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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Epidemiology of Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Lisa R. FRENCH, Auteur ; Armando BERTONE, Auteur ; Krista L. HYDE, Auteur ; Eric FOMBONNE, Auteur

Année de publication :

2013

Importance :

p.3-24

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

In this chapter, we discuss methodological factors which impact the estimation of prevalence of autism spectrum disorders (ASD), and how current trends in prevalence change are being interpreted. Our systematic literature review results in prevalence estimates ranging from 0.063% to 2.6% for ASD, with the best current estimate of prevalence being approximately (74/10,000). Males are affected four to five times more often than females. In addition, a smaller proportion of children diagnosed with an autistic disorder (~32%) compared to that of all ASD children combined (~53%) have normal cognitive functioning. Rate trends analyses confirm an increase in ASD prevalence, and that the possibility of a true increase in incidence should not be ruled out. Explanations for an increase of ASD within and across populations are considered. However, increasing trends in prevalence rates cannot be directly attributed to an increase in the incidence of ASD, due to multiple confounding factors.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

The Behavioral Manifestations of Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

So Hyun KIM, Auteur ; Catherine LORD, Auteur

Année de publication :

2013

Importance :

p.25-37

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Autism spectrum disorder is a neurobiological disorder that is defined purely by observable behaviors, because no reliable biomarkers have yet been found. Since Kanner described autism as a syndrome, the definition of autism has been refined. The original emphasis was on extreme aloofness and positive signs of abnormality in repetitive and sensorimotor behaviors, but currently there is greater awareness of the importance of more subtle reciprocal social communication as a core feature of autism. Significant heterogeneity has been observed in symptom manifestations of ASD associated with various factors including age, gender, cognitive functioning, language levels, adaptive behaviors, and comorbidity. Standard diagnostic instruments have been used widely for the comprehensive assessment of ASD based on information from both caregiver interviews and direct clinical observations. Recently proposed changes in the major framework of ASD diagnostic criteria are also discussed.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Early Manifestations of Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Marianne L. BARTON, Auteur ; Alyssa ORINSTEIN, Auteur ; Eva TROYB, Auteur ; Deborah A. FEIN, Auteur

Année de publication :

2013

Importance :

p.39-53

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Autism is a neuro-developmental disorder defined by deficits in social interaction and communication, and restricted interests and repetitive behaviors. Identification of the earliest signs of the disorder has important implications for understanding the developmental course and potential underlying neural mechanisms. It may also facilitate earlier identification of affected children and more timely and effective intervention. This chapter reviews the literature from both retrospective and prospective studies that identify early biomarkers and behavioral symptoms of atypical social motivation, delayed development of functional communication, and the onset of repetitive behaviors. The data suggest that signs of the disorder are not evident in the first six months of life, but emerge in the second half of the first year. The chapter closes with consideration of potential theoretical models of the available data and a brief discussion of the implications of these data for early diagnosis.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Asperger Syndrome and its Relationships to Autism

Type de document :

texte imprimé

Auteurs :

James C. MCPARTLAND, Auteur ; Fred R. VOLKMAR, Auteur

Année de publication :

2013

Importance :

p.55-67

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Asperger syndrome is one of the pervasive developmental disorders, diagnosed behaviorally and characterized by social impairments and rigid and repetitive interests or behaviors paired with relatively preserved cognitive and verbal facilities. This chapter describes the diagnostic concept and the clinical manifestation of the disorder, as well as guidelines for diagnostic assessment and intervention. Existing research is reviewed within the areas of epidemiology, etiology and pathophysiology, treatment and intervention, and outcome. In closing, future directions for treatment and research are discussed.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Behavioral and Psychosocial Interventions for Individuals with ASD

Type de document :

texte imprimé

Auteurs :

Latha V. SOORYA, Auteur ; Laura A. CARPENTER, Auteur ; Zachary WARREN, Auteur

Année de publication :

2013

Importance :

p.69-84

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

This chapter provides a current overview of behavioral and psychosocial treatments for individuals with ASD. The approaches include empirically based methods as well as popular interventions designed to address core and associated symptoms. The chapter includes reviews of major comprehensive treatment programs and educational programs designed for young children with ASD, as well as targeted treatments to improve core deficits. Interventions designed to reduce problem behaviors, and alternative treatments commonly used in ASD are also addressed. Finally, trends and directions for future behavioral and psychosocial treatment research including a focus on implementation in community settings and designing treatments for older individuals with ASD are discussed.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Current Trends in the Pharmacological Treatment of Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Alexander KOLEVZON, Auteur

