Comprehensive Clinical Phenotyping & Genetic Mapping for the Discovery of Autism Susceptibility Genes

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2012-12-05

teaching students with autism spectrum disorders 4.52 Learn strategies for incorporating IEP goals and district standard into daily teaching...W403 Columbus, OH 43205 Final Report Comprehensive Clinical Phenotyping & Genetic Mapping for the Discovery of Autism Susceptibility Genes...QFOXGHDUHDFRGH 1.0 Summary In 2006, the Central Ohio Registry for Autism (CORA) was initiated as a collaboration between Wright-Patterson Air

Measurement Equivalence of the Autism Symptom Phenotype in Children and Youth

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Duku, Eric; Szatmari, Peter; Vaillancourt, Tracy; Georgiades, Stelios; Thompson, Ann; Liu, Xiao-Qing; Paterson, Andrew D.; Bennett, Terry

2013-01-01

Background: The Autism Diagnostic Interview-Revised (ADI-R) is a gold standard assessment of Autism Spectrum Disorder (ASD) symptoms and behaviours. A key underlying assumption of studies using the ADI-R is that it measures the same phenotypic constructs across different populations (i.e. males/females, younger/older, verbal/nonverbal). The…

New interview and observation measures of the broader autism phenotype : group differentiation

NARCIS (Netherlands)

de Jonge, Maretha; Parr, Jeremy; Rutter, Michael; Wallace, Simon; Kemner, Chantal|info:eu-repo/dai/nl/96717041; Bailey, Anthony; van Engeland, Herman; Pickles, Andrew

To identify the broader autism phenotype (BAP), the Family History Interview subject and informant versions and an observational tool (Impression of Interviewee), were developed. This study investigated whether the instruments differentiated between parents of children with autism, and parents of

New Interview and Observation Measures of the Broader Autism Phenotype : Group Differentiation

NARCIS (Netherlands)

de Jonge, Maretha; Parr, Jeremy; Rutter, Michael; Wallace, Simon; Kemner, Chantal; Bailey, Anthony; van Engeland, Herman; Pickles, Andrew

2015-01-01

To identify the broader autism phenotype (BAP), the Family History Interview subject and informant versions and an observational tool (Impression of Interviewee), were developed. This study investigated whether the instruments differentiated between parents of children with autism, and parents of

Genetically meaningful phenotypic subgroups in autism spectrum disorders.

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Veatch, O J; Veenstra-Vanderweele, J; Potter, M; Pericak-Vance, M A; Haines, J L

2014-03-01

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with strong evidence for genetic susceptibility. However, the effect sizes for implicated chromosomal loci are small, hard to replicate and current evidence does not explain the majority of the estimated heritability. Phenotypic heterogeneity could be one phenomenon complicating identification of genetic factors. We used data from the Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, Vineland Adaptive Behavior Scales, head circumferences, and ages at exams as classifying variables to identify more clinically similar subgroups of individuals with ASD. We identified two distinct subgroups of cases within the Autism Genetic Resource Exchange dataset, primarily defined by the overall severity of evaluated traits. In addition, there was significant familial clustering within subgroups (odds ratio, OR ≈ 1.38-1.42, P definition that should increase power to detect genetic factors influencing risk for ASD. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

The Experiences of Late-Diagnosed Women with Autism Spectrum Conditions: An Investigation of the Female Autism Phenotype

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Bargiela, Sarah; Steward, Robyn; Mandy, William

2016-01-01

We used Framework Analysis to investigate the female autism phenotype and its impact upon the under-recognition of autism spectrum conditions (ASC) in girls and women. Fourteen women with ASC (aged 22-30 years) diagnosed in late adolescence or adulthood gave in-depth accounts of: "pretending to be normal"; of how their gender led various…

The broad autism phenotype in parents of individuals with autism: a systematic review of the literature

Directory of Open Access Journals (Sweden)

Lidia Prata Cruz

2013-12-01

Full Text Available The broad autism phenotype (BAP is a milder manifestation of the defining symptoms of the syndrome in individuals without autism. This study conducted a systematic review of studies about behavioral characteristics of interpersonal relationships, communication and rigidity, as well as about three cognitive models, Theory of Mind, central coherence and executive function, in parents of individuals with autism. The indexed databases were LILACS, IBECS, Web of Science, and MEDLINE, and the studies retrieved were published between 1991 and March 2012. Parents of individuals with autism have more difficulties in interpersonal relationships and in pragmatic language use and have more rigidity traits. The inclusions of the cognitive theories in the group of BAP characteristics were inconclusive.

An ontology for Autism Spectrum Disorder (ASD) to infer ASD phenotypes from Autism Diagnostic Interview-Revised data.

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Mugzach, Omri; Peleg, Mor; Bagley, Steven C; Guter, Stephen J; Cook, Edwin H; Altman, Russ B

2015-08-01

Our goal is to create an ontology that will allow data integration and reasoning with subject data to classify subjects, and based on this classification, to infer new knowledge on Autism Spectrum Disorder (ASD) and related neurodevelopmental disorders (NDD). We take a first step toward this goal by extending an existing autism ontology to allow automatic inference of ASD phenotypes and Diagnostic & Statistical Manual of Mental Disorders (DSM) criteria based on subjects' Autism Diagnostic Interview-Revised (ADI-R) assessment data. Knowledge regarding diagnostic instruments, ASD phenotypes and risk factors was added to augment an existing autism ontology via Ontology Web Language class definitions and semantic web rules. We developed a custom Protégé plugin for enumerating combinatorial OWL axioms to support the many-to-many relations of ADI-R items to diagnostic categories in the DSM. We utilized a reasoner to infer whether 2642 subjects, whose data was obtained from the Simons Foundation Autism Research Initiative, meet DSM-IV-TR (DSM-IV) and DSM-5 diagnostic criteria based on their ADI-R data. We extended the ontology by adding 443 classes and 632 rules that represent phenotypes, along with their synonyms, environmental risk factors, and frequency of comorbidities. Applying the rules on the data set showed that the method produced accurate results: the true positive and true negative rates for inferring autistic disorder diagnosis according to DSM-IV criteria were 1 and 0.065, respectively; the true positive rate for inferring ASD based on DSM-5 criteria was 0.94. The ontology allows automatic inference of subjects' disease phenotypes and diagnosis with high accuracy. The ontology may benefit future studies by serving as a knowledge base for ASD. In addition, by adding knowledge of related NDDs, commonalities and differences in manifestations and risk factors could be automatically inferred, contributing to the understanding of ASD pathophysiology. Copyright �

New Interview and Observation Measures of the Broader Autism Phenotype: Group Differentiation

Science.gov (United States)

de Jonge, Maretha; Parr, Jeremy; Rutter, Michael; Wallace, Simon; Kemner, Chantal; Bailey, Anthony; van Engeland, Herman; Pickles, Andrew

2015-01-01

To identify the broader autism phenotype (BAP), the Family History Interview subject and informant versions and an observational tool (Impression of Interviewee), were developed. This study investigated whether the instruments differentiated between parents of children with autism, and parents of children with Down syndrome (DS). The BAP scores of…

Why We Should Study the Broader Autism Phenotype in Typically Developing Populations

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Landry, Oriane; Chouinard, Philippe A.

2016-01-01

The broader autism phenotype (BAP) is a term applied to individuals with personality and cognitive traits that are similar to but milder than those observed in autism spectrum disorder (ASD). Subtle autistic traits in the core diagnostic domains of social communication and rigid behavior were described in family members of people with an ASD even…

Psychological Adjustment and Sibling Relationships in Siblings of Children with Autism Spectrum Disorders: Environmental Stressors and the Broad Autism Phenotype

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Petalas, Michael A.; Hastings, Richard P.; Nash, Susie; Hall, Louise M.; Joannidi, Helen; Dowey, Alan

2012-01-01

Research with siblings of children with Autism Spectrum Disorders (ASD) suggests that they may be at increased risk for behavioural and emotional problems and relatively poor sibling relationships. This study investigated a diathesis-stress model, whereby the presence of Broad Autism Phenotype features in the typically developing siblings might…

Comprehensive Clinical Phenotyping and Genetic Mapping for the Discovery of Autism Susceptibility Genes

Science.gov (United States)

2013-03-14

behavioral teaching strategies and best practice for teaching students with autism spectrum disorders 4.52 Learn strategies for incorporating IEP goals...AFRL-SA-WP-TR-2013-0013 Comprehensive Clinical Phenotyping and Genetic Mapping for the Discovery of Autism Susceptibility Genes...Genetic Mapping for the Discovery of Autism Susceptibility Genes 5a. CONTRACT NUMBER N/A 5b. GRANT NUMBER N/A 5c. PROGRAM ELEMENT NUMBER N/A 6

Brief Report: Do the Nature of Communication Impairments in Autism Spectrum Disorders Relate to the Broader Autism Phenotype in Parents?

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Taylor, Lauren J.; Maybery, Murray T.; Wray, John; Ravine, David; Hunt, Anna; Whitehouse, Andrew J. O.

2013-01-01

Extensive empirical evidence indicates that the lesser variant of Autism Spectrum Disorders (ASD) involves a communication impairment that is similar to, but milder than, the deficit in clinical ASD. This research explored the relationship between the broader autism phenotype (BAP) among parents, an index of genetic liability for ASD, and proband…

Reframing autism as a behavioral syndrome and not a specific mental disorder: Implications of genetic and phenotypic heterogeneity.

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Tordjman, S; Cohen, D; Coulon, N; Anderson, G M; Botbol, M; Canitano, R; Roubertoux, P L

2017-01-30

Clinical and molecular genetics have advanced current knowledge on genetic disorders associated with autism. A review of diverse genetic disorders associated with autism is presented and for the first time discussed extensively with regard to possible common underlying mechanisms leading to a similar cognitive-behavioral phenotype of autism. The possible role of interactions between genetic and environmental factors, including epigenetic mechanisms, is in particular examined. Finally, the pertinence of distinguishing non-syndromic autism (isolated autism) from syndromic autism (autism associated with genetic disorders) will be reconsidered. Given the high genetic and etiological heterogeneity of autism, autism can be viewed as a behavioral syndrome related to known genetic disorders (syndromic autism) or currently unknown disorders (apparent non-syndromic autism), rather than a specific categorical mental disorder. It highlights the need to study autism phenotype and developmental trajectory through a multidimensional, non-categorical approach with multivariate analyses within autism spectrum disorder but also across mental disorders, and to conduct systematically clinical genetic examination searching for genetic disorders in all individuals (children but also adults) with autism. Copyright © 2017. Published by Elsevier Ltd.

Systematic genotype-phenotype analysis of autism susceptibility loci implicates additional symptoms to co-occur with autism

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Buizer-Voskamp, Jacobine E.; Franke, Lude; Staal, Wouter G.; van Daalen, Emma; Kemner, Chantal; Ophoff, Roel A.; Vorstman, Jacob A. S.; van Engeland, Herman; Wijmenga, Cisca

2010-01-01

Many genetic studies in autism have been performed, resulting in the identification of multiple linkage regions and cytogenetic aberrations, but little unequivocal evidence for the involvement of specific genes exists. By identifying novel symptoms in these patients, enhanced phenotyping of autistic

[Behavioral phenotypes of autism spectrum disorder patients and their parents].

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Situ, Mingjing; Hu, Xiao; Cai, Jia; Guo, Kuifang; Huang, Yi

2015-12-01

To explore the relationship between the behavior phenotypes of patients with autism spectrum disorder (ASD) and their parents through family study. Forty-five core families with ASD and 30 control families from Chengdu area were examined using Autism Spectrum Quotient (AQ). Descriptive statistical analysis, correlation analysis, and Logistic regression analysis were used to investigate the effect of various factors, especially genetic factors that may affect the pathogenesis of ASD. The social skills factor and communication factor of the father's AQ scale, as well as the mother's age of childbearing and AQ social skills factor are related to whether children with ASD (R were 0.46, 0.39, 0.39 and 0.36, Pautism. ASD may be influenced by both genetic and environmental factors. The autistic behavior phenotype of parents is a risk factor for ASD and is associated with developmental anomalies of early childhood.

The broader autism phenotype in infancy: when does it emerge?

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Ozonoff, Sally; Young, Gregory S; Belding, Ashleigh; Hill, Monique; Hill, Alesha; Hutman, Ted; Johnson, Scott; Miller, Meghan; Rogers, Sally J; Schwichtenberg, A J; Steinfeld, Marybeth; Iosif, Ana-Maria

2014-04-01

This study had 3 goals, which were to examine the following: the frequency of atypical development, consistent with the broader autism phenotype, in high-risk infant siblings of children with autism spectrum disorder (ASD); the age at which atypical development is first evident; and which developmental domains are affected. A prospective longitudinal design was used to compare 294 high-risk infants and 116 low-risk infants. Participants were tested at 6, 12, 18, 24, and 36 months of age. At the final visit, outcome was classified as ASD, Typical Development (TD), or Non-TD (defined as elevated Autism Diagnostic Observation Schedule [ADOS] score, low Mullen Scale scores, or both). Of the high-risk group, 28% were classified as Non-TD at 36 months of age. Growth curve models demonstrated that the Non-TD group could not be distinguished from the other groups at 6 months of age, but differed significantly from the Low-Risk TD group by 12 months on multiple measures. The Non-TD group demonstrated atypical development in cognitive, motor, language, and social domains, with differences particularly prominent in the social-communication domain. These results demonstrate that features of atypical development, consistent with the broader autism phenotype, are detectable by the first birthday and affect development in multiple domains. This highlights the necessity for close developmental surveillance of infant siblings of children with ASD, along with implementation of appropriate interventions as needed. Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Broader Autism Phenotype in Siblings of Children with ASD—A Review

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Pisula, Ewa; Ziegart-Sadowska, Karolina

2015-01-01

Although less pronounced, social, cognitive, and personality characteristics associated with autism spectrum disorders (ASD) may be present in people who do not meet ASD diagnostic criteria, especially in first-degree relatives of individuals with ASD. Research on these characteristics, referred to as broader autism phenotype (BAP), provides valuable data on potential expressions of autism-specific deficits in the context of family relations. This paper offers a review of research on BAP in siblings of individuals with ASD, focusing on reports regarding social, communication, and cognitive deficits, published from 1993 to 2014. The studies are divided into two groups based on participants’ age: papers on preschool and older siblings of individuals with ASD; and publications on infants at risk for ASD. On the basis of this review, suggestions are offered for further research and its significance for our understanding of the genetic determinants of autism. PMID:26068453

Repint of "Reframing autism as a behavioral syndrome and not a specific mental disorder: Implications of genetic and phenotypic heterogeneity".

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Tordjman, S; Cohen, D; Anderson, G M; Botbol, M; Canitano, R; Coulon, N; Roubertoux, P L

2018-06-01

Clinical and molecular genetics have advanced current knowledge on genetic disorders associated with autism. A review of diverse genetic disorders associated with autism is presented and for the first time discussed extensively with regard to possible common underlying mechanisms leading to a similar cognitive-behavioral phenotype of autism. The possible role of interactions between genetic and environmental factors, including epigenetic mechanisms, is in particular examined. Finally, the pertinence of distinguishing non-syndromic autism (isolated autism) from syndromic autism (autism associated with genetic disorders) will be reconsidered. Given the high genetic and etiological heterogeneity of autism, autism can be viewed as a behavioral syndrome related to known genetic disorders (syndromic autism) or currently unknown disorders (apparent non-syndromic autism), rather than a specific categorical mental disorder. It highlights the need to study autism phenotype and developmental trajectory through a multidimensional, non-categorical approach with multivariate analyses within autism spectrum disorder but also across mental disorders, and to conduct systematically clinical genetic examination searching for genetic disorders in all individuals (children but also adults) with autism. Copyright © 2018. Published by Elsevier Ltd.

Defining key features of the broad autism phenotype: a comparison across parents of multiple- and single-incidence autism families.

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Losh, Molly; Childress, Debra; Lam, Kristen; Piven, Joseph

2008-06-05

This study examined the frequency of personality, language, and social-behavioral characteristics believed to comprise the broad autism phenotype (BAP), across families differing in genetic liability to autism. We hypothesized that within this unique sample comprised of multiple-incidence autism families (MIAF), single-incidence autism families (SIAF), and control Down syndrome families (DWNS), a graded expression would be observed for the principal characteristics conferring genetic susceptibility to autism, in which such features would express most profoundly among parents from MIAFs, less strongly among SIAFs, and least of all among comparison parents from DWNS families, who should display population base rates. Analyses detected linear expression of traits in line with hypotheses, and further suggested differential intrafamilial expression across family types. In the vast majority of MIAFs both parents displayed BAP characteristics, whereas within SIAFs, it was equally likely that one, both, or neither parent show BAP features. The significance of these findings is discussed in relation to etiologic mechanisms in autism and relevance to molecular genetic studies. (c) 2007 Wiley-Liss, Inc.

Social phenotypes of autism spectrum disorders and Williams syndrome: similarities and differences

Directory of Open Access Journals (Sweden)

Kosuke eAsada

2012-07-01

Full Text Available Autism spectrum disorders (ASD and Williams syndrome (WS both are neurodevelopmental disorders, each with a unique social phenotypic pattern. This review article aims to define the similarities and differences between the social phenotypes of ASD and WS. We review studies that have examined individuals with WS using diagnostic assessments such as the Autism Diagnostic Observation Schedule (ADOS, cross-syndrome direct comparison studies, and studies that have individually examined either disorder. We conclude that (1 Individuals with these disorders show quite contrasting phenotypes for face processing (i.e., preference to faces and eyes and sociability (i.e., interest in and motivation to interact with others, and (2 Although the ADOS and a direct comparison study on pragmatic language ability suggest more deficits in ASD, individuals with WS are similarly impaired on social cognition and communicative skills. In light of these results, we discuss how cross-syndrome comparisons between ASD and WS can contribute to developmental theory, cognitive neuroscience, and the development and choice of clinical treatments.

Broader autistic phenotype in parents of children with autism: Autism Spectrum Quotient-Turkish version.

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Kose, Sezen; Bora, Emre; Erermiş, Serpil; Özbaran, Burcu; Bildik, Tezan; Aydın, Cahide

2013-01-01

The Autism Spectrum Quotient (AQ) is a self-assessment screening instrument for measuring the degree to which an individual of normal intelligence shows autistic traits. Genetic factors could be responsible for the relatives of individuals with autism exhibiting higher than normal rates of autism-related impairments, referred to as the 'broader autism phenotype' (BAP). The aim of this study was to test whether there is a difference between the parents of autistic and those of typically developing children (TDC) on AQ scores in a Turkish sample. The AQ total and subscale scores of the 100 parents (47 fathers, 53 mothers) of children with autistic disorder (AD) were compared with the 100 parents (48 fathers, 52 mothers) of TDC. The parents of AD children scored significantly higher than the TDC parents on total AQ score, and two of five subscale scores; social skills, and communication. The other three subscales (attention to detail, attention switching, imagination) did not differentiate groups. There was no significant difference between mothers and fathers on any AQ scores, neither in the AD nor TDC group. The group × gender interaction was not significant on the total or the five subscale scores of AQ. Social skill and communication subscales differentiate AD parents more successfully, and are more sensitive, as reported in other studies. The present findings confirm that social skill and communication impairments in parents of children with autism spectrum disorders are indicators of BAP. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Ratings of Broader Autism Phenotype and Personality Traits in Optimal Outcomes from Autism Spectrum Disorder.

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Suh, Joyce; Orinstein, Alyssa; Barton, Marianne; Chen, Chi-Ming; Eigsti, Inge-Marie; Ramirez-Esparza, Nairan; Fein, Deborah

2016-11-01

The study examines whether "optimal outcome" (OO) children, despite no longer meeting diagnostic criteria for Autism Spectrum Disorder (ASD), exhibit personality traits often found in those with ASD. Nine zero acquaintance raters evaluated Broader Autism Phenotype (BAP) and Big Five personality traits of 22 OO individuals, 27 high functioning individuals with ASD (HFA), and 23 typically developing (TD) peers. HFA children displayed higher ratings than their peers on all BAP traits. OO were indistinguishable from TD, with the exception of greater extraversion (e.g., increased talkativeness), a potential tendency to be less emotionally stable, and pragmatic language deficits such as getting sidetracked in conversation. Overall, OO individuals are not showing BAP characteristics, but may be subject to other mild ADHD-like characteristics.

The Broader Autism Phenotype in Mothers is Associated with Increased Discordance between Maternal-Reported and Clinician-Observed Instruments That Measure Child Autism Spectrum Disorder

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Rubenstein, Eric; Edmondson Pretzel, Rebecca; Windham, Gayle C.; Schieve, Laura A.; Wiggins, Lisa D.; DiGuiseppi, Carolyn; Olshan, Andrew F.; Howard, Annie G.; Pence, Brian W.; Young, Lisa; Daniels, Julie

2017-01-01

Autism spectrum disorder (ASD) diagnosis relies on parent-reported and clinician-observed instruments. Sometimes, results between these instruments disagree. The broader autism phenotype (BAP) in parent-reporters may be associated with discordance. Study to Explore Early Development data (N = 712) were used to address whether mothers with BAP and…

Theory of Mind Indexes the Broader Autism Phenotype in Siblings of Children with Autism at School Age.

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Tsang, Tawny; Gillespie-Lynch, Kristen; Hutman, Ted

2016-01-01

Subclinical variants of the social-communicative challenges and rigidity that define autism spectrum disorder (ASD) are known as the broader autism phenotype (BAP). The BAP has been conceptualized categorically (as specific to a subset of relatives of individuals with ASD) and dimensionally (as continuously distributed within the general population). The current study examined the compatibility of these two approaches by assessing associations among autism symptoms and social-communicative skills in young school-age children with ASD, children who have a sibling with ASD, and children without a sibling with ASD. Autism symptoms were associated with reduced Theory of Mind (ToM), adaptive skills, cognitive empathy, and language skills across the full sample. Reduced ToM was a core aspect of the BAP in the current sample regardless of whether the BAP was defined categorically (in terms of siblings of children with ASD who exhibited atypical developmental) or dimensionally (in terms of associations with autism symptoms across the entire sample). Early language skills predicted school-age ToM. Findings support the compatibility of categorical and dimensional approaches to the BAP, highlight reduced ToM as a core aspect of the school-age BAP, and suggest that narrative-based approaches to promoting ToM may be beneficial for siblings of children with ASD.

Theory of Mind Indexes the Broader Autism Phenotype in Siblings of Children with Autism at School Age

Directory of Open Access Journals (Sweden)

Tawny Tsang

2016-01-01

Full Text Available Subclinical variants of the social-communicative challenges and rigidity that define autism spectrum disorder (ASD are known as the broader autism phenotype (BAP. The BAP has been conceptualized categorically (as specific to a subset of relatives of individuals with ASD and dimensionally (as continuously distributed within the general population. The current study examined the compatibility of these two approaches by assessing associations among autism symptoms and social-communicative skills in young school-age children with ASD, children who have a sibling with ASD, and children without a sibling with ASD. Autism symptoms were associated with reduced Theory of Mind (ToM, adaptive skills, cognitive empathy, and language skills across the full sample. Reduced ToM was a core aspect of the BAP in the current sample regardless of whether the BAP was defined categorically (in terms of siblings of children with ASD who exhibited atypical developmental or dimensionally (in terms of associations with autism symptoms across the entire sample. Early language skills predicted school-age ToM. Findings support the compatibility of categorical and dimensional approaches to the BAP, highlight reduced ToM as a core aspect of the school-age BAP, and suggest that narrative-based approaches to promoting ToM may be beneficial for siblings of children with ASD.

The phenotypic manifestations of rare genic CNVs in autism spectrum disorder.

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Merikangas, A K; Segurado, R; Heron, E A; Anney, R J L; Paterson, A D; Cook, E H; Pinto, D; Scherer, S W; Szatmari, P; Gill, M; Corvin, A P; Gallagher, L

2015-11-01

Significant evidence exists for the association between copy number variants (CNVs) and Autism Spectrum Disorder (ASD); however, most of this work has focused solely on the diagnosis of ASD. There is limited understanding of the impact of CNVs on the 'sub-phenotypes' of ASD. The objective of this paper is to evaluate associations between CNVs in differentially brain expressed (DBE) genes or genes previously implicated in ASD/intellectual disability (ASD/ID) and specific sub-phenotypes of ASD. The sample consisted of 1590 cases of European ancestry from the Autism Genome Project (AGP) with a diagnosis of an ASD and at least one rare CNV impacting any gene and a core set of phenotypic measures, including symptom severity, language impairments, seizures, gait disturbances, intelligence quotient (IQ) and adaptive function, as well as paternal and maternal age. Classification analyses using a non-parametric recursive partitioning method (random forests) were employed to define sets of phenotypic characteristics that best classify the CNV-defined groups. There was substantial variation in the classification accuracy of the two sets of genes. The best variables for classification were verbal IQ for the ASD/ID genes, paternal age at birth for the DBE genes and adaptive function for de novo CNVs. CNVs in the ASD/ID list were primarily associated with communication and language domains, whereas CNVs in DBE genes were related to broader manifestations of adaptive function. To our knowledge, this is the first study to examine the associations between sub-phenotypes and CNVs genome-wide in ASD. This work highlights the importance of examining the diverse sub-phenotypic manifestations of CNVs in ASD, including the specific features, comorbid conditions and clinical correlates of ASD that comprise underlying characteristics of the disorder.

Narrowing the Broader Autism Phenotype: A Study Using the Communication Checklist-Adult Version (CC-A)

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Whitehouse, Andrew J. O.; Coon, Hilary; Miller, Judith; Salisbury, Bryanna; Bishop, Dorothy V. M.

2010-01-01

This study investigated whether the Communication Checklist-Adult (CC-A) could identify subtypes of social and communication dysfunction in autism probands and their parents. The CC-A is divided into subscales measuring linguistic ability as well as two aspects of social communication: the Pragmatic Skills subscale assesses the level of pragmatic…

Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes

DEFF Research Database (Denmark)

Loviglio, M N; Leleu, M; Männik, K

2017-01-01

Copy number variants (CNVs) are major contributors to genomic imbalance disorders. Phenotyping of 137 unrelated deletion and reciprocal duplication carriers of the distal 16p11.2 220 kb BP2-BP3 interval showed that these rearrangements are associated with autism spectrum disorders and mirror phen...

Levels of Text Comprehension in Children with Autism Spectrum Disorders (ASD): The Influence of Language Phenotype

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Lucas, Rebecca; Norbury, Courtenay Frazier

2014-01-01

Many children with autism spectrum disorders (ASD) have reading comprehension difficulties, but the level of processing at which comprehension is most vulnerable and the influence of language phenotype on comprehension skill is currently unclear. We explored comprehension at sentence and passage levels across language phenotypes. Children with ASD…

Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder.

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Richard, Annie E; Scheffer, Ingrid E; Wilson, Sarah J

2017-04-01

Richard, A.E., I.E. Scheffer and S.J. Wilson. Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder. NEUROSCI BIOBEHAV REV 21(1) XXX-XXX, 2016. To inform on mechanisms underlying the comorbidity of epilepsy and autism spectrum disorder (ASD), we conducted meta-analyses to test whether impaired facial emotion recognition (FER) and theory of mind (ToM), key phenotypic traits of ASD, are more common in people with epilepsy (PWE) than controls. We contrasted these findings with those of relatives of individuals with ASD (ASD-relatives) compared to controls. Furthermore, we examined the relationship of demographic (age, IQ, sex) and epilepsy-related factors (epilepsy onset age, duration, seizure laterality and origin) to FER and ToM. Thirty-one eligible studies of PWE (including 1449 individuals: 77% with temporal lobe epilepsy), and 22 of ASD-relatives (N=1295) were identified by a systematic database search. Analyses revealed reduced FER and ToM in PWE compared to controls (p<0.001), but only reduced ToM in ASD-relatives (p<0.001). ToM was poorer in PWE than ASD-relatives. Only weak associations were found between FER and ToM and epilepsy-related factors. These findings suggest shared mechanisms between epilepsy and ASD, independent of intellectual disability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Can the Five Factor Model of Personality Account for the Variability of Autism Symptom Expression? Multivariate Approaches to Behavioral Phenotyping in Adult Autism Spectrum Disorder.

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Schwartzman, Benjamin C; Wood, Jeffrey J; Kapp, Steven K

2016-01-01

The present study aimed to: determine the extent to which the five factor model of personality (FFM) accounts for variability in autism spectrum disorder (ASD) symptomatology in adults, examine differences in average FFM personality traits of adults with and without ASD and identify distinct behavioral phenotypes within ASD. Adults (N = 828; nASD = 364) completed an online survey with an autism trait questionnaire and an FFM personality questionnaire. FFM facets accounted for 70 % of variance in autism trait scores. Neuroticism positively correlated with autism symptom severity, while extraversion, openness to experience, agreeableness, and conscientiousness negatively correlated with autism symptom severity. Four FFM subtypes emerged within adults with ASD, with three subtypes characterized by high neuroticism and none characterized by lower-than-average neuroticism.

The Role of the Broader Autism Phenotype and Environmental Stressors in the Adjustment of Siblings of Children with Autism Spectrum Disorders in Taiwan and the United Kingdom

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Tsai, Hsiao-Wei Joy; Cebula, Katie; Fletcher-Watson, Sue

2017-01-01

The influence of the broader autism phenotype (BAP) on the adjustment of siblings of children with autism has previously been researched mainly in Western cultures. The present research evaluated a diathesis-stress model of sibling adjustment using a questionnaire study including 80 and 75 mother-typically developing sibling dyads in Taiwan and…

Recognition of emotional facial expressions and broad autism phenotype in parents of children diagnosed with autistic spectrum disorder.

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Kadak, Muhammed Tayyib; Demirel, Omer Faruk; Yavuz, Mesut; Demir, Türkay

2014-07-01

Research findings debate about features of broad autism phenotype. In this study, we tested whether parents of children with autism have problems recognizing emotional facial expression and the contribution of such an impairment to the broad phenotype of autism. Seventy-two parents of children with autistic spectrum disorder and 38 parents of control group participated in the study. Broad autism features was measured with Autism Quotient (AQ). Recognition of Emotional Face Expression Test was assessed with the Emotion Recognition Test, consisting a set of photographs from Ekman & Friesen's. In a two-tailed analysis of variance of AQ, there was a significant difference for social skills (F(1, 106)=6.095; p<.05). Analyses of variance revealed significant difference in the recognition of happy, surprised and neutral expressions (F(1, 106)=4.068, p=.046; F(1, 106)=4.068, p=.046; F(1, 106)=6.064, p=.016). According to our findings, social impairment could be considered a characteristic feature of BAP. ASD parents had difficulty recognizing neutral expressions, suggesting that ASD parents may have impaired recognition of ambiguous expressions as do autistic children. Copyright © 2014 Elsevier Inc. All rights reserved.

A genome-wide association study of autism using the Simons Simplex Collection: Does reducing phenotypic heterogeneity in autism increase genetic homogeneity?

