary pathogenetic component mechanisms. We suggest that an existing model of sufficient cause and component causes can be interpreted as a mechanistic view of etiology and pathogenesis and can serve as an explanatory model for autism causal pathways.

  6. Neurodevelopmental effects of insulin-like growth factor signaling

    Science.gov (United States)

    O’Kusky, John; Ye, Ping

    2012-01-01

    Insulin-like growth factor (IGF) signaling greatly impacts the development and growth of the central nervous system (CNS). IGF-I and IGF-II, two ligands of the IGF system, exert a wide variety of actions both during development and in adulthood, promoting the survival and proliferation of neural cells. The IGFs also influence the growth and maturation of neural cells, augmenting dendritic growth and spine formation, axon outgrowth, synaptogenesis, and myelination. Specific IGF actions, however, likely depend on cell type, developmental stage, and local microenvironmental milieu within the brain. Emerging research also indicates that alterations in IGF signaling likely contribute to the pathogenesis of some neurological disorders. This review summarizes experimental studies and shed light on the critical roles of IGF signaling, as well as its mechanisms, during CNS development. PMID:22710100

  7. Abstracts of the 11th International Conference on Developmental Coordination Disorder (DCD11

    Directory of Open Access Journals (Sweden)

    DCD11 Congress Delegates

    2015-06-01

    Full Text Available CD11 – Developmental coordination disorder and other neurodevelopmental disorders: a focus on comorbidity; Toulouse, France, July 2-4, 2015 Comorbidity refers to the presence of two or more disorders in the same person (especially DCD, dyslexia and attention deficit hyperactivity disorder in terms of developmental disorders. There has been growing interest in the presence of comorbidity in persons with neurodevelopmental disorders. Many recent studies suggest that up to half of all individuals diagnosed with a psychiatric or neurodevelopmental disorder have more than one condition. Comorbidity not only impacts patient outcomes but can also create a significant strain on both family and school life. It can also complicate diagnosis and healthcare organization. The 11th congress on DCD aimed to address some of the important issues surrounding comorbidity in neurodevelopmental disorders. Three main topics were covered during oral and poster presentations: (1 assessment and diagnostic criteria, (2 underlying processes, causal factors, and prognostic markers, and (3 intervention and management of DCD and associated disorders.

  8. Assessing mental health in boys with Duchenne muscular dystrophy: Emotional, behavioural and neurodevelopmental profile in an Italian clinical sample.

    Science.gov (United States)

    Colombo, Paola; Nobile, Maria; Tesei, Alessandra; Civati, Federica; Gandossini, Sandra; Mani, Elisa; Molteni, Massimo; Bresolin, Nereo; D'Angelo, Grazia

    2017-07-01

    To evaluate through a comprehensive protocol, the psychopathological profile of DMD boys. The primary aim of this observational study was to describe the emotional and behavioural profile and the neurodevelopmental problems of Italian boys with Duchenne Muscular Dystrophy (DMD); the secondary aim was to explore the relation between psychopathological profile and DMD genotype. 47 DMD boys, aged 2-18, were included in the study and assessed through structured and validated tools including Wechsler scales or Griffiths for cognitive ability, Child Behavior Check List (CBCL), Youth Self Report (YSR) and Strengths and Difficulties Questionnaire (SDQ) for emotional and behavioural features. Patients "at risk" based on questionnaires scores were evaluated by a clinical structured interview using Development and Well Being Assessment (DAWBA) or Autism Diagnostic Observation Schedule (ADOS), as required. The 47 enrolled patients, defined with a Full Scale Intelligence Quotient (FSIQ) of 80.38 (one SD below average), and presenting a large and significant difference in FSIQ in relation to the site of mutation along the dystrophin gene (distal mutations associated with a more severe cognitive deficit), were showing Internalizing Problems (23.4%) and Autism Spectrum Disorders (14.8%). Interestingly, an association of internalizing problems with distal deletion of the DMD gene is documented. Even though preliminary, these data show that the use of validated clinical instruments, that focus on the impact of emotional/behaviour problems on everyday life, allows to carefully identify clinically significant psychopathology. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  9. Early-Term Birth in Single-Ventricle Congenital Heart Disease After the Fontan Procedure: Neurodevelopmental and Psychiatric Outcomes.

    Science.gov (United States)

    Calderon, Johanna; Stopp, Christian; Wypij, David; DeMaso, David R; Rivkin, Michael; Newburger, Jane W; Bellinger, David C

    2016-12-01

    To investigate the long-term impact of early-term birth (37-38 weeks' gestation) relative to full-term birth (≥39 weeks' gestation) on neurodevelopmental and psychiatric outcomes in adolescents with single-ventricle congenital heart disease (CHD). This cross-sectional cohort study analyzed retrospective medical records from full term adolescents with single-ventricle CHD who underwent the Fontan procedure. Participants underwent neurodevelopmental and psychiatric evaluations, as well as structural brain magnetic resonance imaging. Early-term born adolescents were compared with full-term born adolescents using regression models with adjustments for family social status, birth weight, and genetic abnormality status. Medical and demographic risk factors were examined as well. Compared with the full-term group (n = 100), adolescents born early term (n = 33) scored significantly worse on daily-life executive functions, as measured by the Behavior Rating Inventory of Executive Function parent-report (mean scores: early term, 62.0 ± 10.9; full-term, 55.6 ± 12.2; P = .009) and self-report (P = .02) composites. Adolescents born early term were more likely than those born full term to have a lifetime attention-deficit/hyperactivity disorder (ADHD) diagnosis (early term, 55%; full term, 26%; P = .001). The early-term group also displayed greater psychiatric symptom severity, as indicated by the clinician-reported Brief Psychiatric Rating Scale (mean score: early term, 16.1 ± 8.6; full-term, 12.5 ± 8.2; P = .007). Early-term birth is associated with greater prevalence of executive dysfunction, ADHD diagnosis, and psychiatric problems in adolescents with single-ventricle CHD. Early-term birth should be included as a potential risk factor in the algorithm for closer developmental surveillance in CHD. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Noninvasive Brain Stimulation in Pediatric Attention-Deficit Hyperactivity Disorder (ADHD) : A Review

    NARCIS (Netherlands)

    Rubio, Belen; Boes, Aaron D; Laganiere, Simon; Rotenberg, Alexander; Jeurissen, Danique; Pascual-Leone, Alvaro

    2016-01-01

    Attention-deficit hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in the pediatric population. The clinical management of ADHD is currently limited by a lack of reliable diagnostic biomarkers and inadequate therapy for a minority of patients who do not respond

  11. Cross-sensory gating in schizophrenia and autism spectrum disorder : EEG evidence for impaired brain connectivity?

    NARCIS (Netherlands)

    Magnee, Maurice J. C. M.; Oranje, Bob; van Engeland, Herman; Kahn, Rene S.; Kemner, Chantal

    Autism spectrum disorders (ASD) and schizophrenia are both neurodevelopmental disorders that have extensively been associated with impairments in functional brain connectivity. Using a cross-sensory P50 suppression paradigm, this study investigated low-level audiovisual interactions on cortical EEG

  12. Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism Spectrum Disorder in Male Offspring

    OpenAIRE

    Milada Mahic; Siri Mjaaland; Hege Marie Bøvelstad; Nina Gunnes; Ezra Susser; Michaeline Bresnahan; Anne-Siri Øyen; Bruce Levin; Xiaoyu Che; Deborah Hirtz; Ted Reichborn-Kjennerud; Synnve Schjølberg; Christine Roth; Per Magnus; Camilla Stoltenberg

    2017-01-01

    ABSTRACT Maternal infections during pregnancy are associated with risk of neurodevelopmental disorders, including autism spectrum disorders (ASDs). Proposed pathogenetic mechanisms include fetal infection, placental inflammation, and maternal cytokines or antibodies that cross the placenta. The Autism Birth Cohort comprises mothers, fathers, and offspring recruited in Norway in 1999 to 2008. Through questionnaire screening, referrals, and linkages to a national patient registry, 442 mothers o...

  13. Examining Services for Young Children with Autism Spectrum Disorder: Parent Satisfaction and Predictors of Service Utilization

    Science.gov (United States)

    McIntyre, Laura Lee; Zemantic, Patricia K.

    2017-01-01

    Autism spectrum disorder (ASD) is the fastest growing group of neurodevelopmental disorders in childhood. Earlier detection means an increased need for early intervention and other educational services. This study examined what services a sample of young children with ASD received, what variables predicted service utilization, and how satisfied…

  14. Clinical and pharmacokinetic evaluation of risperidone for the management of autism spectrum disorder

    NARCIS (Netherlands)

    Dinnissen, Mariken; Dietrich, Andrea; van den Hoofdakker, Barbara J.; Hoekstra, Pieter J.

    Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is often accompanied by psychiatric comorbidity. Although there is no medication currently available to treat the core symptoms of ASD, risperidone was the first drug to be approved for use in ASD and is still the

  15. Increasing Communication Skills: A Case Study of a Man with Autism Spectrum Disorder and Vision Loss

    Science.gov (United States)

    Kee, S. Brian; Casey, Laura Baylot; Cea, Clayton R.; Bicard, David F.; Bicard, Sara E.

    2012-01-01

    According to the "Diagnostic and Statistical Manual of Mental Disorders" (DSM-IV-TR; American Psychiatric Association, APA, 2000), autism is a neurodevelopmental disorder that is characterized by impairments in social and communicative behaviors with great variations in ability, depending on developmental level, intelligence, and chronological…

  16. A Review of Neuropsychological and Neuroimaging Research in Autistic Spectrum Disorders: Attention, Inhibition and Cognitive Flexibility

    Science.gov (United States)

    Sanders, Jane; Johnson, Katherine A.; Garavan, Hugh; Gill, Michael; Gallagher, Louise

    2008-01-01

    Autistic spectrum disorders (ASD) are devastating neurodevelopmental disorders of unknown aetiology with characteristic deficits in social interaction, communication and behaviour. Individuals with ASD show deficits in executive function (EF), which are hypothesised to underlie core repetitive, stereotyped behaviours of autism. Neuroimaging…

  17. The neuro-immune axis: Prospect for novel treatments for mental disorders

    NARCIS (Netherlands)

    Kraneveld, Aletta D.; de Theije, Caroline G.M.; van Heesch, Floor; Borre, Yuliya; de Kivit, Sander; Olivier, Berend; Korte, Mechiel; Garssen, Johan

    2014-01-01

    Disturbed bidirectional pathways between the (central) nervous system and immune system have been implicated in various mental disorders, including depressive and neurodevelopmental disorders. In this minireview, the role of the neuro-immune axis and its targetability in relation to major depression

  18. Design Approach of Mathematics Learning Activities in a Digital Environment for Children with Autism Spectrum Disorders

    Science.gov (United States)

    Santos, Maria Isabel; Breda, Ana; Almeida, Ana Margarida

    2017-01-01

    Learning environment on mathematics for autistic children is a prototype of a digital environment with dynamic adaptation features designed to offer activities towards the development of mathematical reasoning in children aged 6-12 years, diagnosed with autism spectrum disorders (ASD), a neurodevelopmental disorder characterized by deficits in…

  19. Quantifying Narrative Ability in Autism Spectrum Disorder: A Computational Linguistic Analysis of Narrative Coherence

    Science.gov (United States)

    Losh, Molly; Gordon, Peter C.

    2014-01-01

    Autism is a neurodevelopmental disorder characterized by serious difficulties with the social use of language, along with impaired social functioning and ritualistic/repetitive behaviors (American Psychiatric Association in "Diagnostic and statistical manual of mental disorders: DSM-5," 5th edn. American Psychiatric Association,…

  20. Clinical Reasoning in the Assessment and Planning for Intervention for Autism Spectrum Disorder

    Science.gov (United States)

    McCrimmon, Adam W.; Yule, Ashleigh E.