Année de publication :

2013

Importance :

p.85-101

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

There has been a significant amount of research into pharmacological treatments in autism spectrum disorders (ASD) over the past several decades. The field has used a targeted symptoms domain approach by borrowing from the existing evidence base in other psychiatric disorders to explore potential treatment effects in ASD. This strategy has been fruitful and led to US Food and Drug Administration (FDA) indications for associated symptoms, including ‘irritability associated with autism’ in the cases of risperidone and aripiprazole. Concurrently, neurobiological evidence has been aggressively pursued and a significant amount of literature has accumulated to describe various biochemical irregularities in ASD. This chapter reviews the current state of evidence in the pharmacological treatment of ASD. Sections are divided into symptom domains, to facilitate ease of clinical use and to describe a rational approach to symptomatic treatment in ASD while arming clinicians with a foundation for making informed treatment decisions.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Novel Therapeutics in Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Evdokia ANAGNOSTOU, Auteur ; Caitlyn MCKEEVER, Auteur ; Azadeh KUSHKI, Auteur

Année de publication :

2013

Importance :

p.103-109

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Although ASD (autistic spectrum disorder) has seen significant gains in the area of therapeutics over the last 2 decades, it has also been characterized by the inability to successfully treat core symptom domains. In this chapter, we discuss challenges faced in this area, including limitations related to measuring outcomes, ability to capture the heterogeneity of ASD adequately, and lack of data in the rapidly growing adult population who have ASD. We then discuss novel approaches to therapeutics research in ASD, which include translating emerging findings from genomics, neuropathology and animal models into treatment, and discuss potential novel molecular targets in this area, such as glutamate/GABA related pathways, oxytocin/vasopressin, and immune modulation. The need to combine such treatments with evolving psychoeducational interventions is highlighted as it has the potential to modify the developmental trajectories of individuals with ASD.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Etiological Heterogeneity in Autism Spectrum Disorders: Role of Rare Variants

Type de document :

texte imprimé

Auteurs :

Catalina BETANCUR, Auteur ; Mary COLEMAN, Auteur

Année de publication :

2013

Importance :

p.113-144

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Autism spectrum disorders (ASD) encompass a group of behaviorally defined developmental disabilities characterized by marked clinical and etiological heterogeneity. There is increasing evidence that ASD can arise from rare, highly penetrant mutations and genomic imbalances. There are at present over 100 disease genes and 50 recurrent genomic imbalances implicated in the etiology of ASD. These genes and loci have so far all been causally implicated in intellectual disability, indicating that these two neurodevelopmental disorders share common genetic bases. Similarly, many genes involved in epilepsy can also result in ASD. These observations indicate that these genes cause a continuum of neurodevelopmental disorders that manifest in different ways depending on other genetic, environmental or stochastic factors. Increased recognition of the etiological heterogeneity of ASD will expand the number of target genes for neurobiological investigations, reveal functional pathways, and assist the development of novel therapeutic approaches.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Copy Number Variation in Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Christian R. MARSHALL, Auteur ; Anath C. LIONEL, Auteur ; Stephen SCHERER, Auteur

Année de publication :

2013

Importance :

p.145-154

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

It is well established that a significant proportion of the risk underlying autism spectrum disorders (ASD) is genetic. The rapid advancement of high-resolution genome scanning technologies has led to several reproducible findings that are beginning to uncover the genetic architecture of ASD. An identifiable genetic etiology exists in approximately 15% of individuals with ASD, with a large proportion of this currently attributable to copy number variations (CNVs). A recent focus of research has been to identify rare (lt; 0.1% frequency), but apparently highly penetrant, CNVs for candidate ASD-risk gene discovery. This strategy has yielded identification of rare de novo or inherited CNVs in upwards of 10% of cases, implicating hundreds of risk genes in ASD, many of which are involved in synaptic function. The discovery of these highly penetrant susceptibility genes has immediate impact on genetic diagnostic testing while also uncovering pathways amenable for therapeutic intervention.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Common Genetic Variants in Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Richard ANNEY, Auteur