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Chaste, Pauline; Klei, Lambertus; Sanders, Stephan J; Hus, Vanessa; Murtha, Michael T; Lowe, Jennifer K; Willsey, A Jeremy; Moreno-De-Luca, Daniel; Yu, Timothy W; Fombonne, Eric; Geschwind, Daniel; Grice, Dorothy E; Ledbetter, David H; Mane, Shrikant M; Martin, Donna M; Morrow, Eric M; Walsh, Christopher A; Sutcliffe, James S; Lese Martin, Christa; Beaudet, Arthur L; Lord, Catherine; State, Matthew W; Cook, Edwin H; Devlin, Bernie

2015-05-01

Phenotypic heterogeneity in autism has long been conjectured to be a major hindrance to the discovery of genetic risk factors, leading to numerous attempts to stratify children based on phenotype to increase power of discovery studies. This approach, however, is based on the hypothesis that phenotypic heterogeneity closely maps to genetic variation, which has not been tested. Our study examines the impact of subphenotyping of a well-characterized autism spectrum disorder (ASD) sample on genetic homogeneity and the ability to discover common genetic variants conferring liability to ASD. Genome-wide genotypic data of 2576 families from the Simons Simplex Collection were analyzed in the overall sample and phenotypic subgroups defined on the basis of diagnosis, IQ, and symptom profiles. We conducted a family-based association study, as well as estimating heritability and evaluating allele scores for each phenotypic subgroup. Association analyses revealed no genome-wide significant association signal. Subphenotyping did not increase power substantially. Moreover, allele scores built from the most associated single nucleotide polymorphisms, based on the odds ratio in the full sample, predicted case status in subsets of the sample equally well and heritability estimates were very similar for all subgroups. In genome-wide association analysis of the Simons Simplex Collection sample, reducing phenotypic heterogeneity had at most a modest impact on genetic homogeneity. Our results are based on a relatively small sample, one with greater homogeneity than the entire population; if they apply more broadly, they imply that analysis of subphenotypes is not a productive path forward for discovering genetic risk variants in ASD. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Narrowing the broader autism phenotype: A study using the Communication Checklist - Adult Version (CC-A)

OpenAIRE

Whitehouse, AJ; Coon, H; Miller, J; Salisbury, B; Bishop, DV

2010-01-01

This study investigated whether the Communication Checklist – Adult (CC-A) could identify subtypes of social and communication dysfunction in autism probands and their parents. The CC-A is divided into subscales measuring linguistic ability as well as two aspects of social communication: the Pragmatic Skills subscale assesses the level of pragmatic oddities (e.g., excessive talking), while the Social Engagement subscale picks up on those behaviours that reflect a more passive communication st...

New Interview and Observation Measures of the Broader Autism Phenotype : Description of Strategy and Reliability Findings for the Interview Measures

NARCIS (Netherlands)

Parr, Jeremy R.; De Jonge, Maretha V.; Wallace, Simon; Pickles, Andrew; Rutter, Michael L.; Le Couteur, Ann S.; van Engeland, Herman; Wittemeyer, Kerstin; Mcconachie, Helen; Roge, Bernadette; Mantoulan, Carine; Pedersen, Lennart; Isager, Torben; Poustka, Fritz; Bolte, Sven; Bolton, Patrick; Weisblatt, Emma; Green, Jonathan; Papanikolaou, Katerina; Baird, Gillian; Bailey, Anthony J.

2015-01-01

Clinical genetic studies confirm the broader autism phenotype (BAP) in some relatives of individuals with autism, but there are few standardized assessment measures. We developed three BAP measures (informant interview, self-report interview, and impression of interviewee observational scale) and

Automatic and controlled processing and the Broad Autism Phenotype.

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Camodeca, Amy; Voelker, Sylvia

2016-01-30

Research related to verbal fluency in the Broad Autism Phenotype (BAP) is limited and dated, but generally suggests intact abilities in the context of weaknesses in other areas of executive function (Hughes et al., 1999; Wong et al., 2006; Delorme et al., 2007). Controlled processing, the generation of search strategies after initial, automated responses are exhausted (Spat, 2013), has yet to be investigated in the BAP, and may be evidenced in verbal fluency tasks. One hundred twenty-nine participants completed the Delis-Kaplan Executive Function System Verbal Fluency test (D-KEFS; Delis et al., 2001) and the Broad Autism Phenotype Questionnaire (BAPQ; Hurley et al., 2007). The BAP group (n=53) produced significantly fewer total words during the 2nd 15" interval compared to the Non-BAP (n=76) group. Partial correlations indicated similar relations between verbal fluency variables for each group. Regression analyses predicting 2nd 15" interval scores suggested differentiation between controlled and automatic processing skills in both groups. Results suggest adequate automatic processing, but slowed development of controlled processing strategies in the BAP, and provide evidence for similar underlying cognitive constructs for both groups. Controlled processing was predictive of Block Design score for Non-BAP participants, and was predictive of Pragmatic Language score on the BAPQ for BAP participants. These results are similar to past research related to strengths and weaknesses in the BAP, respectively, and suggest that controlled processing strategy use may be required in instances of weak lower-level skills. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Can They See It? The Functional Field of View Is Narrower in Individuals with Autism Spectrum Disorder.

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Song, Yongning; Hakoda, Yuji; Sanefuji, Wakako; Cheng, Chen

2015-01-01

Although social cognitive deficits have long been thought to underlie the characteristic and pervasive difficulties with social interaction observed in individuals with autism spectrum disorder (ASD), several recent behavioral and neuroimaging studies have indicated that visual perceptual impairments might also play a role. People with ASD show a robust bias towards detailed information at the expense of global information, although the mechanisms that underlie this phenomenon remain elusive. To address this issue, we investigated the functional field of view in a group of high-functioning children with autism (n = 13) and a paired non-ASD group (n = 13). Our results indicate that the ability to correctly detect and identify stimuli sharply decreases with greater eccentricity from the fovea in people with ASD. Accordingly, a probe analysis revealed that the functional field of view in the ASD group was only about 6.62° of retinal eccentricity, compared with 8.57° in typically developing children. Thus, children with ASD appear to have a narrower functional field of view. These results challenge the conventional hypothesis that the deficit in global processing in individuals with ASD is solely due to weak central coherence. Alternatively, our data suggest that a narrower functional field of view may also contribute to this bias.

Can They See It? The Functional Field of View Is Narrower in Individuals with Autism Spectrum Disorder.

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Yongning Song

Full Text Available Although social cognitive deficits have long been thought to underlie the characteristic and pervasive difficulties with social interaction observed in individuals with autism spectrum disorder (ASD, several recent behavioral and neuroimaging studies have indicated that visual perceptual impairments might also play a role. People with ASD show a robust bias towards detailed information at the expense of global information, although the mechanisms that underlie this phenomenon remain elusive. To address this issue, we investigated the functional field of view in a group of high-functioning children with autism (n = 13 and a paired non-ASD group (n = 13. Our results indicate that the ability to correctly detect and identify stimuli sharply decreases with greater eccentricity from the fovea in people with ASD. Accordingly, a probe analysis revealed that the functional field of view in the ASD group was only about 6.62° of retinal eccentricity, compared with 8.57° in typically developing children. Thus, children with ASD appear to have a narrower functional field of view. These results challenge the conventional hypothesis that the deficit in global processing in individuals with ASD is solely due to weak central coherence. Alternatively, our data suggest that a narrower functional field of view may also contribute to this bias.

Heterogeneity of subclinical autistic traits among parents of children with autism spectrum disorder: Identifying the broader autism phenotype with a data-driven method.

Science.gov (United States)

Bora, Emre; Aydın, Aydan; Saraç, Tuğba; Kadak, Muhammed Tayyib; Köse, Sezen

2017-02-01

Clinical diagnosis of autism spectrum disorder (ASD) can be conceptualized as the extreme end of the distribution of subclinical autistic traits related to genetic susceptibility factors (broad autism phenotype (BAP)) in the general population. Subclinical autistic traits are significantly more common among unaffected first-degree relatives of probands with autism. However, there is a significant heterogeneity of autistic traits in family members of individuals with ASD and severity of autistic traits are not significantly different from controls in the majority of these relatives. The current study investigated the heterogeneity of autistic traits using latent class analysis (LCA) of the Autism Spectrum Quotient (AQ) ratings of 673 parents of children with ASD and 147 parents of typically developing children. Two distinct subgroups, including a "low-scoring" and a "high-scorer (BAP)" groups, were found. In comparison to control parents, a significantly larger proportion (21.1% vs. 7.5%) of parents of ASD were members of BAP group. Communication subscale made a distinctive contribution to the separation of high and low-scoring groups (d = 2.77). Further studies investigating neurobiological and genetic biomarkers and stability of these two subgroups over time are important for understanding the nature of autistic traits in the general population. Autism Res 2017, 10: 321-326. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Facial identity recognition in the broader autism phenotype.

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C Ellie Wilson

Full Text Available BACKGROUND: The 'broader autism phenotype' (BAP refers to the mild expression of autistic-like traits in the relatives of individuals with autism spectrum disorder (ASD. Establishing the presence of ASD traits provides insight into which traits are heritable in ASD. Here, the ability to recognise facial identity was tested in 33 parents of ASD children. METHODOLOGY AND RESULTS: In experiment 1, parents of ASD children completed the Cambridge Face Memory Test (CFMT, and a questionnaire assessing the presence of autistic personality traits. The parents, particularly the fathers, were impaired on the CFMT, but there were no associations between face recognition ability and autistic personality traits. In experiment 2, parents and probands completed equivalent versions of a simple test of face matching. On this task, the parents were not impaired relative to typically developing controls, however the proband group was impaired. Crucially, the mothers' face matching scores correlated with the probands', even when performance on an equivalent test of matching non-face stimuli was controlled for. CONCLUSIONS AND SIGNIFICANCE: Components of face recognition ability are impaired in some relatives of ASD individuals. Results suggest that face recognition skills are heritable in ASD, and genetic and environmental factors accounting for the pattern of heritability are discussed. In general, results demonstrate the importance of assessing the skill level in the proband when investigating particular characteristics of the BAP.

[Early diagnosis of autism: Phenotype-endophenotype].

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Kotsopoulos, S

2015-01-01

Autism Spectrum Disorders have for some time been the focus of intense interest for clinicians and researchers because of the high prevalence of the disorders among children in the community (approximately 1%), their severity and pervasiveness. Particular attention has been paid to the early diagnosis of the disorder and to the intensive therapeutic intervention. Currently the best prognosis for autism lays in the early diagnosis and intervention. Postponing the diagnosis and the intervention beyond infancy is considered loss of precious time. The diagnosis of autism, which begins early in life, was until recently considered that could be reliability made at the age of 3 years. Recent follow up studies however on children at risk for autism (children who had an older sibling with autism) have shown that the clinical signs of autism emerge at the end of the first year and become distinct by the end of the second year when the diagnosis can reliably be made. From a clinical perspective it is noted that the early clinical signs of risk for autism are related to social communication (e.g. limited or absent response when calling his/her name and to joint attention), stereotype behaviours and body movements or unusual handling of objects (e.g. intensive observation of objects and stereotype movements of hands and tapping or spinning), incongruent regulation of emotions (reduced positive and increased negative emotion). There is also delay in developmental characteristics such as the language (both receptive and expressive) and motor (particularly in postural control - characteristic is the drop of the head backwards when the infant is held in horizontal position). Studies on various aspects of the endophenotype of certain clinical signs among infants at risk for Autism Spectrum Disorders, such as avoidance of eye contact, delay in verbal communication and increase of the head circumference, may provide useful information and may assist the clinician on follow up in the

Examining genotypic variation in autism spectrum disorder and its relationship to parental age and phenotype

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Geier DA

2016-07-01

Full Text Available David A Geier,1,2 Janet K Kern,1,3 Lisa K Sykes,2 Mark R Geier1,2 1Research Department, The Institute of Chronic Illnesses, Inc, 2Research Department, CoMeD, Inc, Silver Spring, MD, 3Research Department, CONEM US Autism Research Group, Allen, TX, USA Background: Previous studies on genetic testing of chromosomal abnormalities in individuals diagnosed with autism spectrum disorder (ASD found that ~80% have negative genetic test results (NGTRs and ~20% have positive genetic test results (PGTRs, of which ~7% were probable de novo mutations (PDNMs. Research suggests that parental age is a risk factor for an ASD diagnosis. This study examined genotypic variation in ASD and its relationship to parental age and phenotype.Methods: Phenotype was derived from detailed clinical information, and genotype was derived from high-resolution blood chromosome and blood whole-genome copy number variant genetic testing on a consecutive cohort (born: 1983–2009 of subjects diagnosed with ASD (N=218.Results: Among the subjects examined, 80.3% had NGTRs and 19.7% had PGTRs, of which 6.9% had PDNMs. NGTR subjects were born more recently (the risk of PDNMs decreasing by 12% per more recent birth year and tended to have an increased male–female ratio compared to PDNM subjects. PDNM subjects had significantly increased mean parental age and paternal age at subject’s birth (the risk of a PDNM increasing by 7%–8% per year of parental or paternal age compared to NGTR subjects. PGTR and NGTR subjects showed significant improvements in speech/language/communication with increasing age. PGTR subjects showed significant improvements in sociability, a core feature of an ASD diagnosis, with increasing age, whereas NGTR subjects showed significant worsening in sociability with increasing age.Conclusion: This study helps to elucidate different phenotypic ASD subtypes and may even indicate the need for differential diagnostic classifications. Keywords: genotype, phenotype

The Neuroanatomy of the Autistic Phenotype

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Fahim, Cherine; Meguid, Nagwa A.; Nashaat, Neveen H.; Yoon, Uicheul; Mancini-Marie, Adham; Evans, Alan C.

2012-01-01

The autism phenotype is associated with an excess of brain volume due in part to decreased pruning during development. Here we aimed at assessing brain volume early in development to further elucidate previous findings in autism and determine whether this pattern is restricted to idiopathic autism or shared within the autistic phenotype (fragile X…

Exploring links between genotypes, phenotypes, and clinical predictors of response to early intensive behavioural intervention in Autism Spectrum Disorder

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Valsamma eEapen

2013-09-01

Full Text Available Autism Spectrum Disorder (ASD is amongst the most familial of psychiatric disorders. Twin and family studies have demonstrated a monozygotic concordance rate of 70–90%, dizygotic concordance of around 10% and more than a 20-fold increase in risk for first-degree relatives. Despite major advances in the genetics of autism, the relationship between different aspects of the behavioural and cognitive phenotype and their underlying genetic liability is still unclear. This is complicated by the heterogeneity of autism, which exists at both genetic and phenotypic levels. Given this heterogeneity, one method to find homogeneous entities and link these with specific genotypes would be to pursue endophenotypes. Evidence from neuroimaging, eye tracking and electrophysiology studies supports the hypothesis that, building on genetic vulnerability, ASD emerges from a developmental cascade in which a deficit in attention to social stimuli leads to impaired interactions with primary caregivers. This results in abnormal development of the neurocircuitry responsible for social cognition, which in turn adversely affects later behavioural and functional domains dependent on these early processes, such as language development. Such a model begets a heterogeneous clinical phenotype, and is also supported by studies demonstrating better clinical outcomes with earlier treatment. Treatment response following intensive early behavioural intervention in ASD is also distinctly variable; however, relatively little is known about specific elements of the clinical phenotype that may predict response to current behavioural treatments. This paper overviews the literature regarding genotypes, phenotypes and predictors of response to behavioural intervention in ASD and presents suggestions for future research to explore linkages between these that would enable better identification of, and increased treatment efficacy for, ASD.

Array-CGH Analysis in a Cohort of Phenotypically Well-Characterized Individuals with "Essential" Autism Spectrum Disorders

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Napoli, Eleonora; Russo, Serena; Casula, Laura; Alesi, Viola; Amendola, Filomena Alessandra; Angioni, Adriano; Novelli, Antonio; Valeri, Giovanni; Menghini, Deny; Vicari, Stefano

2018-01-01

Copy-number variants (CNVs) are associated with susceptibility to autism spectrum disorder (ASD). To detect the presence of CNVs, we conducted an array-comparative genomic hybridization (array-CGH) analysis in 133 children with "essential" ASD phenotype. Genetic analyses documented that 12 children had causative CNVs (C-CNVs), 29…

Broad autism phenotype features of Chinese parents with autistic children and their associations with severity of social impairment in probands.

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Shi, Li-Juan; Ou, Jian-Jun; Gong, Jing-Bo; Wang, Su-Hong; Zhou, Yuan-Yue; Zhu, Fu-Rong; Liu, Xu-Dong; Zhao, Jing-Ping; Luo, Xue-Rong

2015-07-23

Parents of children with autism have higher rates of broad autism phenotype (BAP) features than parents of typically developing children (TDC) in Western countries. This study was designed to examine the rate of BAP features in parents of children with autism and the relationship between parental BAP and the social impairment of their children in a Chinese sample. A total of 299 families with autistic children and 274 families with TDC participated in this study. Parents were assessed using the Broad Autism Phenotype Questionnaire (BAPQ), which includes self-report, informant-report, and best-estimate versions. Children were assessed using the Chinese version of the Social Responsiveness Scale (SRS). Parents of children with autism were significantly more likely to have BAP features than were parents of TDC; mothers and fathers in families with autistic children had various BAP features. The total scores of the informant and best-estimate BAPQ versions for fathers were significantly associated with their children's SRS total scores in the autism group, whereas the total scores of the three BAPQ versions for mothers were significantly associated with their children's SRS total scores in the TDC group. In the autism group, the total SRS scores of children with "BAP present" parents (informant and best-estimate) were higher than the total SRS scores of children with"BAP absent" parents. In the TDC group, the total SRS scores of children with "BAP present" parents were higher than the total SRS scores of children with"BAP absent" parents (best-estimate). Parents of autistic children were found to have higher rates of BAP than parents of TDC in a sample of Chinese parents. The BAP features of parents are associated with their children's social functioning in both autism families and TDC families, but the patterns of the associations are different.

Brief Report: Impact of Child Problem Behaviors and Parental Broad Autism Phenotype Traits on Substance Use among Parents of Children with ASD

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Wade, Jordan L.; Cox, Neill Broderick; Reeve, Ronald E.; Hull, Michael

2014-01-01

Using data from the Simons Simplex Collection, the present study examined the impact of child externalizing behavior and parental broad autism phenotype traits on substance use among parents of children with autism spectrum disorder (n = 2,388). For both fathers and mothers, child externalizing behaviors predicted tobacco use (OR = 1.01 and OR =…

Can the Five Factor Model of Personality Account for the Variability of Autism Symptom Expression? Multivariate Approaches to Behavioral Phenotyping in Adult Autism Spectrum Disorder

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Schwartzman, Benjamin C.; Wood, Jeffrey J.; Kapp, Steven K.

2016-01-01

The present study aimed to: determine the extent to which the five factor model of personality (FFM) accounts for variability in autism spectrum disorder (ASD) symptomatology in adults, examine differences in average FFM personality traits of adults with and without ASD and identify distinct behavioral phenotypes within ASD. Adults (N = 828;…

Broad Autism Phenotypic Traits and the Relationship to Sexual Orientation and Sexual Behavior.

Science.gov (United States)

Qualls, Lydia R; Hartmann, Kathrin; Paulson, James F

2018-04-03

Individuals with higher levels of the broad autism phenotype (BAP) have some symptoms of autism spectrum disorder (ASD). Like individuals with ASD, people with higher-BAP may have fewer sexual experiences and may experience more same-sex attraction. This study measured BAP traits, sexual experiences, and sexual orientation in typically developing (TD) individuals to see if patterns of sexual behavior and sexual orientation in higher-BAP resemble those in ASD. Although BAP characteristics did not predict sexual experiences, one BAP measure significantly predicted sexual orientation, β = 0.22, t = 2.72, p = .007, controlling for demographic variables (R 2 change = .04, F = 7.41, p = .007), showing individuals with higher-BAP also reported increased same-sex attraction. This finding supports the hypothesis that individuals with higher-BAP resemble ASD individuals in being more likely than TD individuals to experience same-sex attraction.

Principal genetic syndromes and autism: from phenotypes, proteins to genes%孤独性障碍及其相关的主要遗传综合征:从表型、蛋白到基因

Institute of Scientific and Technical Information of China (English)

侯萌; 王曼捷; Nanbert ZHONG

2006-01-01

Autism is a neurodevelopmental disorder characterized by impairments in social skills, language, and behavior. It is now clear that autism is not a disease, but a syndrome characterized by phenotypic and genetic complexity. The etiology of autism is still poorly understood. Available evidence from a variety of sources strongly suggests that many genetic disorders are frequently associated with autism for their similar phenotypes. Based on this fact, this review begins by highlighting several principal genetic syndromes consistently associated with autism (fragile X, tuberous sclerosis, Angelman syndrome, Pader-Willi syndrome, Rett syndrome, Down syndrome and Turner syndrome). These genetic disorders include both chromosome disorders and single gene disorders. By comparing the similar phenotype, protein marker and candidate genes, we might make some breakthrough in the mechanism of autism and other genetic disorders.

Homogeneous Subgroups of Young Children with Autism Improve Phenotypic Characterization in the Study to Explore Early Development.

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Wiggins, Lisa D; Tian, Lin H; Levy, Susan E; Rice, Catherine; Lee, Li-Ching; Schieve, Laura; Pandey, Juhi; Daniels, Julie; Blaskey, Lisa; Hepburn, Susan; Landa, Rebecca; Edmondson-Pretzel, Rebecca; Thompson, William

2017-11-01

The objective of this study was to identify homogenous classes of young children with autism spectrum disorder (ASD) to improve phenotypic characterization. Children were enrolled in the Study to Explore Early Development between 2 and 5 years of age. 707 children were classified with ASD after a comprehensive evaluation with strict diagnostic algorithms. Four classes of children with ASD were identified from latent class analysis: mild language delay with cognitive rigidity, mild language and motor delay with dysregulation, general developmental delay, and significant developmental delay with repetitive motor behaviors. We conclude that a four-class phenotypic model of children with ASD best describes our data and improves phenotypic characterization of young children with ASD. Implications for screening, diagnosis, and research are discussed.

Exploring sex differences in autistic traits: A factor analytic study of adults with autism.

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Grove, Rachel; Hoekstra, Rosa A; Wierda, Marlies; Begeer, Sander

2017-08-01

Research has highlighted potential differences in the phenotypic and clinical presentation of autism spectrum conditions across sex. Furthermore, the measures utilised to evaluate autism spectrum conditions may be biased towards the male autism phenotype. It is important to determine whether these instruments measure the autism phenotype consistently in autistic men and women. This study evaluated the factor structure of the Autism Spectrum Quotient Short Form in a large sample of autistic adults. It also systematically explored specific sex differences at the item level, to determine whether the scale assesses the autism phenotype equivalently across males and females. Factor analyses were conducted among 265 males and 285 females. A two-factor structure consisting of a social behaviour and numbers and patterns factor was consistent across groups, indicating that the latent autism phenotype is similar among both autistic men and women. Subtle differences were observed on two social behaviour item thresholds of the Autism Spectrum Quotient Short Form, with women reporting scores more in line with the scores expected in autism on these items than men. However, these differences were not substantial. This study showed that the Autism Spectrum Quotient Short Form detects autistic traits equivalently in males and females and is not biased towards the male autism phenotype.

Chromatin regulators, phenotypic robustness and autism risk

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Reut eSuliman

2014-04-01

Full Text Available Though extensively characterized clinically, the causes of autism spectrum disorder (ASD remain a mystery. ASD is known to have a strong genetic basis, but it is genetically very heterogeneous. Recent studies have estimated that de novo disruptive mutations in hundreds of genes may contribute to ASD. However, it is unclear how it is possible for mutations in so many different genes to contribute to ASD. Recent findings suggest that many of the mutations disrupt genes involved in transcription regulation that are expressed prenatally in the developing brain. De novo disruptive mutations are also more frequent in girls with ASD, despite the fact that ASD is more prevalent in boys. In this paper, we hypothesize that loss of robustness may contribute to ASD. Loss of phenotypic robustness may be caused by mutations that disrupt capacitors that operate in the developing brain. This may lead to the release of cryptic genetic variation that contributes to ASD. Reduced robustness is consistent with the observed variability in expressivity and incomplete penetrance. It is also consistent with the hypothesis that the development of the female brain is more robust, and it may explain the higher rate and severity of disruptive de novo mutations in girls with ASD.

A semantic-based method for extracting concept definitions from scientific publications: evaluation in the autism phenotype domain

OpenAIRE

Hassanpour, Saeed; O?Connor, Martin J; Das, Amar K

2013-01-01

Background A variety of informatics approaches have been developed that use information retrieval, NLP and text-mining techniques to identify biomedical concepts and relations within scientific publications or their sentences. These approaches have not typically addressed the challenge of extracting more complex knowledge such as biomedical definitions. In our efforts to facilitate knowledge acquisition of rule-based definitions of autism phenotypes, we have developed a novel semantic-based t...

Exploring Sex Differences in Autistic Traits: A Factor Analytic Study of Adults with Autism

Science.gov (United States)

Grove, Rachel; Hoekstra, Rosa A.; Wierda, Marlies; Begeer, Sander

2017-01-01

Research has highlighted potential differences in the phenotypic and clinical presentation of autism spectrum conditions across sex. Furthermore, the measures utilised to evaluate autism spectrum conditions may be biased towards the male autism phenotype. It is important to determine whether these instruments measure the autism phenotype…

Family function, Parenting Style and Broader Autism Phenotype as Predicting Factors of Psychological Adjustment in Typically Developing Siblings of Children with Autism Spectrum Disorders.

Science.gov (United States)

Mohammadi, Mohammadreza; Zarafshan, Hadi

2014-04-01

Siblings of children with autism are at a greater risk of experiencing behavioral and social problems. Previous researches had focused on environmental variables such as family history of autism spectrum disorders (ASDs), behavior problems in the child with an ASD, parental mental health problems, stressful life events and "broader autism phenotype" (BAP), while variables like parenting style and family function that are shown to influence children's behavioral and psychosocial adjustment are overlooked. The aim of the present study was to reveal how parenting style and family function as well as BAP effect psychological adjustment of siblings of children with autism. The Participants included 65 parents who had one child with an Autism Spectrum Disorder and one typically developing child. Of the children with ASDs, 40 were boys and 25 were girls; and they were diagnosed with ASDs by a psychiatrist based on DSM-IV-TR criteria and Autism Diagnostic Interview-Revised (ADI-R). The Persian versions of the six scales were used to collect data from the families. Pearson's correlation test and regression analysis were used to determine which variables were related to the psychological adjustment of sibling of children with ASDs and which variables predicted it better. Significant relationships were found between Strengths and Difficulties Questionnaire (SDQ) total difficulties, prosocial behaviors and ASDs symptoms severity, parenting styles and some aspects of family function. In addition, siblings who had more BAP characteristics had more behavior problems and less prosocial behavior. Behavioral problems increased and prosocial behavior decreased with permissive parenting style. Besides, both of authoritarian and authoritative parenting styles led to a decrease in behavioral problems and an increase in prosocial behaviors. Our findings revealed that some aspects of family function (affective responsiveness, roles, problem solving and behavior control) were significantly

The Association between Epilepsy and Autism Symptoms and Maladaptive Behaviors in Children with Autism Spectrum Disorder

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Viscidi, Emma W.; Johnson, Ashley L.; Spence, Sarah J.; Buka, Stephen L.; Morrow, Eric M.; Triche, Elizabeth W.

2014-01-01

Epilepsy is common in children with autism spectrum disorder (ASD) but little is known about how seizures impact the autism phenotype. The association between epilepsy and autism symptoms and associated maladaptive behaviors was examined in 2,645 children with ASD, of whom 139 had epilepsy, from the Simons Simplex Collection. Children with ASD and…

Identifying Neurobiological Markers of the Broader Autism Phenotype

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2015-01-01

others: mirror neuron dysfuntion in children with autism spectrum disorders. Nautre Neuroscience, 9(1), 28-30. Eippert, F., Veit, R., Weiskopf...2251-2254. Gallese, V. (2007). Before and below ’ theory of mind ’: embodied simulation and the neural correlates of social cognition...2007). The Simulating Social Mind : The Role of the Mirror Neuron System and Simulation in the Social and Communicative Deficits of Autism Spectrum

Family function, Parenting Style and Broader Autism Phenotype as Predicting Factors of Psychological Adjustment in Typically Developing Siblings of Children with Autism Spectrum Disorders.

Directory of Open Access Journals (Sweden)

Mohammadreza Mohammadi

2014-06-01

Full Text Available Siblings of children with autism are at a greater risk of experiencing behavioral and social problems. Previous researches had focused on environmental variables such as family history of autism spectrum disorders (ASDs, behavior problems in the child with an ASD, parental mental health problems, stressful life events and "broader autism phenotype" (BAP, while variables like parenting style and family function that are shown to influence children's behavioral and psychosocial adjustment are overlooked. The aim of the present study was to reveal how parenting style and family function as well as BAP effect psychological adjustment of siblings of children with autism.The Participants included 65 parents who had one child with an Autism Spectrum Disorder and one typically developing child. Of the children with ASDs, 40 were boys and 25 were girls; and they were diagnosed with ASDs by a psychiatrist based on DSM-IV-TR criteria and Autism Diagnostic Interview-Revised (ADI-R. The Persian versions of the six scales were used to collect data from the families. Pearson's correlation test and regression analysis were used to determine which variables were related to the psychological adjustment of sibling of children with ASDs and which variables predicted it better.Significant relationships were found between Strengths and Difficulties Questionnaire (SDQ total difficulties, prosocial behaviors and ASDs symptoms severity, parenting styles and some aspects of family function. In addition, siblings who had more BAP characteristics had more behavior problems and less prosocial behavior. Behavioral problems increased and prosocial behavior decreased with permissive parenting style. Besides, both of authoritarian and authoritative parenting styles led to a decrease in behavioral problems and an increase in prosocial behaviors. Our findings revealed that some aspects of family function (affective responsiveness, roles, problem solving and behavior control were

Mood Disorders in Mothers of Children on the Autism Spectrum Are Associated with Higher Functioning Autism

OpenAIRE

Vasa, Roma A.; Anderson, Connie; Marvin, Alison R.; Rosenberg, Rebecca E.; Law, J. Kiely; Thorn, Julia; Sarphare, Geeta; Law, Paul A.

2012-01-01

Mood disorders occur more frequently in family members of individuals with autism spectrum disorders (ASD) than in the general population. There may be associations between maternal mood disorder history patterns and specific ASD phenotypes. We therefore examined the relationship between maternal mood disorders and child autism spectrum disorders in 998 mother-child dyads enrolled in a national online autism registry and database. Mothers of children with ASD completed online questionnaires a...

New Interview and Observation Measures of the Broader Autism Phenotype: Description of Strategy and Reliability Findings for the Interview Measures.

Science.gov (United States)

Parr, Jeremy R; De Jonge, Maretha V; Wallace, Simon; Pickles, Andrew; Rutter, Michael L; Le Couteur, Ann S; van Engeland, Herman; Wittemeyer, Kerstin; McConachie, Helen; Roge, Bernadette; Mantoulan, Carine; Pedersen, Lennart; Isager, Torben; Poustka, Fritz; Bolte, Sven; Bolton, Patrick; Weisblatt, Emma; Green, Jonathan; Papanikolaou, Katerina; Baird, Gillian; Bailey, Anthony J

2015-10-01

Clinical genetic studies confirm the broader autism phenotype (BAP) in some relatives of individuals with autism, but there are few standardized assessment measures. We developed three BAP measures (informant interview, self-report interview, and impression of interviewee observational scale) and describe the development strategy and findings from the interviews. International Molecular Genetic Study of Autism Consortium data were collected from families containing at least two individuals with autism. Comparison of the informant and self-report interviews was restricted to samples in which the interviews were undertaken by different researchers from that site (251 UK informants, 119 from the Netherlands). Researchers produced vignettes that were rated blind by others. Retest reliability was assessed in 45 participants. Agreement between live scoring and vignette ratings was very high. Retest stability for the interviews was high. Factor analysis indicated a first factor comprising social-communication items and rigidity (but not other repetitive domain items), and a second factor comprised mainly of reading and spelling impairments. Whole scale Cronbach's alphas were high for both interviews. The correlation between interviews for factor 1 was moderate (adult items 0.50; childhood items 0.43); Kappa values for between-interview agreement on individual items were mainly low. The correlations between individual items and total score were moderate. The inclusion of several factor 2 items lowered the overall Cronbach's alpha for the total set. Both interview measures showed good reliability and substantial stability over time, but the findings were better for factor 1 than factor 2. We recommend factor 1 scores be used for characterising the BAP. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.

Genetic basis of autism: is there a way forward?