    2017-01-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder whose incidence is rising. School-based professionals are in an ideal position to provide the much-needed assessment and intervention supports for students with ASD, as the professionals' placement within a formal system affords the opportunity to observe and support children…

  1. Anatomy and Cell Biology of Autism Spectrum Disorder : Lessons from Human Genetics

    NARCIS (Netherlands)

    Kleijer, Kristel T E; Huguet, Guillaume; Tastet, Julie; Bourgeron, Thomas; Burbach, J P H

    2017-01-01

    Until recently autism spectrum disorder (ASD) was regarded as a neurodevelopmental condition with unknown causes and pathogenesis. In the footsteps of the revolution of genome technologies and genetics, and with its high degree of heritability, ASD became the first neuropsychiatric disorder for

  2. Differences between the family-centered "COPCA" program and traditional infant physical therapy based on neurodevelopmental treatment principles.

    Science.gov (United States)

    Dirks, Tineke; Blauw-Hospers, Cornill H; Hulshof, Lily J; Hadders-Algra, Mijna

    2011-09-01

    Evidence for effectiveness of pediatric physical therapy in infants at high risk for developmental motor disorders is limited. Therefore, "Coping With and Caring for Infants With Special Needs" (COPCA), a family-centered, early intervention program, was developed. The COPCA program is based on 2 components: (1) family involvement and educational parenting and (2) the neuromotor principles of the neuronal group selection theory. The COPCA coach uses principles of coaching to encourage the family's own capacities for solving problems of daily care and incorporating variation, along with trial and error in daily activities. The purpose of this study was to evaluate whether the content of sessions of the home-based, early intervention COPCA program differs from that of traditional infant physical therapy (TIP) sessions, which in the Netherlands are largely based on neurodevelopmental treatment. The study was conducted at the University Medical Center Groningen in the Netherlands. A quantitative video analysis of therapy sessions was conducted with infants participating in a 2-arm randomized trial. Forty-six infants at high risk for developmental motor disorders were randomly assigned to receive COPCA (n=21) or TIP (n=25) between 3 and 6 months corrected age. Intervention sessions were videotaped at 4 and 6 months corrected age and analyzed with a standardized observation protocol for the classification of physical therapy actions. Outcome parameters were relative amounts of time spent on specific physical therapy actions. The content of COPCA and TIP differed substantially. For instance, in TIP sessions, more time was spent on facilitation techniques, including handling, than in COPCA sessions (29% versus 3%, respectively). During COPCA, more time was spent on family coaching and education than during TIP (16% versus 4%, respectively). The major limitation of the study was its restriction to the Netherlands, implying that findings cannot be generalized automatically to

  3. Community survey of attention-deficit/hyperactivity disorder among ...

    African Journals Online (AJOL)

    Background: Attention-deficit/hyperactivity disorder (ADHD) is a common childhood neuro-developmental condition with early onset. ADHD affects children worldwide. However, there is a variation in the prevalence across different countries. In Nigeria, there is paucity of information on the prevalence. To provide the ...

  4. Knowledge of neurodevelopmental profile as one of the XXI century manager’s basic competences

    Directory of Open Access Journals (Sweden)

    Agnieszka Kowalczyk-Kassyk

    2011-01-01

    Full Text Available Majority of situations which man participates in are social situations, which other people attend directly or indirectly. Members of a group are connected with each other by mutual relationships system, which come into existence and change via continuous mutual influencing each other on the feedback rule. It is important to remember that the way how people behave does not only depend on their social group status. It most importantly is dependent on the type of mind they possess, as well as how they proceed with the learning process and which factors determine their individual neurodevelopmental functions. Human brain is responsible also for some disturbances in their behaviour such as: mastering the skills, assimilating facts or knowledge, carrying out defined actions, working systematical and maintaining in accurate speed, accommodation to scope of requirements, conflicts solving, reading of social information and reacting to them. Premises which are mentioned above show the fact that if we want to be an acting manager in modern company we should know the role of eight neurodevelopmental systems and treat them seriously. We are able to define and create optimal conditions for functioning of every mind and following on to form this friendly, effective organisation in which every employee can work at his own pace, using his own unique knowledge, interests and avocations by knowing his and his associates neurodevelopmental functions and having awareness of existing differences in this scope. In conclusion we can state that the XXIc manager’s role reaches far beyond the tasks which are the essence of the profession (management. It concerns such problems as: interaction optimalization between individual human and his work (good individual preferential accommodation to objective environmental requirements, thus creating advantageous organisational climate, reducing psychological costs of work, decreasing tensions, conflicts and also responsibility

  5. Efficacy of Intensive Neurodevelopmental Treatment for Children With Developmental Delay, With or Without Cerebral Palsy

    OpenAIRE

    Lee, Kyoung-Hwan; Park, Jinwoo; Lee, Hojun; Nam, Kiyeun; Park, Tae June; Kim, Hee Jae; Kwon, Bumsun

    2017-01-01

    Objective To evaluate the effectiveness of intensive neurodevelopmental treatment (NDT) on gross motor function for the children having developmental delay (DD), with or without cerebral palsy (CP). Methods Forty-two children had intensive NDT three times weekly, 60 minutes a day, for 3 months, immediately followed by conventional NDT once or twice a week, 30 minutes a day, for another 3 months. We assessed Gross Motor Function Measure (GMFM) over three time points: before conventional NDT, b...

  6. Does Congenital Heart Disease Affect Neurodevelopmental Outcomes in Children with Down Syndrome?

    Science.gov (United States)

    Alsaied, Tarek; Marino, Bradley S; Esbensen, Anna J; Anixt, Julia S; Epstein, Jeffery N; Cnota, James F

    2016-01-01

    The impact that congenital heart disease (CHD) has on the neurodevelopment of children with Down syndrome (DS) is unknown and potentially has implications for targeted early intervention. This study assessed the relationship between CHD that required surgery in the first year of life and neurodevelopmental, behavioral and emotional functioning outcomes in children with DS. A retrospective chart review of 1092 children (0-18 years) with DS who visited a single institution from 8/08-8/13 was performed. Children who underwent at least one of nine neurodevelopmental (cognitive, language, developmental) or academic tests were included in the analysis (N = 178). Cohort was age-divided into infants/toddlers (0-2 years), preschoolers (3-5 years), and school age/adolescent (6-18 years). Test scores of children with DS who underwent cardiac surgery in the first year of life were compared to children with DS without CHD. T test, chi-square and Mann Whitney U tests were used where appropriate. Infants/toddlers with cardiac surgery had lower scores for receptive (P = .01), expressive (P = .021) and composite language (P children with cardiac surgery there were no differences in IQ scores, language scores, or academic achievement scores compared to those without CHD. Also at school-age there was no difference in the incidence of ADHD, executive function or on internalizing and externalizing behavior scores. Children with DS undergoing cardiac surgery during the first year demonstrated poorer neurodevelopmental outcomes as infants/toddler but had no difference at school age compared to children with DS without CHD. These results will guide early interventions to optimize neurodevelopmental outcomes in children with DS and will help with family counseling after CHD repair. © 2016 Wiley Periodicals, Inc.

  7. Identification of neurodevelopmental disabilities in underserved children using telehealth (INvesT): Clinical trial study design.

    Science.gov (United States)

    Ciccia, Angela Hein; Roizen, Nancy; Garvey, Matt; Bielefeld, Roger; Short, Elizabeth J

    2015-11-01

    Children living in poverty are at high risk for delays in development of language and behavior and they experience a discrepancy in diagnosis and access to intervention services. This gap is partially caused by barriers in access as well as traits that are specific to each child and family. The Identification of Neurodevelopmental Disabilities in Underserved Children using Telehealth (INvesT) trial is a novel intervention approach that was specifically designed to address these barriers. The INvesT trial has three primary aims: 1) to reduce the age of identification of neurodevelopmental disability for high-risk, low-income children. 2) To validate the INvesT protocol as a service delivery model that will decrease age of identifications of neurodevelopmental disability for high-risk, low-income children; and 3) to identify important child-specific factors, family-specific factors, and environmental factors that impact feasibility and success of the INvesT trial for high-risk, low-income children. The INvesT trial is an open-label, double-blinded, placebo-controlled multi-level study that includes telehealth risk assessment, telehealth screening, traditional full assessment, and follow through to enrollment in early intervention. The trial is conducted in partnership with an urban community health clinic that largely serves a low-income patient population. The results of the INvesT trial will provide evidence for the use of a telehealth service delivery model to improve access to care for neurodevelopmental disabilities for high-risk, low-income children. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Validation and adaptation of rapid neurodevelopmental assessment instrument for infants in Guatemala.

    Science.gov (United States)

    Thompson, L; Peñaloza, R A; Stormfields, K; Kooistra, R; Valencia-Moscoso, G; Muslima, H; Khan, N Z

    2015-11-01

    Timely detection of neurodevelopmental impairments in children can prompt referral for critical services that may prevent permanent disability. However, screening of impairments is a significant challenge in low-resource countries. We adapted and validated the rapid neurodevelopmental assessment (RNDA) instrument developed in Bangladesh to assess impairment in nine domains: primitive reflexes, gross and fine motor development, vision, hearing, speech, cognition, behaviour and seizures. We conducted a cross-sectional study of 77 infants (0-12 months) in rural Guatemala in July 2012 and July 2013. We assessed inter-rater reliability and predictive validity between the 27-item RNDA and the 325-item Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and concurrent validity based on chronic malnutrition, a condition associated with neurodevelopmental impairments. For both RNDA and BSID-III, standardized scores below 80 were defined as borderline impairment. Children came from rural households (92%), were born to indigenous women of Mayan descent (73%) and had moderate or severe growth stunting (43%). Inter-rater reliability for eight RNDA domains was of moderate to high reliability (weighted κ coefficients, 0.49-0.99). Children screened positive for impairment in fine motor (17%) and gross motor (14%) domains using the RNDA. The RNDA had good concurrent ability; infants who were growth stunted had higher mean levels of impairment in gross motor, speech and cognition domains (all p < 0.001). The RNDA took 20-30 min to complete compared with 45-60 min for BSID-III. Wide-scale implementation of a simple, valid and reliable screening tool like the RNDA by community health workers would facilitate early screening and referral of infants at-risk for neurodevelopmental impairment. © 2015 John Wiley & Sons Ltd.

  9. Modulating Tone to Promote Motor Development Using a Neurofacilitation of Developmental Reaction (NFDR) Approach in Children with Neurodevelopmental Delay

    National Research Council Canada - National Science Library

    Vijay Batra; Meenakshi Batra; Ravindra Mohan Pandey; Vijai Prakash Sharma; Girdhar Gopal Agarwal

    2015-01-01

      [...]assessments of muscle tone and primitive reflex status are crucial parts of motor examinations and the formulation of intervention strategies for children with neurodevelopmental delay (3,4...

  10. Utilization of the Premature Birth Knowledge Scale to Assess Pediatric Provider Knowledge of Neurodevelopmental Outcomes.

    Science.gov (United States)

    Kelly, Michelle M; Dean, Spencer

    Prematurity affects a significant portion (10-12%) of children in the Unites States, with potential for physical, psychological, neurodevelopmental, and behavioral impairments continuing long past the neonatal period. The specific aim of this research was to evaluate pediatric primary and specialty care providers' knowledge and understanding of neurodevelopmental outcomes of children born prematurely. Pediatric nurse practitioner (PNP) members of the National Association of Pediatric Nurse Practitioners participated in an online survey using the 33-item Premature Birth Knowledge Scale (PB-KS) to assess their knowledge of current neurodevelopmental outcomes of children born prematurely. Neither years of practice as a registered nurse nor as a PNP predicted performance on the PB-KS. The mean score on the PB-KS in the PNP sample was 17.8 (possible score = 0-33), with a mean accuracy of 53.9%. Higher scores on the PB-KS were correlated with higher perceived level of preparation to care for children born prematurely. To our knowledge, this is the first study to use the PB-KS with pediatric primary and specialty providers. PNPs are uniquely situated to educate and support families facing the long-term consequences of premature birth; to do so they must maintain accurate understanding of current outcomes. Copyright © 2017 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

  11. An interdisciplinary bronchopulmonary dysplasia program is associated with improved neurodevelopmental outcomes and fewer rehospitalizations.