Année de publication :

2013

Importance :

p.155-167

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Autism spectrum disorders (ASD) have been shown to be highly heritable. In order to understand the genetic risk loci underpinning the heritability estimates, investigators have employed a range of genetic approaches. This chapter examines the approaches that have been applied to identify common variation that may confer risk to individuals with ASD, from linkage studies to positional and biological candidate gene association strategies and finally genome-wide association studies. A number of promising risk loci and genes have been identified; however these findings are tempered by a lack of robust validation. There are a number of challenges to unambiguously identifying common variants that influence the risk of developing ASD since the evidence indicates that common risk variants are likely to be of small effect. Recent large collaborative efforts in schizophrenia and bipolar disorder show that improvements in study power and design can successfully lead to the identification of such risk loci. Future studies in ASD will require tens of thousands of families to identify risk variation of small effect. However, additional advances in genome coverage, sampling, and study design can also be applied to identify those genes and pathways important in the etiology of ASD.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Next-Generation Sequencing For Gene and Pathway Discovery and Analysis in Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Guiqing CAI, Auteur ; Joseph D. BUXBAUM, Auteur

Année de publication :

2013

Importance :

p.169-177

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

High-risk gene mutations and copy number variants have been identified for ASD but many hundreds of genes and loci remain to be identified. Next-generation sequencing (NGS) will provide a cost-effective means of identifying additional ASD risk loci. In this chapter, we introduce current NGS platforms and describe recent NGS successes in characterizing human genomic variation, identifying genetic variation in human disease, and functional analyses of the human genome, including applications around the transcriptome, epigenome and interactome. Ongoing whole-exome and whole-genome sequencing projects in thousands of ASD are summarized as well, which are already identifying new ASD genes.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Mitochondria and Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Robert K. NAVIAUX, Auteur

Année de publication :

2013

Importance :

p.179-193

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Recently, the connections between mitochondria and autism spectrum disorders (ASD) have become increasingly clear. The nature of this connection is more complex than previously thought. A simple reduction in mitochondrial function does not cause ASD. A small but informative fraction of autism is caused by single-gene defects or DNA copy number variations, with the large majority of ASD being the result of variation in hundreds of genes and loci, interacting with environmental and other factors. The crossroads of genes and environment is metabolism. Mitocellular hormesis is the adaptation of cellular and mitochondrial metabolism to environmental change. Changes in nutrition, infectious agents, environmental toxicants, intellectual attention, and physical activity each play a role in mitocellular hormesis during children’s development. Definite mitochondrial disease is responsible for less than 5% of ASD, however, pathological disturbances in mitochondrial metabolism leading to excitotoxicity may lie at the heart of a larger proportion of ASD.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Parental and Perinatal Risk Factors for Autism: Epidemiological Findings and Potential Mechanisms

Type de document :

texte imprimé

Auteurs :

Sven SANDIN, Auteur ; Alexander KOLEVZON, Auteur ; Stephen Z. LEVINE, Auteur ; Christina M. HULTMAN, Auteur ; Abraham REICHENBERG, Auteur

Année de publication :

2013

Importance :

p.195-202

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

There is evidence that non-heritable familial pre- or perinatal factors play a role in the etiology of autism and autism spectrum disorders (ASD). According to current evidence from epidemiological studies, two groups of factors show a consistent relationship with ASD: advancing parental age and preterm birth and intrauterine growth restriction. Using a systematic review and meta-analysis of epidemiological studies incorporating a comprehensive assessment of risk factors, we have examined the evidence for an association between advancing parental age, low birth weight, preterm birth and being born small for gestational age, and risk for ASD in the offspring. Advancing maternal age (35 or older), and paternal age (40 or older), show a consistent relationship with ASD. Current evidence also supports a relationship between low birth weight (lt; 2,500 grams), preterm birth (lt; 37 weeks) and being born small for gestational age, and ASD. Future research should continue to examine these variables using large, population-based cohorts in order to offer a more refined modeling of risk and potential confounders, and to attempt to distinguish between autism and spectrum disorders. Identifying common and unique risk factors may be important to understand shared and non-shared etiologies.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

The Environment in Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Kristen LYALL, Auteur ; Rebecca J. SCHMIDT, Auteur ; Irva HERTZ-PICCIOTTO, Auteur

Année de publication :