Science.gov (United States)

Eapen, Valsamma

2011-05-01

This paper outlines some of the key findings from genetic research carried out in the last 12-18 months, which indicate that autism spectrum disorder (ASD) is a complex disorder involving interactions between genetic, epigenetic and environmental factors. The current literature highlights the presence of genetic and phenotypic heterogeneity in ASD with a number of underlying pathogenetic mechanisms. In this regard, there are at least three phenotypic presentations with distinct genetic underpinnings: autism plus phenotype characterized by syndromic ASD caused by rare, single-gene disorders; broad autism phenotype caused by genetic variations in single or multiple genes, each of these variations being common and distributed continually in the general population, but resulting in varying clinical phenotypes when it reaches a certain threshold through complex gene-gene and gene-environment interactions; and severe and specific phenotype caused by 'de-novo' mutations in the patient or transmitted through asymptomatic carriers of such mutation. Understanding the neurobiological processes by which genotypes become phenotypes, along with the advances in developmental neuroscience and neuronal networks at the cellular and molecular level, is paving the way for translational research involving targeted interventions of affected molecular pathways and early intervention programs that promote normal brain responses to stimuli and alter the developmental trajectory.

Is synaesthesia more common in autism?

OpenAIRE

Baron-Cohen, Simon; Johnson, Donielle; Asher, Julian; Wheelwright, Sally; Fisher, Simon E; Gregersen, Peter K; Allison, Carrie

2013-01-01

Background Synaesthesia is a neurodevelopmental condition in which a sensation in one modality triggers a perception in a second modality. Autism (shorthand for Autism Spectrum Conditions) is a neurodevelopmental condition involving social-communication disability alongside resistance to change and unusually narrow interests or activities. Whilst on the surface they appear distinct, they have been suggested to share common atypical neural connectivity. Methods In the present study, we carried...

Social Communication and Theory of Mind in Boys with Autism and Fragile X Syndrome

Directory of Open Access Journals (Sweden)

Molly eLosh

2012-08-01

Full Text Available Impairments in the social use of language, or pragmatics, constitute a core characteristic of autism. Problems with pragmatic language have also been documented in fragile X syndrome, a monogenic condition that is the most common known genetic cause of autism. Evidence suggests that social cognitive ability, or theory of mind, may also be impaired in both conditions, and in autism, may importantly relate to pragmatic language ability. Given the substantial overlap observed in autism and FXS, this study aimed to better define those social-communicative phenotypes that overlap in these two conditions by comparing pragmatic language ability and theory of mind in children with idiopathic autism and children with FXS, with and without autism, as well as children with Down syndrome and typically developing controls. We further examined correlations between these cognitive-behavioral phenotypes and molecular genetic variation related to FMR1 in the FXS group. Results indicated that children with idiopathic autism and those with FXS and autism performed comparably on direct-assessment measures of pragmatic language and theory of mind, whereas those with FXS only did not differ from controls. Theory of mind was related to pragmatic language ability in all groups. Pragmatic language and theory of mind also correlated with genetic variation at the FMR1 locus (CGG repeats and percent methylation. These results point towards substantial overlap in the social and language phenotypes in autism and FXS and suggest a molecular genetic basis to these phenotypic profiles.

Recent Research on the Etiologies of Autism.

Science.gov (United States)

Fisher, Eileen; Van Dyke, Don C.; Sears, Lonnie; Matzen, Jane; Lin-Dyken, Deborah; McBrien, Dianne M.

1999-01-01

Reviews recent research on the etiologies of autism, including genetic research, anatomic and neuroimaging studies, topics in neurophysiology research (including serotonin, dopamine, and opiods), immunologic research, studies of autism phenotype, and electroencephalographic studies. It concludes that, as of yet, research has found no clear…

Autism Spectrum Disorders Associated with Chromosomal Abnormalities

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Lo-Castro, Adriana; Benvenuto, Arianna; Galasso, Cinzia; Porfirio, Cristina; Curatolo, Paolo

2010-01-01

Autism spectrum disorders (ASDs) constitute a class of severe neurodevelopmental conditions with complex multifactorial and heterogeneous etiology. Despite high estimates of heritability, genetic causes of ASDs remain elusive, due to a high degree of genetic and phenotypic heterogeneity. So far, several "monogenic" forms of autism have been…

Autism spectrum disorder profile in neurofibromatosis type I.

Science.gov (United States)

Garg, Shruti; Plasschaert, Ellen; Descheemaeker, Mie-Jef; Huson, Susan; Borghgraef, Martine; Vogels, Annick; Evans, D Gareth; Legius, Eric; Green, Jonathan

2015-06-01

Neurofibromatosis Type 1 (NF1) is a common autosomal dominant single-gene disorder, in which the co-occurrence of autism spectrum disorder (ASD) has attracted considerable research interest recently with prevalence estimates of 21-40%. However, detailed characterization of the ASD behavioral phenotype in NF1 is still lacking. This study characterized the phenotypic profile of ASD symptomatology presenting in 4-16 year old children with NF1 (n = 36) using evidence from parent-rated Social Responsiveness Scale and researcher autism diagnostic observation Scale-2. Compared to IQ-matched reference groups of children with autism and ASD, the NF1 profile shows overall similarity but improved eye contact, less repetitive behaviors and better language skills.

The International Collaboration for Autism Registry Epidemiology (iCARE): Multinational Registry-Based Investigations of Autism Risk Factors and Trends

Science.gov (United States)

Schendel, Diana E.; Bresnahan, Michaeline; Carter, Kim W.; Francis, Richard W.; Gissler, Mika; Grønborg, Therese K.; Gross, Raz; Gunnes, Nina; Hornig, Mady; Hultman, Christina M.; Langridge, Amanda; Lauritsen, Marlene B.; Leonard, Helen; Parner, Erik T.; Reichenberg, Abraham; Sandin, Sven; Sourander, Andre; Stoltenberg, Camilla; Suominen, Auli; Surén, Pål; Susser, Ezra

2013-01-01

The International Collaboration for Autism Registry Epidemiology (iCARE) is the first multinational research consortium (Australia, Denmark, Finland, Israel, Norway, Sweden, USA) to promote research in autism geographical and temporal heterogeneity, phenotype, family and life course patterns, and etiology. iCARE devised solutions to challenges in…

Phenotypic continuum between autism and schizophrenia: Evidence from the Movie for the Assessment of Social Cognition (MASC).

Science.gov (United States)

Martinez, Gilles; Alexandre, Charlotte; Mam-Lam-Fook, Célia; Bendjemaa, Narjes; Gaillard, Raphaël; Garel, Patricia; Dziobek, Isabel; Amado, Isabelle; Krebs, Marie-Odile

2017-07-01

Schizophrenic (SCZ) and autism (ASD) spectrum disorders share several features including social cognition impairments. In SCZ, the link between symptomatic dimensions and social cognition deficits remains unclear. The Movie for the Assessment of Social Cognition (MASC) test, available in several languages including English, investigates mental state attribution capabilities in complex interpersonal situations. After its translation into French, we used MASC to direct compare social cognition in 36 young participants with SCZ to 19 with ASD and 20 healthy controls (HC) matched for gender, age (18-25y.o.) and level of education. The MASC discriminated each group from the others, patients with SCZ exhibiting difficulties compared to ASD (MASC total score 28.1 (4) and 24.2 (6.6), respectively; pautism quotient, and with disorganization symptoms. Finally, in SCZ, over-mentalizing difficulties were correlated with age at disease onset. Our results demonstrate the validity of the French version of the MASC and bring direct evidence supporting the hypothesis of a phenotypic continuum between autism and schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

Social Communication and Theory of Mind in Boys with Autism and Fragile X Syndrome

Science.gov (United States)

Losh, Molly; Martin, Gary E.; Klusek, Jessica; Hogan-Brown, Abigail L.; Sideris, John

2012-01-01

Impairments in the social use of language, or pragmatics, constitute a core characteristic of autism. Problems with pragmatic language have also been documented in fragile X syndrome (FXS), a monogenic condition that is the most common known genetic cause of autism. Evidence suggests that social cognitive ability, or theory of mind, may also be impaired in both conditions, and in autism, may importantly relate to pragmatic language ability. Given the substantial overlap observed in autism and FXS, this study aimed to better define those social-communicative phenotypes that overlap in these two conditions by comparing pragmatic language ability and theory of mind in children with idiopathic autism and children with FXS, with and without autism, as well as children with Down syndrome and typically developing controls. We further examined correlations between these cognitive-behavioral phenotypes and molecular genetic variation related to the Fragile X Mental Retardation-1 gene (FMR1) in the FXS group. Results indicated that children with idiopathic autism and those with FXS and autism performed comparably on direct-assessment measures of pragmatic language and theory of mind, whereas those with FXS only did not differ from controls. Theory of mind was related to pragmatic language ability in all groups. Pragmatic language and theory of mind also correlated with genetic variation at the FMR1 locus (Cytosine-Guanine-Guanine repeats and percent methylation). These results point toward substantial overlap in the social and language phenotypes in autism and FXS and suggest a molecular genetic basis to these phenotypic profiles. PMID:22934085

Social communication and theory of mind in boys with autism and fragile x syndrome.

Science.gov (United States)

Losh, Molly; Martin, Gary E; Klusek, Jessica; Hogan-Brown, Abigail L; Sideris, John

2012-01-01

Impairments in the social use of language, or pragmatics, constitute a core characteristic of autism. Problems with pragmatic language have also been documented in fragile X syndrome (FXS), a monogenic condition that is the most common known genetic cause of autism. Evidence suggests that social cognitive ability, or theory of mind, may also be impaired in both conditions, and in autism, may importantly relate to pragmatic language ability. Given the substantial overlap observed in autism and FXS, this study aimed to better define those social-communicative phenotypes that overlap in these two conditions by comparing pragmatic language ability and theory of mind in children with idiopathic autism and children with FXS, with and without autism, as well as children with Down syndrome and typically developing controls. We further examined correlations between these cognitive-behavioral phenotypes and molecular genetic variation related to the Fragile X Mental Retardation-1 gene (FMR1) in the FXS group. Results indicated that children with idiopathic autism and those with FXS and autism performed comparably on direct-assessment measures of pragmatic language and theory of mind, whereas those with FXS only did not differ from controls. Theory of mind was related to pragmatic language ability in all groups. Pragmatic language and theory of mind also correlated with genetic variation at the FMR1 locus (Cytosine-Guanine-Guanine repeats and percent methylation). These results point toward substantial overlap in the social and language phenotypes in autism and FXS and suggest a molecular genetic basis to these phenotypic profiles.

Hedonic capacity in the broader autism phenotype: Should social anhedonia be considered a characteristic feature?

Directory of Open Access Journals (Sweden)

Derek eNovacek

2016-05-01

Full Text Available Impairments in social motivational processes may partially explain the differences in social interaction seen among individuals with autism spectrum disorder (ASD. The social motivation hypothesis would predict an association between reduced hedonic capacity and ASD. However, to date, findings have been mixed regarding hedonic deficits among individuals with ASD; adults report lower levels of both social and physical pleasure whereas adolescents only report experiencing lower social pleasure. Moreover, previous studies examining the association between anhedonia and autistic traits have not used measures of hedonic response or taken temporal aspects of pleasure into account. The present study examined associations between autistic traits and the experience of pleasure using a nonclinical sample of young adults to further clarify the nature of hedonic deficits in the broader autism phenotype (BAP. Results revealed that autistic traits were negatively associated with both the experience of social pleasure as well as general pleasure, although the association was stronger for social pleasure. Regression analyses revealed that reduced social pleasure was a better predictor of autistic traits than general pleasure. Together these findings suggest that reduced social hedonic capacity is associated with autistic traits in the general population and should be included in conceptualizations of the BAP.

Autism.

Science.gov (United States)

Levy, Susan E; Mandell, David S; Schultz, Robert T

2009-11-07

Autism spectrum disorders are characterised by severe deficits in socialisation, communication, and repetitive or unusual behaviours. Increases over time in the frequency of these disorders (to present rates of about 60 cases per 10,000 children) might be attributable to factors such as new administrative classifications, policy and practice changes, and increased awareness. Surveillance and screening strategies for early identification could enable early treatment and improved outcomes. Autism spectrum disorders are highly genetic and multifactorial, with many risk factors acting together. Genes that affect synaptic maturation are implicated, resulting in neurobiological theories focusing on connectivity and neural effects of gene expression. Several treatments might address core and comorbid symptoms. However, not all treatments have been adequately studied. Improved strategies for early identification with phenotypic characteristics and biological markers (eg, electrophysiological changes) might hopefully improve effectiveness of treatment. Further knowledge about early identification, neurobiology of autism, effective treatments, and the effect of this disorder on families is needed.

Mood Disorders in Mothers of Children on the Autism Spectrum Are Associated with Higher Functioning Autism

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Roma A. Vasa

2012-01-01

Full Text Available Mood disorders occur more frequently in family members of individuals with autism spectrum disorders (ASD than in the general population. There may be associations between maternal mood disorder history patterns and specific ASD phenotypes. We therefore examined the relationship between maternal mood disorders and child autism spectrum disorders in 998 mother-child dyads enrolled in a national online autism registry and database. Mothers of children with ASD completed online questionnaires addressing their child’s ASD as well as their own mood disorder history. In multivariate logistic regression models of ASD diagnoses, the odds of an Asperger disorder versus autistic disorder diagnosis were higher among those children whose mothers had a lifetime history of bipolar disorder (OR 2.11, CI 1.20, 3.69 or depression (OR 1.62, CI 1.19, 2.19. Further, maternal mood disorder onset before first pregnancy was associated with higher odds (OR 2.35, CI 1.48, 3.73 of an Asperger versus autism diagnosis among this sample of children with ASD. These data suggest that differences in maternal mood disorder history may be associated with ASD phenotype in offspring.

The Autism Mental Status Exam: Sensitivity and Specificity Using DSM-5 Criteria for Autism Spectrum Disorder in Verbally Fluent Adults

Science.gov (United States)

Grodberg, David; Weinger, Paige M.; Halpern, Danielle; Parides, Michael; Kolevzon, Alexander; Buxbaum, Joseph D.

2014-01-01

The phenotypic heterogeneity of adults suspected of autism spectrum disorder (ASD) requires a standardized diagnostic approach that is feasible in all clinical settings. The autism mental status exam (AMSE) is an eight-item observational assessment that structures the observation and documentation of social, communicative and behavioral signs and…

Investigating the cross-cultural validity of DSM-5 autism spectrum disorder: evidence from Finnish and UK samples.

Science.gov (United States)

Mandy, William; Charman, Tony; Puura, Kaija; Skuse, David

2014-01-01

The recent Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) reformulation of autism spectrum disorder has received empirical support from North American and UK samples. Autism spectrum disorder is an increasingly global diagnosis, and research is needed to discover how well it generalises beyond North America and the United Kingdom. We tested the applicability of the DSM-5 model to a sample of Finnish young people with autism spectrum disorder (n = 130) or the broader autism phenotype (n = 110). Confirmatory factor analysis tested the DSM-5 model in Finland and compared the fit of this model between Finnish and UK participants (autism spectrum disorder, n = 488; broader autism phenotype, n = 220). In both countries, autistic symptoms were measured using the Developmental, Diagnostic and Dimensional Interview. Replicating findings from English-speaking samples, the DSM-5 model fitted well in Finnish autism spectrum disorder participants, outperforming a Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) model. The DSM-5 model fitted equally well in Finnish and UK autism spectrum disorder samples. Among broader autism phenotype participants, this model fitted well in the United Kingdom but poorly in Finland, suggesting that cross-cultural variability may be greatest for milder autistic characteristics. We encourage researchers with data from other cultures to emulate our methodological approach, to map any cultural variability in the manifestation of autism spectrum disorder and the broader autism phenotype. This would be especially valuable given the ongoing revision of the International Classification of Diseases-11th Edition, the most global of the diagnostic manuals.

Phenotypic expression of autoimmune autistic disorder (AAD): a major subset of autism.

Science.gov (United States)

Singh, Vijendra K

2009-01-01

Autism causes incapacitating neurologic problems in children that last a lifetime. The author of this article previously hypothesized that autism may be caused by autoimmunity to the brain, possibly triggered by a viral infection. This article is a summary of laboratory findings to date plus new data in support of an autoimmune pathogenesis for autism. Autoimmune markers were analyzed in the sera of autistic and normal children, but the cerebrospinal fluid (CSF) of some autistic children was also analyzed. Laboratory procedures included enzyme-linked immunosorbent assay and protein immunoblotting assay. Autoimmunity was demonstrated by the presence of brain autoantibodies, abnormal viral serology, brain and viral antibodies in CSF, a positive correlation between brain autoantibodies and viral serology, elevated levels of proinflammatory cytokines and acute-phase reactants, and a positive response to immunotherapy. Many autistic children harbored brain myelin basic protein autoantibodies and elevated levels of antibodies to measles virus and measles-mumps-rubella (MMR) vaccine. Measles might be etiologically linked to autism because measles and MMR antibodies (a viral marker) correlated positively to brain autoantibodies (an autoimmune marker)--salient features that characterize autoimmune pathology in autism. Autistic children also showed elevated levels of acute-phase reactants--a marker of systemic inflammation. The scientific evidence is quite credible for our autoimmune hypothesis, leading to the identification of autoimmune autistic disorder (AAD) as a major subset of autism. AAD can be identified by immune tests to determine immune problems before administering immunotherapy. The author has advanced a speculative neuroautoimmune (NAI) model for autism, in which virus-induced autoimmunity is a key player. The latter should be targeted by immunotherapy to help children with autism.

Outcomes in Adult Life among Siblings of Individuals with Autism

Science.gov (United States)

Howlin, Patricia; Moss, Philippa; Savage, Sarah; Bolton, Patrick; Rutter, Michael

2015-01-01

Little is known about adult siblings of individuals with autism. We report on cognitive, social and mental health outcomes in 87 adult siblings (mean age 39 years). When younger all had been assessed either as being "unaffected" by autism (n = 69) or as meeting criteria for the "Broader Autism Phenotype" (BAP, n = 18). As…

The Broad Autism (EndoPhenotype: Neurostructural And Neurofunctional Correlates In Parents Of Individuals With Autism Spectrum Disorders

Directory of Open Access Journals (Sweden)

Lucia Billeci

2016-07-01

Full Text Available Autism Spectrum Disorders (ASD are a set of neurodevelopmental disorders with an early-onset and a strong genetic component in their pathogenesis. According to genetic and epidemiological data, ASD relatives present personality traits similar to, but not as severe as the defining features of ASD, which have been indicated as the Broader Autism Phenotype (BAP. BAP features seem to be more prevalent in first-degree relatives of individuals with ASD than in the general population. Characterizing brain profiles of relatives of autistic probands may help to understand ASD endophenotype. The aim of this review was to provide an up-to-date overview of research findings on the neurostructural and neurofunctional substrates in parents of individuals with ASD (pASD. The primary hypothesis was that, like for the behavioral profile, the pASD express an intermediate neurobiological pattern between ASD individuals and healthy controls.The 13 reviewed studies evaluated structural magnetic resonance imaging (MRI brain volumes, chemical signals using magnetic resonance spectroscopy (MRS, task-related functional activation by functional magnetic resonance imaging (fMRI, electroencephalography (EEG, or magnetoencephalography (MEG in pASD. The studies showed that pASD are generally different from healthy controls at a structural and functional level despite often not behaviorally impaired. More atypicalities in neural patterns of pASD seem to be associated with higher scores at BAP assessment. Some of the observed atypicalities are the same of the ASD probands. In addition, the pattern of neural correlates in pASD resembles that of adult individuals with ASD, or it is specific, possibly due to a compensatory mechanism are the same as those detected in ASD subjects. Future studies should ideally include a group of pASD and HC with their ASD and non-ASD probands respectively. They should subgrouping the pASD according to the BAP scores, considering gender as a

The transgenerational inheritance of autism-like phenotypes in mice exposed to valproic acid during pregnancy.

Science.gov (United States)

Choi, Chang Soon; Gonzales, Edson Luck; Kim, Ki Chan; Yang, Sung Min; Kim, Ji-Woon; Mabunga, Darine Froy; Cheong, Jae Hoon; Han, Seol-Heui; Bahn, Geon Ho; Shin, Chan Young

2016-11-07

Autism spectrum disorder (ASD) is a heterogeneously pervasive developmental disorder in which various genetic and environmental factors are believed to underlie its development. Recently, epigenetics has been suggested as a novel concept for ASD aetiology with a proposition that epigenetic marks can be transgenerationally inherited. Based on this assumption of epigenetics, we investigated the transgenerational inheritance of ASD-like behaviours and their related synaptic changes in the VPA animal model of ASD. The first generation (F1) VPA-exposed offspring exhibited autistic-like impaired sociability and increased marble burying. They also showed increased seizure susceptibility, hyperactivity and decreased anxiety. We mated the VPA-exposed F1 male offspring with naïve females to produce the second generation (F2), and then similarly mated the F2 to deliver the third generation (F3). Remarkably, the autism-like behavioural phenotypes found in F1 persisted to the F2 and F3. Additionally, the frontal cortices of F1 and F3 showed some imbalanced expressions of excitatory/inhibitory synaptic markers, suggesting a transgenerational epigenetic inheritance. These results open the idea that E/I imbalance and ASD-like behavioural changes induced by environmental insults in mice can be epigenetically transmitted, at least, to the third generation. This study could help explain the unprecedented increase in ASD prevalence.

Identification of chromosome 7 inversion breakpoints in an autistic family narrows candidate region for autism susceptibility.

Science.gov (United States)

Cukier, Holly N; Skaar, David A; Rayner-Evans, Melissa Y; Konidari, Ioanna; Whitehead, Patrice L; Jaworski, James M; Cuccaro, Michael L; Pericak-Vance, Margaret A; Gilbert, John R

2009-10-01

Chromosomal breaks and rearrangements have been observed in conjunction with autism and autistic spectrum disorders. A chromosomal inversion has been previously reported in autistic siblings, spanning the region from approximately 7q22.1 to 7q31. This family is distinguished by having multiple individuals with autism and associated disabilities. The region containing the inversion has been strongly implicated in autism by multiple linkage studies, and has been particularly associated with language defects in autism as well as in other disorders with language components. Mapping of the inversion breakpoints by FISH has localized the inversion to the region spanning approximately 99-108.75 Mb of chromosome 7. The proximal breakpoint has the potential to disrupt either the coding sequence or regulatory regions of a number of cytochrome P450 genes while the distal region falls in a relative gene desert. Copy number variant analysis of the breakpoint regions detected no duplication or deletion that could clearly be associated with disease status. Association analysis in our autism data set using single nucleotide polymorphisms located near the breakpoints showed no significant association with proximal breakpoint markers, but has identified markers near the distal breakpoint ( approximately 108-110 Mb) with significant associations to autism. The chromosomal abnormality in this family strengthens the case for an autism susceptibility gene in the chromosome 7q22-31 region and targets a candidate region for further investigation.

From Asperger's Autistischen Psychopathen to DSM-5 Autism Spectrum Disorder and Beyond: A Subthreshold Autism Spectrum Model.

Science.gov (United States)

Dell'Osso, Liliana; Luche, Riccardo Dalle; Gesi, Camilla; Moroni, Ilenia; Carmassi, Claudia; Maj, Mario

2016-01-01

Growing interest has recently been devoted to partial forms of autism, lying at the diagnostic boundaries of those conditions previously diagnosed as Asperger's Disorder. This latter includes an important retrieval of the European classical psychopathological concepts of adult autism to which Hans Asperger referred in his work. Based on the review of Asperger's Autistische Psychopathie , from first descriptions through the DSM-IV Asperger's Disorder and up to the recent DSM-5 Autism Spectrum Disorder, the paper aims to propose a Subthreshold Autism Spectrum Model that encompasses not only threshold-level manifestations but also mild/atypical symptoms, gender-specific features, behavioral manifestations and personality traits associated with Autism Spectrum Disorder. This model includes, but is not limited to, the so-called broad autism phenotype spanning across the general population that does not fully meet Autism Spectrum Disorder criteria. From this perspective, we propose a subthreshold autism as a unique psychological/behavioral model for research that could help to understand the neurodevelopmental trajectories leading from autistic traits to a broad range of mental disorders.

The Biolinguistics of Autism: Emergent Perspectives

OpenAIRE

Nicolas J. Bourguignon; Aparna Nadig; Daniel Valois

2012-01-01

This contribution attempts to import the study of autism into the biolinguistics program by reviewing the current state of knowledge on its neurobiology, physiology and verbal phenotypes from a comparative vantage point. A closer look at alternative approaches to the primacy of social cognition impairments in autism spectrum disorders suggests fundamental differences in every aspect of language comprehension and production, suggesting productive directions of research in auditory and visual s...

A semantic-based method for extracting concept definitions from scientific publications: evaluation in the autism phenotype domain.

Science.gov (United States)

Hassanpour, Saeed; O'Connor, Martin J; Das, Amar K

2013-08-12

A variety of informatics approaches have been developed that use information retrieval, NLP and text-mining techniques to identify biomedical concepts and relations within scientific publications or their sentences. These approaches have not typically addressed the challenge of extracting more complex knowledge such as biomedical definitions. In our efforts to facilitate knowledge acquisition of rule-based definitions of autism phenotypes, we have developed a novel semantic-based text-mining approach that can automatically identify such definitions within text. Using an existing knowledge base of 156 autism phenotype definitions and an annotated corpus of 26 source articles containing such definitions, we evaluated and compared the average rank of correctly identified rule definition or corresponding rule template using both our semantic-based approach and a standard term-based approach. We examined three separate scenarios: (1) the snippet of text contained a definition already in the knowledge base; (2) the snippet contained an alternative definition for a concept in the knowledge base; and (3) the snippet contained a definition not in the knowledge base. Our semantic-based approach had a higher average rank than the term-based approach for each of the three scenarios (scenario 1: 3.8 vs. 5.0; scenario 2: 2.8 vs. 4.9; and scenario 3: 4.5 vs. 6.2), with each comparison significant at the p-value of 0.05 using the Wilcoxon signed-rank test. Our work shows that leveraging existing domain knowledge in the information extraction of biomedical definitions significantly improves the correct identification of such knowledge within sentences. Our method can thus help researchers rapidly acquire knowledge about biomedical definitions that are specified and evolving within an ever-growing corpus of scientific publications.

Communication problems in children with autism and intellectual disability : depicting the phenotype

NARCIS (Netherlands)

Maljaars, Janne Pieternella Wilhelmina

2012-01-01

Children with autism and intellectual disability form a particularly vulnerable group, as both disorders have a significant impact on the way and level of information processing and communication. However, children with autism and co-occurring intellectual disability are often excluded from

Re-examining the cognitive phenotype in autism: a study with young Chinese children.

Science.gov (United States)

Lam, Yan Grace

2013-12-01

Deficits consistently found in autism include an impaired "theory of mind", weak central coherence, and deficits in executive function. The current study examined whether this traditional cluster of symptoms existed in a group of Chinese-speaking children with autism. Sixteen high-functioning, non-retarded children with autism were matched to 16 typically developing (TD) children on gender, non-verbal IQ and age. Non-verbal IQ's of all participants were measured using the Raven Progressive Matrices. Each participant was tested individually on measures of "theory of mind", central coherence and executive function. Results indicated that most, but not all, participants with autism performed significantly poorer on two standard measures of first-order "theory of mind," although there was no significant difference on two other measures of that domain. As expected, they performed significantly worse on executive function tasks. However, the hypothesis of weak central coherence in autism was not substantiated. There was no evidence that these three cognitive impairments co-existed in individuals with autism. More likely, each of these deficits appears singly or in pair instead of forming a cluster. Copyright © 2013 Elsevier Ltd. All rights reserved.

Redox Abnormalities as a Vulnerability Phenotype for Autism and Related Alternations in CNS Development

Science.gov (United States)

2009-10-01

2004. MECP2 structural and 3’-UTR variants in schizophrenia , autism and other psychiatric diseases: a possible association with autism. Am J Med...inhibition, thus potentially enabling enhancement of remyelination. Role: PI Award letter dated 12/11/06 Noble (PI) Cure Autism Now Foundation 02/05

The valproic acid-induced rodent model of autism.

Science.gov (United States)

Nicolini, Chiara; Fahnestock, Margaret

2018-01-01

Autism is a lifelong neurodevelopmental disorder characterized by impairments in social communication and interaction and by repetitive patterns of behavior, interests and activities. While autism has a strong genetic component, environmental factors including toxins, pesticides, infection and drugs are known to confer autism susceptibility, likely by inducing epigenetic changes. In particular, exposure to valproic acid (VPA) during pregnancy has been demonstrated to increase the risk of autism in children. Furthermore, rodents prenatally exposed to this drug display behavioral phenotypes characteristics of the human condition. Indeed, in utero exposure of rodents to VPA represents a robust model of autism exhibiting face, construct and predictive validity. This model might better represent the many cases of idiopathic autism which are of environmental/epigenetic origins than do transgenic models carrying mutations in single autism-associated genes. The VPA model provides a valuable tool to investigate the neurobiology underlying autistic behavior and to screen for novel therapeutics. Here we review the VPA-induced rodent model of autism, highlighting its importance and reliability as an environmentally-induced animal model of autism. Copyright © 2017 Elsevier Inc. All rights reserved.

The Broad Autism (Endo)Phenotype: Neurostructural and Neurofunctional Correlates in Parents of Individuals with Autism Spectrum Disorders

OpenAIRE

Billeci, Lucia; Calderoni, Sara; Conti, Eugenia; Gesi, Camilla; Carmassi, Claudia; Dell'Osso, Liliana; Cioni, Giovanni; Muratori, Filippo; Guzzetta, Andrea

2016-01-01

Autism Spectrum Disorders (ASD) are a set of neurodevelopmental disorders with an early-onset and a strong genetic component in their pathogenesis. According to genetic and epidemiological data, ASD relatives present personality traits similar to, but not as severe as the defining features of ASD, which have been indicated as the “Broader Autism Phenotype” (BAP). BAP features seem to be more prevalent in first-degree relatives of individuals with ASD than in the general population. Characteri...

Autistic disorder in patients with Williams-Beuren syndrome: a reconsideration of the Williams-Beuren syndrome phenotype.

Science.gov (United States)

Tordjman, Sylvie; Anderson, George M; Botbol, Michel; Toutain, Annick; Sarda, Pierre; Carlier, Michèle; Saugier-Veber, Pascale; Baumann, Clarisse; Cohen, David; Lagneaux, Céline; Tabet, Anne-Claude; Verloes, Alain

2012-01-01

Williams-Beuren syndrome (WBS), a rare developmental disorder caused by deletion of contiguous genes at 7q11.23, has been characterized by strengths in socialization (overfriendliness) and communication (excessive talkativeness). WBS has been often considered as the polar opposite behavioral phenotype to autism. Our objective was to better understand the range of phenotypic expression in WBS and the relationship between WBS and autistic disorder. The study was conducted on 9 French individuals aged from 4 to 37 years old with autistic disorder associated with WBS. Behavioral assessments were performed using Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) scales. Molecular characterization of the WBS critical region was performed by FISH. FISH analysis indicated that all 9 patients displayed the common WBS deletion. All 9 patients met ADI-R and ADOS diagnostic criteria for autism, displaying stereotypies and severe impairments in social interaction and communication (including the absence of expressive language). Additionally, patients showed improvement in social communication over time. The results indicate that comorbid autism and WBS is more frequent than expected and suggest that the common WBS deletion can result in a continuum of social communication impairment, ranging from excessive talkativeness and overfriendliness to absence of verbal language and poor social relationships. Appreciation of the possible co-occurrence of WBS and autism challenges the common view that WBS represents the opposite behavioral phenotype of autism, and might lead to improved recognition of WBS in individuals diagnosed with autism.

Autism Spectrum Disorder and intact executive functioning.

Science.gov (United States)

Ferrara, R; Ansermet, F; Massoni, F; Petrone, L; Onofri, E; Ricci, P; Archer, T; Ricci, S

2016-01-01

Earliest notions concerning autism (Autism Spectrum Disorders, ASD) describe the disturbance in executive functioning. Despite altered definition, executive functioning, expressed as higher cognitive skills required complex behaviors linked to the prefrontal cortex, are defective in autism. Specific difficulties in children presenting autism or verbal disabilities at executive functioning levels have been identified. Nevertheless, the developmental deficit of executive functioning in autism is highly diversified with huge individual variation and may even be absent. The aim of the present study to examine the current standing of intact executive functioning intact in ASD. Analysis of ASD populations, whether high-functioning, Asperger's or autism Broad Phenotype, studied over a range of executive functions including response inhibition, planning, cognitive flexibility, cognitive inhibition, and alerting networks indicates an absence of damage/impairment compared to the typically-developed normal control subjects. These findings of intact executive functioning in ASD subjects provide a strong foundation on which to construct applications for growth environments and the rehabilitation of autistic subjects.