    Science.gov (United States)

    Shepherd, E G; Knupp, A M; Welty, S E; Susey, K M; Gardner, W P; Gest, A L

    2012-01-01

    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.

  12. Early Life Characteristics and Neurodevelopmental Phenotypes in the Mount Sinai Children's Environmental Health Center.

    Science.gov (United States)

    Furlong, Melissa; Herring, Amy H; Goldman, Barbara D; Daniels, Julie L; Wolff, Mary S; Engel, Lawrence S; Engel, Stephanie M

    2017-11-24

    Neurodevelopmental outcomes including behavior, executive functioning, and IQ exhibit complex correlational structures, although they are often treated as independent in etiologic studies. We performed a principal components analysis of the behavioral assessment system for children, the behavior rating inventory of executive functioning, and the Wechsler scales of intelligence in a prospective birth cohort, and estimated associations with early life characteristics. We identified seven factors: (1) impulsivity and externalizing, (2) executive functioning, (3) internalizing, (4) perceptual reasoning, (5) adaptability, (6) processing speed, and (7) verbal intelligence. Prenatal fish consumption, maternal education, preterm birth, and the home environment were important predictors of various neurodevelopmental factors. Although maternal smoking was associated with more adverse externalizing, executive functioning, and adaptive composite scores in our sample, of the orthogonally-rotated factors, smoking was only associated with the impulsivity and externalizing factor ([Formula: see text] - 0.82, 95% CI - 1.42, - 0.23). These differences may be due to correlations among outcomes that were accounted for by using a phenotypic approach. Dimension reduction may improve upon traditional approaches by accounting for correlations among neurodevelopmental traits.

  13. An investigation of language abilities in individuals with high-functioning autism and asperger’s disorder

    OpenAIRE

    Speirs, Samantha Jane

    2017-01-01

    Autism and Asperger’s disorder are complex neurodevelopmental disorders that share many clinical deficits in social, language, motor and behvioural symptoms (American Psychiatric Association, 2000; World Health Organization, 1992). Current diagnostic criteria differentiate the disorders on the basis of the presence (autism) or absence (Asperger’s disorder) of significant language delays prior to 3 years of age. There has been an ongoing debate regarding whether autism and Aspergers disorder (...

  14. A Short Review on the Current Understanding of Autism Spectrum Disorders

    OpenAIRE

    Park, Hye Ran; Lee, Jae meen; Moon, Hyo Eun; Lee, Dong Soo; Kim, Bung-Nyun; Kim, Jinhyun; Kim, Dong Gyu; Paek,Sun Ha

    2016-01-01

    Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by a deficit in social behaviors and nonverbal interactions such as reduced eye contact, facial expression, and body gestures in the first 3 years of life. It is not a single disorder, and it is broadly considered to be a multi-factorial disorder resulting from genetic and non-genetic risk factors and their interaction. Genetic studies of ASD have identified mutations that interfere with typical neurodevelop...

  15. Annual Research Review: Infant development, autism, and ADHD - early pathways to emerging disorders

    OpenAIRE

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

    2015-01-01

    BackgroundAutism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) are two of the most common neurodevelopmental disorders, with a high degree of co-occurrence.MethodsProspective longitudinal studies of infants who later meet criteria for ASD or ADHD offer the opportunity to determine whether the two disorders share developmental pathways.ResultsProspective studies of younger siblings of children with autism have revealed a range of infant behavioral and neural mark...

  16. Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study.

    Science.gov (United States)

    Lindenburg, Irene T; Smits-Wintjens, Vivianne E; van Klink, Jeanine M; Verduin, Esther; van Kamp, Inge L; Walther, Frans J; Schonewille, Henk; Doxiadis, Ilias I; Kanhai, Humphrey H; van Lith, Jan M; van Zwet, Erik W; Oepkes, Dick; Brand, Anneke; Lopriore, Enrico

    2012-02-01

    To determine the incidence and risk factors for neurodevelopmental impairment (NDI) in children with hemolytic disease of the fetus/newborn treated with intrauterine transfusion (IUT). Neurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests, including the Bayley Scales of Infant Development, the Wechsler Preschool and Primary Scale of Intelligence, and the Wechsler Intelligence Scale for Children, according to the children's age. Primary outcome was the incidence of neurodevelopmental impairment defined as at least one of the following: cerebral palsy, severe developmental delay, bilateral deafness, and/or blindness. A total of 291 children were evaluated at a median age of 8.2 years (range, 2-17 years). Cerebral palsy was detected in 6 (2.1%) children, severe developmental delay in 9 (3.1%) children, and bilateral deafness in 3 (1.0%) children. The overall incidence of neurodevelopmental impairment was 4.8% (14/291). In a multivariate regression analysis including only preoperative risk factors, severe hydrops was independently associated with neurodevelopmental impairment (odds ratio, 11.2; 95% confidence interval, 1.7-92.7). Incidence of neurodevelopmental impairment in children treated with intrauterine transfusion for fetal alloimmune anemia is low (4.8%). Prevention of fetal hydrops, the strongest preoperative predictor for impaired neurodevelopment, by timely detection, referral and treatment may improve long-term outcome. Copyright © 2012 Mosby, Inc. All rights reserved.

  17. Research Review: Executive function deficits in fetal alcohol spectrum disorders and attention-deficit/hyperactivity disorder - a meta-analysis.

    Science.gov (United States)

    Kingdon, Danielle; Cardoso, Christopher; McGrath, Jennifer J

    2016-02-01

    Attention-deficit/hyperactivity disorder (ADHD)-like symptoms are common in fetal alcohol spectrum disorders (FASD). FASD and ADHD groups both display executive function impairments; however, there is ongoing debate whether the pattern and magnitude of executive function deficits differs between these two types of disorders. An electronic literature search was conducted (PubMed, PsychInfo; 1972-2013) to identify studies comparing the executive functioning of children with FASD with ADHD or control groups. FASD groups included those with and without dysmorphy (i.e., FAS, pFAS, ARND, and other FASD diagnoses). Effect sizes (Hedges' g, standardized mean difference) were calculated. Random effects meta-analytic models were performed using the metafor package for R. Fifty-one studies met inclusion criteria (FASD N = 2,115; ADHD N = 453; controls N = 1,990). Children with FASD showed the strongest and most consistent deficits in planning, fluency, and set-shifting compared to controls (Hedges' g = -0.94, -0.78) and children with ADHD (Hedges' g = -0.72, -0.32). FASD was associated with moderate to large impairments in working memory, compared to controls (Hedges' g = -.84, -.58) and small impairments relative to groups with ADHD (Hedges' g = -.26). Smaller and less consistent deficits were found on measures of inhibition and vigilance relative to controls (Hedges' g = -0.52, -0.31); FASD and ADHD were not differentiated on these measures. Moderator analyses indicated executive dysfunction was associated with older age, dysmorphy, and larger group differences in IQ. Sex and diagnostic system were not consistently related to effect size. While FASD is associated with global executive impairments, executive function weaknesses are most consistent for measures of planning, fluency, and set-shifting. Neuropsychological measures assessing these executive function domains may improve differential diagnosis and treatment of FASD. © 2015 Association for Child and Adolescent

  18. Brief Report: The Prevalence of Neurofibromatosis Type 1 among Children with Autism Spectrum Disorder Identified by the Autism and Developmental Disabilities Monitoring Network

    Science.gov (United States)

    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

    2016-01-01

    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…

  19. The ESSENCE in Child Psychiatry: Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations

    Science.gov (United States)

    Gillberg, Christopher

    2010-01-01

    Co-existence of disorders--including attention-deficit/hyperactivity disorder, oppositional defiant disorder, tic disorder, developmental coordination disorder, and autism spectrum disorder--and sharing of symptoms across disorders (sometimes referred to as comorbidity) is the rule rather than the exception in child psychiatry and developmental…

  20. Early-adult outcome of child and adolescent mental disorders as evidenced by a national-based case register survey

    DEFF Research Database (Denmark)

    Castagnini, Augusto; Foldager, Leslie; Caffo, Ernesto

    2016-01-01

    groups at 6–16 years and exhibited a characteristic male preponderance; while affective, eating, neurotic, stress-related and adjustment disorders were more common in girls. Over a mean follow-up period of 10.1 years, 1666 (27.6%) cases, mean age 23.4 years, were referred for treatment to mental health...... selected all those (n = 6043) who were enrolled for the first time in the Danish Psychiatric Register with an ICD-10 F00–99 diagnosis in 1995–1997, and identified any mental disorder for which they received treatment up to 2009. Results Neurodevelopmental and conduct disorders were the principal diagnostic...... services, and they had a markedly higher risk than the general population (RR 5.1; 95% CI 4.9–5.4). Affective, eating, neurodevelopmental, obsessive–compulsive and psychotic disorders had the strongest continuity. Heterotypic transitions were observed for affective, eating, neurodevelopmental, personality...

  1. Neuroimaging Endophenotypes in Autism Spectrum Disorder

    Science.gov (United States)

    Mahajan, Rajneesh; Mostofsky, Stewart H.

    2015-01-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder that has a strong genetic basis, and is heterogeneous in its etiopathogenesis and clinical presentation. Neuroimaging studies, in concert with neuropathological and clinical research, have been instrumental in delineating trajectories of development in children with ASD. Structural neuroimaging has revealed ASD to be a disorder with general and regional brain enlargement, especially in the frontotemporal cortices, while functional neuroimaging studies have highlighted diminished connectivity, especially between frontal-posterior regions. The diverse and specific neuroimaging findings may represent potential neuroendophenotypes, and may offer opportunities to further understand the etiopathogenesis of ASD, predict treatment response and lead to the development of new therapies. PMID:26234701

  2. ESSENCE-Q – used as a screening tool for neurodevelopmental problems in public health checkups for young children in south Japan

    Science.gov (United States)

    Hatakenaka, Yuhei; Ninomiya, Hitoshi; Billstedt, Eva; Fernell, Elisabeth; Gillberg, Christopher

    2017-01-01

    Background Screening for developmental disorders is an important task for Child Health Care. The concept of ESSENCE (early symptomatic syndromes eliciting neurodevelopmental clinical examinations) was created to cover all types of early developmental disorders and the ESSENCE-Questionnaire (ESSENCE-Q containing 12 questions with possible total scores ranging from 0 to 22) was developed as a tool for early detection of these disorders. The aim of this study was to perform a validation study in a public health situation in Japan. Methods The psychometric properties of the ESSENCE-Q, completed by mothers, public health nurses (PHNs), and psychologists at 18-month (n=143 children) and 36-month (n=149 children) checkups were evaluated in a small city of Japan. Results were validated against clinical ESSENCE diagnoses. Receiver operating characteristic curves were generated and compared by using the area under the curve (AUC). Optimal cutoff values were explored. Results At the 18-month checkup, AUC by mothers was 0.72, by PHNs 0.86, and by psychologists 0.82. An optimal cutoff was 3 with a high negative predictive value (NPV). At the 36-month checkup, AUC by mothers was 0.57, by PHNs 0.82, and by psychologists 0.87. Optimal cutoff was 2 with high NPV. Conclusion The ESSENCE-Q completed by PHNs and psychologists had good diagnostic validity. The results suggested that almost all children scoring under cutoff would not have any ESSENCE problems/diagnoses. PMID:28546752

  3. A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking.

    Directory of Open Access Journals (Sweden)