2013

Importance :

p.203-214

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

A growing body of literature has begun to uncover associations between autism and a range of environmental agents. Several maternal infections, certain medications, and exposures to air pollution in the prenatal period have been linked to autism spectrum disorders (ASD) with replication by at least a second research group. Factors with emerging evidence include maternal nutritional status, smoking, and use of pesticides. These exposures may act directly on basic processes in neurodevelopment, such as molecular signaling, epigenetic imprinting, cell migration, and synaptogenesis, while indirect effects through immune dysregulation or endocrine disruption may also be relevant. Reports on season of birth/conception and autism risk are consistent with infections, nutrients, and pesticides. It is recommended that key strategies rely on large epidemiological studies with standardized confirmation of diagnoses and collection of biospecimens and environmental samples. These in turn can help to (1) determine critical time periods when susceptibility to specific environmental factors is enhanced; (2) uncover gene—environment interactions that elucidate mechanisms; and (3) identify early biomarkers that will enable intervention to be introduced at the youngest possible ages.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Hormonal Influences in Typical Development: Implications for Autism

Type de document :

texte imprimé

Auteurs :

Bonnie AUYEUNG, Auteur ; Simon BARON-COHEN, Auteur

Année de publication :

2013

Importance :

p.215-232

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Autism Spectrum Conditions (ASC) are strongly biased towards males, with a male:female ratio of 4:1 for classic autism and over 10:1 for Asperger Syndrome. The cause of the observed sex difference in ASC remains a topic of debate. The Extreme Male Brain (EMB) theory proposes that autism is an exaggeration of typical sex differences in empathizing and systemizing. Although this theory originally defined the ‘male and ‘female’ brain purely in psychometric terms, it has since been suggested that increased levels of prenatal androgens (particularly testosterone) may produce excessive masculinization of the brain and thereby increase the risk of ASC. An important candidate mechanism for the development of sex-typical behavior is exposure to hormones such as testosterone during pregnancy. Evidence that elevated testosterone levels may be a risk factor for ASC is discussed.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Immune Abnormalities and Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Majannie ELOI AKINTUDE, Auteur ; Luke HEUER, Auteur ; Judy VAN DE WATER, Auteur

Année de publication :

2013

Importance :

p.233-248

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

This chapter explores the link between autism spectrum disorders and the immune system. It begins with a discussion of basic immunology for each topic, integrated with a comprehensive review of the most recent studies describing dysfunction of the immune system in the context of autism. Although many of these observations are still under investigation with respect to their mechanistic relevance to autism, they remain valuable as biologic markers in the quest for understanding the etiology and pathology of this complex disorder

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Structural and Functional MRI Studies of Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Kimberly A. STIGLER, Auteur ; Christopher J. MCDOUGLE, Auteur

Année de publication :

2013

Importance :

p.251-266

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Structural and functional magnetic resonance imaging (MRI) research has significantly contributed to our understanding of the neurobiology of autism spectrum disorders (ASD). Structural MRI studies have demonstrated increased total brain volume, as well as an atypical trajectory of neurodevelopment in children with ASD. Differences in cortical gray and white matter volume have also been recorded in affected individuals, with diffusion tensor imaging revealing decreased white matter integrity at a microstructural level. Functional MRI research has found abnormalities in cortical activation and connectivity in ASD via task-based approaches. In addition, resting state studies have revealed atypical patterns of connectivity in the default-mode network. Despite these encouraging findings, additional large-scale neuroimaging studies are needed to further inform the neurobiological underpinnings of ASD.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

DTI and Tractography in the Autistic Brain

Type de document :

texte imprimé

Auteurs :

Timothy P.L. ROBERTS, Auteur ; Jeffrey I. BERMAN, Auteur ; Ragini VERMA, Auteur

Année de publication :