Plant phenomics and the need for physiological phenotyping across scales to narrow the genotype-to-phenotype knowledge gap

Czech Academy of Sciences Publication Activity Database

Grosskinsky, D. K.; Svensgaard, J.; Christensen, S.; Roitsch, Thomas

2015-01-01

Roč. 66, č. 18 (2015), s. 5429-5440 ISSN 0022-0957 Institutional support: RVO:67179843 Keywords : External phenotype * genome–environment–management interaction * genome–phenome map * internal phenotype * phenomics * physiological traits * physiology * plant phenotyping * predictors Subject RIV: EH - Ecology, Behaviour Impact factor: 5.677, year: 2015

Plant phenomics and the need for physiological phenotyping across scales to narrow the genotype-to-phenotype knowledge gap

DEFF Research Database (Denmark)

Grosskinsky, Dominik Kilian; Svensgaard, Jesper; Christensen, Svend

2015-01-01

Plants are affected by complex genome×environment×management interactions which determine phenotypic plasticity as a result of the variability of genetic components. Whereas great advances have been made in the cost-efficient and high-throughput analyses of genetic information and non-invasive ph......Plants are affected by complex genome×environment×management interactions which determine phenotypic plasticity as a result of the variability of genetic components. Whereas great advances have been made in the cost-efficient and high-throughput analyses of genetic information and non......-invasive phenotyping, the large-scale analyses of the underlying physiological mechanisms lag behind. The external phenotype is determined by the sum of the complex interactions of metabolic pathways and intracellular regulatory networks that is reflected in an internal, physiological, and biochemical phenotype......, ultimately enabling the in silico assessment of responses under defined environments with advanced crop models. This will allow generation of robust physiological predictors also for complex traits to bridge the knowledge gap between genotype and phenotype for applications in breeding, precision farming...

Modeling the Phenotypic Architecture of Autism Symptoms from Time of Diagnosis to Age 6

Science.gov (United States)

Georgiades, Stelios; Boyle, Michael; Szatmari, Peter; Hanna, Steven; Duku, Eric; Zwaigenbaum, Lonnie; Bryson, Susan; Fombonne, Eric; Volden, Joanne; Mirenda, Pat; Smith, Isabel; Roberts, Wendy; Vaillancourt, Tracy; Waddell, Charlotte; Bennett, Teresa; Elsabbagh, Mayada; Thompson, Ann

2014-01-01

The latent class structure of autism symptoms from the time of diagnosis to age 6 years was examined in a sample of 280 children with autism spectrum disorder. Factor mixture modeling was performed on 26 algorithm items from the Autism Diagnostic Interview-Revised at diagnosis (Time 1) and again at age 6 (Time 2). At Time 1, a…

Vitamin D treatment during pregnancy prevents autism-related phenotypes in a mouse model of maternal immune activation.

Science.gov (United States)

Vuillermot, Stephanie; Luan, Wei; Meyer, Urs; Eyles, Darryl

2017-01-01

Prenatal exposure to infection is a recognized environmental risk factor for neuropsychiatric disorders of developmental origins such as autism or schizophrenia. Experimental work in animals indicates that this link is mediated by maternal immune activation (MIA) involving interactions between cytokine-associated inflammatory events, oxidative stress, and other pathophysiological processes such as hypoferremia and zinc deficiency. Maternal administration of the viral mimic polyriboinosinic-polyribocytidylic acid (poly(I:C)) in mice produces several behavioral phenotypes in adult offspring of relevance to autism spectrum disorder (ASD) and other neurodevelopmental disorders. Here, we investigated whether some of these phenotypes might also present in juveniles. In addition, given the known immunomodulatory and neuroprotective effects of vitamin D, we also investigated whether the co-administration of vitamin D could block MIA-induced ASD-related behaviors. We co-administered the hormonally active form of vitamin D, 1α,25 dihydroxy vitamin D3 (1,25OHD), simultaneously with poly(I:C) and examined (i) social interaction, stereotyped behavior, emotional learning and memory, and innate anxiety-like behavior in juveniles and (ii) the levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in maternal plasma and fetal brains. We show that like adult offspring that were exposed to MIA, juveniles display similar deficits in social approach behavior. Juvenile MIA offspring also show abnormal stereotyped digging and impaired acquisition and expression of tone-cued fear conditioning. Importantly, our study reveals that prenatal administration of 1,25OHD abolishes all these behavioral deficits in poly(I:C)-treated juveniles. However, prenatal administration of vitamin D had no effect on pro-inflammatory cytokine levels in dams or in fetal brains suggesting the anti-inflammatory actions of vitamin D are not the critical mechanism for its preventive actions in this ASD

Predictors of Mental Health in Chinese Parents of Children with Autism Spectrum Disorder (ASD)

Science.gov (United States)

Su, Xueyun; Cai, Ru Ying; Uljarevic, Mirko

2018-01-01

The aim of this study was to explore the influence of parental intolerance of Uncertainty (IU), sensory sensitivity (SS) and Broader Autism Phenotype (BAP), as well as the severity of their children's autism symptoms and co-morbid symptoms, on the mental health of Chinese parents of children with autism spectrum disorder (ASD). One hundred and…

A multisite study of the clinical diagnosis of different autism spectrum disorders.

Science.gov (United States)

Lord, Catherine; Petkova, Eva; Hus, Vanessa; Gan, Weijin; Lu, Feihan; Martin, Donna M; Ousley, Opal; Guy, Lisa; Bernier, Raphael; Gerdts, Jennifer; Algermissen, Molly; Whitaker, Agnes; Sutcliffe, James S; Warren, Zachary; Klin, Ami; Saulnier, Celine; Hanson, Ellen; Hundley, Rachel; Piggot, Judith; Fombonne, Eric; Steiman, Mandy; Miles, Judith; Kanne, Stephen M; Goin-Kochel, Robin P; Peters, Sarika U; Cook, Edwin H; Guter, Stephen; Tjernagel, Jennifer; Green-Snyder, Lee Anne; Bishop, Somer; Esler, Amy; Gotham, Katherine; Luyster, Rhiannon; Miller, Fiona; Olson, Jennifer; Richler, Jennifer; Risi, Susan

2012-03-01

Best-estimate clinical diagnoses of specific autism spectrum disorders (autistic disorder, pervasive developmental disorder-not otherwise specified, and Asperger syndrome) have been used as the diagnostic gold standard, even when information from standardized instruments is available. To determine whether the relationships between behavioral phenotypes and clinical diagnoses of different autism spectrum disorders vary across 12 university-based sites. Multisite observational study collecting clinical phenotype data (diagnostic, developmental, and demographic) for genetic research. Classification trees were used to identify characteristics that predicted diagnosis across and within sites. Participants were recruited through 12 university-based autism service providers into a genetic study of autism. A total of 2102 probands (1814 male probands) between 4 and 18 years of age (mean [SD] age, 8.93 [3.5] years) who met autism spectrum criteria on the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule and who had a clinical diagnosis of an autism spectrum disorder. Best-estimate clinical diagnoses predicted by standardized scores from diagnostic, cognitive, and behavioral measures. Although distributions of scores on standardized measures were similar across sites, significant site differences emerged in best-estimate clinical diagnoses of specific autism spectrum disorders. Relationships between clinical diagnoses and standardized scores, particularly verbal IQ, language level, and core diagnostic features, varied across sites in weighting of information and cutoffs. Clinical distinctions among categorical diagnostic subtypes of autism spectrum disorders were not reliable even across sites with well-documented fidelity using standardized diagnostic instruments. Results support the move from existing subgroupings of autism spectrum disorders to dimensional descriptions of core features of social affect and fixated, repetitive behaviors

Optimizing the phenotyping of rodent ASD models: enrichment analysis of mouse and human neurobiological phenotypes associated with high-risk autism genes identifies morphological, electrophysiological, neurological, and behavioral features

Directory of Open Access Journals (Sweden)

Buxbaum Joseph D

2012-02-01

Full Text Available Abstract Background There is interest in defining mouse neurobiological phenotypes useful for studying autism spectrum disorders (ASD in both forward and reverse genetic approaches. A recurrent focus has been on high-order behavioral analyses, including learning and memory paradigms and social paradigms. However, well-studied mouse models, including for example Fmr1 knockout mice, do not show dramatic deficits in such high-order phenotypes, raising a question as to what constitutes useful phenotypes in ASD models. Methods To address this, we made use of a list of 112 disease genes etiologically involved in ASD to survey, on a large scale and with unbiased methods as well as expert review, phenotypes associated with a targeted disruption of these genes in mice, using the Mammalian Phenotype Ontology database. In addition, we compared the results with similar analyses for human phenotypes. Findings We observed four classes of neurobiological phenotypes associated with disruption of a large proportion of ASD genes, including: (1 Changes in brain and neuronal morphology; (2 electrophysiological changes; (3 neurological changes; and (4 higher-order behavioral changes. Alterations in brain and neuronal morphology represent quantitative measures that can be more widely adopted in models of ASD to understand cellular and network changes. Interestingly, the electrophysiological changes differed across different genes, indicating that excitation/inhibition imbalance hypotheses for ASD would either have to be so non-specific as to be not falsifiable, or, if specific, would not be supported by the data. Finally, it was significant that in analyses of both mouse and human databases, many of the behavioral alterations were neurological changes, encompassing sensory alterations, motor abnormalities, and seizures, as opposed to higher-order behavioral changes in learning and memory and social behavior paradigms. Conclusions The results indicated that mutations

Classifying Autism Spectrum Disorders by ADI-R: Subtypes or Severity Gradient?

Science.gov (United States)

Cholemkery, Hannah; Medda, Juliane; Lempp, Thomas; Freitag, Christine M.

2016-01-01

To reduce phenotypic heterogeneity of Autism spectrum disorders (ASD) and add to the current diagnostic discussion this study aimed at identifying clinically meaningful ASD subgroups. Cluster analyses were used to describe empirically derived groups based on the Autism Diagnostic Interview-revised (ADI-R) in a large sample of n = 463 individuals…

Imagination in human social cognition, autism, and psychotic-affective conditions.

Science.gov (United States)

Crespi, Bernard; Leach, Emma; Dinsdale, Natalie; Mokkonen, Mikael; Hurd, Peter

2016-05-01

Complex human social cognition has evolved in concert with risks for psychiatric disorders. Recently, autism and psychotic-affective conditions (mainly schizophrenia, bipolar disorder, and depression) have been posited as psychological 'opposites' with regard to social-cognitive phenotypes. Imagination, considered as 'forming new ideas, mental images, or concepts', represents a central facet of human social evolution and cognition. Previous studies have documented reduced imagination in autism, and increased imagination in association with psychotic-affective conditions, yet these sets of findings have yet to be considered together, or evaluated in the context of the diametric model. We first review studies of the components, manifestations, and neural correlates of imagination in autism and psychotic-affective conditions. Next, we use data on dimensional autism in healthy populations to test the hypotheses that: (1) imagination represents the facet of autism that best accounts for its strongly male-biased sex ratio, and (2) higher genetic risk of schizophrenia is associated with higher imagination, in accordance with the predictions of the diametric model. The first hypothesis was supported by a systematic review and meta-analysis showing that Imagination exhibits the strongest male bias of all Autism Quotient (AQ) subscales, in non-clinical populations. The second hypothesis was supported, for males, by associations between schizophrenia genetic risk scores, derived from a set of single-nucleotide polymorphisms, and the AQ Imagination subscale. Considered together, these findings indicate that imagination, especially social imagination as embodied in the default mode human brain network, mediates risk and diametric dimensional phenotypes of autism and psychotic-affective conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Twin Studies in Autism: What Might They Say about Genetic and Environmental Influences

Science.gov (United States)

Anderson, George M.

2012-01-01

Genetic and epigenetic differences exist within monozygote twin-pairs and might be especially important in the expression of autism. Assuming phenotypic differences between monozygotic twins are due to environmental influences may lead to mistaken conclusions regarding the relative genetic and environmental contribution to autism risk.

phenotype correlation of methylene tetrahydrofolate reductase ...

African Journals Online (AJOL)

Rabah M. Shawky

2014-06-21

Jun 21, 2014 ... children with autism and to correlate them with different phenotypes. Subjects and ... of impairments in communication, reciprocal social interac- tions, and ... isolation was obtained from peripheral blood samples using the spin ... IQ, while ten of them (50%) had mild mental retardation and six patients (30%) ...

Atypical resource allocation may contribute to many aspects of autism

Directory of Open Access Journals (Sweden)

Emily J. Goldknopf

2013-12-01

Full Text Available Based on a review of the literature and on reports by people with autism, this paper suggests that atypical resource allocation is a factor that contributes to many aspects of autism spectrum conditions, including difficulties with language and social cognition, atypical sensory and attentional experiences, executive and motor challenges, and perceptual and conceptual strengths and weaknesses. Drawing upon resource theoretical approaches that suggest that perception, cognition, and action draw upon multiple pools of resources, the approach states that compared with resources in typical cognition, resources in autism are narrowed or reduced, especially in people with strong sensory symptoms. In narrowed attention, resources are restricted to smaller areas and to fewer modalities, stages of processing, and cognitive processes than in typical cognition; resources may be more intense than in typical cognition. In reduced attentional capacity, overall resources are reduced; resources may be restricted to fewer modalities, stages of processing, and cognitive processes than in typical cognition, or the amount of resources allocated to each area or process may be reduced. Possible neural bases of the hypothesized atypical resource allocation, relations to other approaches, limitations, and tests of the hypotheses are discussed.

Preclinical Testing of Novel Oxytocin Receptor Activators in Models of Autism Phenotypes

Science.gov (United States)

2015-11-30

higher incidence of autism observed in male versus female children . BALB/cByJ Cohort 1 (n ¼ 6 per treatment group; 6e7 weeks of age) was tested for acute...Veenstra-Vanderweele, J., 2011. A systematic review of medical treatments for children with autism spectrum disorders. Pediatrics 127, e1312ee1321. Melis...R.L., Leserman, J., Jarskog, L.F., Penn, D.L., 2011. Intranasal oxytocin reduces psychotic symptoms and improves theory of mind and social perception

Early Social, Imitation, Play, and Language Abilities of Young Non-Autistic Siblings of Children with Autism

Science.gov (United States)

Toth, Karen; Dawson, Geraldine; Meltzoff, Andrew N.; Greenson, Jessica; Fein, Deborah

2007-01-01

Studies are needed to better understand the broad autism phenotype in young siblings of children with autism. Cognitive, adaptive, social, imitation, play, and language abilities were examined in 42 non-autistic siblings and 20 toddlers with no family history of autism, ages 18-27 months. Siblings, as a group, were below average in expressive…

Quantitative Autism Traits in First Degree Relatives: Evidence for the Broader Autism Phenotype in Fathers, but Not in Mothers and Siblings

Science.gov (United States)

De la Marche, Wouter; Noens, Ilse; Luts, Jan; Scholte, Evert; Van Huffel, Sabine; Steyaert, Jean

2012-01-01

Autism spectrum disorder (ASD) symptoms are present in unaffected relatives and individuals from the general population. Results are inconclusive, however, on whether unaffected relatives have higher levels of quantitative autism traits (QAT) or not. This might be due to differences in research populations, because behavioral data and molecular…

Autism: cause factors, early diagnosis and therapies.

Science.gov (United States)

Bhat, Shreya; Acharya, U Rajendra; Adeli, Hojjat; Bairy, G Muralidhar; Adeli, Amir

2014-01-01

Autism spectrum disorder (ASD) is a complex neurobiological disorder characterized by neuropsychological and behavioral deficits. Cognitive impairment, lack of social skills, and stereotyped behavior are the major autistic symptoms, visible after a certain age. It is one of the fastest growing disabilities. Its current prevalence rate in the U.S. estimated by the Centers for Disease Control and Prevention is 1 in 68 births. The genetic and physiological structure of the brain is studied to determine the pathology of autism, but diagnosis of autism at an early age is challenging due to the existing phenotypic and etiological heterogeneity among ASD individuals. Volumetric and neuroimaging techniques are explored to elucidate the neuroanatomy of the ASD brain. Nuroanatomical, neurochemical, and neuroimaging biomarkers can help in the early diagnosis and treatment of ASD. This paper presents a review of the types of autism, etiologies, early detection, and treatment of ASD.

Characterization of the Pathological and Biochemical Markers that Correlate to the Clinical Features of Autism

Science.gov (United States)

2012-10-01

Theory of Mind .” MIT Press, Cambridge. Baron-Cohen, S., Campbell, R., Karmiloff-Smith, A., Grant, J., Walker, J. (1999). Are children with autism ...the age of 3 years (1). Autism is heterogeneous, both phenotypically and etiologically. In 44.6% of affected children , autism is associated with cogni...confirmed a high prevalence of autism ; 20 (69%) of 29 children and young adults with idic(15) had an ASD (29). TABLE 1. Material Examined Group Case No

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…

Does rubella cause autism: a 2015 reappraisal?

Directory of Open Access Journals (Sweden)

Jill eHutton

2016-02-01

Full Text Available In the 1970s, Stella Chess found a high prevalence of autism in children with congenital rubella syndrome (CRS, 200 times that of the general population at the time. Many researchers quote this fact to add proof to the current theory that maternal infection with immune system activation in pregnancy leads to autism in the offspring. This rubella and autism association is presented with the notion that rubella has been eliminated in today’s world. CRS cases are no longer typically seen, yet autistic children often share findings of CRS including deafness, congenital heart defects and to a lesser extent visual changes. Autistic children commonly have hyperactivity and spasticity, as do CRS children. Both autistic and CRS individuals may develop type 1 diabetes as young adults. Neuropathology of CRS infants may reveal cerebral vasculitis with narrowed lumens and cerebral necrosis. Neuroradiologic findings of children with CRS show calcifications, periventricular leukomalacia, and dilated perivascular spaces. Neuroradiology of autism has also demonstrated hyperintensities, leukomalacia and prominent perivascular spaces. PET studies of autistic individuals exhibit decreased perfusion to areas of the brain similarly affected by rubella. In both autism and CRS, certain changes in the brain have implicated the immune system. Several children with autism lack antibodies to rubella, as do children with CRS. These numerous similarities increase the probability of an association between rubella virus and autism.Rubella and autism cross many ethnicities in many countries. Contrary to current belief, rubella has not been eradicated and globally affects up to 5% of pregnant women. Susceptibility continues as vaccines are not given worldwide and are not fully protective. Rubella might still cause autism, even in vaccinated populations.

Does Rubella Cause Autism: A 2015 Reappraisal?

Science.gov (United States)

Hutton, Jill

2016-01-01

In the 1970s, Stella Chess found a high prevalence of autism in children with congenital rubella syndrome (CRS), 200 times that of the general population at the time. Many researchers quote this fact to add proof to the current theory that maternal infection with immune system activation in pregnancy leads to autism in the offspring. This rubella and autism association is presented with the notion that rubella has been eliminated in today's world. CRS cases are no longer typically seen; yet, autistic children often share findings of CRS including deafness, congenital heart defects, and to a lesser extent visual changes. Autistic children commonly have hyperactivity and spasticity, as do CRS children. Both autistic and CRS individuals may develop type 1 diabetes as young adults. Neuropathology of CRS infants may reveal cerebral vasculitis with narrowed lumens and cerebral necrosis. Neuroradiological findings of children with CRS show calcifications, periventricular leukomalacia, and dilated perivascular spaces. Neuroradiology of autism has also demonstrated hyperintensities, leukomalacia, and prominent perivascular spaces. PET studies of autistic individuals exhibit decreased perfusion to areas of the brain similarly affected by rubella. In both autism and CRS, certain changes in the brain have implicated the immune system. Several children with autism lack antibodies to rubella, as do children with CRS. These numerous similarities increase the probability of an association between rubella virus and autism. Rubella and autism cross many ethnicities in many countries. Contrary to current belief, rubella has not been eradicated and globally affects up to 5% of pregnant women. Susceptibility continues as vaccines are not given worldwide and are not fully protective. Rubella might still cause autism, even in vaccinated populations.

The duplication 17p13.3 phenotype

DEFF Research Database (Denmark)

Curry, Cynthia J; Rosenfeld, Jill A; Grant, Erica

2013-01-01

. Older patients were often overweight. Three variant phenotypes included cleft lip/palate (CLP), split hand/foot with long bone deficiency (SHFLD), and a connective tissue phenotype resembling Marfan syndrome. The duplications in patients with clefts appear to disrupt ABR, while the SHFLD phenotype......Chromosome 17p13.3 is a gene rich region that when deleted is associated with the well-known Miller-Dieker syndrome. A recently described duplication syndrome involving this region has been associated with intellectual impairment, autism and occasional brain MRI abnormalities. We report 34...... was associated with duplication of BHLHA9 as noted in two recent reports. The connective tissue phenotype did not have a convincing critical region. Our experience with this large cohort expands knowledge of this diverse duplication syndrome....

Brief Report: Autism-Like Traits Are Associated with Enhanced Ability to Disembed Visual Forms

Science.gov (United States)

Sabatino DiCriscio, Antoinette; Troiani, Vanessa

2017-01-01

Atypical visual perceptual skills are thought to underlie unusual visual attention in autism spectrum disorders. We assessed whether individual differences in visual processing skills scaled with quantitative traits associated with the broader autism phenotype (BAP). Visual perception was assessed using the Figure-ground subtest of the Test of…

Treatment Resistant Epilepsy in Autism Spectrum Disorder: Increased Risk for Females.

Science.gov (United States)

Blackmon, Karen; Bluvstein, Judith; MacAllister, William S; Avallone, Jennifer; Misajon, Jade; Hedlund, Julie; Goldberg, Rina; Bojko, Aviva; Mitra, Nirmala; Giridharan, Radha; Sultan, Richard; Keller, Seth; Devinsky, Orrin

2016-02-01

The male:female ratio in autism spectrum disorder (ASD) averages greater than 4:1 while the male:female ratio of ASD with epilepsy averages less than 3:1. This indicates an elevated risk of epilepsy in females with ASD; yet, it is unknown whether phenotypic features of epilepsy and ASD differ between males and females with this comorbidity. The goal of this study is to investigate sex differences in phenotypic features of epilepsy and ASD in a prospective sample of 130 children and young adults with an initial ASD diagnosis and subsequent epilepsy diagnosis. All participants were characterized by standardized diagnostic inventories, parent/caregiver completed questionnaires, and medical/academic record review. Diagnostic classifications of epilepsy, ASD, and intellectual disability were performed by board certified neurologists and a pediatric neuropsychologist. Results demonstrated a lower male:female ratio (1.8:1) in individuals with ASD and treatment-resistant epilepsy relative to those with ASD and treatment-responsive epilepsy (4.9:1), indicating a higher risk of treatment-resistant epilepsy in females. Mild neuroimaging abnormalities were more common in females than males and this was associated with increased risk of treatment-resistance. In contrast, ASD symptom severity was lower in females compared with males. Findings distinguish females with ASD and epilepsy as a distinct subgroup at higher risk for a more severe epilepsy phenotype in the context of a less severe ASD phenotype. Increased risk of anti-epileptic treatment resistance in females with ASD and epilepsy suggests that comprehensive genetic, imaging, and neurologic screening and enhanced treatment monitoring may be indicated for this subgroup. Autism Res 2016, 9: 311-320. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Social Behavior and Autism Traits in a Sex Chromosomal Disorder: Klinefelter (47XXY) Syndrome

Science.gov (United States)

van Rijn, Sophie; Swaab, Hanna; Aleman, Andre; Kahn, Rene S.

2008-01-01

Although Klinefelter syndrome (47,XXY) has been associated with psychosocial difficulties, knowledge of the social behavioral phenotype is limited. We examined specific social abilities and autism traits in Klinefelter syndrome. Scores of 31 XXY men on the Scale for Interpersonal Behavior and the Autism Spectrum Questionnaire were compared to 24…

[Autism and epigenetics. A model of explanation for the understanding of the genesis in autism spectrum disorders].

Science.gov (United States)

Arberas, Claudia; Ruggieri, Víctor

2013-01-01

Autism spectrum disorders are characterized by impairment of social integration and language development and restricted interests. Autism spectrum disorders manifest during childhood and may have a varying clinical expression over the years related to different therapeutic approaches, behavior-modifying drugs, and environmental factors, among others. So far, the genetic alterations identified are not sufficient to explain the genesis of all these processes, as many of the mutations found are also present in unaffected individuals. Findings on the underlying biological and pathophysiological mechanisms of entities strongly associated with autism spectrum disorders, such as Rett, fragile X, Angelman, and fetal alcohol syndromes, point to the role of epigenetic changes in disorders of neurodevelopment. Epigenetic phenomena are normal biological processes necessary for cell and thus human life, especially related to embryonic development. Different phenomena that affect epigenetic processes (changes that change operation or expression of a gene, without modifying the DNA structure) have also been shown to be important in the genesis of neurodevelopmental disorders. Alterations in the epigenetic mechanism may be reversible, which may explain the variation in the autism phenotype over time. Here we analyze the normal epigenetic mechanisms, autism spectrum disorders, their association with specific entities associated with altered epigenetic mechanisms, and possible therapeutic approaches targeting these alterations.

Neuroanatomic alterations and social and communication deficits in monozygotic twins discordant for autism disorder.

Science.gov (United States)

Mitchell, Shanti R; Reiss, Allan L; Tatusko, Danielle H; Ikuta, Ichiro; Kazmerski, Dana B; Botti, Jo-Anna C; Burnette, Courtney P; Kates, Wendy R

2009-08-01

Investigating neuroanatomic differences in monozygotic twins who are discordant for autism can help unravel the relative contributions of genetics and environment to this pervasive developmental disorder. The authors used magnetic resonance imaging (MRI) to investigate several brain regions of interest in monozygotic twins who varied in degree of phenotypic discordance for narrowly defined autism. The subjects were 14 pairs of monozygotic twins between the ages of 5 and 14 years old and 14 singleton age- and gender-matched typically developing comparison subjects. The monozygotic twin group was a cohort of children with narrowly defined autistic deficits and their co-twins who presented with varying levels of autistic deficits. High-resolution MRIs were acquired and volumetric/area measurements obtained for the frontal lobe, amygdala, and hippocampus and subregions of the prefrontal cortex, corpus callosum, and cerebellar vermis. No neurovolumetric/area differences were found between twin pairs. Relative to typically developing comparison subjects, dorsolateral prefrontal cortex volumes and anterior areas of the corpus callosum were significantly altered in autistic twins, and volumes of the posterior vermis were altered in both autistic twins and co-twins. Intraclass correlation analysis of brain volumes between children with autism and their co-twins indicated that the degree of within-pair neuroanatomic concordance varied with brain region. In the group of subjects with narrowly defined autism only, dorsolateral prefrontal cortex, amygdala, and posterior vermis volumes were significantly associated with the severity of autism based on scores from the Autism Diagnostic Observation Schedule-Generic. These findings support previous research demonstrating alterations in the prefrontal cortex, corpus callosum, and posterior vermis in children with autism and further suggest that alterations are associated with the severity of the autism phenotype. Continued research

A review of gene-environment correlations and their implications for autism: a conceptual model.

Science.gov (United States)

Meek, Shantel E; Lemery-Chalfant, Kathryn; Jahromi, Laudan B; Valiente, Carlos

2013-07-01

A conceptual model is proposed that explains how gene-environment correlations and the multiplier effect function in the context of social development in individuals with autism. The review discusses the current state of autism genetic research, including its challenges, such as the genetic and phenotypic heterogeneity of the disorder, and its limitations, such as the lack of interdisciplinary work between geneticists and social scientists. We discuss literature on gene-environment correlations in the context of social development and draw implications for individuals with autism. The review expands upon genes, behaviors, types of environmental exposure, and exogenous variables relevant to social development in individuals on the autism spectrum, and explains these factors in the context of the conceptual model to provide a more in-depth understanding of how the effects of certain genetic variants can be multiplied by the environment to cause largely phenotypic individual differences. Using the knowledge gathered from gene-environment correlations and the multiplier effect, we outline novel intervention directions and implications. PsycINFO Database Record (c) 2013 APA, all rights reserved.

No association between a common single nucleotide polymorphism, rs4141463, in the MACROD2 gene and autism spectrum disorder.

Science.gov (United States)

Curran, Sarah; Bolton, Patrick; Rozsnyai, Kinga; Chiocchetti, Andreas; Klauck, Sabine M; Duketis, Eftichia; Poustka, Fritz; Schlitt, Sabine; Freitag, Christine M; Lee, Irene; Muglia, Pierandrea; Poot, Martin; Staal, Wouter; de Jonge, Maretha V; Ophoff, Roel A; Lewis, Cathryn; Skuse, David; Mandy, Will; Vassos, Evangelos; Fossdal, Ragnheidur; Magnusson, Páll; Hreidarsson, Stefan; Saemundsen, Evald; Stefansson, Hreinn; Stefansson, Kari; Collier, David

2011-09-01

The Autism Genome Project (AGP) Consortium recently reported genome-wide significant association between autism and an intronic single nucleotide polymorphism marker, rs4141463, within the MACROD2 gene. In the present study we attempted to replicate this finding using an independent case-control design of 1,170 cases with autism spectrum disorder (ASD) (874 of which fulfilled narrow criteria for Autism (A)) from five centers within Europe (UK, Germany, the Netherlands, Italy, and Iceland), and 35,307 controls. The combined sample size gave us a non-centrality parameter (NCP) of 11.9, with 93% power to detect allelic association of rs4141463 at an alpha of 0.05 with odds ratio of 0.84 (the best odds ratio estimate of the AGP Consortium data), and for the narrow diagnosis of autism, an NCP of 8.9 and power of 85%. Our case-control data were analyzed for association, stratified by each center, and the summary statistics were combined using the meta-analysis program, GWAMA. This resulted in an odds ratio (OR) of 1.03 (95% CI 0.944-1.133), with a P-value of 0.5 for ASD and OR of 0.99 (95% CI 0.88-1.11) with P-value = 0.85 for the Autism (A) sub-group. Therefore, this study does not provide support for the reported association between rs4141463 and autism. Copyright © 2011 Wiley-Liss, Inc.

Limited impact of Cntn4 mutation on autism-related traits in developing and adult C57BL/6J mice

OpenAIRE

Molenhuis, Remco T.; Bruining, Hilgo; Remmelink, Esther; de Visser, Leonie; Loos, Maarten; Burbach, J. Peter H.; Kas, Martien J. H.

2016-01-01

Background Mouse models offer an essential tool to unravel the impact of genetic mutations on autism-related phenotypes. The behavioral impact of some important candidate gene models for autism spectrum disorder (ASD) has not yet been studied, and existing characterizations mostly describe behavioral phenotypes at adult ages, disregarding the developmental nature of the disorder. In this context, the behavioral influence of CNTN4, one of the strongest suggested ASD candidate genes, is unknown...

Autism Spectrum Disorder in Children Adopted After Early Care Breakdown

OpenAIRE

Green, Jonathan; Leadbitter, Kathy; Kay, Catherine; Sharma, Kishan

2016-01-01

Syndromic autism has been described in children adopted after orphanage rearing. We investigated whether the same existed in children adopted after family breakdown. Families of 54/60 adopted children aged 6?11?years (mean 102?months; SD 20; 45?% male) returned screening questionnaires for autism spectrum disorder (ASD); 21/54 (39?%) screened positive. Detailed in-person phenotyping of screen positive cases showed ASD in 6/54 (11?%), Broad ASD (sub threshold traits) in 10/54 (18.5?%); 5/54 (9...

Diagnosis, treatment, and neurobiology of autism in children.