    Swati Khare

    Full Text Available The autosomal dominant spinocerebellar ataxias (SCAs are a diverse group of neurological disorders anchored by the phenotypes of motor incoordination and cerebellar atrophy. Disease heterogeneity is appreciated through varying comorbidities: dysarthria, dysphagia, oculomotor and/or retinal abnormalities, motor neuron pathology, epilepsy, cognitive impairment, autonomic dysfunction, and psychiatric manifestations. Our study focuses on SCA13, which is caused by several allelic variants in the voltage-gated potassium channel KCNC3 (Kv3.3. We detail the clinical phenotype of four SCA13 kindreds that confirm causation of the KCNC3R423H allele. The heralding features demonstrate congenital onset with non-progressive, neurodevelopmental cerebellar hypoplasia and lifetime improvement in motor and cognitive function that implicate compensatory neural mechanisms. Targeted expression of human KCNC3R423H in Drosophila triggers aberrant wing veins, maldeveloped eyes, and fused ommatidia consistent with the neurodevelopmental presentation of patients. Furthermore, human KCNC3R423H expression in mammalian cells results in altered glycosylation and aberrant retention of the channel in anterograde and/or endosomal vesicles. Confirmation of the absence of plasma membrane targeting was based on the loss of current conductance in cells expressing the mutant channel. Mechanistically, genetic studies in Drosophila, along with cellular and biophysical studies in mammalian systems, demonstrate the dominant negative effect exerted by the mutant on the wild-type (WT protein, which explains dominant inheritance. We demonstrate that ocular co-expression of KCNC3R423H with Drosophila epidermal growth factor receptor (dEgfr results in striking rescue of the eye phenotype, whereas KCNC3R423H expression in mammalian cells results in aberrant intracellular retention of human epidermal growth factor receptor (EGFR. Together, these results indicate that the neurodevelopmental

  4. A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking.

    Science.gov (United States)

    Khare, Swati; Nick, Jerelyn A; Zhang, Yalan; Galeano, Kira; Butler, Brittany; Khoshbouei, Habibeh; Rayaprolu, Sruti; Hathorn, Tyisha; Ranum, Laura P W; Smithson, Lisa; Golde, Todd E; Paucar, Martin; Morse, Richard; Raff, Michael; Simon, Julie; Nordenskjöld, Magnus; Wirdefeldt, Karin; Rincon-Limas, Diego E; Lewis, Jada; Kaczmarek, Leonard K; Fernandez-Funez, Pedro; Nick, Harry S; Waters, Michael F

    2017-01-01

    The autosomal dominant spinocerebellar ataxias (SCAs) are a diverse group of neurological disorders anchored by the phenotypes of motor incoordination and cerebellar atrophy. Disease heterogeneity is appreciated through varying comorbidities: dysarthria, dysphagia, oculomotor and/or retinal abnormalities, motor neuron pathology, epilepsy, cognitive impairment, autonomic dysfunction, and psychiatric manifestations. Our study focuses on SCA13, which is caused by several allelic variants in the voltage-gated potassium channel KCNC3 (Kv3.3). We detail the clinical phenotype of four SCA13 kindreds that confirm causation of the KCNC3R423H allele. The heralding features demonstrate congenital onset with non-progressive, neurodevelopmental cerebellar hypoplasia and lifetime improvement in motor and cognitive function that implicate compensatory neural mechanisms. Targeted expression of human KCNC3R423H in Drosophila triggers aberrant wing veins, maldeveloped eyes, and fused ommatidia consistent with the neurodevelopmental presentation of patients. Furthermore, human KCNC3R423H expression in mammalian cells results in altered glycosylation and aberrant retention of the channel in anterograde and/or endosomal vesicles. Confirmation of the absence of plasma membrane targeting was based on the loss of current conductance in cells expressing the mutant channel. Mechanistically, genetic studies in Drosophila, along with cellular and biophysical studies in mammalian systems, demonstrate the dominant negative effect exerted by the mutant on the wild-type (WT) protein, which explains dominant inheritance. We demonstrate that ocular co-expression of KCNC3R423H with Drosophila epidermal growth factor receptor (dEgfr) results in striking rescue of the eye phenotype, whereas KCNC3R423H expression in mammalian cells results in aberrant intracellular retention of human epidermal growth factor receptor (EGFR). Together, these results indicate that the neurodevelopmental consequences of

  5. Disruption of Trophic Inhibitory Signaling in Autism Sepctrum Disorders

    Science.gov (United States)

    2016-12-01

    responses. This switch is known to be delayed in several neurodevelopmental disorders including Fragile X Syndrome , some forms of syndromic and non...Fragile X mouse model. We found: 1) that EGABA development was not disrupted in the mouse model of Angelman Syndrome 2) EGABA development was delayed in...bumetanide to mice rescues synaptic and circuit dysfunction in Fragile X mice. 15. SUBJECT TERMS Autism Spectrum Disorders, Fragile X Syndrome Angelman

  6. Aggression in autism spectrum disorder: presentation and treatment options

    OpenAIRE

    Erickson, Craig; Srivorakiat,Laura; Wink,Logan; Pedapati,Ernest; Fitzpatrick,Sarah

    2016-01-01

    Sarah E Fitzpatrick, Laura Srivorakiat, Logan K Wink, Ernest V Pedapati, Craig A Erickson Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent difficulties in social communication and social interaction, coupled with restricted, repetitive patterns of behavior or interest. Research indicates that aggression rates may be h...

  7. Magnesium supplementation in children with attention deficit hyperactivity disorder

    OpenAIRE

    El Baza, Farida; AlShahawi, Heba Ahmed; Zahra, Sally; AbdelHakim, Rana Ahmed

    2016-01-01

    Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with associated mineral deficiency. Aim: To assess magnesium level in ADHD children and compare it to the normal levels in children. Then, to detect the effect of magnesium supplementation as an add on therapy, on magnesium deficient patients. Methods: The study was conducted on 25 patients with ADHD and 25 controls. All subjects had magnesium estimation in serum and hair. ADHD children w...

  8. Social Cognition in Children with High-Functioning Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder. Associations with Executive Functions

    OpenAIRE

    Ana Miranda; Carmen Berenguer; Belén Roselló; Inmaculada Baixauli; Carla Colomer

    2017-01-01

    Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders characterized by social impairments. The first objective of this study was to analyze social cognition deficits of children with ADHD, high-functioning ASD (HFASD), and typical development (TD) in their performance on explicit and applied measures of theory of mind (ToM). The second objective was to investigate the relationships between executive functions and social cognition i...

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

    Science.gov (United States)

    Clarkson, Jessica

    2014-01-01

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

  10. Social (Pragmatic) Communication Disorder and Its Relation to the Autism Spectrum: Dilemmas Arising from the DSM-5 Classification

    Science.gov (United States)

    Brukner-Wertman, Yael; Laor, Nathaniel; Golan, Ofer

    2016-01-01

    DSM-5 introduced two diagnoses describing neurodevelopmental deficits in social communication (SC); Autism Spectrum Disorder (ASD) and Social (Pragmatic) Communication Disorder (SPCD). These diagnoses are differentiated by Repetitive and Restricted Behaviors (RRB), required for an ASD diagnosis and absent in SPCD. We highlight the gaps between the…

  11. Assessment of Body Composition Using Whole Body Air-Displacement Plethysmography in Children with and without Developmental Coordination Disorder

    Science.gov (United States)

    Cairney, John; Hay, John; Veldhuizen, Scott; Faught, Brent

    2011-01-01

    Developmental coordination disorder (DCD) is a neuro-developmental disorder characterized by poor fine and/or gross motor coordination. Children with DCD are hypothesized to be at increased risk for overweight and obesity from inactivity due to their motor coordination problems. Although previous studies have found evidence to support this…

  12. Trajectories Leading to Autism Spectrum Disorders Are Affected by Paternal Age: Findings from Two Nationally Representative Twin Studies

    Science.gov (United States)

    Lundstrom, Sebastian; Haworth, Claire M. A.; Carlstrom, Eva; Gillberg, Christopher; Mill, Jonathan; Rastam, Maria; Hultman, Christina M.; Ronald, Angelica; Anckarsater, Henrik; Plomin, Robert; Lichtenstein, Paul; Reichenberg, Abraham

    2010-01-01

    Background: Despite extensive efforts, the causes of autism remain unknown. Advancing paternal age has been associated with various neurodevelopmental disorders. We aim to investigate three unresolved questions: (a) What is the association between paternal age and autism spectrum disorders (ASD)?; (b) Does paternal age moderate the genetic and…

  13. Executive Function, Social Emotional Learning, and Social Competence in School-Aged Boys with Autism Spectrum Disorder

    Science.gov (United States)

    Berard, Nathalie; Loutzenhiser, Lynn; Sevigny, Phillip R.; Alfano, Dennis P.

    2017-01-01

    Autism Spectrum Disorder (ASD) is an aetiologically complex neurodevelopmental disorder characterized by deficits in social functioning. Children with ASD display a wide range of social competence and more variability in social domains as compared with either communication or repetitive behaviour domains. There is limited understanding of factors…

  14. Family quality of life among families with a child who has a severe neurodevelopmental disability: Impact of family and child socio-demographic factors.

    Science.gov (United States)

    Schertz, Mitchell; Karni-Visel, Yael; Tamir, Ada; Genizi, Jacob; Roth, Dana

    2016-01-01

    We aimed to examine family quality of life (FQOL) of Northern Israeli families having a child with a severe neurodevelopmental disability and its relation to socio-demographics. The cohort included caregivers of 70 children ages (mean ± standard deviation) 5.36 ± 3.53 years. Families were two-parent (85.7%), lived in the periphery (67.1%) and included Jews (60%), Muslims (18.6%), Druze (14.3%) and Christians (7.1%). Religiosity included: secular (38.6%), traditional (31.4%), religious (30%). Children's diagnosis included autistic spectrum disorder (41.4%), intellectual disability (21.4%), cerebral palsy (17.1%), genetic syndromes (17.1%) and sensorineural hearing loss (2.9%). Degree of support (1-minimal,5-greatest) required by the child was 3.67 ± 1.28 for physical and 3.49 ± 1.36 for communication. Primary caregivers completed the FQOL Survey. Domain scores were highest for family relations and lowest for financial well-being. Dimension scores were highest for importance and lowest for opportunities. Overall FQOL approximated average. Jewish families and residents of a major urban area reported higher and more religious families reported lower overall FQOL. Regression analysis found ethnicity contributing to overall FQOL and domain scores with residence contributing to support from services. Ethnicity and child dependence contributed to dimension scores. Northern Israeli families having a child with a severe neurodevelopmental disability report average FQOL scores. However, family and child dependence characteristics affect FQOL scores. Professionals working with these families should consider FQOL information when making recommendations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Preterm birth–associated neurodevelopmental impairment estimates at regional and global levels for 2010

    Science.gov (United States)

    Blencowe, Hannah; Lee, Anne CC; Cousens, Simon; Bahalim, Adil; Narwal, Rajesh; Zhong, Nanbert; Chou, Doris; Say, Lale; Modi, Neena; Katz, Joanne; Vos, Theo; Marlow, Neil; Lawn, Joy E.

    2013-01-01

    Background: In 2010, there were an estimated 15 million preterm births worldwide (preterm babies according to the level of care. A compartmental model was used to estimate the number of impaired postneonatal survivors following preterm birth in 2010. A separate model (DisMod-MR) was used to estimate years lived with disability (YLDs) for the global burden of disease 2010 study. Disability adjusted life years (DALYs) were calculated as the sum of YLDs and years of life lost (YLLs). Results: In 2010, there were an estimated 13 million preterm births who survived beyond the first month. Of these, 345,000 (2.7%, uncertainty range: 269,000–420,000) were estimated to have moderate or severe neurodevelopmental impairment, and a further 567,000 (4.4%, (445,000–732,000)) were estimated to have mild neurodevelopmental impairment. Many more have specific learning or behavioral impairments or reduced physical or mental health. Fewest data are available where the burden is heaviest. Preterm birth was responsible for 77 million DALYs, 3.1% of the global total, of which only 3 million were YLDs. Conclusion: Most preterm births (>90%) survive without neurodevelopmental impairment. Developing effective means of prevention of preterm birth should be a longer term priority, but major burden reduction could be made immediately with improved coverage and quality of care. Improved newborn care would reduce mortality, especially in low-income countries and is likely to reduce impairment in survivors, particularly in middle-income settings. PMID:24366461

  16. Structural cerebral abnormalities and neurodevelopmental status in single ventricle congenital heart disease before Fontan procedure.