2013

Importance :

p.267-279

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Diffusion tensor imaging (DTI) and associated fiber tractography are an emerging MRI technique for studying white matter of the brain. This chapter presents an introduction to the physical and biological bases of diffusion in white matter and the development and analysis of diffusion tensor imaging. It also includes visualization of white matter fiber tracts and quantification of physical diffusion parameters, such as the mean diffusivity (MD) and fractional anisotropy (FA) that might be used to index white matter maturation. A review of the recent findings made using DTI in ASD (autism spectrum disorder) is presented, focusing on studies with large (gt;20) sample sizes. Common themes of elevated mean diffusivity and diminished fractional anisotropy emerge, especially in structures of the frontal and temporal lobes, but also in the corpus callosum. Voxel-based as well as regional connectivity approaches to extracting quantitative information from DTI are discussed along with approaches involving machine learning of pattern classifiers to distinguish ASD from TD and also identify key features (structures, regions or connections) that contribute most to that discrimination ability. Limitations of tractography based on DTI are discussed along with the emerging advance of high angular resolution diffusion imaging (HARDI) as a means to overcome DTI limitations in regions of complex white matter organization.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Attentional Network Deficits in Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Jin FAN, Auteur

Année de publication :

2013

Importance :

p.281-288

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Attentional dysfunction is one of the most consistent findings in individuals with autism spectrum disorders (ASD). However, the significance of such findings for the pathophysiology of autism is unclear. To elucidate the relationship of ASD and attention, deficits in each of several functions of attention are examined by conceptualizing attention as an organ system. The functions of attention are alerting, orienting, and executive control, each with their own neuroanatomy and neurochemistry. The findings related to attentional difficulties in autism may best be explained as deficits among attentional functions and their interactions. Such deficits are important to the development and maintenance of cognitive and social dysfunction in ASD, and may constitute a key biomarker for these disorders.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

The Cerebellum in Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Margaret L. BAUMAN, Auteur ; Thomas L. KEMPER, Auteur

Année de publication :

2013

Importance :

p.289-295

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Autism spectrum disorders (ASD) are a group of behaviorally defined disorders characterized by impaired social interaction, delayed and disordered language, isolated areas of interest and an insistence on sameness. Although specific causes of ASD are not fully known, both genetic and environmental factors are believed to play a role. One of the most consistently abnormal regions of the autistic brain is the cerebellum. This chapter describes some of the gross and microscopic features of the cerebellum in the autistic brain and suggests possible correlations between these findings and clinical symptoms of the disorder.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

The Amygdala in Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

John T. MORGAN, Auteur ; Christine W. NORDAHL, Auteur ; Cynthia M. SCHUMANN, Auteur

Année de publication :

2013

Importance :

p.297-312

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

The amygdala plays a critical role in detecting and responding to biologically relevant environmental stimuli. It is also considered a major component of a network of brain regions often referred to as the ‘social brain’. Given the social abnormalities that are a hallmark of autism spectrum disorders (ASD), the amygdala has long been suspected to be aberrant in the disorder. Functional magnetic resonance imaging (MRI) studies reveal abnormalities in amygdala activation to social stimuli, such as emotional facial expressions. Structural MRI studies have shown that the amygdala undergoes an abnormal developmental trajectory including early overgrowth that may be primarily driven by a specific subgroup of individuals with ASD. Postmortem cellular studies reveal that abnormalities in the neuronal and glial composition of the amygdala likely underlie these functional and structural alterations. Interdisciplinary integration of an array of experimental approaches will hold the key to a full understanding of amygdala abnormality in ASD.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Discrete Cortical Neuropathology in Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Neha UPPAL, Auteur ; Patrick R. HOF, Auteur

Année de publication :

2013

Importance :

p.313-325

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Autism spectrum disorders (ASD) are the most inheritable of psychiatric disorders, although precise genetic alterations have only been identified in about 20% of cases. The major impact of the condition on the development and social integration of affected children has led to a marked increase in research efforts focusing on the possible roles of neuropathological processes underlying it. This chapter provides an overview of the literature on the cortical neuropathology of ASD. Postmortem studies are pivotal for cell-level exploration, especially in the context of brain regions which consistently show altered patterns of activation in functional magnetic resonance imaging studies. Cortical alterations known to occur in ASD are reviewed, including abnormalities in neuronal morphology, neurotransmitter systems, and cytoarchitectural organization. We focus in particular on abnormalities of the prefrontal cortex, the inferior frontal cortex, fusiform gyrus, the insular cortex, the cingulate cortex, and the hippocampus.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

The Minicolumnopathy of Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Manuel F. CASANOVA, Auteur

Année de publication :