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Lainhart, J E; Piven, J

1995-08-01

Autism is a developmental neuropsychiatric disorder defined by the presence of social and communicative deficits, restricted and repetitive behaviors and interests, and a characteristic course. Research suggests that hereditary factors play a principal role in the etiology of most cases. A phenotype broader than autism, including milder social and language-based cognitive deficits, appears to be inherited. Although the pathogenesis is unknown, neurobiologic mechanisms clearly underlie the disorder. Neuropathologic studies have demonstrated abnormalities in limbic structures, the cerebellum, and the cortex. New advances in behavioral therapies and pharmacologic treatment are important components of successful multidisciplinary treatment of this disorder.

[Co-occurrence of anxiety and autism. The social error and allostatic load hypotheses].

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Paula-Perez, Isabel

2013-02-22

INTRODUCTION. The concept of comorbidity in neurodevelopmental disorders like autism is sometimes ambiguous. The co-occurrence of anxiety and autism is clinically significant, yet it is not always easy to determine whether it is a 'real' comorbidity, where the two comorbid conditions are phenotypically and aetiologically identical to what that anxiety would mean in persons with a neurotypical development, whether it is an anxiety that has been phenotypically modified by the pathological processes of the autism spectrum disorders, thus resulting in a specific variant of these latter, or whether we are dealing with a false comorbidity resulting from rather inaccurate differential diagnoses. DEVELOPMENT. The article puts forward two hypotheses to explain this co-occurrence, which provide each other with feedback and are little more than our reflections on the scientific evidence we have available today, but expressed aloud. The first is the 'social error' hypothesis, which considers that the maladjustments in the social behaviour of persons with autism (which arises from alterations affecting the processes involved in social cognition) help to aggravate anxiety in autism. The second hypothesis, referring to allostatic load, holds that anxiety is a response to chronic stress, wear or exhaustion that is produced by the hyperactivation of certain structures in the limbic system. CONCLUSIONS. The prototypical manifestations of anxiety present in the person with autism are not always related with the same biopsychosocial variables as those observed in persons without autism. Evidence points to hyper-reactive flee-or-fight responses (hypervigilance) when the person finds him or herself outside their comfort zone, and supports the hypotheses of 'social error' and of decompensation of the allostatic mechanism that makes it possible to cope with stress.

New Perspectives on Rodent Models of Advanced Paternal Age: Relevance to Autism

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Claire J Foldi

2011-06-01

Full Text Available Offspring of older fathers have an increased risk of various adverse health outcomes, including autism and schizophrenia. With respect to biological mechanisms for this association, there are many more germline cell divisions in the life history of a sperm relative to that of an oocyte. This leads to more opportunities for copy error mutations in germ cells from older fathers. Evidence also suggests that epigenetic patterning in the sperm from older men is altered. Rodent models provide an experimental platform to examine the association between paternal age and brain development. Several rodent models of advanced paternal age (APA have been published with relevance to intermediate phenotypes related to autism. All four published APA models vary in key features creating a lack of consistency with respect to behavioural phenotypes. A consideration of common phenotypes that emerge from these APA-related mouse models may be informative in the exploration of the molecular and neurobiological correlates of APA.

Early Social, Imitation, Play, and Language Abilities of Young Non-Autistic Siblings of Children with Autism

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Toth, Karen; Dawson, Geraldine; Meltzoff, Andrew N.; Greenson, Jessica; Fein, Deborah

2007-01-01

Studies are needed to better understand the broad autism phenotype in young siblings of children with autism. Cognitive, adaptive, social, imitation, play, and language abilities were examined in 42 non-autistic siblings and 20 toddlers with no family history of autism, ages 18–27 months. Siblings, as a group, were below average in expressive language and composite IQ, had lower mean receptive language, adaptive behavior, and social communication skills, and used fewer words, distal gestures,...

Variation in the autism candidate gene GABRB3 modulates tactile sensitivity in typically developing children

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Tavassoli Teresa

2012-07-01

Full Text Available Abstract Background Autism spectrum conditions have a strong genetic component. Atypical sensory sensitivities are one of the core but neglected features of autism spectrum conditions. GABRB3 is a well-characterised candidate gene for autism spectrum conditions. In mice, heterozygous Gabrb3 deletion is associated with increased tactile sensitivity. However, no study has examined if tactile sensitivity is associated with GABRB3 genetic variation in humans. To test this, we conducted two pilot genetic association studies in the general population, analysing two phenotypic measures of tactile sensitivity (a parent-report and a behavioural measure for association with 43 SNPs in GABRB3. Findings Across both tactile sensitivity measures, three SNPs (rs11636966, rs8023959 and rs2162241 were nominally associated with both phenotypes, providing a measure of internal validation. Parent-report scores were nominally associated with six SNPs (P Conclusions This is the first human study to show an association between GABRB3 variation and tactile sensitivity. This provides support for the evidence from animal models implicating the role of GABRB3 variation in the atypical sensory sensitivity in autism spectrum conditions. Future research is underway to directly test this association in cases of autism spectrum conditions.

Association Between the Probability of Autism Spectrum Disorder and Normative Sex-Related Phenotypic Diversity in Brain Structure

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Andrews, Derek S.; Gudbrandsen, Christina M.; Marquand, Andre F.; Ginestet, Cedric E.; Daly, Eileen M.; Murphy, Clodagh M.; Lai, Meng-Chuan; Lombardo, Michael V.; Ruigrok, Amber N. V.; Bullmore, Edward T.; Suckling, John; Williams, Steven C. R.; Baron-Cohen, Simon; Craig, Michael C.; Murphy, Declan G. M.

2017-01-01

Importance Autism spectrum disorder (ASD) is 2 to 5 times more common in male individuals than in female individuals. While the male preponderant prevalence of ASD might partially be explained by sex differences in clinical symptoms, etiological models suggest that the biological male phenotype carries a higher intrinsic risk for ASD than the female phenotype. To our knowledge, this hypothesis has never been tested directly, and the neurobiological mechanisms that modulate ASD risk in male individuals and female individuals remain elusive. Objectives To examine the probability of ASD as a function of normative sex-related phenotypic diversity in brain structure and to identify the patterns of sex-related neuroanatomical variability associated with low or high probability of ASD. Design, Setting, and Participants This study examined a cross-sectional sample of 98 right-handed, high-functioning adults with ASD and 98 matched neurotypical control individuals aged 18 to 42 years. A multivariate probabilistic classification approach was used to develop a predictive model of biological sex based on cortical thickness measures assessed via magnetic resonance imaging in neurotypical controls. This normative model was subsequently applied to individuals with ASD. The study dates were June 2005 to October 2009, and this analysis was conducted between June 2015 and July 2016. Main Outcomes and Measures Sample and population ASD probability estimates as a function of normative sex-related diversity in brain structure, as well as neuroanatomical patterns associated with low or high ASD probability in male individuals and female individuals. Results Among the 98 individuals with ASD, 49 were male and 49 female, with a mean (SD) age of 26.88 (7.18) years. Among the 98 controls, 51 were male and 47 female, with a mean (SD) age of 27.39 (6.44) years. The sample probability of ASD increased significantly with predictive probabilities for the male neuroanatomical brain phenotype. For

Replicable in vivo physiological and behavioral phenotypes of the Shank3B null mutant mouse model of autism.

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Dhamne, Sameer C; Silverman, Jill L; Super, Chloe E; Lammers, Stephen H T; Hameed, Mustafa Q; Modi, Meera E; Copping, Nycole A; Pride, Michael C; Smith, Daniel G; Rotenberg, Alexander; Crawley, Jacqueline N; Sahin, Mustafa

2017-01-01

Autism spectrum disorder (ASD) is a clinically and biologically heterogeneous condition characterized by social, repetitive, and sensory behavioral abnormalities. No treatments are approved for the core diagnostic symptoms of ASD. To enable the earliest stages of therapeutic discovery and development for ASD, robust and reproducible behavioral phenotypes and biological markers are essential to establish in preclinical animal models. The goal of this study was to identify electroencephalographic (EEG) and behavioral phenotypes that are replicable between independent cohorts in a mouse model of ASD. The larger goal of our strategy is to empower the preclinical biomedical ASD research field by generating robust and reproducible behavioral and physiological phenotypes in animal models of ASD, for the characterization of mechanistic underpinnings of ASD-relevant phenotypes, and to ensure reliability for the discovery of novel therapeutics. Genetic disruption of the SHANK3 gene, a scaffolding protein involved in the stability of the postsynaptic density in excitatory synapses, is thought to be responsible for a relatively large number of cases of ASD. Therefore, we have thoroughly characterized the robustness of ASD-relevant behavioral phenotypes in two cohorts, and for the first time quantified translational EEG activity in Shank3B null mutant mice. In vivo physiology and behavioral assays were conducted in two independently bred and tested full cohorts of Shank3B null mutant ( Shank3B KO) and wildtype littermate control (WT) mice. EEG was recorded via wireless implanted telemeters for 7 days of baseline followed by 20 min of recording following pentylenetetrazol (PTZ) challenge. Behaviors relevant to the diagnostic and associated symptoms of ASD were tested on a battery of established behavioral tests. Assays were designed to reproduce and expand on the original behavioral characterization of Shank3B KO mice. Two or more corroborative tests were conducted within each

Heterozygous ambra1 deficiency in mice: a genetic trait with autism-like behavior restricted to the female gender.

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Dere, Ekrem; Dahm, Liane; Lu, Derek; Hammerschmidt, Kurt; Ju, Anes; Tantra, Martesa; Kästner, Anne; Chowdhury, Kamal; Ehrenreich, Hannelore

2014-01-01

Autism-spectrum disorders (ASD) are heterogeneous, highly heritable neurodevelopmental conditions affecting around 0.5% of the population across cultures, with a male/female ratio of approximately 4:1. Phenotypically, ASD are characterized by social interaction and communication deficits, restricted interests, repetitive behaviors, and reduced cognitive flexibility. Identified causes converge at the level of the synapse, ranging from mutation of synaptic genes to quantitative alterations in synaptic protein expression, e.g., through compromised transcriptional or translational control. We wondered whether reduced turnover and degradation of synapses, due to deregulated autophagy, would lead to similar phenotypical consequences. Ambra1, strongly expressed in cortex, hippocampus, and striatum, is a positive regulator of Beclin1, a principal player in autophagosome formation. While homozygosity of the Ambra1 null mutation causes embryonic lethality, heterozygous mice with reduced Ambra1 expression are viable, reproduce normally, and lack any immediately obvious phenotype. Surprisingly, comprehensive behavioral characterization of these mice revealed an autism-like phenotype in Ambra1 (+/-) females only, including compromised communication and social interactions, a tendency of enhanced stereotypies/repetitive behaviors, and impaired cognitive flexibility. Reduced ultrasound communication was found in adults as well as pups, which achieved otherwise normal neurodevelopmental milestones. These features were all absent in male Ambra1 (+/-) mice. As a first hint explaining this gender difference, we found a much stronger reduction of Ambra1 protein in the cortex of Ambra1 (+/-) females compared to males. To conclude, Ambra1 deficiency can induce an autism-like phenotype. The restriction to the female gender of autism-generation by a defined genetic trait is unique thus far and warrants further investigation.

Heterozygous Ambra1 deficiency in mice: A genetic trait with autism-like behavior restricted to the female gender

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Ekrem eDere

2014-05-01

Full Text Available Autism spectrum disorders (ASD are heterogeneous, highly heritable neurodevelopmental conditions affecting around 0.5% of the population across cultures, with a male/female ratio of ~4:1. Phenotypically, ASD are characterized by social interaction and communication deficits, restricted interests, repetitive behaviors, and reduced cognitive flexibility. Identified causes converge at the level of the synapse, ranging from mutation of synaptic genes to quantitative alterations in synaptic protein expression, e.g. through compromised transcriptional or translational control. We wondered whether reduced turnover and degradation of synapses, due to deregulated autophagy, would lead to similar phenotypical consequences. Ambra1, strongly expressed in cortex, hippocampus and striatum, is a positive regulator of Beclin1, a principal player in autophagosome formation. While homozygosity of the Ambra1 null mutation causes embryonic lethality, heterozygous mice with reduced Ambra1 expression are viable, reproduce normally, and lack any immediately obvious phenotype. Surprisingly, comprehensive behavioral characterization of these mice revealed an autism-like phenotype in Ambra1+/- females only, including compromised communication and social interactions, a tendency of enhanced stereotypies/repetitive behaviors, and impaired cognitive flexibility. Reduced ultrasound communication was found in adults as well as pups which achieved otherwise normal neurodevelopmental milestones. These features were all absent in male Ambra1+/- mice. As a first hint explaining this gender difference, we found a much stronger reduction of Ambra1 protein in the cortex of Ambra1+/- females compared to males. To conclude, Ambra1 deficiency can induce an autism-like phenotype. The restriction to the female gender of autism-generation by a defined genetic trait is unique thus far and warrants further investigation.

High-fat diet exacerbates cognitive rigidity and social deficiency in the BTBR mouse model of autism.

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Zilkha, N; Kuperman, Y; Kimchi, T

2017-03-14

The global increase in rates of obesity has been accompanied by a similar surge in the number of autism diagnoses. Accumulating epidemiological evidence suggest a possible link between overweight and the risk for autism spectrum disorders (ASD), as well as autism severity. In laboratory animals, several studies have shown a connection between various environmental factors, including diet-induced obesity, and the development of autism-related behaviors. However, the effect of high-fat or imbalanced diet on a pre-existing autism-like phenotype is unclear. In this study, we employed the BTBR inbred mouse strain, a well-established mouse model for autism, to assess the impact of inadequate fattening nutrition on the autism-related behavioral phenotype. Male mice were fed by high-fat diet (HFD) or control balanced diet (control) from weaning onward, and tested in a series of behavioral assays as adults. In addition, we measured the hypothalamic expression levels of several genes involved in oxytocin and dopamine signaling, in search of a possible neurobiological underlying mechanism. As an internal control, we also employed similar metabolic and behavioral measures on neurotypical C57 mice. Compared to control-fed mice, BTBR mice fed by HFD showed marked aggravation in autism-related behaviors, manifested in increased cognitive rigidity and diminished preference for social novelty. Moreover, the total autism composite (severity) score was higher in the HFD group, and positively correlated with higher body weight. Finally, we revealed negative correlations associating dopamine signaling factors in the hypothalamus, to autism-related severity and body weight. In contrast, we found no significant effects of HFD on autism-related behaviors of C57 mice, though the metabolic effects of the diet were similar for both strains. Our results indicate a direct causative link between diet-induced obesity and worsening of a pre-existing autism-related behavior and emphasize the need

The ethics of complexity. Genetics and autism, a literature review.

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Hens, Kristien; Peeters, Hilde; Dierickx, Kris

2016-04-01

It is commonly believed that the etiology of autism is at least partly explained through genetics. Given the complexity of autism and the variability of the autistic phenotype, genetic research and counseling in this field are also complex and associated with specific ethical questions. Although the ethics of autism genetics, especially with regard to reproductive choices, has been widely discussed on the public fora, an in depth philosophical or bioethical reflection on all aspects of the theme seems to be missing. With this literature review we wanted to map the basic questions and answers that exist in the bioethical literature on autism genetics, research, counseling and reproduction, and provide suggestions as to how the discussion can proceed. We found 19 papers that fitted the description of "bioethics literature focusing on autism genetics," and analyzed their content to distill arguments and themes. We concluded that because of the complexity of autism, and the uncertainty with regard to its status, more ethical reflection is needed before definite conclusions and recommendations can be drawn. Moreover, there is a dearth of bioethical empirical studies querying the opinions of all parties, including people with autism themselves. Such empirical bioethical studies should be urgently done before bioethical conclusions regarding the aims and desirability of research into autism genes can be done. Also, fundamental philosophical reflection on concepts of disease should accompany research into the etiology of autism. © 2016 Wiley Periodicals, Inc.

A case report of two male siblings with autism and duplication of Xq13-q21, a region including three genes predisposing for autism.

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Wentz, Elisabet; Vujic, Mihailo; Kärrstedt, Ewa-Lotta; Erlandsson, Anna; Gillberg, Christopher

2014-05-01

Autism spectrum disorder, severe behaviour problems and duplication of the Xq12 to Xq13 region have recently been described in three male relatives. To describe the psychiatric comorbidity and dysmorphic features, including craniosynostosis, of two male siblings with autism and duplication of the Xq13 to Xq21 region, and attempt to narrow down the number of duplicated genes proposed to be leading to global developmental delay and autism. We performed DNA sequencing of certain exons of the TWIST1 gene, the FGFR2 gene and the FGFR3 gene. We also performed microarray analysis of the DNA. In addition to autism, the two male siblings exhibited severe learning disability, self-injurious behaviour, temper tantrums and hyperactivity, and had no communicative language. Chromosomal analyses were normal. Neither of the two siblings showed mutations of the sequenced exons known to produce craniosynostosis. The microarray analysis detected an extra copy of a region on the long arm of chromosome X, chromosome band Xq13.1-q21.1. Comparison of our two cases with previously described patients allowed us to identify three genes predisposing for autism in the duplicated chromosomal region. Sagittal craniosynostosis is also a new finding linked to the duplication.

Limited impact of Cntn4 mutation on autism-related traits in developing and adult C57BL/6J mice

NARCIS (Netherlands)

Molenhuis, Remco T; Bruining, Hilgo; Remmelink, Esther; de Visser, Leonie; Loos, Maarten; Burbach, J Peter H; Kas, Martien J H

2016-01-01

BACKGROUND: Mouse models offer an essential tool to unravel the impact of genetic mutations on autism-related phenotypes. The behavioral impact of some important candidate gene models for autism spectrum disorder (ASD) has not yet been studied, and existing characterizations mostly describe

Neurodevelopmental Hypothesis about the Etiology of Autism Spectrum Disorders

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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.

The Fragile X Syndrome: Behavioral Phenotype and Learning Disabilities

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Claudia GRAU RUBIO

2016-04-01

Full Text Available In this article, we describe the behavioral phenotype of individuals with Fragile X Syndrome and its impact in the educational scope. This syndrome is characterized by difficulties in sensory integration, cognitive deficits (verbal reasoning, abstract/ visual and cuantitative skills, short term memory, sequential processing, attention and executive processes, language disorders (phonetic-phonologicals, semanticals, morphosyntacticals and pragmaticals and communication disorders, social anxiety, general hyperarousal, autism, non autistic social difficulties, attention deficit and hyperactivity, and learning disabilities. The behavioral phenotype is highly variable and depends on sex, age, and mutation status (full mutation or premutation. The behavioural phenotype has important repercussions in education, as it enables us to understand the learning disabilities and to develop specific intervention strategies.

Autism Spectrum Disorders and Neuropathology of the Cerebellum

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David R Hampson

2015-11-01

Full Text Available The cerebellum contains the largest number of neurons and synapses of any structure in the central nervous system. The concept that the cerebellum is solely involved in fine motor function has become outdated; substantial evidence has accumulated linking the cerebellum with higher cognitive functions including language. Cerebellar deficits have been implicated in autism for more than two decades. The computational power of the cerebellum is essential for many, if not most of the processes that are perturbed in autism including language and communication, social interactions, stereotyped behavior, motor activity and motor coordination, and higher cognitive functions. The link between autism and cerebellar dysfunction should not be surprising to those who study its cellular, physiological, and functional properties. Postmortem studies have revealed neuropathological abnormalities in cerebellar cellular architecture while studies on mouse lines with cell loss or mutations in single genes restricted to cerebellar Purkinje cells have also strongly implicated this brain structure in contributing to the autistic phenotype. This connection has been further substantiated by studies investigating brain damage in humans restricted to the cerebellum. In this review, we summarize advances in research on idiopathic autism and three genetic forms of autism that highlight the key roles that the cerebellum plays in this spectrum of neurodevelopmental disorders.

Autism spectrum disorders and neuropathology of the cerebellum.

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Hampson, David R; Blatt, Gene J

2015-01-01

The cerebellum contains the largest number of neurons and synapses of any structure in the central nervous system. The concept that the cerebellum is solely involved in fine motor function has become outdated; substantial evidence has accumulated linking the cerebellum with higher cognitive functions including language. Cerebellar deficits have been implicated in autism for more than two decades. The computational power of the cerebellum is essential for many, if not most of the processes that are perturbed in autism including language and communication, social interactions, stereotyped behavior, motor activity and motor coordination, and higher cognitive functions. The link between autism and cerebellar dysfunction should not be surprising to those who study its cellular, physiological, and functional properties. Postmortem studies have revealed neuropathological abnormalities in cerebellar cellular architecture while studies on mouse lines with cell loss or mutations in single genes restricted to cerebellar Purkinje cells have also strongly implicated this brain structure in contributing to the autistic phenotype. This connection has been further substantiated by studies investigating brain damage in humans restricted to the cerebellum. In this review, we summarize advances in research on idiopathic autism and three genetic forms of autism that highlight the key roles that the cerebellum plays in this spectrum of neurodevelopmental disorders.

High-Resolution Chromosome Ideogram Representation of Currently Recognized Genes for Autism Spectrum Disorders

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Merlin G. Butler

2015-03-01

Full Text Available Recently, autism-related research has focused on the identification of various genes and disturbed pathways causing the genetically heterogeneous group of autism spectrum disorders (ASD. The list of autism-related genes has significantly increased due to better awareness with advances in genetic technology and expanding searchable genomic databases. We compiled a master list of known and clinically relevant autism spectrum disorder genes identified with supporting evidence from peer-reviewed medical literature sources by searching key words related to autism and genetics and from authoritative autism-related public access websites, such as the Simons Foundation Autism Research Institute autism genomic database dedicated to gene discovery and characterization. Our list consists of 792 genes arranged in alphabetical order in tabular form with gene symbols placed on high-resolution human chromosome ideograms, thereby enabling clinical and laboratory geneticists and genetic counsellors to access convenient visual images of the location and distribution of ASD genes. Meaningful correlations of the observed phenotype in patients with suspected/confirmed ASD gene(s at the chromosome region or breakpoint band site can be made to inform diagnosis and gene-based personalized care and provide genetic counselling for families.

Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors.

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Rothwell, Patrick E; Fuccillo, Marc V; Maxeiner, Stephan; Hayton, Scott J; Gokce, Ozgun; Lim, Byung Kook; Fowler, Stephen C; Malenka, Robert C; Südhof, Thomas C

2014-07-03

In humans, neuroligin-3 mutations are associated with autism, whereas in mice, the corresponding mutations produce robust synaptic and behavioral changes. However, different neuroligin-3 mutations cause largely distinct phenotypes in mice, and no causal relationship links a specific synaptic dysfunction to a behavioral change. Using rotarod motor learning as a proxy for acquired repetitive behaviors in mice, we found that different neuroligin-3 mutations uniformly enhanced formation of repetitive motor routines. Surprisingly, neuroligin-3 mutations caused this phenotype not via changes in the cerebellum or dorsal striatum but via a selective synaptic impairment in the nucleus accumbens/ventral striatum. Here, neuroligin-3 mutations increased rotarod learning by specifically impeding synaptic inhibition onto D1-dopamine receptor-expressing but not D2-dopamine receptor-expressing medium spiny neurons. Our data thus suggest that different autism-associated neuroligin-3 mutations cause a common increase in acquired repetitive behaviors by impairing a specific striatal synapse and thereby provide a plausible circuit substrate for autism pathophysiology. Copyright © 2014 Elsevier Inc. All rights reserved.

Does sex influence the diagnostic evaluation of autism spectrum disorder in adults?

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Wilson, C Ellie; Murphy, Clodagh M; McAlonan, Grainne; Robertson, Dene M; Spain, Debbie; Hayward, Hannah; Woodhouse, Emma; Deeley, P Quinton; Gillan, Nicola; Ohlsen, J Chris; Zinkstok, Janneke; Stoencheva, Vladimira; Faulkner, Jessica; Yildiran, Hatice; Bell, Vaughan; Hammond, Neil; Craig, Michael C; Murphy, Declan GM

2016-01-01

It is unknown whether sex influences the diagnostic evaluation of autism spectrum disorder, or whether male and female adults within the spectrum have different symptom profiles. This study reports sex differences in clinical outcomes for 1244 adults (935 males and 309 females) referred for autism spectrum disorder assessment. Significantly, more males (72%) than females (66%) were diagnosed with an autism spectrum disorder of any subtype (x2 = 4.09; p = 0.04). In high-functioning autism spectrum disorder adults (IQ > 70; N = 827), there were no significant sex differences in severity of socio-communicative domain symptoms. Males had significantly more repetitive behaviours/restricted interests than females (p = 0.001, d = 0.3). A multivariate analysis of variance indicated a significant interaction between autism spectrum disorder subtype (full-autism spectrum disorder/partial-autism spectrum disorder) and sex: in full-autism spectrum disorder, males had more severe socio-communicative symptoms than females; for partial-autism spectrum disorder, the reverse was true. There were no sex differences in prevalence of co-morbid psychopathologies. Sex influenced diagnostic evaluation in a clinical sample of adults with suspected autism spectrum disorder. The sexes may present with different manifestations of the autism spectrum disorder phenotype and differences vary by diagnostic subtype. Understanding and awareness of adult female repetitive behaviours/restricted interests warrant attention and sex-specific diagnostic assessment tools may need to be considered. PMID:26802113

The effects of birth order and birth interval on the phenotypic expression of autism spectrum disorder.

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Loren A Martin

Full Text Available A rise in the prevalence of diagnosed cases of autism spectrum disorder (ASD has been reported in several studies in recent years. While this rise in ASD prevalence is at least partially related to increased awareness and broadened diagnostic criteria, the role of environmental factors cannot be ruled out, especially considering that the cause of most cases of ASD remains unknown. The study of families with multiple affected children can provide clues about ASD etiology. While the majority of research on ASD multiplex families has focused on identifying genetic anomalies that may underlie the disorder, the study of symptom severity across ASD birth order may provide evidence for environmental factors in ASD. We compared social and cognitive measures of behavior between over 300 first and second affected siblings within multiplex autism families obtained from the Autism Genetic Resource Exchange dataset. Measures included nonverbal IQ assessed with the Ravens Colored Progressive Matrices, verbal IQ assessed with the Peabody Picture Vocabulary Test, and autism severity assessed with the Social Responsiveness Scale (SRS, an instrument established as a quantitative measure of autism. The results indicated that females were more severely impacted by ASD than males, especially first affected siblings. When first and second affected siblings were compared, significant declines in nonverbal and verbal IQ scores were observed. In addition, SRS results demonstrated a significant increase in autism severity between first and second affected siblings consistent with an overall decline in function as indicated by the IQ data. These results remained significant after controlling for the age and sex of the siblings. Surprisingly, the SRS scores were found to only be significant when the age difference between siblings was less than 2 years. These results suggest that some cases of ASD are influenced by a dosage effect involving unknown epigenetic

Coalitional game theory as a promising approach to identify candidate autism genes.

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Gupta, Anika; Sun, Min Woo; Paskov, Kelley Marie; Stockham, Nate Tyler; Jung, Jae-Yoon; Wall, Dennis Paul

2018-01-01

Despite mounting evidence for the strong role of genetics in the phenotypic manifestation of Autism Spectrum Disorder (ASD), the specific genes responsible for the variable forms of ASD remain undefined. ASD may be best explained by a combinatorial genetic model with varying epistatic interactions across many small effect mutations. Coalitional or cooperative game theory is a technique that studies the combined effects of groups of players, known as coalitions, seeking to identify players who tend to improve the performance--the relationship to a specific disease phenotype--of any coalition they join. This method has been previously shown to boost biologically informative signal in gene expression data but to-date has not been applied to the search for cooperative mutations among putative ASD genes. We describe our approach to highlight genes relevant to ASD using coalitional game theory on alteration data of 1,965 fully sequenced genomes from 756 multiplex families. Alterations were encoded into binary matrices for ASD (case) and unaffected (control) samples, indicating likely gene-disrupting, inherited mutations in altered genes. To determine individual gene contributions given an ASD phenotype, a "player" metric, referred to as the Shapley value, was calculated for each gene in the case and control cohorts. Sixty seven genes were found to have significantly elevated player scores and likely represent significant contributors to the genetic coordination underlying ASD. Using network and cross-study analysis, we found that these genes are involved in biological pathways known to be affected in the autism cases and that a subset directly interact with several genes known to have strong associations to autism. These findings suggest that coalitional game theory can be applied to large-scale genomic data to identify hidden yet influential players in complex polygenic disorders such as autism.

Autism

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... Staying Safe Videos for Educators Search English Español Autism KidsHealth / For Teens / Autism What's in this article? ... With Autism? Print en español Autismo What Is Autism? Autism (also called "autism spectrum disorder") is a ...

Language performance in siblings of nonverbal children with autism.

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Levy, Yonata; Bar-Yuda, Chanit

2011-05-01

The study focuses on language and cognitive abilities of siblings of the linguistically most affected children with autism (i.e. siblings of nonverbal children - SIBS-ANV). Twenty-eight SIBS-ANV (17 boys), ages 4-9 years, took part in the study. All children attended regular schools, and none had received a diagnosis of autism. Controls were 27 typically developing children (SIBS-TD; 16 boys) matched to the SIBS-ANV on age, family background, socioeconomic status and type of school they attended. Significant IQ differences, as well as language differences as measured on the Clinical Evaluation of Language Fundamentals (CELF), emerged between SIBS-ANV and SIBS-TD. However, differences in the language scores mostly disappeared when PIQ and FSIQ were controlled for. Furthermore, grammatical analysis of spontaneous speech samples produced in the course of testing did not reveal any significant differences between the groups. These results add to recent work suggesting that language deficits may not be part of the Broad Autism Phenotype (BAP). It further suggests that the cognitive deficit characteristic of nonverbal people with autism may be familial.

Changes in insulin-like growth factor signaling alter phenotypes in Fragile X Mice.

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Wise, T L

2017-02-01

Fragile X syndrome (FXS) is an inherited form of intellectual disability that is usually caused by expansion of a polymorphic CGG repeat in the 5' untranslated region of the X-linked FMR1 gene, which leads to hypermethylation and transcriptional silencing. Two non-neurological phenotypes of FXS are enlarged testes and connective tissue dysplasia, which could be caused by alterations in a growth factor signaling pathway. FXS patients also frequently have autistic-like symptoms, suggesting that the signaling pathways affected in FXS may overlap with those affected in autism. Identifying these pathways is important for both understanding the effects of FMR1 inactivation and developing treatments for both FXS and autism. Here we show that decreasing the levels of the insulin-like growth factor (Igf) receptor 1 corrects a number of phenotypes in the mouse model of FXS, including macro-orchidism, and that increasing the levels of IGF2 exacerbates the seizure susceptibility phenotype. These results suggest that the pathways altered by the loss of the FMR1-encoded protein (FMRP) may overlap with the pathways affected by changes in Igf signaling or that one or more of the proteins that play a role in Igf signaling could interact with FMRP. They also indicate a new set of potential targets for drug treatment of FXS and autism spectrum disorders. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Potential Biomarkers for Diagnosis and Screening of Autism Spectrum Disorders

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Anna Meiliana

2014-12-01

Full Text Available BACKGROUND: Autism spectrum disorder (ASD is a highly heritable neurodevelopmental condition, which is typically characterized by a triad of symptoms: impaired social communication, social reciprocity and repetitive stereotypic behavior. While the behavioral phenotype of ASD is well described, the search for reliable ‘autism biomarkers’ continues. CONTENT: Insulin growth factor (IGF is essential for the myelination of developing fetal neurons; this is in addition to the well-known links between IGF, maternal inflammation, infection and autism supporting IGF as a potential marker. Combining IGF data with data regarding levels of the known markers, serotonin and anti-myelin basic protein, in order to calculate an autism index, could provide a new diagnostic method for at-risk neonates. Disruptions to multiple pathophysiological systems, including redox, folate, methylation, tryptophan metabolism, and mitochondrial metabolism, have been well documented in autistic patients. Maternal infection and inflammation have known links with autism. Autoimmunity has therefore been a well-studied area of autism research. The potential of using autoantibodies as novel biomarkers for autism, in addition to providing insights into the neurodevelopmental processes that lead to autism. SUMMARY: The six proposed causes of autism involve both metabolic and immunologic dysfunctions and include: increased oxidative stress; decreased methionine metabolism and trans-sulfuration: aberrant free and bound metal burden; gastrointestinal (GI disturbances; immune/inflammation dysregulation; and autoimmune targeting. A newborn screening program for early-onset ASD should be capable of utilizing a combination of ASD-associated biomarkers representative of the six proposed causes of autism in order to identify newborns at risk. The biomarkers discussed in this article are useful to guide the selection, efficacy and sufficiency of biomedical interventions, which would likely

Comprehensive Analysis of the 16p11.2 Deletion and Null Cntnap2 Mouse Models of Autism Spectrum Disorder.