    Science.gov (United States)

    Knirsch, Walter; Mayer, Kristina Nadine; Scheer, Ianina; Tuura, Ruth; Schranz, Dietmar; Hahn, Andreas; Wetterling, Kristina; Beck, Ingrid; Latal, Beatrice; Reich, Bettina

    2017-04-01

    Neonates with single ventricle congenital heart disease are at risk for structural cerebral abnormalities. Little is known about the further evolution of cerebral abnormalities until Fontan procedure. Between August 2012 and July 2015, we conducted a prospective cross-sectional two centre study using cerebral magnetic resonance imaging (MRI) and neuro-developmental outcome assessed by the Bayley-III. Forty-seven children (31 male) were evaluated at a mean age of 25.9 ± 3.4 months with hypoplastic left heart syndrome (25) or other single ventricle (22). Cerebral MRI was abnormal in 17 patients (36.2%) including liquor space enlargements (10), small grey (9) and minimal white (5) matter injuries. Eight of 17 individuals had combined lesions. Median (range) cognitive composite score (CCS) (100, 65-120) and motor composite score (MCS) (97, 55-124) were comparable to the reference data, while language composite score (LCS) (97, 68-124) was significantly lower ( P  = 0.040). Liquor space enlargement was associated with poorer performance on all Bayley-III subscores (CCS: P  = 0.02; LCS: P  = 0.002; MCS: P  = 0.013). The number of re-operations [odds ratio (OR) 2.2, 95% confidence interval (CI) 1.1-4.3] ( P  = 0.03) and re-interventions (OR 2.1, 95% CI 1.1-3.8) ( P  = 0.03) was associated with a higher rate of overall MRI abnormalities. Cerebral MRI abnormalities occur in more than one third of children with single ventricle, while the neuro-developmental status is less severely affected before Fontan procedure. Liquor space enlargement is the predominant MRI finding associated with poorer neuro-developmental status, warranting further studies to determine aetiology and further evolution until school-age.

  17. Maternal obesity affects fetal neurodevelopmental and metabolic gene expression: a pilot study.

    Directory of Open Access Journals (Sweden)

    Andrea G Edlow

    Full Text Available OBJECTIVE: One in three pregnant women in the United States is obese. Their offspring are at increased risk for neurodevelopmental and metabolic morbidity. Underlying molecular mechanisms are poorly understood. We performed a global gene expression analysis of mid-trimester amniotic fluid cell-free fetal RNA in obese versus lean pregnant women. METHODS: This prospective pilot study included eight obese (BMI≥30 and eight lean (BMI<25 women undergoing clinically indicated mid-trimester genetic amniocentesis. Subjects were matched for gestational age and fetal sex. Fetuses with abnormal karyotype or structural anomalies were excluded. Cell-free fetal RNA was extracted from amniotic fluid and hybridized to whole genome expression arrays. Genes significantly differentially regulated in 8/8 obese-lean pairs were identified using paired t-tests with the Benjamini-Hochberg correction (false discovery rate of <0.05. Biological interpretation was performed with Ingenuity Pathway Analysis and the BioGPS gene expression atlas. RESULTS: In fetuses of obese pregnant women, 205 genes were significantly differentially regulated. Apolipoprotein D, a gene highly expressed in the central nervous system and integral to lipid regulation, was the most up-regulated gene (9-fold. Apoptotic cell death was significantly down-regulated, particularly within nervous system pathways involving the cerebral cortex. Activation of the transcriptional regulators estrogen receptor, FOS, and STAT3 was predicted in fetuses of obese women, suggesting a pro-estrogenic, pro-inflammatory milieu. CONCLUSION: Maternal obesity affects fetal neurodevelopmental and metabolic gene expression as early as the second trimester. These findings may have implications for postnatal neurodevelopmental and metabolic abnormalities described in the offspring of obese women.

  18. with neurodevelopmental

    African Journals Online (AJOL)

    clumsiness, mixed dominance or a specific learning disability. They correlated developmental milestones with seven levels of brainstem and cortical function and postulated that a block at any one of these levels precludes development of functions controlled by higher levels. This is caused by an interruption in the sensory ...

  19. Epidemiology of pervasive developmental disorders.

    Science.gov (United States)

    Fombonne, Eric

    2009-06-01

    This article reviews the results of 43 studies published since 1966 that provided estimates for the prevalence of pervasive developmental disorders (PDDs), including autistic disorder, Asperger disorder, PDD not otherwise specified, and childhood disintegrative disorder. The prevalence of autistic disorder has increased in recent surveys and current estimates of prevalence are around 20/10,000, whereas the prevalence for PDD not otherwise specified is around 30/10,000 in recent surveys. Prevalence of Asperger disorder is much lower than that for autistic disorder and childhood disintegrative disorder is a very rare disorder with a prevalence of about 2/100,000. Combined all together, recent studies that have examined the whole spectrum of PDDs have consistently provided estimates in the 60-70/10,000 range, making PDD one of the most frequent childhood neurodevelopmental disorders. The meaning of the increase in prevalence in recent decades is reviewed. There is evidence that the broadening of the concept, the expansion of diagnostic criteria, the development of services, and improved awareness of the condition have played a major role in explaining this increase, although it cannot be ruled out that other factors might have also contributed to that trend.

  20. PPREMO: a prospective cohort study of preterm infant brain structure and function to predict neurodevelopmental outcome.

    Science.gov (United States)

    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

    2015-09-16

    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

  1. Quantitative Evaluation System of Soft Neurological Signs for Children with Attention Deficit Hyperactivity Disorder

    Directory of Open Access Journals (Sweden)

    Miki Kaneko

    2016-01-01

    Full Text Available Attention deficit hyperactivity disorder (ADHD is a neurodevelopmental disorder characterized by symptoms of inattention, hyperactivity, and impulsivity. Soft neurological signs (SNS are minor neurological abnormalities in motor performance, and are used as one evaluation method for neurodevelopmental delays in children with ADHD. Our aim is to establish a quantitative evaluation system for children with ADHD. We focused on the arm movement called pronation and supination, which is one such soft neurological sign. Thirty three children with ADHD aged 7–11 years (27 males, six females and twenty five adults participants aged 21–29 years old (19 males, six females participated in our experiments. Our results suggested that the pronation and supination function in children with ADHD has a tendency to lag behind that of typically developing children by several years. From these results, our system has a possibility to objectively evaluate the neurodevelopmental delay of children with ADHD.

  2. The effect of kangaroo care on neurodevelopmental outcomes in preterm infants.

    Science.gov (United States)

    Head, Lauren M

    2014-01-01

    Preterm birth is associated with long-term deficits in executive functioning and cognitive performance. As advances in neonatal care enable more preterm infants to survive, development of strategies to address high rates of neurodevelopmental disabilities and poor academic achievement in preterm infants are crucial. Evidence suggests that infants' brains are plastic in nature and, therefore, can be shaped by the environment. Kangaroo care has become popularized as a means of modifying the stress of the NICU environment. However, few studies have examined whether kangaroo care affects neurodevelopmental outcomes in preterm infants. This review examined available literature that investigated the effect of kangaroo care on cognition in preterm infants. Current evidence suggests that short-term benefits of kangaroo care are associated with improved neurodevelopment. However, few studies have examined the long-term impact of kangaroo care on cognitive outcomes in preterm infants. To address neurological disparities in children born preterm, research using kangaroo care as a strategy to improve neurodevelopment in preterm infants is warranted.

  3. Tourette Syndrome and Learning Disabilities: a focus on correlations in a neurodevelopmental perspective

    Directory of Open Access Journals (Sweden)

    Brambilla Emma

    2016-04-01

    Full Text Available People with Tourette Syndrome (TS frequently show the presence of Learning Disabilities (LD at school age. Literature investigating the correlation between TS and LD is limited: studies focus on the incidence of this correlation, the impact on school achievement and the number of fields affected by these difficulties, show neuropsychological diseases in comorbility and reveal a discrepancy between IQ scores and school results. The most important evidence shows that in some children the appearance of LD and tics coincide. In a neurodevelopmental approach, the origin of both symptoms, TS and LD, can be explained observing the nervous system’s maturation process, through specific steps, which lead to the acquisition of visual, aural and tactile competence, and allow the development of mobility, language and manual ability. As they all develop along a continuum, neurodevelopmental levels that have not been completed always imply neuro-functional anomalies, which can be observed with brain-imaging techniques. Investigating this correlation in a neuropsychological perspective would be useful not only to better understand the underlying functional aspects, but also to properly plan good rehabilitation strategies to apply in everyday clinical practice.

  4. Chronic vortioxetine treatment in rodents modulates gene expression of neurodevelopmental and plasticity markers.

    Science.gov (United States)

    Waller, Jessica A; Tamm, Joseph A; Abdourahman, Aicha; Pehrson, Alan L; Li, Yan; Cajina, Manuel; Sánchez, Connie

    2017-02-01

    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.

  5. Personality Traits Elucidate Sex Differences in Attention-Deficit/Hyperactivity Disorder Comorbidity During Early Childhood

    OpenAIRE

    Martel, Michelle M.; Gremillion, Monica L.; Tackett, Jennifer L.

    2013-01-01

    Attention-Deficit/Hyperactivity Disorder (ADHD) is highly comorbid with other childhood disorders, and there are striking sex differences in this comorbidity, particularly during early childhood. For example, boys with ADHD are more likely to exhibit comorbid disruptive behavior and neurodevelopmental disorders, compared to girls, during early childhood. Yet, explanations for these well-established sex differences remain in short supply. The current study evaluated the novel hypothesis that p...

  6. Sleep disorders in children and teens. Helping patients and their families get some rest.

    Science.gov (United States)

    Garcia, J; Wills, L

    2000-03-01

    Diagnosing sleep disorders in children and adolescents is challenging and rewarding and requires integration of medical, neurodevelopmental, and behavioral histories. Most patients can be successfully treated once a thorough evaluation has been completed and age-appropriate differential diagnosis of common sleep disorders has been considered. With appropriate knowledge and tools, physicians may find that pediatric sleep disorders are some of the most treatable problems in medicine.

  7. Cortical complexity in bipolar disorder applying a spherical harmonics approach.

    Science.gov (United States)

    Nenadic, Igor; Yotter, Rachel A; Dietzek, Maren; Langbein, Kerstin; Sauer, Heinrich; Gaser, Christian

    2017-05-30

    Recent studies using surface-based morphometry of structural magnetic resonance imaging data have suggested that some changes in bipolar disorder (BP) might be neurodevelopmental in origin. We applied a novel analysis of cortical complexity based on fractal dimensions in high-resolution structural MRI scans of 18 bipolar disorder patients and 26 healthy controls. Our region-of-interest based analysis revealed increases in fractal dimensions (in patients relative to controls) in left lateral orbitofrontal cortex and right precuneus, and decreases in right caudal middle frontal, entorhinal cortex, and right pars orbitalis, and left fusiform and posterior cingulate cortices. While our analysis is preliminary, it suggests that early neurodevelopmental pathologies might contribute to bipolar disorder, possibly through genetic mechanisms. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  8. HIV-associated neurodevelopmental delay: prevalence, predictors and persistence in relation to antiretroviral therapy initiation and viral suppression.