2013

Importance :

p.327-333

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Cortical development arises from the epistatic interaction of multiple gene polymorphisms and transcriptional programs, their epigenetic modifications, expression patterns of morphogens and other small molecules, and incipient patterns of synaptic activity, all subject to developmental noise. These mechanisms exhibit redundancy and crosstalk so that a stable phenotypic distribution is maintained in the face of stochastic effects and (epi-)genetic perturbations. The resulting constrained programs of differentiation, migration, and neuronal development provide a basis for emergent patterns of information flow within the developing minicolumn, which may in turn feed back to further refine the formation of its circuits. In autism, our research has shown the existence of supernumerary columns with significant diminution in their peripheral neuropil. This finding, along with descriptions of ‘epigenetic’ heterotopias, suggests a dysregulation of periventricular germinal cell divisions. The heterochronicity of periventricular cell divisions provides an uncoupling between the radial migrating system and the tangential migration of inhibitory elements.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Inhibitory and Excitatory Systems in Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Gene J. BLATT, Auteur

Année de publication :

2013

Importance :

p.335-346

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

It has been 50 years since elevated levels of serotonin (5-HT) were identified in the blood of some individuals with autism spectrum disorders (ASD) yet most research on genetics, behavior, imaging, and neurochemistry has occurred in the last decade. With technological advances occurring in every aspect of research, it is now apparent that there are abnormalities in a variety of neurotransmitter systems, but central changes are directed toward specific types of transporters and/or receptors within each system. Three major systems are discussed in this chapter: GABA, glutamate, and 5-HT, and the chapter focuses on experimental evidence that implicates features of each system that potentially affect the excitatory:inhibitory (E/I) balance in the ASD brain. Disruption of the E/I balance in the direction of either decreased inhibition or elevated excitatory activity, or both, may contribute to altered connectivity and give rise to the ASD phenotype. Modern methods are directed toward increasing our understanding of the etiologies of the disorder.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Clinicopathological Stratification of Idiopathic Autism and Autism with 15q11.2–q13 Duplications

Type de document :

texte imprimé

Auteurs :

Jerzy WEGIEL, Auteur ; N. Carolyn SCHANEN, Auteur ; Edwin H. Jr COOK, Auteur ; W. Ted BROWN, Auteur ; Izabela KUCHNA, Auteur ; Krzysztof NOWICKI, Auteur ; Jarek WEGIEL, Auteur ; Humi IMAKI, Auteur ; Shuang Yong MA, Auteur ; Eric LONDON, Auteur ; Thomas WISNIEWSKI, Auteur

Année de publication :

2013

Importance :

p.347-359

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Postmortem studies of brains of individuals with idiopathic autism and 15q11.2–q13 duplications autism (dup(15)) identify a cluster of neuropathological features differentiating these cohorts. They show a need for both reclassification of autism according to etiology, clinical presentation and neuropathology, and a commonality of clinical and neuropathological traits justifying autism diagnosis. The features differentiating these cohorts include: (a) maternal origin in patients with dup(15); (b) autism in 78% of subjects; (c) more severe clinical phenotypes, with intellectual deficit (100%), early-onset of severe or intractable seizures in 78% of subjects, and increased prevalence (up to 67%) of sudden unexplained death; (d) high prevalence of microcephaly, with mean brain weight 300g less than in idiopathic autism; (e) several-fold increase in the number of developmental abnormalities, including defects of migration and dysplastic changes, especially numerous in the hippocampal formation; and (f) significant increase in the intraneuronal amyloid load, reflecting enhanced amyloid-β precursor protein processing with α-secretase.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Mouse Behavioral Models for Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

William C. WETSEL, Auteur ; Sheryl S. MOY, Auteur ; Yong-hui JIANG, Auteur

Année de publication :

2013

Importance :

p.363-378

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Autism spectrum disorders (ASD) involve impaired development of social interaction and communication, as well as restricted, repetitive, and stereotyped behaviors. ASD has high heritability and certain chromosomal regions and at risk genes are associated with the conditions. Experiments with inbred and outbred rodent models of ASD have revealed procedures that can partially or fully rescue the phenotype; metabotropic GluR5 antagonists appear especially promising in certain models. We summarize behavioral approaches for analyzing mouse models for ASD and review studies in Shank3 mice as a specific example. As SHANK3 variants are identified as a risk factor for autism, mouse lines have been developed with deletions in exons 4–9, exons 13–16, and exon 21 that display, to varying degrees, ASD-like behaviors. Future research with Shank3 lines and other genetic models should help determine the mechanistic basis for both core symptomatologies and divergent behavioral profiles in ASD.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Nonhuman Primate Models for Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Melissa D. BAUMAN, Auteur ; David G. AMARAL, Auteur