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Daniela Brunner

Full Text Available Autism spectrum disorder comprises several neurodevelopmental conditions presenting symptoms in social communication and restricted, repetitive behaviors. A major roadblock for drug development for autism is the lack of robust behavioral signatures predictive of clinical efficacy. To address this issue, we further characterized, in a uniform and rigorous way, mouse models of autism that are of interest because of their construct validity and wide availability to the scientific community. We implemented a broad behavioral battery that included but was not restricted to core autism domains, with the goal of identifying robust, reliable phenotypes amenable for further testing. Here we describe comprehensive findings from two known mouse models of autism, obtained at different developmental stages, using a systematic behavioral test battery combining standard tests as well as novel, quantitative, computer-vision based systems. The first mouse model recapitulates a deletion in human chromosome 16p11.2, found in 1% of individuals with autism. The second mouse model harbors homozygous null mutations in Cntnap2, associated with autism and Pitt-Hopkins-like syndrome. Consistent with previous results, 16p11.2 heterozygous null mice, also known as Del(7Slx1b-Sept14Aam weighed less than wild type littermates displayed hyperactivity and no social deficits. Cntnap2 homozygous null mice were also hyperactive, froze less during testing, showed a mild gait phenotype and deficits in the three-chamber social preference test, although less robust than previously published. In the open field test with exposure to urine of an estrous female, however, the Cntnap2 null mice showed reduced vocalizations. In addition, Cntnap2 null mice performed slightly better in a cognitive procedural learning test. Although finding and replicating robust behavioral phenotypes in animal models is a challenging task, such functional readouts remain important in the development of

Commentary: Potential Neurobiologic Mechanisms through Which Metabolic Disorders Could Relate to Autism.

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Johnston, Michael V.

2000-01-01

To illustrate the possible relationships between metabolic disorders and autism, this commentary reviews findings from studies on the characteristics of individuals with Rett syndrome that indicate the genetic mechanism of transcriptional dysregulation can produce pathologic phenotypes which resemble metabolic disorders that stunt axonodendritic…

Solitary mammals provide an animal model for autism spectrum disorders.

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Reser, Jared Edward

2014-02-01

Species of solitary mammals are known to exhibit specialized, neurological adaptations that prepare them to focus working memory on food procurement and survival rather than on social interaction. Solitary and nonmonogamous mammals, which do not form strong social bonds, have been documented to exhibit behaviors and biomarkers that are similar to endophenotypes in autism. Both individuals on the autism spectrum and certain solitary mammals have been reported to be low on measures of affiliative need, bodily expressiveness, bonding and attachment, direct and shared gazing, emotional engagement, conspecific recognition, partner preference, separation distress, and social approach behavior. Solitary mammals also exhibit certain biomarkers that are characteristic of autism, including diminished oxytocin and vasopressin signaling, dysregulation of the endogenous opioid system, increased Hypothalamic-pituitary-adrenal axis (HPA) activity to social encounters, and reduced HPA activity to separation and isolation. The extent of these similarities suggests that solitary mammals may offer a useful model of autism spectrum disorders and an opportunity for investigating genetic and epigenetic etiological factors. If the brain in autism can be shown to exhibit distinct homologous or homoplastic similarities to the brains of solitary animals, it will reveal that they may be central to the phenotype and should be targeted for further investigation. Research of the neurological, cellular, and molecular basis of these specializations in other mammals may provide insight for behavioral analysis, communication intervention, and psychopharmacology for autism.

Examination of tetrahydrobiopterin pathway genes in autism.

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Schnetz-Boutaud, N C; Anderson, B M; Brown, K D; Wright, H H; Abramson, R K; Cuccaro, M L; Gilbert, J R; Pericak-Vance, M A; Haines, J L

2009-11-01

Autism is a complex disorder with a high degree of heritability and significant phenotypic and genotypic heterogeneity. Although candidate gene studies and genome-wide screens have failed to identify major causal loci associated with autism, numerous studies have proposed association with several variations in genes in the dopaminergic and serotonergic pathways. Because tetrahydrobiopterin (BH4) is the essential cofactor in the synthesis of these two neurotransmitters, we genotyped 25 SNPs in nine genes of the BH4 pathway in a total of 403 families. Significant nominal association was detected in the gene for 6-pyruvoyl-tetrahydropterin synthase, PTS (chromosome 11), with P = 0.009; this result was not restricted to an affected male-only subset. Multilocus interaction was detected in the BH4 pathway alone, but not across the serotonin, dopamine and BH4 pathways.

Social-Ecological Correlates in Adult Autism Outcome Studies: A Scoping Review.

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Anderson, Kristy A; Roux, Anne M; Kuo, Alice; Shattuck, Paul T

2018-04-01

The transition into adulthood is a critical period in the life course that shapes later outcomes. Many adults on the autism spectrum fare poorly across a wide range of quality of life indicators. Understanding the multilevel factors that influence transition outcomes is necessary to develop strategies that promote better outcomes. In this scoping review, we characterize the use of social-ecological factors in adult autism outcome studies, identify understudied areas of research, and provide recommendations for future research. We conducted a literature search for studies in which the relationship between social-ecological factors and transition outcomes among transition-age youth with autism was assessed. We organized variables used in studies across 5 levels of influence: family-, interpersonal-, institutional-, community-, and policy-level factors. Our findings reveal that both breadth and depth of social-ecological factors usage in autism outcomes studies is limited because of the narrow inclusion of variables across social-ecological levels, the overreliance on a limited number of national data sets, and the overall lack of variation in research design. We propose 9 recommendations to inform the development of multilevel studies. Copyright © 2018 by the American Academy of Pediatrics.

Molecular and phenotypic abnormalities in individuals with germline heterozygous PTEN mutations and autism.

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Frazier, T W; Embacher, R; Tilot, A K; Koenig, K; Mester, J; Eng, C

2015-09-01

PTEN is a tumor suppressor associated with an inherited cancer syndrome and an important regulator of ongoing neural connectivity and plasticity. The present study examined molecular and phenotypic characteristics of individuals with germline heterozygous PTEN mutations and autism spectrum disorder (ASD) (PTEN-ASD), with the aim of identifying pathophysiologic markers that specifically associate with PTEN-ASD and that may serve as targets for future treatment trials. PTEN-ASD patients (n=17) were compared with idiopathic (non-PTEN) ASD patients with (macro-ASD, n=16) and without macrocephaly (normo-ASD, n=38) and healthy controls (n=14). Group differences were evaluated for PTEN pathway protein expression levels, global and regional structural brain volumes and cortical thickness measures, neurocognition and adaptive behavior. RNA expression patterns and brain characteristics of a murine model of Pten mislocalization were used to further evaluate abnormalities observed in human PTEN-ASD patients. PTEN-ASD had a high proportion of missense mutations and showed reduced PTEN protein levels. Compared with the other groups, prominent white-matter and cognitive abnormalities were specifically associated with PTEN-ASD patients, with strong reductions in processing speed and working memory. White-matter abnormalities mediated the relationship between PTEN protein reductions and reduced cognitive ability. The Pten(m3m4) murine model had differential expression of genes related to myelination and increased corpus callosum. Processing speed and working memory deficits and white-matter abnormalities may serve as useful features that signal clinicians that PTEN is etiologic and prompting referral to genetic professionals for gene testing, genetic counseling and cancer risk management; and could reveal treatment targets in trials of treatments for PTEN-ASD.

Comorbidity of intellectual disability confounds ascertainment of autism: implications for genetic diagnosis.

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Polyak, Andrew; Kubina, Richard M; Girirajan, Santhosh

2015-10-01

While recent studies suggest a converging role for genetic factors towards risk for nosologically distinct disorders including autism, intellectual disability (ID), and epilepsy, current estimates of autism prevalence fail to take into account the impact of comorbidity of these disorders on autism diagnosis. We aimed to assess the effect of comorbidity on the diagnosis and prevalence of autism by analyzing 11 years (2000-2010) of special education enrollment data on approximately 6.2 million children per year. We found a 331% increase in the prevalence of autism from 2000 to 2010 within special education, potentially due to a diagnostic recategorization from frequently comorbid features such as ID. The decrease in ID prevalence equaled an average of 64.2% of the increase of autism prevalence for children aged 3-18 years. The proportion of ID cases potentially undergoing recategorization to autism was higher (P = 0.007) among older children (75%) than younger children (48%). Some US states showed significant negative correlations between the prevalence of autism compared to that of ID while others did not, suggesting state-specific health policy to be a major factor in categorizing autism. Further, a high frequency of autistic features was observed when individuals with classically defined genetic syndromes were evaluated for autism using standardized instruments. Our results suggest that current ascertainment practices are based on a single facet of autism-specific clinical features and do not consider associated comorbidities that may confound diagnosis. Longitudinal studies with detailed phenotyping and deep molecular genetic analyses are necessary to completely understand the cause of this complex disorder. © 2015 Wiley Periodicals, Inc.

The relationship between tics, OC, ADHD and autism symptoms : A cross-disorder symptom analysis in Gilles de la Tourette syndrome patients and family-members

NARCIS (Netherlands)

van Dijk, H.M.; van de Schoot, A.G.J.; Rijkeboer, M.M.; Mathews, C.A.; Cath, D.C.

2016-01-01

Gilles de la Tourette's syndrome (GTS) is a disorder in which obsessive-compulsive (OC), Attention Deficit Hyperactivity Disorder (ADHD) and autism symptoms occur in up to 60% of patients, suggesting shared etiology. We explored the phenotypic structure of tic, OC, ADHD, and autism symptoms as

SERT Ileu425Val in autism, Asperger syndrome and obsessive-compulsive disorder.

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Wendland, Jens R; DeGuzman, Theresa B; McMahon, Francis; Rudnick, Gary; Detera-Wadleigh, Sevilla D; Murphy, Dennis L

2008-02-01

SERT I425V, an uncommon missense single nucleotide polymorphism producing a gain-of-function of the serotonin transporter (SERT), was originally found to segregate with a primarily obsessive-compulsive disorder (OCD) but complexly comorbid phenotype in two unrelated families. As two individuals with SERT I425V and OCD also had Asperger syndrome (AS), an autism spectrum disorder, and as other rare SERT variants have recently shown significant associations with autism, we set out to extend our original OCD study by genotyping additional autism/AS and OCD samples. Case-control association study of SERT I425V in 210 AS/autism probands and 215 controls, plus 335 OCD probands and their family members. SERT I425V was not found in any of the individuals with AS/autism, OCD alone or OCD comorbid with AS and other disorders, or in controls. This results in new estimates of SERT I425V having a 1.5% prevalence in 530 individuals with OCD from five unrelated families genotyped by us and by one other group and a 0.23% frequency in four control populations totaling 1300 individuals, yielding a continuing significant OCD-control difference (Fisher's exact test corrected for family coefficient of identity P=0.004, odds ratio=6.54). As several other uncommon, less well quantitated genetic variations occur with an OCD phenotype, including chromosomal anomalies and some other rare gene variants (SGCE, GCH1 and SLITRK1), a tentative conclusion is that OCD resembles other complex disorders in being etiologically heterogeneous and in having both highly penetrant familial subtypes associated with rare alleles or chromosomal anomalies, as well as having a more common, polygenetic form that may involve polymorphisms in such genes as BDNF, COMT, GRIN2beta, TPH2, HTR2A and SLC1A1.

A large de novo distal 16p11.2 deletion in a patient with normal intelligence: Evidence for a neuropsychological phenotype

NARCIS (Netherlands)

Egger, J.I.M.; Verhoeven, W.M.A.; Verbeeck, W.J.C.; Leeuw, N. de

2014-01-01

Objective: The 16p11.2 microdeletion syndrome is characterized by a wide range of phenotypic expressions and is often associated with developmental delay, symptoms from the autism spectrum, epilepsy, congenital anomalies and obesity. Usually, these phenotypes are related to a proximal 16p11.2

Neuropsychological phenotype of a patient with a de novo 970 kb interstitial deletion in the distal 16p11.2 region

NARCIS (Netherlands)

Egger, J.I.; Verhoeven, W.M.A.; Verbeeck, W.J.C.; Leeuw, N. de

2014-01-01

The 16p11.2 microdeletion syndrome is characterized by a wide range of phenotypic expressions and is frequently associated with developmental delay, symptoms from the autism spectrum, epilepsy, congenital anomalies, and obesity. These phenotypes are often related to a proximal 16p11.2 deletion of

Neuropsychological phenotype of a patient with a de novo 970 kb interstitial deletion in the distal 16p11.2 region

NARCIS (Netherlands)

J.I.M. Egger (Jos); W.M.A. Verhoeven (Wim); W. Verbeeck (Wim); N. de Leeuw (Nicole)

2014-01-01

textabstractThe 16p11.2 microdeletion syndrome is characterized by a wide range of phenotypic expressions and is frequently associated with developmental delay, symptoms from the autism spectrum, epilepsy, congenital anomalies, and obesity. These phenotypes are often related to a proximal 16p11.2

Autism and Related Disorders

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McPartland, James; Volkmar, Fred R.

2012-01-01

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

Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13.

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Nurmi, Erika L; Dowd, Michael; Tadevosyan-Leyfer, Ovsanna; Haines, Jonathan L; Folstein, Susan E; Sutcliffe, James S

2003-07-01

Autism displays a remarkably high heritability but a complex genetic etiology. One approach to identifying susceptibility loci under these conditions is to define more homogeneous subsets of families on the basis of genetically relevant phenotypic or biological characteristics that vary from case to case. The authors performed a principal components analysis, using items from the Autism Diagnostic Interview, which resulted in six clusters of variables, five of which showed significant sib-sib correlation. The utility of these phenotypic subsets was tested in an exploratory genetic analysis of the autism candidate region on chromosome 15q11-q13. When the Collaborative Linkage Study of Autism sample was divided, on the basis of mean proband score for the "savant skills" cluster, the heterogeneity logarithm of the odds under a recessive model at D15S511, within the GABRB3 gene, increased from 0.6 to 2.6 in the subset of families in which probands had greater savant skills. These data are consistent with the genetic contribution of a 15q locus to autism susceptibility in a subset of affected individuals exhibiting savant skills. Similar types of skills have been noted in individuals with Prader-Willi syndrome, which results from deletions of this chromosomal region.

Clustering autism: using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity.

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Ellegood, J; Anagnostou, E; Babineau, B A; Crawley, J N; Lin, L; Genestine, M; DiCicco-Bloom, E; Lai, J K Y; Foster, J A; Peñagarikano, O; Geschwind, D H; Pacey, L K; Hampson, D R; Laliberté, C L; Mills, A A; Tam, E; Osborne, L R; Kouser, M; Espinosa-Becerra, F; Xuan, Z; Powell, C M; Raznahan, A; Robins, D M; Nakai, N; Nakatani, J; Takumi, T; van Eede, M C; Kerr, T M; Muller, C; Blakely, R D; Veenstra-VanderWeele, J; Henkelman, R M; Lerch, J P

2015-02-01

Autism is a heritable disorder, with over 250 associated genes identified to date, yet no single gene accounts for >1-2% of cases. The clinical presentation, behavioural symptoms, imaging and histopathology findings are strikingly heterogeneous. A more complete understanding of autism can be obtained by examining multiple genetic or behavioural mouse models of autism using magnetic resonance imaging (MRI)-based neuroanatomical phenotyping. Twenty-six different mouse models were examined and the consistently found abnormal brain regions across models were parieto-temporal lobe, cerebellar cortex, frontal lobe, hypothalamus and striatum. These models separated into three distinct clusters, two of which can be linked to the under and over-connectivity found in autism. These clusters also identified previously unknown connections between Nrxn1α, En2 and Fmr1; Nlgn3, BTBR and Slc6A4; and also between X monosomy and Mecp2. With no single treatment for autism found, clustering autism using neuroanatomy and identifying these strong connections may prove to be a crucial step in predicting treatment response.

Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder

NARCIS (Netherlands)

Yuen, Ryan K C; Merico, Daniele; Bookman, Matt; Howe, Jennifer L.; Thiruvahindrapuram, Bhooma; Patel, Rohan V.; Whitney, Joe; Deflaux, Nicole; Bingham, Jonathan; Wang, Zhuozhi; Pellecchia, Giovanna; Buchanan, Janet A.; Walker, Susan; Marshall, Christian R.; Uddin, Mohammed; Zarrei, Mehdi; Deneault, Eric; D'Abate, Lia; Chan, Ada J S; Koyanagi, Stephanie; Paton, Tara; Pereira, Sergio L.; Hoang, Ny; Engchuan, Worrawat; Higginbotham, Edward J.; Ho, Karen; Lamoureux, Sylvia; Li, Weili; MacDonald, Jeffrey R.; Nalpathamkalam, Thomas; Sung, Wilson W L; Tsoi, Fiona J.; Wei, John; Xu, Lizhen; Tasse, Anne Marie; Kirby, Emily; Van Etten, William; Twigger, Simon; Roberts, Wendy; Drmic, Irene; Jilderda, Sanne; Modi, Bonnie Mackinnon; Kellam, Barbara; Szego, Michael; Cytrynbaum, Cheryl; Weksberg, Rosanna; Zwaigenbaum, Lonnie; Woodbury-Smith, Marc; Brian, Jessica; Senman, Lili; Iaboni, Alana; Doyle-Thomas, Krissy; Thompson, Ann; Chrysler, Christina; Leef, Jonathan; Savion-Lemieux, Tal; Smith, Isabel M.; Liu, Xudong; Nicolson, Rob; Seifer, Vicki; Fedele, Angie; Cook, Edwin H.; Dager, Stephen; Estes, Annette; Gallagher, Louise; Malow, Beth A.; Parr, Jeremy R.; Spence, Sarah J.; Vorstman, Jacob; Frey, Brendan J.; Robinson, James T.; Strug, Lisa J.; Fernandez, Bridget A.; Elsabbagh, Mayada; Carter, Melissa T.; Hallmayer, Joachim; Knoppers, Bartha M.; Anagnostou, Evdokia; Szatmari, Peter; Ring, Robert H.; Glazer, David; Pletcher, Mathew T.; Scherer, Stephen W.

2017-01-01

We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information,

Autism and epistemology IV: Does autism need a theory of mind?

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Fisch, Gene S

2013-10-01

In their article, "Does the autistic child have a 'theory of mind'?," Baron-Cohen et al. [1985] proposed a novel paradigm to explain social impairment in children diagnosed as autistic (AD). Much research has been undertaken since their article went to print. The purpose of this commentary is to gauge whether Theory of Mind (ToM)-or lack thereof-is a valid model for explaining abnormal social behavior in children with AD. ToM is defined as "the ability to impute mental states to oneself and to others" and "the ability to make inferences about what other people believe to be the case." The source for their model was provided by an article published earlier by Premack and Woodruff, "Does the chimpanzee have a theory of mind?" Later research in chimpanzees did not support a ToM in primates. From the outset, ToM as a neurocognitive model of autism has had many shortcomings-methodological, logical, and empirical. Other ToM assumptions, for example, its universality in all children in all cultures and socioeconomic conditions, are not supported by data. The age at which a ToM emerges, or events that presage a ToM, are too often not corroborated. Recent studies of mirror neurons, their location and interconnections in brain, their relationship to social behavior and language, and the effect of lesions there on speech, language and social behavior, strongly suggests that a neurobiological as opposed to neurocognitive model of autism is a more parsimonious explanation for the social and behavioral phenotypes observed in autism. Copyright © 2013 Wiley Periodicals, Inc.

Study the Relationship of Executive Functions with Behavioral Symptoms in Children with High-Functioning Autism

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Vali Shiri

2015-10-01

Full Text Available Objective: The relation between autism disorder’s symptoms and cognitive capabilities can help with a better phenotype description of this disorder and can facilitate its pathological evaluation and treatment. Destruction of executive functions seems to be one of the cognitive reasons of potential phenotype in autism disorder. Thus, the present paper aims to study the relationship between executive dysfunction and autism disorder’s symptoms. Materials & Methods: In this cross-sectional research, 50 children with high-functioning autism were selected using convenience sampling method from Behara, Tehranpars and Roshd centers. Then, the GARS test and Autism Spectrum Screening Questionnaire was completed by therapists and neuropsychological tests of Strop and continuous performance test and shift attention were taken by the subjects. Pearson correlation coefficient and multi-variant regression were used for data analysis. Results: There is a significant positive relationship between selective attention with communicative and social interaction symptoms, sustained attention with social interaction symptoms and repetitive behaviors, shifting attention with communicative, social interaction and repetitive behavior symptoms (P<0.001 (P<0.01 (P<0.05. In addition, the results of regression analysis also revealed that selective attention and shifting attention can predict communication, and sustained attention can predict social interaction and repetitive behaviors symptoms (P<0.01 (P<0.05. Conclusion: The results obtained by this study indicate the significant role of executive functions in autistic symptoms. Thus, it is recommended to consider new treatment interventions in repairing executive functions for treatment of children with autistic disorder.

Impaired Sulfate Metabolism and Epigenetics: Is There a Link in Autism?

Directory of Open Access Journals (Sweden)

Samantha Hartzell

2012-10-01

Full Text Available Autism is a brain disorder involving social, memory, and learning deficits, that normally develops prenatally or early in childhood. Frustratingly, many research dollars have as yet failed to identify the cause of autism. While twin concordance studies indicate a strong genetic component, the alarming rise in the incidence of autism in the last three decades suggests that environmental factors play a key role as well. This dichotomy can be easily explained if we invoke a heritable epigenetic effect as the primary factor. Researchers are just beginning to realize the huge significance of epigenetic effects taking place during gestation in influencing the phenotypical expression. Here, we propose the novel hypothesis that sulfates deficiency in both the mother and the child, brought on mainly by excess exposure to environmental toxins and inadequate sunlight exposure to the skin, leads to widespread hypomethylation in the fetal brain with devastating consequences. We show that many seemingly disparate observations regarding serum markers, neuronal pathologies, and nutritional deficiencies associated with autism can be integrated to support our hypothesis.

Behavioural and cognitive sex/gender differences in autism spectrum condition and typically developing males and females.

Science.gov (United States)

Hull, Laura; Mandy, William; Petrides, K V

2017-08-01

Studies assessing sex/gender differences in autism spectrum conditions often fail to include typically developing control groups. It is, therefore, unclear whether observed sex/gender differences reflect those found in the general population or are particular to autism spectrum conditions. A systematic search identified articles comparing behavioural and cognitive characteristics in males and females with and without an autism spectrum condition diagnosis. A total of 13 studies were included in meta-analyses of sex/gender differences in core autism spectrum condition symptoms (social/communication impairments and restricted/repetitive behaviours and interests) and intelligence quotient. A total of 20 studies were included in a qualitative review of sex/gender differences in additional autism spectrum condition symptoms. For core traits and intelligence quotient, sex/gender differences were comparable in autism spectrum conditions and typical samples. Some additional autism spectrum condition symptoms displayed different patterns of sex/gender differences in autism spectrum conditions and typically developing groups, including measures of executive function, empathising and systemising traits, internalising and externalising problems and play behaviours. Individuals with autism spectrum conditions display typical sex/gender differences in core autism spectrum condition traits, suggesting that diagnostic criteria based on these symptoms should take into account typical sex/gender differences. However, awareness of associated autism spectrum condition symptoms should include the possibility of different male and female phenotypes, to ensure those who do not fit the 'typical' autism spectrum condition presentation are not missed.

Evidence for a Cultural Influence on Field-Independence in Autism Spectrum Disorder

Science.gov (United States)

Koh, Hwan Cui; Milne, Elizabeth

2012-01-01

Field-independence, or weak central coherence, is a recognised phenotype of autism spectrum disorder (ASD). There is also evidence of cultural variation in this perceptual style, as neurotypical individuals from Western nations are more field-independent than neurotypical individuals from East-Asian nations. The majority of research on perceptual…

Phelan-McDermid syndrome in two adult brothers: Atypical bipolar disorder as its psychopathological phenotype?

NARCIS (Netherlands)

Verhoeven, W.M.A.; Egger, J.I.M.; Willemsen, M.H.; Leijer, G.J.M. de; Kleefstra, T.

2012-01-01

The 22q13.3 deletion, or Phelan-McDermid syndrome, is characterized by global intellectual disability, generalized hypotonia, severely delayed or absent speech associated with features of autism spectrum disorder, and minor dysmorphisms. Its behavioral phenotype comprises sleep disturbances,

Phelan-McDermid syndrome in two adult brothers: atypical bipolar disorder as its psychopathological phenotype?

NARCIS (Netherlands)

Verhoeven, W.M.; Egger, J.I.; Willemsen, M.H.; de Leijer, G.J.; Kleefstra, T.

2012-01-01

The 22q13.3 deletion, or Phelan-McDermid syndrome, is characterized by global intellectual disability, generalized hypotonia, severely delayed or absent speech associated with features of autism spectrum disorder, and minor dysmorphisms. Its behavioral phenotype comprises sleep disturbances,

Phelan-McDermid syndrome in two adult brothers: Atypical bipolar disorder as its psychopathological phenotype?

NARCIS (Netherlands)

W.M.A. Verhoeven (Wim); J.I.M. Egger (Jos); M.H. Willemsen; G.J.M. de Leijer (Gert); T. Kleefstra (Tjitske)

2012-01-01

textabstractThe 22q13.3 deletion, or Phelan-McDermid syndrome, is characterized by global intellectual disability, generalized hypotonia, severely delayed or absent speech associated with features of autism spectrum disorder, and minor dysmorphisms. Its behavioral phenotype comprises sleep

Categorical and dimensional structure of autism spectrum disorders: the nosologic validity of Asperger Syndrome.

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Kamp-Becker, Inge; Smidt, Judith; Ghahreman, Mardjan; Heinzel-Gutenbrunner, Monika; Becker, Katja; Remschmidt, Helmut

2010-08-01

There is an ongoing debate whether a differentiation of autistic subtypes, especially between Asperger Syndrome (AS) and high-functioning-autism (HFA) is possible and if so, whether it is a categorical or dimensional one. The aim of this study was to examine the possible clustering of responses in different symptom domains without making any assumption concerning diagnostic appreciation. About 140 children and adolescents, incorporating 52 with a diagnosis of AS, 44 with HFA, 8 with atypical autism and 36 with other diagnoses, were examined. Our study does not support the thesis that autistic disorders are discrete phenotypes. On the contrary, it provides evidence that e.g. AS and autism are not qualitatively distinct disorders, but rather different quantitative manifestations of the same disorder.

Social behavior and autism traits in a sex chromosomal disorder : Klinefelter (47XXY) syndrome

NARCIS (Netherlands)

van Rijn, Sophie; Swaab, Hanna; Aleman, Andre; Kahn, Rene S.

2008-01-01

Although Klinefelter syndrome (47,XXY) has been associated with psychosocial difficulties, knowledge of the social behavioral phenotype is limited. We examined specific social abilities and autism traits in Klinefelter syndrome. Scores of 31 XXY men on the Scale for Interpersonal Behavior and the

Often Asked but Rarely Answered: Can Asians Meet DSM-5/ICD-10 Autism Spectrum Disorder Criteria?

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Kim, So Hyun; Koh, Yun-Joo; Lim, Eun-Chung; Kim, Soo-Jeong; Leventhal, Bennett L.

2016-01-01

Abstract Objectives: To evaluate whether Asian (Korean children) populations can be validly diagnosed with autism spectrum disorder (ASD) using Western-based diagnostic instruments and criteria based on Diagnostic and Statistical Manual on Mental Disorders, 5th edition (DSM-5). Methods: Participants included an epidemiologically ascertained 7–14-year-old (N = 292) South Korean cohort from a larger prevalence study (N = 55,266). Main outcomes were based on Western-based diagnostic methods for Korean children using gold standard instruments, Autism Diagnostic Interview-Revised, and Autism Diagnostic Observation Schedule. Factor analysis and ANOVAs were performed to examine factor structure of autism symptoms and identify phenotypic differences between Korean children with ASD and non-ASD diagnoses. Results: Using Western-based diagnostic methods, Korean children with ASD were successfully identified with moderate-to-high diagnostic validity (sensitivities/specificities ranging 64%–93%), strong internal consistency, and convergent/concurrent validity. The patterns of autism phenotypes in a Korean population were similar to those observed in a Western population with two symptom domains (social communication and restricted and repetitive behavior factors). Statistically significant differences in the use of socially acceptable communicative behaviors (e.g., direct gaze, range of facial expressions) emerged between ASD versus non-ASD cases (mostly p Korean children) typically use elements of reciprocal social interactions similar to those in the West. Therefore, standardized diagnostic methods widely used for ASD in Western culture can be validly used as part of the assessment process and research with Koreans and, possibly, other Asians. PMID:27315155

Recent Advances in the Pathogenesis of Syndromic Autisms

Directory of Open Access Journals (Sweden)

A. Benvenuto

2009-01-01

Full Text Available Background. Current advances in genetic technology continue to expand the list of medical conditions associated with autism. Clinicians have to identify specific autistic-related syndromes, and to provide tailored counseling. The aim of this study is to elucidate recent advances in autism research that offer important clues into pathogenetic mechanisms of syndromic autism and relevant implications for clinical practice. Data Sources. The PubMed database was searched with the keywords “autism” and “chromosomal abnormalities,” “metabolic diseases,” “susceptibility loci.” Results. Defined mutations, genetic syndromes, and metabolic diseases account for up to 20% of autistic patients. Metabolic and mitochondrial defects may have toxic effects on the brain cells, causing neuronal loss and altered modulation of neurotransmission systems. Alterations of the neocortical excitatory/inhibitory balance and perturbations of interneurons' development represent the most probable pathogenetic mechanisms underlying the autistic phenotype in Fragile X-Syndrome and Tuberous Sclerosis Complex. Chromosomal abnormalities and potential candidate genes are strongly implicated in the disruption of neural connections, brain growth, and synaptic/dendritic morphology. Conclusion. Metabolic testing may be appropriate if specific symptoms are present. High-resolution chromosome analysis may be recommended if a specific diagnosis is suspected because of obvious dysmorphisms. Identifying cryptic chromosomal abnormalities by whole genome microarray analysis can increase the understanding of the neurobiological pathways to autism.

Longitudinal development of thalamic and internal capsule microstructure in autism spectrum disorder.

Science.gov (United States)

McLaughlin, Kristine; Travers, Brittany G; Dadalko, Olga I; Dean, Douglas C; Tromp, Do; Adluru, Nagesh; Destiche, Daniel; Freeman, Abigail; Prigge, Molly D; Froehlich, Alyson; Duffield, Tyler C; Zielinski, Brandon A; Bigler, Erin D; Lange, Nicholas; Anderson, Jeff S; Alexander, Andrew L; Lainhart, Janet E

2018-03-01

The thalamus is a key sensorimotor relay area that is implicated in autism spectrum disorder (ASD). However, it is unknown how the thalamus and white-matter structures that contain thalamo-cortical fiber connections (e.g., the internal capsule) develop from childhood into adulthood and whether this microstructure relates to basic motor challenges in ASD. We used diffusion weighted imaging in a cohort-sequential design to assess longitudinal development of the thalamus, and posterior- and anterior-limbs of the internal capsule (PLIC and ALIC, respectively) in 89 males with ASD and 56 males with typical development (3-41 years; all verbal). Our results showed that the group with ASD exhibited different developmental trajectories of microstructure in all regions, demonstrating childhood group differences that appeared to approach and, in some cases, surpass the typically developing group in adolescence and adulthood. The PLIC (but not ALIC nor thalamus) mediated the relation between age and finger-tapping speed in both groups. Yet, the gap in finger-tapping speed appeared to widen at the same time that the between-group gap in the PLIC appeared to narrow. Overall, these results suggest that childhood group differences in microstructure of the thalamus and PLIC become less robust in adolescence and adulthood. Further, finger-tapping speed appears to be mediated by the PLIC in both groups, but group differences in motor speed that widen during adolescence and adulthood suggest that factors beyond the microstructure of the thalamus and internal capsule may contribute to atypical motor profiles in ASD. Autism Res 2018, 11: 450-462. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Microstructure of the thalamus, a key sensory and motor brain area, appears to develop differently in individuals with autism spectrum disorder (ASD). Microstructure is important because it informs us of the density and organization of different brain tissues. During

Transposition of the great arteries - a phenotype associated with 16p11.2 duplications?