    Science.gov (United States)

    Strehlau, R; Kuhn, L; Abrams, E J; Coovadia, A

    2016-11-01

    HIV infection in infancy may influence the developing brain, leading to adverse neurodevelopmental consequences. We aim to describe neurodevelopmental characteristics of a cohort of HIV-infected infants and young children prior to antiretroviral therapy (ART) initiation and after achieving viral suppression. As part of the Neverest 2 trial, 195 HIV-infected children under 2 years of age were assessed using the Ages and Stages Questionnaire (ASQ) prior to ART initiation and at subsequent age-appropriate time points after ART had been started. The ASQ is a simple screening questionnaire used to identify children at risk of neurodevelopmental delays. Questionnaires completed by the parent/caregiver assess neurodevelopmental functioning in five domains: communication, gross motor, fine motor, problem solving and personal-social. Median age pre-ART was 8.8 months (range 2.2-24.9) and 53.9% were male. Mean time to viral suppression was 9.4 months (range 5.9-14.5). Compared with pre-ART better outcomes were reported at time of viral suppression with a lower proportion of children failing the gross motor (31.5% vs. 13%, p = 0.0002), fine motor (21.3% vs. 10.2%, p = 0.017), problem solving (26.9% vs. 9.3%, p = 0.0003) and personal-social (19.6% vs. 7.4%, p = 0.019) domains. However, there was no change in the communication domain (14.8% vs. 12.0%, p = 0.6072). Although achieving viral suppression on ART resulted in significant improvements in markers of neurodevelopmental function of young HIV-infected children, potential neurodevelopmental delays still persisted in a large proportion. Further interventions are needed to limit potential disabilities and maximize developmental outcomes. © 2016 John Wiley & Sons Ltd.

  9. The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs

    Directory of Open Access Journals (Sweden)

    Barrington Keith J

    2001-02-01

    Full Text Available Abstract Background Recent reports have raised concerns that postnatal steroids may cause neuro-developmental impairment in preterm infants. This systematic review was performed with the objective of determining whether glucocorticoid therapy, to prevent or treat bronchopulmonary dysplasia, impairs neuro-developmental outcomes in preterm infants. Method A systematic review of the literature was performed. Medline was searched and articles retrieved using predefined criteria. Data from randomized controlled trials with adequate neuro-developmental follow up (to at least one year were entered into a meta-analysis to determine the effects of postnatal treatment of preterm infants with glucocorticoids. Cerebral palsy rates, and neuro-developmental impairment (developmental score more than 2SD below the mean, or cerebral palsy or blindness were analyzed. The studies were divided into 2 groups according to the extent of contamination of the results by treatment of controls with steroids after the initial study period, those with less than 30% contamination, and those with more than 30% contamination or size of contamination not reported. Results Postnatal steroid therapy is associated with an increase in cerebral palsy and neuro-developmental impairment. The studies with less contamination show a greater effect of the steroids, consistent with a real direct toxic effect of steroids on the developing central nervous system. The typical relative risk for the development of cerebral palsy derived from studies with less than 30% contamination is 2.86 (95% CI 1.95, 4.19. The typical relative risk for the development of neuro-developmental disability among followed up infants from studies with less than 30% contamination is 1.66 (95% CI 1.26, 2.19. From this subgroup of studies, the number of premature infants who need to be treated to have one more infant with cerebral palsy (number needed to harm, NNH is 7; to have one more infant with neuro-developmental

  10. Fetal alcohol spectrum disorders among children in a Brazilian orphanage.

    Science.gov (United States)

    Strömland, Kerstin; Ventura, Liana O; Mirzaei, Layla; Fontes de Oliveira, Keyla; Marcelino Bandim, José; Parente Ivo, Adriana; Brandt, Carlos

    2015-03-01

    The objective was to investigate the frequency of fetal alcohol spectrum disorders (FASD) and ophthalmologic anomalies in orphanage children in Brazil. A prospective study was performed on 94 children living in an orphanage in Brazil. The children were examined by a multidisciplinary team consisting of specialists in pediatrics, neurology, psychology, neuropsychiatry, and ophthalmology. The main reasons for living in the orphanage, in 61% of the children, were negligence, child abuse, and abandonment. Of all the children studied, 50% had mothers with known alcohol abuse and 47% had one or more diagnoses of neurodevelopmental/behavioral and/or cognitive deficits. General developmental delay was found in 18%, intellectual disability in 3%, cognitive impairment in 27%, attention-deficit/hyperactivity disorder in 14%, and autism in 3%. Altogether 17% had FASD, comprising three children with fetal alcohol syndrome (FAS), six with partial FAS, and seven with alcohol-related neurodevelopmental disorder. 16% had ophthalmological findings such as poor vision, strabismus, and dysmorphology of the optic nerves. Twenty-eight children (30%) were adopted from the orphanage; of these, six had FASD (two FAS, three partial FAS, one alcohol-related neurodevelopmental disorder), five had attention-deficit/hyperactivity disorder, and eight had developmental delay. Nearly half of the children living in the orphanage had neurodevelopmental disorders and a considerable number showed signs of damage from prenatal alcohol exposure. A broader look at the problem of FASD in Brazil and other South American countries is desirable to document the burden of disease and provide data for targeting prevention efforts. © 2014 Wiley Periodicals, Inc.

  11. Research Review: Executive function deficits in fetal alcohol spectrum disorders and attention-deficit/hyperactivity disorder – a meta-analysis

    Science.gov (United States)

    Kingdon, Danielle; Cardoso, Christopher; McGrath, Jennifer J.

    2018-01-01

    Background Attention-deficit/hyperactivity disorder (ADHD)-like symptoms are common in fetal alcohol spectrum disorders (FASD). FASD and ADHD groups both display executive function impairments; however, there is ongoing debate whether the pattern and magnitude of executive function deficits differs between these two types of disorders. Methods An electronic literature search was conducted (PubMed, PsychInfo; 1972–2013) to identify studies comparing the executive functioning of children with FASD with ADHD or control groups. FASD groups included those with and without dysmorphy (i.e., FAS, pFAS, ARND, and other FASD diagnoses). Effect sizes (Hedges’ g, standardized mean difference) were calculated. Random effects meta-analytic models were performed using the metafor package for R. Results Fifty-one studies met inclusion criteria (FASD N = 2,115; ADHD N = 453; controls N = 1,990). Children with FASD showed the strongest and most consistent deficits in planning, fluency, and set-shifting compared to controls (Hedges’ g = −0.94, −0.78) and children with ADHD (Hedges’ g = −0.72, −0.32). FASD was associated with moderate to large impairments in working memory, compared to controls (Hedges’ g = −.84, −.58) and small impairments relative to groups with ADHD (Hedges’ g = −.26). Smaller and less consistent deficits were found on measures of inhibition and vigilance relative to controls (Hedges’ g = −0.52, −0.31); FASD and ADHD were not differentiated on these measures. Moderator analyses indicated executive dysfunction was associated with older age, dysmorphy, and larger group differences in IQ. Sex and diagnostic system were not consistently related to effect size. Conclusions While FASD is associated with global executive impairments, executive function weaknesses are most consistent for measures of planning, fluency, and set-shifting. Neuropsychological measures assessing these executive function domains may improve differential diagnosis

  12. Relationship between Proton Magnetic Resonance Spectroscopy of Frontoinsular Gray Matter and Neurodevelopmental Outcomes in Very Low Birth Weight Children at the Age of 4.

    Directory of Open Access Journals (Sweden)

    Wojciech Durlak

    Full Text Available Very low birth weight is associated with long term neurodevelopmental complications. Macroscopic brain abnormalities in prematurity survivors have been investigated in several studies. However, there is limited data regarding local cerebral metabolic status and neurodevelopmental outcomes. The purpose of this study was to characterize the relationship between proton magnetic resonance spectra in basal ganglia, frontal white matter and frontoinsular gray matter, neurodevelopmental outcomes assessed with the Leiter scale and the Developmental Test of Visual Perception and selected socioeconomic variables in a cohort of very low birth weight children at the age of four. Children were divided in three groups based on the severity of neurodevelopmental impairment. There were no differences in spectroscopy in basal ganglia and frontal white matter between the groups. Lower concentrations of N-acetylaspartate (NAA, choline (Cho and myoinositol (mI were observed in the frontoinsular cortex of the left hemisphere in children with neurodevelopmental impairment compared to children with normal neurodevelopmental outcomes. Higher parental education, daycare attendance and breastfeeding after birth were associated with more favorable neurodevelopmental prognosis, whereas rural residence was more prevalent in children with moderate and severe impairment. Our study demonstrates the role of long term neurometabolic disruption in the left frontoinsular cortex and selected socioeconomic variables in determination of neurodevelopmental prognosis in prematurity survivors.

  13. Cannabinoid Receptor Type 2, but Not Type 1, Is Up-Regulated in Peripheral Blood Mononuclear Cells of Children Affected by Autistic Disorders

    Science.gov (United States)

    Siniscalco, Dario; Sapone, Anna; Giordano, Catia; Cirillo, Alessandra; de Magistris, Laura; Rossi, Francesco; Fasano, Alessio; Bradstreet, James Jeffrey; Maione, Sabatino; Antonucci, Nicola

    2013-01-01

    Autistic disorders (ADs) are heterogeneous neurodevelopmental disorders arised by the interaction of genes and environmental factors. Dysfunctions in social interaction and communication skills, repetitive and stereotypic verbal and non-verbal behaviours are common features of ADs. There are no defined mechanisms of pathogenesis, rendering…

  14. Is It Normal to Be a Principal Mindreader? Revising Theories of Social Cognition on the Basis of Schizophrenia and High Functioning Autism-Spectrum Disorders

    Science.gov (United States)

    Froese, Tom; Stanghellini, Giovanni; Bertelli, Marco O.

    2013-01-01

    Schizophrenia and high functioning autism-spectrum disorders (ASD) are neurodevelopmental conditions that mainly impair social competence, while general intelligence (IQ) is spared. Both disorders have a strong ancillary role in theoretical research on social cognition. Recently the debate has started to be inflected by embodied and…

  15. Reduced Tract Integrity of the Model for Social Communication Is a Neural Substrate of Social Communication Deficits in Autism Spectrum Disorder

    Science.gov (United States)

    Lo, Yu-Chun; Chen, Yu-Jen; Hsu, Yung-Chin; Tseng, Wen-Yih Isaac; Gau, Susan Shur-Fen

    2017-01-01

    Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with social communication deficits as one of the core symptoms. Recently, a five-level model for the social communication has been proposed in which white matter tracts corresponding to each level of the model are identified. Given that the model for social communication…

  16. "SLC2A3" Single-Nucleotide Polymorphism and Duplication Influence Cognitive Processing and Population-Specific Risk for Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Merker, Sören; Reif, Andreas; Ziegler, Georg C.; Weber, Heike; Mayer, Ute; Ehlis, Ann-Christine; Conzelmann, Annette; Johansson, Stefan; Müller-Reible, Clemens; Nanda, Indrajit; Haaf, Thomas; Ullmann, Reinhard; Romanos, Marcel; Fallgatter, Andreas J.; Pauli, Paul; Strekalova, Tatyana; Jansch, Charline; Vasquez, Alejandro Arias; Haavik, Jan; Ribasés, Marta; Ramos-Quiroga, Josep Antoni; Buitelaar, Jan K.; Franke, Barbara; Lesch, Klaus-Peter

    2017-01-01

    Background: Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of…

  17. Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders

    DEFF Research Database (Denmark)

    Wolff, Markus; Johannesen, Katrine M.; Hedrich, Ulrike B. S.

    2017-01-01

    Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infa...

  18. Estimating the Burden of Disease for Autism Spectrum Disorders in Spain in 2003

    Science.gov (United States)

    Sanchez-Valle, Elena; Posada, Manuel; Villaverde-Hueso, Ana; Tourino, Eva; Ferrari-Arroyo, Maria Jose; Boada, Leticia; Martin-Arribas, Maria Concepcion; Canal, Ricardo; Fuentes-Biggi, Joaquin

    2008-01-01

    Autism Spectrum Disorders (ASD) are lifelong neurodevelopmental disabilities. Burden of Disease is an indicator that provides important information on health status and outcomes such as premature mortality and disability. In order to estimate the burden of disease of ASD in the Spanish population during 2003, we followed the procedures used in the…

  19. Physical Activity and Fitness in Children with Developmental Coordination Disorder: A Systematic Review

    Science.gov (United States)

    Rivilis, Irina; Hay, John; Cairney, John; Klentrou, Panagiota; Liu, Jian; Faught, Brent E.