Année de publication :

2013

Importance :

p.379-390

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Autism is a complex neurodevelopmental disorder characterized by impairments in social interaction and verbal and nonverbal communication, and the occurrence of pathological repetitive behaviors or circumscribed interests. As discussed more completely in other chapters, the defining characteristics are manifest in a spectrum of severity, leading to the term autism spectrum disorders (ASD) to encompass this heterogeneity. ASD are challenging to study in human populations because of the heterogeneity of symptoms, lack of consistent biomarkers, and the complex interplay between genetic and environmental risk factors. In recent years, some progress has been made in developing animal models of autism. These animal models provide an experimental system to evaluate hypotheses that, for ethical and practical reasons, are impossible to test using human subjects. However, a major challenge for complex brain disorders such as autism is to model a human disorder that has impairments of complex cognitive functions in a nonhuman species. In this chapter, we summarize different approaches to modeling features of autism in nonhuman primates, focusing on the rhesus macaque (Macacca mulatta). We review expectations for a valid nonhuman primate model of autism, evaluate the strengths and weaknesses of current nonhuman primate models, and highlight promising future directions for integrating neuroscience research into these models.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Inducible Pluripotent Stem Cells In Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Alysson Renato MUOTRI, Auteur

Année de publication :

2013

Importance :

p.391-399

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

The generation of human neurons from patients with autism spectrum disorders (ASD) offers a novel and complementary opportunity for basic research and the development of therapeutic compounds aiming to revert or ameliorate this family of conditions. Neurons “in-a-dish” from monogenic and other single locus forms of ASD opened new avenues for the stratification of different subtypes of autism. This chapter covers the conceptual and practical issues related to modeling ASD using induced pluripotent stem cells.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

A 15q11–q13 Duplication Mouse Model of Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Toru TAKUMI, Auteur ; Keita FUKUMOTO, Auteur ; Jun NOMURA, Auteur

Année de publication :

2013

Importance :

p.401-408

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Autism spectrum disorders (ASD) are developmental brain disorders manifested by abnormal social behavior. Recent human genetic studies have revealed various copy number variations in ASD. Duplication of human chromosome 15q11–q13 is known to be most frequently associated with cytogenetic abnormality in ASD. Human chromosome 15q11–q13, also known to include imprinted genes, is well conserved to mouse chromosome 7. By a chromosome-engineering technique, we developed a mouse model for 15q11–q13 duplication. Paternally derived duplication (patDp/+) mice show abnormal behavior including abnormal social interaction, alteration in the developmental course of ultrasonic vocalizations, and resistance to change in reversal learning. Reduced serotonin (5-HT) is observed in the brain of patDp/+ mice during development, suggesting that this abnormal 5-HT level may affect social behavior. A 15q11–q13 duplication model mouse will facilitate future studies in genetics of developmental brain disorders and serve as an invaluable tool for therapeutic development.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Fragile X Syndrome and Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

W. Ted BROWN, Auteur ; Ira L. COHEN, Auteur

Année de publication :

2013

Importance :

p.409-419

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Fragile X syndrome (FXS) is the most common monogenic form of intellectual disability, and is strongly associated with autism spectrum disorders (ASD). There is wide variation in the severity of symptoms, which may be due in part to modifier genes, such as MAOA. The most consistently observed behavioral feature is social avoidance, which may be secondary to problems with arousal modulation. This social avoidance distinguishes ASD associated with fragile X from idiopathic ASD. The fragile X gene (FMR1) encodes an RNA binding protein (FMRP) that modulates, primarily by suppression of translation, the expression of approximately 4% of brain genes. The mGluR theory of fragile X postulates that over-activity of glutamate excitatory pathways play a major role in symptomatology. Animal models, particularly mouse and Drosophila knockouts, are providing insights into the underlying pathophysiology and are leading to the development of targeted treatments. Current drug trials in FXS are being carried out and may lead to approved drugs, which may be beneficial for ASD as well.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

MeCP2 and Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Sarrita ADAMS, Auteur ; Janine M. LASALLE, Auteur