Science.gov (United States)

Karunanithi, Zarmiga; Vestergaard, Else Marie; Lauridsen, Mette H

2017-12-26

Genetic analyses of patients with transposition of the great arteries have identified rare copy number variations, suggesting that they may be significant to the aetiology of the disease. This paper reports the identification of a 16p11.2 microduplication, a variation that has yet to be reported in association with transposition of the great arteries. The 16p11.2 microduplication is associated with autism spectrum disorder and developmental delay, but with highly variable phenotypic effects. Autism and attention deficit disorders are observed more frequently in children with congenital heart disease than in the general population. Neonatal surgery is proposed as a risk factor, but as yet unidentified genetic abnormalities should also be taken into account. Thus, congenital heart abnormalities may constitute a part of the phenotypic spectrum associated with duplications at 16p11.2. We suggest chromosomal microarray be considered part of the diagnostic work-up in patients with transposition of the great arteries.

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…

Comparison of Fecal Microbiota in Children with Autism Spectrum Disorders and Neurotypical Siblings in the Simons Simplex Collection

OpenAIRE

Son, Joshua S.; Zheng, Ling J.; Rowehl, Leahana M.; Tian, Xinyu; Zhang, Yuanhao; Zhu, Wei; Litcher-Kelly, Leighann; Gadow, Kenneth D.; Gathungu, Grace; Robertson, Charles E.; Ir, Diana; Frank, Daniel N.; Li, Ellen

2015-01-01

In order to assess potential associations between autism spectrum disorder (ASD) phenotype, functional GI disorders and fecal microbiota, we recruited simplex families, which had only a single ASD proband and neurotypical (NT) siblings, through the Simons Simplex Community at the Interactive Autism Network (SSC@IAN). Fecal samples and metadata related to functional GI disorders and diet were collected from ASD probands and NT siblings of ASD probands (age 7–14). Functional gastrointestinal di...

Mitochondrial disease in autism spectrum disorder patients: a cohort analysis.

Science.gov (United States)

Weissman, Jacqueline R; Kelley, Richard I; Bauman, Margaret L; Cohen, Bruce H; Murray, Katherine F; Mitchell, Rebecca L; Kern, Rebecca L; Natowicz, Marvin R

2008-01-01

Previous reports indicate an association between autism spectrum disorders (ASD) and disorders of mitochondrial oxidative phosphorylation. One study suggested that children with both diagnoses are clinically indistinguishable from children with idiopathic autism. There are, however, no detailed analyses of the clinical and laboratory findings in a large cohort of these children. Therefore, we undertook a comprehensive review of patients with ASD and a mitochondrial disorder. We reviewed medical records of 25 patients with a primary diagnosis of ASD by DSM-IV-TR criteria, later determined to have enzyme- or mutation-defined mitochondrial electron transport chain (ETC) dysfunction. Twenty-four of 25 patients had one or more major clinical abnormalities uncommon in idiopathic autism. Twenty-one patients had histories of significant non-neurological medical problems. Nineteen patients exhibited constitutional symptoms, especially excessive fatigability. Fifteen patients had abnormal neurological findings. Unusual developmental phenotypes included marked delay in early gross motor milestones (32%) and unusual patterns of regression (40%). Levels of blood lactate, plasma alanine, and serum ALT and/or AST were increased at least once in 76%, 36%, and 52% of patients, respectively. The most common ETC disorders were deficiencies of complex I (64%) and complex III (20%). Two patients had rare mtDNA mutations of likely pathogenicity. Although all patients' initial diagnosis was idiopathic autism, careful clinical and biochemical assessment identified clinical findings that differentiated them from children with idiopathic autism. These and prior data suggest a disturbance of mitochondrial energy production as an underlying pathophysiological mechanism in a subset of individuals with autism.

Mitochondrial disease in autism spectrum disorder patients: a cohort analysis.

Directory of Open Access Journals (Sweden)

Jacqueline R Weissman

Full Text Available Previous reports indicate an association between autism spectrum disorders (ASD and disorders of mitochondrial oxidative phosphorylation. One study suggested that children with both diagnoses are clinically indistinguishable from children with idiopathic autism. There are, however, no detailed analyses of the clinical and laboratory findings in a large cohort of these children. Therefore, we undertook a comprehensive review of patients with ASD and a mitochondrial disorder.We reviewed medical records of 25 patients with a primary diagnosis of ASD by DSM-IV-TR criteria, later determined to have enzyme- or mutation-defined mitochondrial electron transport chain (ETC dysfunction. Twenty-four of 25 patients had one or more major clinical abnormalities uncommon in idiopathic autism. Twenty-one patients had histories of significant non-neurological medical problems. Nineteen patients exhibited constitutional symptoms, especially excessive fatigability. Fifteen patients had abnormal neurological findings. Unusual developmental phenotypes included marked delay in early gross motor milestones (32% and unusual patterns of regression (40%. Levels of blood lactate, plasma alanine, and serum ALT and/or AST were increased at least once in 76%, 36%, and 52% of patients, respectively. The most common ETC disorders were deficiencies of complex I (64% and complex III (20%. Two patients had rare mtDNA mutations of likely pathogenicity.Although all patients' initial diagnosis was idiopathic autism, careful clinical and biochemical assessment identified clinical findings that differentiated them from children with idiopathic autism. These and prior data suggest a disturbance of mitochondrial energy production as an underlying pathophysiological mechanism in a subset of individuals with autism.

Overlap Between Autism Spectrum Disorders and Attention Deficit Hyperactivity Disorder: Searching for Distinctive/Common Clinical Features.

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Craig, Francesco; Lamanna, Anna Linda; Margari, Francesco; Matera, Emilia; Simone, Marta; Margari, Lucia

2015-06-01

Recent studies support several overlapping traits between autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD), assuming the existence of a combined phenotype. The aim of our study was to evaluate the common or distinctive clinical features between ASD and ADHD in order to identify possible different phenotypes that could have a clinical value. We enrolled 181 subjects divided into four diagnostic groups: ADHD group, ASD group, ASD+ADHD group (that met diagnostic criteria for both ASD and ADHD), and control group. Intelligent quotient (IQ), emotional and behavior problems, ADHD symptoms, ASD symptoms, and adaptive behaviors were investigated through the following test: Wechsler Intelligence Scale for Children, Wechsler Preschool and Primary Scale of Intelligence or Leiter International Performances Scale Revised, Child Behavior Checklist, Conners' Rating Scales-Revised, SNAP-IV Rating Scale, the Social Communication Questionnaire, Vineland Adaptive Behavior Scales. The ASD+ADHD group differs from ADHD or ASD in some domains such as lower IQ mean level and a higher autistic symptoms severity. However, the ASD+ADHD group shares inattention and hyperactivity deficit and some emotional and behavior problems with the ADHD group, while it shares adaptive behavior impairment with ASD group. These findings provide a new understanding of clinical manifestation of ASD+ADHD phenotype, they may also inform a novel treatment target. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.

Theory of mind abilities in young siblings of children with autism.

Science.gov (United States)

Shaked, Michal; Gamliel, Ifat; Yirmiya, Nurit

2006-03-01

Deficits in theory of mind (ToM), evident in most individuals with autism, have been suggested as a core deficit of autism. ToM difficulties in young siblings of children with autism (SIBS-A) compared to siblings of typically developing children (SIBS-TD) would place the former within the broad phenotype. We examined ToM's possible associations with measures of language, cognition, and daily living skills. Participants comprised 24 SIBS-A and 24 matched SIBSTD aged 4.6 years. They completed the false belief and the strange stories tasks. We also collected measures of verbal and cognitive ability and daily living skills. Non-significant differences emerged between the groups on both ToM tasks. Differences did emerge in within-group associations between ToM ability and receptive language. The conclusion is that SIBS-A show resilience in ToM abilities. Possibly, these deficits are not genetically transferred to siblings, at least as measured in laboratory-based ToM tasks.

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

for array comparative genomic hybridization, with WTCCC controls (n = 4,783). The phenotypic analysis was then extended using the DECIPHER database. We followed up association using an autism patient cohort (n = 3,143) compared with six additional control groups (n = 6,469). In the clinical discovery series...... (ASD) and similar secondary phenotypes were identified with ELP4 deletions, as well as another six (out of nine) with neurodevelopmental phenotypes from DECIPHER. CNVs at ELP4 were only present in 1/11,252 controls. We found a significant excess of CNVs in discovery cases compared with controls, P = 7...

Autism Society

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... Español Improving the lives of all affected by autism. The Autism Society is the nation's leading grassroots ... more Improving the lives of all affected by autism. The Autism Society is the nation's leading grassroots ...

Linking neocortical, cognitive, and genetic variability in autism with alterations of brain plasticity: the Trigger-Threshold-Target model.

Science.gov (United States)

Mottron, Laurent; Belleville, Sylvie; Rouleau, Guy A; Collignon, Olivier

2014-11-01

The phenotype of autism involves heterogeneous adaptive traits (strengths vs. disabilities), different domains of alterations (social vs. non-social), and various associated genetic conditions (syndromic vs. nonsyndromic autism). Three observations suggest that alterations in experience-dependent plasticity are an etiological factor in autism: (1) the main cognitive domains enhanced in autism are controlled by the most plastic cortical brain regions, the multimodal association cortices; (2) autism and sensory deprivation share several features of cortical and functional reorganization; and (3) genetic mutations and/or environmental insults involved in autism all appear to affect developmental synaptic plasticity, and mostly lead to its upregulation. We present the Trigger-Threshold-Target (TTT) model of autism to organize these findings. In this model, genetic mutations trigger brain reorganization in individuals with a low plasticity threshold, mostly within regions sensitive to cortical reallocations. These changes account for the cognitive enhancements and reduced social expertise associated with autism. Enhanced but normal plasticity may underlie non-syndromic autism, whereas syndromic autism may occur when a triggering mutation or event produces an altered plastic reaction, also resulting in intellectual disability and dysmorphism in addition to autism. Differences in the target of brain reorganization (perceptual vs. language regions) account for the main autistic subgroups. In light of this model, future research should investigate how individual and sex-related differences in synaptic/regional brain plasticity influence the occurrence of autism. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of regulatory architecture on broad versus narrow sense heritability.

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Yunpeng Wang

Full Text Available Additive genetic variance (VA and total genetic variance (VG are core concepts in biomedical, evolutionary and production-biology genetics. What determines the large variation in reported VA /VG ratios from line-cross experiments is not well understood. Here we report how the VA /VG ratio, and thus the ratio between narrow and broad sense heritability (h(2 /H(2 , varies as a function of the regulatory architecture underlying genotype-to-phenotype (GP maps. We studied five dynamic models (of the cAMP pathway, the glycolysis, the circadian rhythms, the cell cycle, and heart cell dynamics. We assumed genetic variation to be reflected in model parameters and extracted phenotypes summarizing the system dynamics. Even when imposing purely linear genotype to parameter maps and no environmental variation, we observed quite low VA /VG ratios. In particular, systems with positive feedback and cyclic dynamics gave more non-monotone genotype-phenotype maps and much lower VA /VG ratios than those without. The results show that some regulatory architectures consistently maintain a transparent genotype-to-phenotype relationship, whereas other architectures generate more subtle patterns. Our approach can be used to elucidate these relationships across a whole range of biological systems in a systematic fashion.

Early diagnosis of autism and impact on prognosis: a narrative review

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Fernell E

2013-02-01

Full Text Available Elisabeth Fernell,1 Mats Anders Eriksson,1,2 Christopher Gillberg11Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2Department of Women's and Children's Health, Karolinska Institute, Stockholm, SwedenAbstract: Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neurodevelopmental deviations, with core symptoms that can probably be related to a deficiency in the social instinct. Underlying the cognitive impairments there are physiological brain problems, caused by a large number of medical factors. This narrative review of systematic reviews and meta-analyses from the last 5 years (2008–2012 presents aspects from many areas in autism spectrum disorder research, with a particular focus on early intervention and the subsequent impact on prognosis. Other major areas discussed are epidemiology, early symptoms and screening, early diagnosis, neuropsychology, medical factors, and the existence of comorbidities. There is limited evidence that any of the broadband “early intervention” programs are effective in changing the natural long-term outcome for many individuals with an early diagnosis of autism. However, there is some evidence that Early Intensive Behavioral Intervention (EIBI is an effective treatment for some children with ASD. Nevertheless, there is emerging consensus that early diagnosis and information are needed in order that an autism-friendly environment be “created” around affected individuals.Keywords: autism spectrum disorder, epidemiology, screening, etiology, intervention, outcome

Phenotype of asthma-chronic obstructive pulmonary disease overlap syndrome.

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Rhee, Chin Kook

2015-07-01

Many patients with asthma or chronic obstructive pulmonary disease (COPD) have overlapping characteristics of both diseases. By spirometric definition, patients with both fixed airflow obstruction (AO) and bronchodilator reversibility or fixed AO and bronchial hyperresponsiveness can be considered to have asthma-COPD overlap syndrome (ACOS). However, patients regarded to have ACOS by spirometric criteria alone are heterogeneous and can be classified by phenotype. Eosinophilic inflammation, a history of allergic disease, and smoke exposure are important components in the classification of ACOS. Each phenotype has a different underlying pathophysiology, set of characteristics, and prognosis. Medical treatment for ACOS should be tailored according to phenotype. A narrower definition of ACOS that includes both spirometric and clinical criteria is needed.

Restriction Spectrum Imaging As a Potential Measure of Cortical Neurite Density in Autism

OpenAIRE

Carper, Ruth A.; Treiber, Jeffrey M.; White, Nathan S.; Kohli, Jiwandeep S.; M?ller, Ralph-Axel

2017-01-01

Autism postmortem studies have shown various cytoarchitectural anomalies in cortical and limbic areas including increased cell packing density, laminar disorganization, and narrowed minicolumns. However, there is little evidence on dendritic and axonal organization in ASD. Recent imaging techniques have the potential for non-invasive, in vivo studies of small-scale structure in the human brain, including gray matter. Here, Restriction Spectrum Imaging (RSI), a multi-shell diffusion-weighted i...

The relationship between executive functioning, central coherence, and repetitive behaviors in the high-functioning autism spectrum.

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South, Mikle; Ozonoff, Sally; McMahon, William M

2007-09-01

This study examined the relationship between everyday repetitive behavior (primary symptoms of autism) and performance on neuropsychological tests of executive function and central coherence (secondary symptoms). It was hypothesized that the frequency and intensity of repetitive behavior would be positively correlated with laboratory measures of cognitive rigidity and weak central coherence. Participants included 19 individuals (ages 10-19) with high-functioning autism spectrum disorders (ASD group) and 18 age- and IQ-matched typically developing controls (TD group). There was partial support in the ASD group for the link between repetitive behavior and executive performance (the Wisconsin Card Sorting Task). There was no support for a link between repetitive behavior and measures of central coherence (a Gestalt Closure test and the Embedded Figures Test). Further research on repetitive behaviors in autism may benefit from a focus on narrow behavioral and cognitive constructs rather than general categories.

Lessons learned from studying syndromic autism spectrum disorders.

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Sztainberg, Yehezkel; Zoghbi, Huda Y

2016-10-26

Syndromic autism spectrum disorders represent a group of childhood neurological conditions, typically associated with chromosomal abnormalities or mutations in a single gene. The discovery of their genetic causes has increased our understanding of the molecular pathways critical for normal cognitive and social development. Human studies have revealed that the brain is particularly sensitive to changes in dosage of various proteins from transcriptional and translational regulators to synaptic proteins. Investigations of these disorders in animals have shed light on previously unknown pathogenic mechanisms leading to the identification of potential targets for therapeutic intervention. The demonstration of reversibility of several phenotypes in adult mice is encouraging, and brings hope that with novel therapies, skills and functionality might improve in affected children and young adults. As new research reveals points of convergence between syndromic and nonsyndromic autism spectrum disorders, we believe there will be opportunities for shared therapeutics for this class of conditions.

Overproduction of Upper-Layer Neurons in the Neocortex Leads to Autism-like Features in Mice

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Wei-Qun Fang

2014-12-01

Full Text Available Summary: The functional integrity of the neocortex depends upon proper numbers of excitatory and inhibitory neurons; however, the consequences of dysregulated neuronal production during the development of the neocortex are unclear. As excess cortical neurons are linked to the neurodevelopmental disorder autism, we investigated whether the overproduction of neurons leads to neocortical malformation and malfunction in mice. We experimentally increased the number of pyramidal neurons in the upper neocortical layers by using the small molecule XAV939 to expand the intermediate progenitor population. The resultant overpopulation of neurons perturbs development of dendrites and spines of excitatory neurons and alters the laminar distribution of interneurons. Furthermore, these phenotypic changes are accompanied by dysregulated excitatory and inhibitory synaptic connection and balance. Importantly, these mice exhibit behavioral abnormalities resembling those of human autism. Thus, our findings collectively suggest a causal relationship between neuronal overproduction and autism-like features, providing developmental insights into the etiology of autism. : Fang et al. generated a mouse model with excessive excitatory neurons in the neocortex by manipulating embryonic neurogenesis. Overproduction of neurons results in autism-like anatomical and behavioral features. These findings suggest a causal relationship between overproduction of neurons and cortical malfunction and provide developmental insights into the etiology of autism.

[Diagnostics of the genetic causes of autism spectrum disorders - a clinical geneticist's view].

Science.gov (United States)

Szczaluba, Krzysztof

2014-01-01

Explanation of the genetic basis of autism spectrum disorders has, for many decades, been a part of interest of researchers and clinicians. In recent years, thanks to modern molecular and cytogenetic techniques, a significant progress has been achieved in the diagnosis of genetic causes of autism. This applies particularly, but not exclusively, to those cases of autism that are accompanied by other clinical signs (i. e. complex phenotypes). The important clinical markers belong to different categories, and include congenital defects/anomalies, dysmorphism and macro-/microcephaly, to name the few. Thus, the choice of the diagnostic strategy depends on the clinical and pedigree information and, under Polish circumstances, the availability of specific diagnostic techniques and the amount of reimbursement under the National Health Service. Overall, the identification of the genetic causes of autism spectrum disorders is possible in about 10-30% of patients. In this paper the practical aspects of the use of different diagnostic techniques are briefly described. Some clinical examples and current recommendations for the diagnosis of patients with autism spectrum disorders are also presented. The point of view of a specialist in clinical genetics, increasingly involved, as part of the multidisciplinary care team, in the diagnostics of an autistic child has been demonstrated.

Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism.

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Jun Li

Full Text Available Autism spectrum disorder (ASD is a group of neurodevelopmental disorders with a strong genetic component. Many lines of evidence indicated that ASD shares common genetic variants with other psychiatric disorders (for example, schizophrenia. Previous studies detected that calcium channels are involved in the etiology of many psychiatric disorders including schizophrenia and autism. Significant association between CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit and schizophrenia was detected. Furthermore, rare mutation in CACNA1C is suggested to cause Timothy syndrome, a multisystem disorder including autism-associated phenotype. However, there is no evidence for association between CACNA1C and autism in Chinese Han population. To investigate the association between single nucleotide polymorphisms (SNP in CACNA1C and autism, we first performed a family-based association study between eighteen SNPs in CACNA1C and autism in 239 trios. All SNPs were genotyped by using Sequenom genotyping platform. Two SNPs (rs1006737 and rs4765905 have a trend of association with autism. To further confirm the association between these two SNPs with autism, we expanded the sample size to 553 trios by adding 314 trios. Association analyses for SNPs and haplotype were performed by using family-based association test (FBAT and Haploview software. Permutation tests were used for multiple testing corrections of the haplotype analyses (n=10,000. The significance level for all statistical tests was two-tailed (p<0.05. The results demonstrated that G allele of rs1006737 and G allele of rs4765905 showed a preferential transmission to affected offspring in 553 trios (p=0.035. Haplotype analyses showed that two haplotypes constructed from rs1006737 and rs4765905 were significantly associated with autism (p=0.030, 0.023, respectively; Global p=0.046. These results were still significant after permutation correction (n=10,000, p=0.027. Our research suggests

Structural Covariance Networks in Children with Autism or ADHD.

Science.gov (United States)

Bethlehem, R A I; Romero-Garcia, R; Mak, E; Bullmore, E T; Baron-Cohen, S

2017-08-01

While autism and attention-deficit/hyperactivity disorder (ADHD) are considered distinct conditions from a diagnostic perspective, clinically they share some phenotypic features and have high comorbidity. Regardless, most studies have focused on only one condition, with considerable heterogeneity in their results. Taking a dual-condition approach might help elucidate shared and distinct neural characteristics. Graph theory was used to analyse topological properties of structural covariance networks across both conditions and relative to a neurotypical (NT; n = 87) group using data from the ABIDE (autism; n = 62) and ADHD-200 datasets (ADHD; n = 69). Regional cortical thickness was used to construct the structural covariance networks. This was analysed in a theoretical framework examining potential differences in long and short-range connectivity, with a specific focus on relation between central graph measures and cortical thickness. We found convergence between autism and ADHD, where both conditions show an overall decrease in CT covariance with increased Euclidean distance between centroids compared with a NT population. The 2 conditions also show divergence. Namely, there is less modular overlap between the 2 conditions than there is between each condition and the NT group. The ADHD group also showed reduced cortical thickness and lower degree in hub regions than the autism group. Lastly, the ADHD group also showed reduced wiring costs compared with the autism groups. Our results indicate a need for taking an integrated approach when considering highly comorbid conditions such as autism and ADHD. Furthermore, autism and ADHD both showed alterations in the relation between inter-regional covariance and centroid distance, where both groups show a steeper decline in covariance as a function of distance. The 2 groups also diverge on modular organization, cortical thickness of hub regions and wiring cost of the covariance network. Thus, on some network features the

Opioid peptides and gastrointestinal symptoms in autism spectrum disorders

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Cristiane P. Lázaro

2016-01-01

Full Text Available Autism spectrum disorders (ASDs are characterized by deficits in the individual’s ability to socialize, communicate, and use the imagination, in addition to stereotyped behaviors. These disorders have a heterogenous phenotype, both in relation to symptoms and regarding severity. Organic problems related to the gastrointestinal tract are often associated with ASD, including dysbiosis, inflammatory bowel disease, exocrine pancreatic insufficiency, celiac disease, indigestion, malabsorption, food intolerance, and food allergies, leading to vitamin deficiencies and malnutrition. In an attempt to explain the pathophysiology involved in autism, a theory founded on opioid excess has been the focus of various investigations, since it partially explains the symptomatology of the disorder. Another hypothesis has been put forward whereby the probable triggers of ASDs would be related to the presence of bacteria in the bowel, oxidative stress, and intestinal permeability. The present update reviews these hypotheses.

Empirically Based Phenotypic Profiles of Children with Pervasive Developmental Disorders : Interpretation in the Light of the DSM-5

NARCIS (Netherlands)

Greaves-Lord, Kirstin; Eussen, Mart L. J. M.; Verhulst, Frank C.; Minderaa, Ruud B.; Mandy, William; Hudziak, James J.; Steenhuis, Mark Peter; de Nijs, Pieter F.; Hartman, Catharina A.

This study aimed to contribute to the Diagnostic and Statistical Manual (DSM) debates on the conceptualization of autism by investigating (1) whether empirically based distinct phenotypic profiles could be distinguished within a sample of mainly cognitively able children with pervasive developmental

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 ...

A multimodal approach to emotion recognition ability in autism spectrum disorders

OpenAIRE

Jones, C.; Pickles, A.; Falcaro, M.; Marsden, A.; Happé, F.; Scott, S.; Sauter, D.; Tregay, J.; Phillips, R.; Baird, G.; Simonoff, E.; Charman, T.

2011-01-01

Background:  Autism spectrum disorders (ASD) are characterised by social and communication difficulties in day-to-day life, including problems in recognising emotions. However, experimental investigations of emotion recognition ability in ASD have been equivocal, hampered by small sample sizes, narrow IQ range and over-focus on the visual modality. Methods:  We tested 99 adolescents (mean age 15;6 years, mean IQ 85) with an ASD and 57 adolescents without an ASD (mean age 15;6 years, mean IQ 8...

Autism-like Deficits in Shank3-Deficient Mice Are Rescued by Targeting Actin Regulators

Directory of Open Access Journals (Sweden)

Lara J. Duffney

2015-06-01

Full Text Available Haploinsufficiency of the Shank3 gene, which encodes a scaffolding protein at glutamatergic synapses, is a highly prevalent and penetrant risk factor for autism. Using combined behavioral, electrophysiological, biochemical, imaging, and molecular approaches, we find that Shank3-deficient mice exhibit autism-like social deficits and repetitive behaviors, as well as the significantly diminished NMDA receptor (NMDAR synaptic function and synaptic distribution in prefrontal cortex. Concomitantly, Shank3-deficient mice have a marked loss of cortical actin filaments, which is associated with the reduced Rac1/PAK activity and increased activity of cofilin, the major actin depolymerizing factor. The social deficits and NMDAR hypofunction are rescued by inhibiting cofilin or activating Rac1 in Shank3-deficient mice and are induced by inhibiting PAK or Rac1 in wild-type mice. These results indicate that the aberrant regulation of synaptic actin filaments and loss of synaptic NMDARs contribute to the manifestation of autism-like phenotypes. Thus, targeting actin regulators provides a strategy for autism treatment.

Common variation in the autism risk gene CNTNAP2, brain structural connectivity and multisensory speech integration.

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Ross, Lars A; Del Bene, Victor A; Molholm, Sophie; Jae Woo, Young; Andrade, Gizely N; Abrahams, Brett S; Foxe, John J

2017-11-01

Three lines of evidence motivated this study. 1) CNTNAP2 variation is associated with autism risk and speech-language development. 2) CNTNAP2 variations are associated with differences in white matter (WM) tracts comprising the speech-language circuitry. 3) Children with autism show impairment in multisensory speech perception. Here, we asked whether an autism risk-associated CNTNAP2 single nucleotide polymorphism in neurotypical adults was associated with multisensory speech perception performance, and whether such a genotype-phenotype association was mediated through white matter tract integrity in speech-language circuitry. Risk genotype at rs7794745 was associated with decreased benefit from visual speech and lower fractional anisotropy (FA) in several WM tracts (right precentral gyrus, left anterior corona radiata, right retrolenticular internal capsule). These structural connectivity differences were found to mediate the effect of genotype on audiovisual speech perception, shedding light on possible pathogenic pathways in autism and biological sources of inter-individual variation in audiovisual speech processing in neurotypicals. Copyright © 2017 Elsevier Inc. All rights reserved.

School-age outcomes of infants at risk for autism spectrum disorder.

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Miller, Meghan; Iosif, Ana-Maria; Young, Gregory S; Hill, Monique; Phelps Hanzel, Elise; Hutman, Ted; Johnson, Scott; Ozonoff, Sally

2016-06-01

Studies of infants at risk for autism spectrum disorder (ASD) have proliferated, but few of these samples have been followed longer-term. We conducted a follow-up study, at age 5.5-9 years, of younger siblings of children with ASD (high-risk group, n = 79) or typical development (low-risk group, n = 60), originally recruited as infants. Children with ASD were excluded because of the focus on understanding the range of non-ASD outcomes among high-risk siblings. Using examiner ratings, parent ratings, and standardized assessments, we evaluated differences in clinical outcomes, psychopathology symptoms, autism symptoms, language skills, and nonverbal cognitive abilities. After adjusting for covariates, the high-risk group had increased odds of any clinically elevated/impaired score across measures relative to the low-risk group (43% vs. 12%, respectively). The high-risk group also had increased odds of examiner-rated Clinical Concerns (CC) outcomes (e.g., ADHD concerns, broader autism phenotype, speech-language difficulties, anxiety/mood problems, learning problems) relative to the low-risk group (38% vs. 13%, respectively). The high-risk group with CC outcomes had higher parent-reported psychopathology and autism symptoms, and lower directly-assessed language skills, than the Low-Risk Typically Developing (TD) and High-Risk TD groups, which did not differ. There were no differences in nonverbal cognitive skills. For some in the high-risk group, clinical concerns persisted from early childhood, whereas for others clinical concerns were first evident at school-age. Results suggest continued vulnerability in at least a subgroup of school-age children with a family history of ASD and suggest that this population may benefit from continued screening and monitoring into the school-age years. Autism Res 2016, 9: 632-642. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals

Phenotyping, Etiological Factors, and Biomarkers: Toward Precision Medicine in Autism Spectrum Disorders

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2016-01-01

ABSTRACT: Despite the progress made in understanding the biology of autism spectrum disorder (ASD), effective biological interventions for the core symptoms remain elusive. Because of the etiological heterogeneity of ASD, identification of a “one-size-fits-all” treatment approach will likely continue to be challenging. A meeting was convened at the University of Missouri and the Thompson Center to discuss strategies for stratifying patients with ASD for the purpose of moving toward precision medicine. The “white paper” presented here articulates the challenges involved and provides suggestions for future solutions. PMID:27676697

The dwarf phenotype in GH240B mice, haploinsufficient for the autism candidate gene Neurobeachin, is caused by ectopic expression of recombinant human growth hormone.

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Nuytens, Kim; Tuand, Krizia; Fu, Quili; Stijnen, Pieter; Pruniau, Vincent; Meulemans, Sandra; Vankelecom, Hugo; Creemers, John W M

2014-01-01

Two knockout mouse models for the autism candidate gene Neurobeachin (Nbea) have been generated independently. Although both models have similar phenotypes, one striking difference is the dwarf phenotype observed in the heterozygous configuration of the GH240B model that is generated by the serendipitous insertion of a promoterless human growth hormone (hGH) genomic fragment in the Nbea gene. In order to elucidate this discrepancy, the dwarfism present in this Nbea mouse model was investigated in detail. The growth deficiency in Nbea+/- mice coincided with an increased percentage of fat mass and a decrease in bone mineral density. Low but detectable levels of hGH were detected in the pituitary and hypothalamus of Nbea+/- mice but not in liver, hippocampus nor in serum. As a consequence, several members of the mouse growth hormone (mGH) signaling cascade showed altered mRNA levels, including a reduction in growth hormone-releasing hormone mRNA in the hypothalamus. Moreover, somatotrope cells were less numerous in the pituitary of Nbea+/- mice and both contained and secreted significantly less mGH resulting in reduced levels of circulating insulin-like growth factor 1. These findings demonstrate that the random integration of the hGH transgene in this mouse model has not only inactivated Nbea but has also resulted in the tissue-specific expression of hGH causing a negative feedback loop, mGH hyposecretion and dwarfism.

The Autism‐Spectrum Quotient in Siblings of People With Autism

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Allison, Carrie; Smith, Paula; Ring, Howard; Auyeung, Bonnie; Baron‐Cohen, Simon

2016-01-01

This study measures the distribution of autistic traits, using the autism‐spectrum quotient (AQ), in siblings of individuals with autism spectrum conditions (ASC). Total AQ scores, along with AQ subscales, were collected from child, adolescent and adult controls, siblings, and volunteers with ASC using one of the three age‐appropriate versions of the instrument: the AQ (adult self‐report), the AQ‐adolescent and AQ‐child (both parent‐reports). We examined the effect of Group (case, sibling and control) and AQ version (adult, adolescent and adult) on total and subscale scores. In addition, we tested for sex differences in all groups and on all versions. We found that in male and female adults, AQ scores in siblings fell between cases and controls (cases > siblings > controls). In children and adolescents, female siblings also scored higher than control females (female cases > female siblings > female controls), but there was no difference between male siblings and controls (male cases > male siblings = male controls). An investigation of subscale scores revealed that male siblings only differed from controls on the “Communication” subscale (male cases > male siblings > male controls), while female siblings differed from controls on all subscales except “Imagination” (female cases > female siblings > female controls). This study confirms the broader autism phenotype in siblings, and reveals this is modulated by sex and AQ version. Autism Res 2017, 10: 289–297. © 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research. PMID:27333365

HNF1B-associated clinical phenotypes: the kidney and beyond.