    2011-01-01

    Developmental coordination disorder (DCD) is a neurodevelopmental condition characterized by poor motor proficiency that interferes with a child's activities of daily living. Activities that most young children engage in such as running, walking, and jumping are important for the proper development of fitness and overall health. However, children…

  20. Baroreflex Sensitivity Is Reduced in Adolescents with Probable Developmental Coordination Disorder

    Science.gov (United States)

    Coverdale, Nicole S.; O'Leary, Deborah D.; Faught, Brent E.; Chirico, Daniele; Hay, John; Cairney, John

    2012-01-01

    Developmental coordination disorder (DCD) is a neurodevelopmental condition characterized by poor motor skills leading to a significant impairment in activities of daily living. Compared to typically developing children, those with DCD are less fit and physically active, and have increased body fat. This is an important consequence as both…

  1. Fever and infections in pregnancy and risk of attention deficit/hyperactivity disorder in the offspring

    DEFF Research Database (Denmark)

    Dreier, Julie Werenberg; Andersen, Anne-Marie Nybo; Hvolby, Allan

    2016-01-01

    Background: Fever and infections are common events during pregnancy, and have been shown to be associated with neurodevelopmental impairment in the offspring. The evidence in relation to attention deficit/hyperactivity disorder (ADHD) is, however, nonexistent for fever and limited for infections...

  2. Atypical Pupillary Light Reflex and Heart Rate Variability in Children with Autism Spectrum Disorder

    Science.gov (United States)

    Daluwatte, Chathuri; Miles, Judith H.; Christ, Shawn E.; Beversdorf, David Q.; Takahashi, T. Nicole; Yao, Gang

    2013-01-01

    We investigated pupillary light reflex (PLR) in 152 children with ASD, 116 typically developing (TD) children, and 36 children with non-ASD neurodevelopmental disorders (NDDs). Heart rate variability (HRV) was measured simultaneously to study potential impairments in the autonomic nervous system (ANS) associated with ASD. The results showed that…

  3. Social Responsiveness and Competence in Prader-Willi Syndrome: Direct Comparison to Autism Spectrum Disorder

    Science.gov (United States)

    Dimitropoulos, Anastasia; Ho, Alan; Feldman, Benjamin

    2013-01-01

    Prader-Willi syndrome (PWS), a neurodevelopmental disorder primarily characterized by hyperphagia and food preoccupations, is caused by the absence of expression of the paternally active genes in the proximal arm of chromosome 15. Although maladaptive behavior and the cognitive profile in PWS have been well characterized, social functioning has…

  4. First-Degree Relatives of Young Children with Autism Spectrum Disorders: Some Gender Aspects

    Science.gov (United States)

    Eriksson, Mats Anders; Westerlund, Joakim; Anderlid, Britt Marie; Gillberg, Christopher; Fernell, Elisabeth

    2012-01-01

    Prenatal risk factors, with special focus on gender distribution of neurodevelopmental and psychiatric conditions were analysed in first-degree relatives in a population-based group of young children with autism spectrum disorders (ASD). Multiple information sources were combined. This group was contrasted with the general population regarding…

  5. Effects of Cannabis on Neurocognitive Functioning: Recent Advances, Neurodevelopmental Influences, and Sex Differences

    Science.gov (United States)

    Crane, Natania A.; Schuster, Randi Melissa; Fusar-Poli, Paolo; Gonzalez, Raul

    2012-01-01

    Decades of research have examined the effects of cannabis on neurocognition. Recent advances in this field provide us with a better understanding of how cannabis use influences neurocognition both acutely (during intoxication) and non-acutely (after acute effects subside). Evidence of problems with episodic memory is one of the most consistent findings reported; however, several other neurocognitive domains appear to be adversely affected by cannabis use under various conditions. There is significant variability in findings across studies, thus a discussion of potential moderators is increasingly relevant. The purpose of this review was to 1) provide an update on research of cannabis’ acute and non-acute effects on neurocognition, with a focus on findings since 2007 and 2) suggest and discuss how neurodevelopmental issues and sex differences may influence cannabis effects on neurocognition. Finally we discuss how future investigations may lead to better understanding of the complex interplay among cannabis, stages of neurodevelopment, and sex on neurocognitive functioning. PMID:23129391

  6. Both Low Blood Glucose and Insufficient Treatment Confer Risk of Neurodevelopmental Impairment in Congenital Hyperinsulinism

    DEFF Research Database (Denmark)

    Rasmussen, Annett Helleskov; Melikyan, Maria; Globa, Evgenia

    2017-01-01

    BACKGROUND/AIMS: Congenital hyperinsulinism (CHI) is a heterogeneous disease most frequently caused by KATP-channel (ABCC8 and KCNJ11) mutations, with neonatal or later onset, variable severity, and with focal or diffuse pancreatic involvement as the two major histological types. CHI confers a high.......023; and treatment delay from first symptom to expert center >5 days; OR 4.0 (1.0-16.6), trend p = 0.05. In multivariate analysis (n = 31) for early predictors with exclusion of brain MRI, treatment delay from first symptom to expert center >5 days conferred a significantly increased risk of neurodevelopment...... seen in uni- or multivariate analysis. CONCLUSION: Not only very low blood glucose, but also insufficient treatment as expressed by delay until expert center hospitalization, increased the risk of neurodevelopmental impairment. This novel finding calls for improvements in spread of knowledge about CHI...

  7. Haploinsufficiency of NR4A2 is associated with a neurodevelopmental phenotype with prominent language impairment.

    Science.gov (United States)

    Reuter, Miriam S; Krumbiegel, Mandy; Schlüter, Gregor; Ekici, Arif B; Reis, André; Zweier, Christiane

    2017-08-01

    Non-recurrent deletions in 2q24.1, minimally overlapping two genes, NR4A2 and GPD2, were recently described in individuals with language impairment and behavioral and cognitive symptoms. We herewith report on a female patient with a similar phenotype of severe language and mild cognitive impairment, in whom we identified a de novo deletion covering only NR4A2. NR4A2 encodes a transcription factor highly expressed in brain regions critical for speech and language and implicated in dopaminergic neuronal development. Our findings of a de novo deletion of NR4A2 in an individual with mild intellectual disability and prominent speech and language impairment provides further evidence for NR4A2 haploinsufficiency being causative for neurodevelopmental and particularly language phenotypes. © 2017 Wiley Periodicals, Inc.

  8. Etiological Analysis of Neurodevelopmental Disabilities: Single-Center Eight-Year Clinical Experience in South China

    Directory of Open Access Journals (Sweden)

    Li Guo

    2011-01-01

    Full Text Available Etiology determination of neurodevelopmental disabilities (NDDs currently remains a worldwide common challenge on child health. We herein reported the etiology distribution feature in a cohort of 285 Chinese patients with NDDs. Although concrete NDD etiologies in 48.4% of the total patients could not be identified, genetic diseases (with the proportion of 35.8% in the total cases including inborn errors of metabolism (IEM and congenital dysmorphic diseases, constituted the commonest etiology category for NDDs in this study. The two key experimental technologies in pediatric metabolomics, gas chromatography-mass spectrometry (GC-MS, and tandem mass spectrometry (MS-MS, proved to be substantially helpful for the exploration of the NDD etiologies in this clinical investigation. The findings in this paper provided latest epidemiologic information on the etiology distribution of NDDs in Chinese, and the syndromic NDDs caused by citrin deficiency and the novel chromosomal karyotype, respectively, further expanded the etiology spectrum of NDDs.

  9. An Investigation of Bilateral Isokinematic Training and Neurodevelopmental Therapy in Improving Use of the Affected Hand in Children with Hemiplegia

    Science.gov (United States)

    Sheppard, Loretta; Mudie, Heather; Froude, Elspeth

    2007-01-01

    Motor impairment in children with hemiplegic cerebral palsy leads to a predominance of use of the unaffected hand. This impedes development of bimanual skills and deprives the affected side of the stimulus needed for normal growth. Occupational therapists aim to improve use of the affected hand, traditionally using Neurodevelopmental Therapy.…

  10. Neonatal Gram Negative and Candida Sepsis Survival and Neurodevelopmental Outcome at the Corrected Age of 24 Months

    NARCIS (Netherlands)

    T.R. de Haan (Timo Robert); L. Beckers (Loes); R.C.J. de Jonge (Rogier); L. Spanjaard (Lodewijk); L. van Toledo (Letty); D. Pajkrt (Dasja); A.G. van Wassenaer (Aleid); J.H. van der Lee (Johanna)

    2013-01-01

    textabstractObjectives: To evaluate the long term neurodevelopmental outcome of premature infants exposed to either gram- negative sepsis (GNS) or neonatal Candida sepsis (NCS), and to compare their outcome with premature infants without sepsis. Methods: Historical cohort study in a population of

  11. An optimized gene set for transcriptomics based neurodevelopmental toxicity prediction in the neural embryonic stem cell test

    NARCIS (Netherlands)

    Pennings, J.L.A.; Theunissen, P.T.; Piersma, A.H.|info:eu-repo/dai/nl/071276947

    2012-01-01

    The murine neural embryonic stem cell test (ESTn) is an in vitro model for neurodevelopmental toxicity testing. Recent studies have shown that application of transcriptomics analyses in the ESTn is useful for obtaining more accurate predictions as well as mechanistic insights. Gene expression

  12. Brain Volumes at Term-Equivalent Age in Preterm Infants : Imaging Biomarkers for Neurodevelopmental Outcome through Early School Age

    NARCIS (Netherlands)

    Keunen, Kristin; Išgum, Ivana; van Kooij, Britt J M; Anbeek, Petronella; van Haastert, Ingrid C; Koopman-Esseboom, Corine; van Stam, Petronella C; Nievelstein, Rutger A J; Viergever, Max A; de Vries, Linda S; Groenendaal, Floris; Benders, Manon J N L

    OBJECTIVE: To evaluate the relationship between brain volumes at term and neurodevelopmental outcome through early school age in preterm infants. STUDY DESIGN: One hundred twelve preterm infants (born mean gestational age 28.6 ± 1.7 weeks) were studied prospectively with magnetic resonance imaging

  13. Effects of early nutrition and growth on brain volumes, white matter microstructure, and neurodevelopmental outcome in preterm newborns.

    Science.gov (United States)

    Coviello, Caterina; Keunen, Kristin; Kersbergen, Karina J; Groenendaal, Floris; Leemans, Alexander; Peels, Barbara; Isgum, Ivana; Viergever, Max A; de Vries, Linda S; Buonocore, Giuseppe; Carnielli, Virgilio P; Benders, Manon J N L

    2018-01-01

    BackgroundThis study aimed to investigate the effect of nutrition and growth during the first 4 weeks after birth on cerebral volumes and white matter maturation at term equivalent age (TEA) and on neurodevelopmental outcome at 2 years' corrected age (CA), in preterm infants.MethodsOne hundred thirty-one infants born at a gestational age (GA) brain development.