Année de publication :

2013

Importance :

p.421-436

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Autism spectrum disorders (ASD) are characterized by complex genetic etiologies. Within ASD are a number of syndromic disorders with known genetic bases and autistic features. Rett syndrome (RTT) is an X-linked dominant ASD caused by mutations in the DNA methyl-binding protein MeCP2. A variety of mouse models of MeCP2 deficiency and over-expression have been generated and revealed the role of MeCP2 at the center of a number of other ASD-relevant pathways controlling synapse number and strength. In this chapter, we review the evidence for overlap in MeCP2 function with other ASD implicated genes, including FMR1, MEF2C, FOXG1, CNTNAP2, SHANK3, TSC2, UBE3A, and SYN1. In addition, we discuss what mouse models with these genetic deficiencies have revealed about the specific deficits of synaptic function in ASD and the normal orchestration of synaptic plasticity in the early postnatal brain.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

SHANK2 and SHANK3 Mutations Implicate Glutamate Signaling Abnormalities in Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Hala HARONY-NICOLAS, Auteur ; Ozlem Bozdagi GUNAL, Auteur ; Joseph D. BUXBAUM, Auteur

Année de publication :

2013

Importance :

p.437-448

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

The SHANK family of genes encodes proteins (Shank1, 2, 3) that are core components of the postsynaptic density. Shank proteins contain multiple domains involved in protein-protein interactions, which link glutamate receptors to the actin cytoskeleton. Recent genetic and functional data implicate mutations in the human Shank2 and Shank3 genes in autism spectrum disorders (ASD). Several genetic mutations and rare copy number variants in these genes have been identified in ASD patients, with SHANK3 disruption now being one of the most common monogenic forms of ASD. Given that Shank and Shank promote the formation, maturation, and enlargement of dendritic spines, supporting the role of synaptic pathology in ASD, it becomes important to make use of animal (typically mouse and rat) models lacking Shanks, to study the underlying synaptic and neuronal pathophysiology of ASD. To this end, different Shank3 rodent models have been generated in an effort to explain the role of SHANK3 mutations in ASD, with the aim of identifying potential therapeutic targets for ASD that can also be tested in these animal models. In the current chapter we summarize in vitro and in vivo studies on Shank proteins, and relate these findings to the dysregulation of glutamate signaling in ASD.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

PI3K Signaling and miRNA Regulation in Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Showming KWOK, Auteur ; Nikolaos MELLIOS, Auteur ; Mriganka SUR, Auteur

Année de publication :

2013

Importance :

p.449-459

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Despite the heterogeneity of autism spectrum disorders (ASD), dysregulation of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway has emerged as one potentially common and unifying theme. Multiple genes linked to syndromic or non-syndromic forms of ASD appear to interplay with small non-coding RNAs to generate a complex and interconnected molecular network that, when perturbed, results in alterations in protein synthesis and aberrant synaptic plasticity. In this chapter we attempt to elucidate the interactions between ASD-related genes and PI3K/Akt/mTOR signaling, with particular mention of the contribution of microRNAs (miRNAs), a category of non-coding RNAs with increased relevance to brain disorders.

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in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM

Titre :

Getting from 1,000 Genes to a Triad of Symptoms: The Emerging Role of Systems Biology in Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Joseph D. BUXBAUM, Auteur

Année de publication :

2013

Importance :

p.461-471

Langues :

Anglais (eng)

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Systems biological approaches will be required in autism spectrum disorders (ASD) to understand how a highly diverse set of genes can, when altered, lead to a well-defined behavioral phenotype. As our understanding of convergent pathways increases, we will begin to understand more about brain development and the molecular basis for brain function and behavior. One important outcome from systems biological analyses is the ability to identify driver genes within pathways and networks. Driver genes can be used for the validation of networks, and also represent high-impact genes for drug development. In this way, systems biological approaches will also inform drug discovery efforts. We provide a brief summary of systems-level analyses of common and rare genetic variation in ASD and of genes that are differentially expressed in postmortem ASD brain samples. In addition, we highlight some issues that will need to be resolved before systems biological approaches will be reliably useful in ASD research

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Technology Tools for Students with Autism	BOSER, Katharina I.
Le sens du mouvement	BERTHOZ, Alain

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Centre d'Information et de Documentation
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