  14. The Validity of the Bayley-III and DDST-II in Preterm Infants With Neurodevelopmental Impairment: A Pilot Study.

    Science.gov (United States)

    Jeong, Seong Uk; Kim, Ghi Chan; Jeong, Ho Joong; Kim, Dong Kyu; Hong, Yoo Rha; Kim, Hui Dong; Park, Seok Gyo; Sim, Young-Joo

    2017-10-01

    To identify the usefulness of both the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III) and Denver Developmental Screening Test II (DDST-II) in preterm babies with neurodevelopmental impairment, considering the detection rate as regulation of criteria. Retrospective medical chart reviews which included the Bayley-III and DDST-II, were conducted for 69 preterm babies. Detection rate of neurodevelopmental impairment in preterm babies were investigated by modulating scaled score of the Bayley-III. The detection rate of DDST-II was identified by regarding more than 1 caution as an abnormality. Then detection rates of each corrected age group were verified using conventional criteria. When applying conventional criteria, 22 infants and 35 infants were detected as preterm babies with neurodevelopmental impairment, as per the Bayley-III and DDST-II evaluation, respectively. Detection rates increased by applying abnormal criteria that specified as less than 11 points in the Bayley-III scaled score. In DDST-II, detection rates rose from 50% to 68.6% using modified criteria. The detection rates were highest when performed after 12 months corrected age, being 100% in DDST II. The detection rate also increased when applying the modified criteria in both the Bayley-III and DDST-II. Accurate neurologic examination is more important for detection of preterm babies with neurodevelopmental impairment. We suggest further studies for the accurate modification of the detection criteria in DDST-II and the Bayley-III for preterm babies.

  15. Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy.

    LENUS (Irish Health Repository)

    Nadeem, Montasser

    2012-01-31

    BACKGROUND: To examine the blood glucose profile and the relationship between blood glucose levels and neurodevelopmental outcome in term infants with hypoxic-ischaemic encephalopathy. METHODS: Blood glucose values within 72 hours of birth were collected from 52 term infants with hypoxic-ischaemic encephalopathy. Hypoglycaemia [< 46.8 mg\\/dL (2.6 mmol\\/L)] and hyperglycaemia [> 150 mg\\/dL (8.3 mmol\\/L)] were correlated to neurodevelopmental outcome at 24 months of age. RESULTS: Four fifths of the 468 blood samples were in the normoglycaemic range (392\\/468:83.8%). Of the remaining 76 samples, 51.3% were in the hypoglycaemic range and (48.7%) were hyperglycaemic. A quarter of the hypoglycaemic samples (28.2%:11\\/39) and a third of the hyperglycaemic samples (32.4%:12\\/37) were recorded within the first 30 minutes of life. Mean (SD) blood glucose values did not differ between infants with normal and abnormal outcomes [4.89(2.28) mmol\\/L and 5.02(2.35) mmol\\/L, p value = 0.15] respectively. In term infants with hypoxic-ischaemic encephalopathy, early hypoglycaemia (between 0-6 hours of life) was associated with adverse outcome at 24 months of age [OR = 5.8, CI = 1.04-32)]. On multivariate analysis to adjust for grade of HIE this association was not statistically significant. Late hypoglycaemia (6-72 hours of life) was not associated with abnormal outcome [OR = 0.22, CI (0.04-1.14)]. The occurrence of hyperglycaemia was not associated with adverse outcome. CONCLUSION: During the first 72 hours of life, blood glucose profile in infants with hypoxic-ischaemic encephalopathy varies widely despite a management protocol. Early hypoglycaemia (0-6 hours of life) was associated with severe HIE, and thereby; adverse outcome.

  16. Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy

    LENUS (Irish Health Repository)

    Nadeem, Montasser

    2011-02-04

    Abstract Background To examine the blood glucose profile and the relationship between blood glucose levels and neurodevelopmental outcome in term infants with hypoxic-ischaemic encephalopathy. Methods Blood glucose values within 72 hours of birth were collected from 52 term infants with hypoxic-ischaemic encephalopathy. Hypoglycaemia [< 46.8 mg\\/dL (2.6 mmol\\/L)] and hyperglycaemia [> 150 mg\\/dL (8.3 mmol\\/L)] were correlated to neurodevelopmental outcome at 24 months of age. Results Four fifths of the 468 blood samples were in the normoglycaemic range (392\\/468:83.8%). Of the remaining 76 samples, 51.3% were in the hypoglycaemic range and (48.7%) were hyperglycaemic. A quarter of the hypoglycaemic samples (28.2%:11\\/39) and a third of the hyperglycaemic samples (32.4%:12\\/37) were recorded within the first 30 minutes of life. Mean (SD) blood glucose values did not differ between infants with normal and abnormal outcomes [4.89(2.28) mmol\\/L and 5.02(2.35) mmol\\/L, p value = 0.15] respectively. In term infants with hypoxic-ischaemic encephalopathy, early hypoglycaemia (between 0-6 hours of life) was associated with adverse outcome at 24 months of age [OR = 5.8, CI = 1.04-32)]. On multivariate analysis to adjust for grade of HIE this association was not statistically significant. Late hypoglycaemia (6-72 hours of life) was not associated with abnormal outcome [OR = 0.22, CI (0.04-1.14)]. The occurrence of hyperglycaemia was not associated with adverse outcome. Conclusion During the first 72 hours of life, blood glucose profile in infants with hypoxic-ischaemic encephalopathy varies widely despite a management protocol. Early hypoglycaemia (0-6 hours of life) was associated with severe HIE, and thereby; adverse outcome.

  17. Etiological Subgroups of Small-for-Gestational-Age: Differential Neurodevelopmental Outcomes.

    Directory of Open Access Journals (Sweden)

    Xiuhong Li

    Full Text Available It remains unclear why substantial variations in neurodevelopmental outcomes exist within small-for-gestational-age (SGA children. We prospectively compared 5-y neurodevelopmental outcomes across SGA etiological subgroups.Children born SGA (N = 1050 from U.S. Early Childhood Longitudinal Study-Birth Cohort (2001-2007 was divided into etiological subgroups by each of 7 well-established prenatal risk factors. We fit linear regression models to compare 5-y reading, math, gross motor and fine motor scores across SGA subgroups, adjusting for socio-demographic confounders.Compared to singleton SGA subgroup, multiple-birth SGA subgroup had lower mean reading (adjusted mean difference, -4.08 [95% confidence interval, -6.10, -2.06] and math (-2.22 [-3.61, -0.84] scores. These disadvantages in reading and math existed only among multiple-birth SGA subgroup without ovulation stimulation (reading, -4.50 [-6.64, -2.36]; math, -2.91 [-4.37, -1.44], but not among those with ovulation stimulation (reading, -2.33 [-6.24, 1.57]; math 0.63 [-1.86, 3.12]. Compared to singleton SGA subgroup without maternal smoking and inadequate gestational weight gain, singleton SGA subgroup with co-occurrence of maternal smoking and inadequate gestational weight gain (GWG had lower mean reading (-4.81 [-8.50, -1.12] and math (-2.95 [-5.51, -0.38] scores. These differences were not mediated by Apgar score.Multiple-birth SGA subgroups (vs. singleton SGA or singleton SGA subgroup with co-occurrence of smoking and inadequate GWG (vs. singleton SGA subgroup without maternal smoking and inadequate gestational weight gain have poorer cognitive development up to 5 y.

  18. Abnormal neurodevelopmental outcomes are common in children with transient congenital hyperinsulinism

    Directory of Open Access Journals (Sweden)

    Bindu Hima Avatapalle

    2013-05-01

    Full Text Available Introduction: Neuroglycopaenia is recognised to be associated with abnormal neurodevelopmental outcomes in 26-44% of children with persistent congenital hyperinsulinism (P-CHI. The prevalence of abnormal neurodevelopment in transient CHI (T-CHI is not known. We have aimed to investigate abnormal neurodevelopment and associated factors in T-CHI and P-CHI. Materials and Methods: A cohort of children with CHI (n=67, age 2.5-5 years was assessed at follow up review and noted to have normal or abnormal (mild or severe neurodevelopmental outcomes for the domains of speech and language, motor and vision. Children were classified as P-CHI (n=33, if they had undergone surgery or remained on medical therapy, or T-CHI (n=34, if medical treatment for hypoglycaemia was stopped. Results: Overall, abnormal neurodevelopment was present in 26 (39% children with CHI, of whom 18 (69% were severe. Importantly, the incidence of abnormal neurodevelopment in T-CHI was similar to that in P-CHI (30% v 47% respectively, p=0.16. The prevalence of severe abnormal neurodevelopment in speech, motor and vision domains was similar in both T-CHI and P-CHI children. For this cohort, we found that the severity of disease (based upon maximal diazoxide dose, [odds ratio (95% confidence intervals 1.3 (1.1;1.5, p=0.03] and early presentation of CHI <7 days following birth [5.9 (1.3;27.8, p=0.02] were significantly associated with abnormal neurodevelopment. There was no significant association with gender, genotype or the histopathological basis of CHI. Conclusions: Abnormal neurodevelopment was evident in one third of children with both T-CHI and P-CHI, early presentation and severe CHI being risk factors. Early recognition and rapid correction of hypoglycaemia are advocated to avoid abnormal neurodevelopment in children with CHI.

  19. Learning Disabilities in Extremely Low Birth Weight Children and Neurodevelopmental Profiles at Preschool Age.

    Science.gov (United States)

    Squarza, Chiara; Picciolini, Odoardo; Gardon, Laura; Giannì, Maria L; Murru, Alessandra; Gangi, Silvana; Cortinovis, Ivan; Milani, Silvano; Mosca, Fabio

    2016-01-01

    At school age extremely low birth weight (ELBW) and extremely low gestational age (ELGAN) children are more likely to show Learning Disabilities (LDs) and difficulties in emotional regulation. The aim of this study was to investigate the incidence of LDs at school age and to detect neurodevelopmental indicators of risk for LDs at preschool ages in a cohort of ELBW/ELGAN children with broadly average intelligence. All consecutively newborns 2001-2006 admitted to the same Institution entered the study. Inclusion criteria were BW learning disabilities at school age was investigated through a parent-report questionnaire at children's age range 9-10 years. Neurodevelopmental profiles were assessed through the Griffiths Mental Development Scales at 1 and 2 years of corrected age and at 3, 4, 5, and 6 years of chronological age and were analyzed comparing two groups of children: those with LDs and those without. At school age 24 on 102 (23.5%) of our ELBW/ELGAN children met criteria for LDs in one or more areas, with 70.8% comorbidity with emotional/attention difficulties. Children with LDs scored significantly lower in the Griffiths Locomotor and Language subscales at 2 years of corrected age and in the Personal-social, Performance and Practical Reasoning subscales at 5 years of chronological age. Our findings suggest that, among the early developmental indicators of adverse school outcome, there is a poor motor experimentation, language delay, and personal-social immaturity. Cognitive rigidity and poor ability to manage practical situations also affect academic attainment. Timely detection of these early indicators of risk is crucial to assist the transition to school.

  20. Neurodevelopmental Outcomes of Extremely Preterm Infants Randomized to Stress Dose Hydrocortisone.

    Directory of Open Access Journals (Sweden)

    Nehal A Parikh

    Full Text Available To compare the effects of stress dose hydrocortisone therapy with placebo on survival without neurodevelopmental impairments in high-risk preterm infants.We recruited 64 extremely low birth weight (birth weight ≤1000 g infants between the ages of 10 and 21 postnatal days who were ventilator-dependent and at high-risk for bronchopulmonary dysplasia. Infants were randomized to a tapering 7-day course of stress dose hydrocortisone or saline placebo. The primary outcome at follow-up was a composite of death, cognitive or language delay, cerebral palsy, severe hearing loss, or bilateral blindness at a corrected age of 18-22 months. Secondary outcomes included continued use of respiratory therapies and somatic growth.Fifty-seven infants had adequate data for the primary outcome. Of the 28 infants randomized to hydrocortisone, 19 (68% died or survived with impairment compared with 22 of the 29 infants (76% assigned to placebo (relative risk: 0.83; 95% CI, 0.61 to 1.14. The rates of death for those in the hydrocortisone and placebo groups were 31% and 41%, respectively (P = 0.42. Randomization to hydrocortisone also did not significantly affect the frequency of supplemental oxygen use, positive airway pressure support, or need for respiratory medications.In high-risk extremely low birth weight infants, stress dose hydrocortisone therapy after 10 days of age had no statistically significant effect on the incidence of death or neurodevelopmental impairment at 18-22 months. These results may inform the design and conduct of future clinical trials.ClinicalTrials.gov NCT00167544.