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Bockenhauer, Detlef; Jaureguiberry, Graciana

2016-05-01

Mutations in HNF1B, the gene encoding hepatocyte nuclear factor 1β are the most commonly identified genetic cause of renal malformations. HNF1B was first identified as a disease gene for diabetes (MODY5) in 1997, and its involvement in renal disease was subsequently noted through clinical observations in pedigrees affected by MODY5. Since then, a whole spectrum of associated phenotypes have been reported, including genital malformations, autism, epilepsy, gout, hypomagnesaemia, primary hyperparathyroidism, liver and intestinal abnormalities and a rare form of kidney cancer. The most commonly identified mutation, in approximately 50 % of patients, is an entire gene deletion occurring in the context of a 17q12 chromosomal microdeletion that also includes several other genes. Some of the associated phenotypes, especially the neurologic ones, appear to occur only in the context of this microdeletion and thus may not be directly linked to HNF1B. Here we review the spectrum of associated phenotypes and discuss potential implications for clinical management.

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

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

2015-01-01

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

Duplication of 17(p11.2p11.2) in a male child with autism and severe language delay.

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Nakamine, Alisa; Ouchanov, Leonid; Jiménez, Patricia; Manghi, Elina R; Esquivel, Marcela; Monge, Silvia; Fallas, Marietha; Burton, Barbara K; Szomju, Barbara; Elsea, Sarah H; Marshall, Christian R; Scherer, Stephen W; McInnes, L Alison

2008-03-01

Duplications of 17(p11.2p11.2) have been associated with various behavioral manifestations including attention deficits, obsessive-compulsive symptoms, autistic traits, and language delay. We are conducting a genetic study of autism and are screening all cases for submicroscopic chromosomal abnormalities, in addition to standard karyotyping, and fragile X testing. Using array-based comparative genomic hybridization analysis of data from the Affymetrix GeneChip(R) Human Mapping Array set, we detected a duplication of approximately 3.3 Mb on chromosome 17p11.2 in a male child with autism and severe expressive language delay. The duplication was confirmed by measuring the copy number of genomic DNA using quantitative polymerase chain reaction. Gene expression analyses revealed increased expression of three candidate genes for the Smith-Magenis neurobehavioral phenotype, RAI1, DRG2, and RASD1, in transformed lymphocytes from Case 81A, suggesting gene dosage effects. Our results add to a growing body of evidence suggesting that duplications of 17(p11.2p11.2) result in language delay as well as autism and related phenotypes. As Smith-Magenis syndrome is also associated with language delay, a gene involved in acquisition of language may lie within this interval. Whether a parent of origin effect, gender of the case, the presence of allelic variation, or changes in expression of genes outside the breakpoints influence the resultant phenotype remains to be determined. (c) 2007 Wiley-Liss, Inc.

Use of machine learning to shorten observation-based screening and diagnosis of autism.

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Wall, D P; Kosmicki, J; Deluca, T F; Harstad, E; Fusaro, V A

2012-04-10

The Autism Diagnostic Observation Schedule-Generic (ADOS) is one of the most widely used instruments for behavioral evaluation of autism spectrum disorders. It is composed of four modules, each tailored for a specific group of individuals based on their language and developmental level. On average, a module takes between 30 and 60 min to deliver. We used a series of machine-learning algorithms to study the complete set of scores from Module 1 of the ADOS available at the Autism Genetic Resource Exchange (AGRE) for 612 individuals with a classification of autism and 15 non-spectrum individuals from both AGRE and the Boston Autism Consortium (AC). Our analysis indicated that 8 of the 29 items contained in Module 1 of the ADOS were sufficient to classify autism with 100% accuracy. We further validated the accuracy of this eight-item classifier against complete sets of scores from two independent sources, a collection of 110 individuals with autism from AC and a collection of 336 individuals with autism from the Simons Foundation. In both cases, our classifier performed with nearly 100% sensitivity, correctly classifying all but two of the individuals from these two resources with a diagnosis of autism, and with 94% specificity on a collection of observed and simulated non-spectrum controls. The classifier contained several elements found in the ADOS algorithm, demonstrating high test validity, and also resulted in a quantitative score that measures classification confidence and extremeness of the phenotype. With incidence rates rising, the ability to classify autism effectively and quickly requires careful design of assessment and diagnostic tools. Given the brevity, accuracy and quantitative nature of the classifier, results from this study may prove valuable in the development of mobile tools for preliminary evaluation and clinical prioritization-in particular those focused on assessment of short home videos of children--that speed the pace of initial evaluation

Modifiable risk factors for schizophrenia and autism--shared risk factors impacting on brain development.

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Hamlyn, Jess; Duhig, Michael; McGrath, John; Scott, James

2013-05-01

Schizophrenia and autism are two poorly understood clinical syndromes that differ in age of onset and clinical profile. However, recent genetic and epidemiological research suggests that these two neurodevelopmental disorders share certain risk factors. The aims of this review are to describe modifiable risk factors that have been identified in both disorders, and, where available, collate salient systematic reviews and meta-analyses that have examined shared risk factors. Based on searches of Medline, Embase and PsycINFO, inspection of review articles and expert opinion, we first compiled a set of candidate modifiable risk factors associated with autism. Where available, we next collated systematic-reviews (with or without meta-analyses) related to modifiable risk factors associated with both autism and schizophrenia. We identified three modifiable risk factors that have been examined in systematic reviews for both autism and schizophrenia. Advanced paternal age was reported as a risk factor for schizophrenia in a single meta-analysis and as a risk factor in two meta-analyses for autism. With respect to pregnancy and birth complications, for autism one meta-analysis identified maternal diabetes and bleeding during pregnancy as risks factors for autism whilst a meta-analysis of eight studies identified obstetric complications as a risk factor for schizophrenia. Migrant status was identified as a risk factor for both autism and schizophrenia. Two separate meta-analyses were identified for each disorder. Despite distinct clinical phenotypes, the evidence suggests that at least some non-genetic risk factors are shared between these two syndromes. In particular, exposure to drugs, nutritional excesses or deficiencies and infectious agents lend themselves to public health interventions. Studies are now needed to quantify any increase in risk of either autism or schizophrenia that is associated with these modifiable environmental factors. Copyright © 2012 Elsevier Inc

How autism became autism

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Evans, Bonnie

2013-01-01

This article argues that the meaning of the word ‘autism’ experienced a radical shift in the early 1960s in Britain which was contemporaneous with a growth in epidemiological and statistical studies in child psychiatry. The first part of the article explores how ‘autism’ was used as a category to describe hallucinations and unconscious fantasy life in infants through the work of significant child psychologists and psychoanalysts such as Jean Piaget, Lauretta Bender, Leo Kanner and Elwyn James Anthony. Theories of autism were then associated both with schizophrenia in adults and with psychoanalytic styles of reasoning. The closure of institutions for ‘mental defectives’ and the growth in speech therapy services in the 1960s and 1970s encouraged new models for understanding autism in infants and children. The second half of the article explores how researchers such as Victor Lotter and Michael Rutter used the category of autism to reconceptualize psychological development in infants and children via epidemiological studies. These historical changes have influenced the form and function of later research into autism and related conditions. PMID:24014081

Autism: Diagnosis

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... Information Publications Awards Partners Contact Us ¿Qué es Autismo? Donate Home What is Autism? What is Autism? ... Information Publications Awards Partners Contact Us ¿Qué es Autismo? Diagnosis Home / What is Autism? / Diagnosis Expand Medical ...

MELAS syndrome, cardiomyopathy, rhabdomyolysis, and autism associated with the A3260G mitochondrial DNA mutation.

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Connolly, Barbara S; Feigenbaum, Annette S J; Robinson, Brian H; Dipchand, Anne I; Simon, David K; Tarnopolsky, Mark A

2010-11-12

The A to G transition mutation at position 3260 of the mitochondrial genome is usually associated with cardiomyopathy and myopathy. One Japanese kindred reported the phenotype of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS syndrome) in association with the A3260G mtDNA mutation. We describe the first Caucasian cases of MELAS syndrome associated with the A3260G mutation. Furthermore, this mutation was associated with exercise-induced rhabdomyolysis, hearing loss, seizures, cardiomyopathy, and autism in the large kindred. We conclude that the A3260G mtDNA mutation is associated with wide phenotypic heterogeneity with MELAS and other "classical" mitochondrial phenotypes being manifestations. Copyright © 2010 Elsevier Inc. All rights reserved.

Perspective-taking abilities in the balance between autism tendencies and psychosis proneness.

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Abu-Akel, Ahmad M; Wood, Stephen J; Hansen, Peter C; Apperly, Ian A

2015-06-07

Difficulties with the ability to appreciate the perspective of others (mentalizing) is central to both autism and schizophrenia spectrum disorders. While the disorders are diagnostically independent, they can co-occur in the same individual. The effect of such co-morbidity is hypothesized to worsen mentalizing abilities. The recent influential 'diametric brain theory', however, suggests that the disorders are etiologically and phenotypically diametrical, predicting opposing effects on one's mentalizing abilities. To test these contrasting hypotheses, we evaluated the effect of psychosis and autism tendencies on the perspective-taking (PT) abilities of 201 neurotypical adults, on the assumption that autism tendencies and psychosis proneness are heritable dimensions of normal variation. We show that while both autism tendencies and psychosis proneness induce PT errors, their interaction reduced these errors. Our study is, to our knowledge, the first to observe that co-occurring autistic and psychotic traits can exert opposing influences on performance, producing a normalizing effect possibly by way of their diametrical effects on socio-cognitive abilities. This advances the notion that some individuals may, to some extent, be buffered against developing either illness or present fewer symptoms owing to a balanced expression of autistic and psychosis liability. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Phenotypic Characteristics of Autism Spectrum Disorder in a Diverse Sample of Somali and Other Children

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Esler, Amy N.; Hall-Lande, Jennifer; Hewitt, Amy

2017-01-01

The potential for culture to impact diagnosis of autism spectrum disorder (ASD) is high, yet remains largely unstudied. This study examined differences across racial/ethnic groups in ASD symptoms, cognitive and adaptive skills, and related behaviors in children with ASD that included a unique subgroup, children from the Somali diaspora. Somali…

The Interaction between the Immune System and Epigenetics in the Etiology of Autism Spectrum Disorders.

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Nardone, Stefano; Elliott, Evan

2016-01-01

Recent studies have firmly established that the etiology of autism includes both genetic and environmental components. However, we are only just beginning to elucidate the environmental factors that might be involved in the development of autism, as well as the molecular mechanisms through which they function. Mounting epidemiological and biological evidence suggest that prenatal factors that induce a more activated immune state in the mother are involved in the development of autism. In parallel, molecular studies have highlighted the role of epigenetics in brain development as a process susceptible to environmental influences and potentially causative of autism spectrum disorders (ASD). In this review, we will discuss converging evidence for a multidirectional interaction between immune system activation in the mother during pregnancy and epigenetic regulation in the brain of the fetus that may cooperate to produce an autistic phenotype. This interaction includes immune factor-induced changes in epigenetic signatures in the brain, dysregulation of epigenetic modifications specifically in genomic regions that encode immune functions, and aberrant epigenetic regulation of microglia. Overall, the interaction between immune system activation in the mother and the subsequent epigenetic dysregulation in the developing fetal brain may be a main consideration for the environmental factors that cause autism.

Biomarkers for Autism and for Gastrointestinal and Sleep Problems in Autism

Science.gov (United States)

2015-12-01

Award Number: W81XWH-10-1-0889 TITLE: Biomarkers for Autism and for Gastrointestinal and Sleep Problems in Autism PRINCIPAL INVESTIGATOR...29Sep2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER AR093240 Biomarkers for Autism and for Gastrointestinal and Sleep Problems in Autism 5b. GRANT NUMBER...and daytime excretions of melatonin sulfate were not significantly different between typically developing (TD) toddlers and toddlers with autism

Complex autism spectrum disorder in a patient with a 17q12 microduplication.

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Brandt, Tracy; Desai, Khyati; Grodberg, David; Mehta, Lakshmi; Cohen, Ninette; Tryfon, Ana; Kolevzon, Alexander; Soorya, Latha; Buxbaum, Joseph D; Edelmann, Lisa

2012-05-01

Autism spectrum disorders (ASDs) are phenotypically complex developmental neuropsychiatric disorders affecting approximately 0.6% of the population. About 30-70% of affected children are also considered to have intellectual disability (ID). The underlying genetic causes of ASDs are diverse with a defined etiology in 16-20%. Array comparative genomic hybridization (aCGH) has proven useful in identifying sub-microscopic chromosome aberrations in a subset of patients, some of which have been shown to be recurrent. One such aberration is the 1.4 Mb microdeletion at chromosome 17q12, which has been reported to be associated with renal disease, growth restriction, diabetes, cognitive impairment, seizures, and in some cases an ASD. Patients with the reciprocal chromosome 17q12 microduplication typically have also been identified with ID and in some cases seizures and behavioral abnormalities. Here we report a patient with a de novo, 1.4 Mb microduplication diagnosed with significant ID involving complex deficits and autism. To our knowledge, this is the first report of a patient with the 17q12 microduplication and a complex ASD phenotype. Copyright © 2012 Wiley Periodicals, Inc.

The relationship between tics, OC, ADHD and autism symptoms: A cross- disorder symptom analysis in Gilles de la Tourette syndrome patients and family-members.

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Huisman-van Dijk, Hilde M; Schoot, Rens van de; Rijkeboer, Marleen M; Mathews, Carol A; Cath, Daniëlle C

2016-03-30

Gilles de la Tourette's syndrome (GTS) is a disorder in which obsessive-compulsive (OC), Attention Deficit Hyperactivity Disorder (ADHD) and autism symptoms occur in up to 60% of patients, suggesting shared etiology. We explored the phenotypic structure of tic, OC, ADHD, and autism symptoms as measured by the YGTSS,Y-BOCS,CAARS and AQ, in 225 GTS patients and 371 family members. First, Confirmatory Factor Analyses (CFA) were performed on the symptom structure of each separate symptom scale. Second, the symptom dimensions derived from each scale were combined in one model, and correlations between them were calculated. Using the correlation matrix, Exploratory Factor Analyses (EFA) were performed on the symptom dimensions across the scales. EFA revealed a five factor structure: tic/aggression/symmetry; OC symptoms/compulsive tics/ numbers and patterns; ADHD symptoms; autism symptoms; and hoarding/inattention symptoms. The results are partly in line with the traditional categorical boundaries of the symptom scales used, and partly reveal a symptom structure that cuts through the diagnostic categories. This phenotypic structure might more closely reflect underlying etiologies than a structure that classically describes GTS patients according to absence or presence of comorbid OCD, ADHD and autism, and might inform both future genetic and treatment studies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparative Study of Children with ADHD Only, Autism Spectrum Disorder + ADHD, and Chronic Multiple Tic Disorder + ADHD

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Gadow, Kenneth D.; DeVincent, Carla J.; Schneider, Jayne

2009-01-01

Objective: Identification of differences among children with ADHD only, autism spectrum disorder (ASD)+ADHD, and chronic multiple tic disorder (CMTD)+ADHD may lead to better understanding of clinical phenotypes. Method: Children were evaluated using the parent- and teacher-completed questionnaires. Results: All three groups were highly similar in…

Empirically Based Phenotypic Profiles of Children with Pervasive Developmental Disorders: Interpretation in the Light of the DSM-5

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Greaves-Lord, Kirstin; Eussen, Mart L. J. M.; Verhulst, Frank C.; Minderaa, Ruud B.; Mandy, William; Hudziak, James J.; Steenhuis, Mark Peter; de Nijs, Pieter F.; Hartman, Catharina A.

2013-01-01

This study aimed to contribute to the Diagnostic and Statistical Manual (DSM) debates on the conceptualization of autism by investigating (1) whether empirically based distinct phenotypic profiles could be distinguished within a sample of mainly cognitively able children with pervasive developmental disorder (PDD), and (2) how profiles related to…

Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism

OpenAIRE

Parikshak, Neelroop N.; Luo, Rui; Zhang, Alice; Won, Hyejung; Lowe, Jennifer K.; Chandran, Vijayendran; Horvath, Steve; Geschwind, Daniel H.

2013-01-01

Genetic studies have identified dozens of autism spectrum disorder (ASD) susceptibility genes, raising two critical questions: 1) do these genetic loci converge on specific biological processes, and 2) where does the phenotypic specificity of ASD arise, given its genetic overlap with intellectual disability (ID)? To address this, we mapped ASD and ID risk genes onto co-expression networks representing developmental trajectories and transcriptional profiles representing fetal and adult cortica...

The dwarf phenotype in GH240B mice, haploinsufficient for the autism candidate gene Neurobeachin, is caused by ectopic expression of recombinant human growth hormone.

Directory of Open Access Journals (Sweden)

Kim Nuytens

Full Text Available Two knockout mouse models for the autism candidate gene Neurobeachin (Nbea have been generated independently. Although both models have similar phenotypes, one striking difference is the dwarf phenotype observed in the heterozygous configuration of the GH240B model that is generated by the serendipitous insertion of a promoterless human growth hormone (hGH genomic fragment in the Nbea gene. In order to elucidate this discrepancy, the dwarfism present in this Nbea mouse model was investigated in detail. The growth deficiency in Nbea+/- mice coincided with an increased percentage of fat mass and a decrease in bone mineral density. Low but detectable levels of hGH were detected in the pituitary and hypothalamus of Nbea+/- mice but not in liver, hippocampus nor in serum. As a consequence, several members of the mouse growth hormone (mGH signaling cascade showed altered mRNA levels, including a reduction in growth hormone-releasing hormone mRNA in the hypothalamus. Moreover, somatotrope cells were less numerous in the pituitary of Nbea+/- mice and both contained and secreted significantly less mGH resulting in reduced levels of circulating insulin-like growth factor 1. These findings demonstrate that the random integration of the hGH transgene in this mouse model has not only inactivated Nbea but has also resulted in the tissue-specific expression of hGH causing a negative feedback loop, mGH hyposecretion and dwarfism.

Autism Assets

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Sarahan, Neal; Copas, Randy

2014-01-01

The Center for Disease Control estimates that 1 in 88 children have been identified with autism (CDC, 2012). Autism is often associated with other psychiatric, developmental, neurological, and genetic diagnoses. However, the majority (62%) of children identified on the autism spectrum do not have intellectual disability. Instead, they are hurting.…

Sera from children with autism induce autistic features which can be rescued with a CNTF small peptide mimetic in rats.

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Kazim, Syed Faraz; Cardenas-Aguayo, Maria Del Carmen; Arif, Mohammad; Blanchard, Julie; Fayyaz, Fatima; Grundke-Iqbal, Inge; Iqbal, Khalid

2015-01-01

Autism is a neurodevelopmental disorder characterized clinically by impairments in social interaction and verbal and non-verbal communication skills as well as restricted interests and repetitive behavior. It has been hypothesized that altered brain environment including an imbalance in neurotrophic support during early development contributes to the pathophysiology of autism. Here we report that sera from children with autism which exhibited abnormal levels of various neurotrophic factors induced cell death and oxidative stress in mouse primary cultured cortical neurons. The effects of sera from autistic children were rescued by pre-treatment with a ciliary neurotrophic factor (CNTF) small peptide mimetic, Peptide 6 (P6), which was previously shown to exert its neuroprotective effect by modulating CNTF/JAK/STAT pathway and LIF signaling and by enhancing brain derived neurotrophic factor (BDNF) expression. Similar neurotoxic effects and neuroinflammation were observed in young Wistar rats injected intracerebroventricularly with autism sera within hours after birth. The autism sera injected rats demonstrated developmental delay and deficits in social communication, interaction, and novelty. Both the neurobiological changes and the behavioral autistic phenotype were ameliorated by P6 treatment. These findings implicate the involvement of neurotrophic imbalance during early brain development in the pathophysiology of autism and a proof of principle of P6 as a potential therapeutic strategy for autism.

Cognitive abilities in siblings of children with autism spectrum disorders.

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Gizzonio, Valentina; Avanzini, Pietro; Fabbri-Destro, Maddalena; Campi, Cristina; Rizzolatti, Giacomo

2014-07-01

The aim of the present study was to assess the cognitive profiles of children with autistic spectrum disorder and of their healthy siblings (Siblings). With the term cognitive profile, we indicate the relationship extant among the values of verbal and performance subtests of the Wechsler Intelligence Scale. The conducted statistical analyses indicated that, although siblings showed a normal intelligent quotient and did not differ in this aspect from typically developing group, their cognitive profile was amazingly similar to that of their relatives affected by autism. A k-means clustering analysis on the values of single subtests further confirmed this result, showing a clear separation between typically developing children on the one side, and autistics and their siblings on the other. We suggest that the common cognitive profile observed in autistic children and their siblings could represent a marker of liability to autism and, thus, a possible intermediate phenotype of this syndrome.

15q13.3 homozygous knockout mouse model display epilepsy-, autism- and schizophrenia-related phenotypes

DEFF Research Database (Denmark)

Forsingdal, A; Fejgin, Kim; Nielsen, Viggo

2016-01-01

The 15q13.3 microdeletion syndrome is caused by a 1.5-MB hemizygous microdeletion located on 15q13.3 affecting seven genes: FAN1; MTMR10; TRPM1; miR-211; KLF13; OTUD7A; and CHRNA7. The 15q13.3 microdeletion increases the risk of intellectual disability, epilepsy, autism spectrum disorder...

Prenatal Valproate Exposure and Risk of Autism Spectrum Disorders and Childhood Autism

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Christensen, Jakob; Grønborg, Therese Koops; Sørensen, Merete Juul; Schendel, Diana; Parner, Erik Thorlund; Pedersen, Lars Henning; Vestergaard, Mogens

2015-01-01

Importance Valproate is used for the treatment of epilepsy and other neuropsychological disorders and may be the only treatment option for women of childbearing potential. However, prenatal exposure to valproate may increase the risk of autism. Objective To determine whether prenatal exposure to valproate is associated with an increased risk of autism in offspring. Design, Setting, and Participants Population-based study of all children born alive in Denmark from 1996 to 2006. National registers were used to identify children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders (childhood autism [autistic disorder], Asperger syndrome, atypical autism, and other or unspecified pervasive developmental disorders). We analyzed the risks associated with all autism spectrum disorders as well as childhood autism. Data were analyzed by Cox regression adjusting for potential confounders (maternal age at conception, paternal age at conception, parental psychiatric history, gestational age, birth weight, sex, congenital malformations, and parity). Children were followed up from birth until the day of autism spectrum disorder diagnosis, death, emigration, or December 31, 2010, whichever came first. Main Outcomes and Measures Absolute risk (cumulative incidence) and the hazard ratio (HR) of autism spectrum disorder and childhood autism in children after exposure to valproate in pregnancy. Results Of 655 615 children born from 1996 through 2006, 5437 were identified with autism spectrum disorder, including 2067 with childhood autism. The mean age of the children at end of follow-up was 8.84 years (range, 4-14; median, 8.85). The estimated absolute risk after 14 years of follow-up was 1.53% (95% CI, 1.47%- 1.58%) for autism spectrum disorder and 0.48% (95% CI, 0.46%-0.51%) for childhood autism. Overall, the 508 children exposed to valproate had an absolute risk of 4.42% (95% CI, 2.59%-7.46%) for autism spectrum disorder (adjusted HR, 2.9 [95% CI, 1

Clinical heterogeneity among people with high functioning autism spectrum conditions: evidence favouring a continuous severity gradient

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Woodbury-Smith Marc

2008-02-01

Full Text Available Abstract Background Autism Spectrum Conditions (ASCs are characterized by a high degree of clinical heterogeneity, but the extent to which this variation represents a severity gradient versus discrete phenotypes is unclear. This issue has complicated genetic studies seeking to investigate the genetic basis of the high hereditability observed clinically in those with an ASC. The aim of this study was to examine the possible clustering of symptoms associated with ASCs to determine whether the observed distribution of symptom type and severity supported either a severity or a symptom subgroup model to account for the phenotypic variation observed within the ASCs. Methods We investigated the responses of a group of adults with higher functioning ASCs on the fifty clinical features examined in the Autism Spectrum Quotient, a screening questionnaire used in the diagnosis of higher functioning ASCs. In contrast to previous studies we have used this instrument with no a priori assumptions about any underlying factor structure of constituent items. The responses obtained were analyzed using complete linkage hierarchical cluster analysis. For the members of each cluster identified the mean score on each Autism Spectrum Quotient question was calculated. Results Autism Spectrum Quotient responses from a total of 333 individuals between the ages of 16.6 and 78.0 years were entered into the hierarchical cluster analysis. The four cluster solution was the one that generated the largest number of clusters that did not also include very small cluster sizes, defined as a membership comprising 10 individuals or fewer. Examination of these clusters demonstrated that they varied in total Autism Spectrum Quotient but that the profiles across the symptoms comprising the Autism Spectrum Quotient did not differ independently of this severity factor. Conclusion These results are consistent with a unitary spectrum model, suggesting that the clinical heterogeneity observed

Neurorehabilitation of Social Dysfunctions: A Model-based Neurofeedback Approach for Low and High-Functioning Autism

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Jaime A. Pineda

2014-08-01

Full Text Available Autism Spectrum Disorder (ASD is an increasingly prevalent condition with core deficits in the social domain. Understanding its neuroetiology is critical to providing insights into the relationship between neuroanatomy, physiology and social behaviors, including imitation learning, language, empathy, theory of mind, and even self-awareness. Equally important is the need to find ways to arrest its increasing prevalence and to ameliorate its symptoms. In this perspective, we highlight neurofeedback studies as viable treatment options for high-functioning as well as low-functioning children with ASD. Specifically, we focus on neurofeedback interventions combined with other kinds of behavioral conditioning to induce neuroplastic changes that can address the full spectrum of the autism phenotype.

Autism

DEFF Research Database (Denmark)

Aggernaes, Bodil

2018-01-01

The concept of autism has changed across time, from the Bleulerian concept, which defined it as one of several symptoms of dementia praecox, to the present-day concept representing a pervasive development disorder. The present theoretical contribution to this special issue of EJN on autism...... introduces new theoretical ideas and discusses them in light of selected prior theories, clinical examples, and recent empirical evidence. The overall aim is to identify some present challenges of diagnostic practice and autism research and to suggest new pathways that may help direct future research. Future...

A Subset of Autism-Associated Genes Regulate the Structural Stability of Neurons

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Lin, Yu-Chih; Frei, Jeannine A.; Kilander, Michaela B. C.; Shen, Wenjuan; Blatt, Gene J.

2016-01-01

Autism spectrum disorder (ASD) comprises a range of neurological conditions that affect individuals’ ability to communicate and interact with others. People with ASD often exhibit marked qualitative difficulties in social interaction, communication, and behavior. Alterations in neurite arborization and dendritic spine morphology, including size, shape, and number, are hallmarks of almost all neurological conditions, including ASD. As experimental evidence emerges in recent years, it becomes clear that although there is broad heterogeneity of identified autism risk genes, many of them converge into similar cellular pathways, including those regulating neurite outgrowth, synapse formation and spine stability, and synaptic plasticity. These mechanisms together regulate the structural stability of neurons and are vulnerable targets in ASD. In this review, we discuss the current understanding of those autism risk genes that affect the structural connectivity of neurons. We sub-categorize them into (1) cytoskeletal regulators, e.g., motors and small RhoGTPase regulators; (2) adhesion molecules, e.g., cadherins, NCAM, and neurexin superfamily; (3) cell surface receptors, e.g., glutamatergic receptors and receptor tyrosine kinases; (4) signaling molecules, e.g., protein kinases and phosphatases; and (5) synaptic proteins, e.g., vesicle and scaffolding proteins. Although the roles of some of these genes in maintaining neuronal structural stability are well studied, how mutations contribute to the autism phenotype is still largely unknown. Investigating whether and how the neuronal structure and function are affected when these genes are mutated will provide insights toward developing effective interventions aimed at improving the lives of people with autism and their families. PMID:27909399

Fundamental challenges for autism research: the science-practice gap, demarcating autism and the unsuccessful search for the neurobiological basis of autism.

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Verhoeff, Berend

2015-08-01

One of the central aims of autism research is to identify specific neurodevelopmental mechanisms that cause and explain the visible autistic signs and symptoms. In this short paper, I argue that the persistent search for autism-specific pathophysiologies has two fundamental difficulties. The first regards the growing gap between basic autism science and clinical practice. The second regards the difficulties with demarcating autism as a psychiatric condition. Instead of the unremitting search for the neurobiological basis of autism, I suggest that basic autism research should focus on experiences of impairment and distress, and on how these experiences relate to particular (autistic) behaviors in particular circumstances, regardless of whether we are dealing with an autism diagnosis or not.

Brief Report: Phenotypic Differences and Their Relationship to Paternal Age and Gender in Autism Spectrum Disorder

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Vierck, Esther; Silverman, Jeremy M.

2015-01-01

Two modes of inheritance have been proposed in autism spectrum disorder, transmission though pre-existing variants and de novo mutations. Different modes may lead to different symptom expressions in affected individuals. De novo mutations become more likely with advancing paternal age suggesting that paternal age may predict phenotypic…

Autism through the Lifespan

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... Information Publications Awards Partners Contact Us ¿Qué es Autismo? Donate Home What is Autism? What is Autism? ... Information Publications Awards Partners Contact Us ¿Qué es Autismo? Autism through the Lifespan Home / Living with Autism / ...

Perinatal exposure to low dose glufosinate ammonium induces autism-like phenotypes in mice.

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Anthony eLaugeray

2014-11-01

Full Text Available Glufosinate ammonium (GLA is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in normalized brain weight of the offspring. In addition, reduced expression of Pten and Peg3 - two genes implicated in autism-like deficits – was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between perinatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods.

Autism Spectrum Disorder (ASD)

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... Español (Spanish) Recommend on Facebook Tweet Share Compartir Autism spectrum disorder (ASD) is a developmental disability that can cause ... work. Autism: What's New MMWR article: Prevalence of Autism Spectrum Disorder Data Community Report Press release: Autism Prevalence Slightly ...

Postural Control Impairments in Individuals With Autism Spectrum Disorder: A Critical Review of Current Literature

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Memari, Amir Hossein; Ghanouni, Parisa; Shayestehfar, Monir; Ghaheri, Banafsheh

2014-01-01

Context: Motor impairments in individuals with autism spectrum disorder (ASD) have been frequently reported. In this review, we narrow our focus on postural control impairments to summarize current literature for patterns, underlying mechanisms, and determinants of posture in this population. Evidence Acquisition: A literature search was conducted through Medline, ISI web of Knowledge, Scopus and Google Scholar to include studies between 1992 and February 2013. Results: Individuals with ASD have problems in maintaining postural control in infancy that well persists into later years. However, the patterns and underlying mechanisms are still unclear. Conclusions: Examining postural control as an endophenotype or early diagnostic marker of autism is a conceptual premise which should be considered in future investigations. At the end of the review, methodological recommendations on the assessment of postural control have also been provided. PMID:25520765

A behavioral comparison of male and female adults with high functioning autism spectrum conditions.

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Meng-Chuan Lai

Full Text Available Autism spectrum conditions (ASC affect more males than females in the general population. However, within ASC it is unclear if there are phenotypic sex differences. Testing for similarities and differences between the sexes is important not only for clinical assessment but also has implications for theories of typical sex differences and of autism. Using cognitive and behavioral measures, we investigated similarities and differences between the sexes in age- and IQ-matched adults with ASC (high-functioning autism or Asperger syndrome. Of the 83 (45 males and 38 females participants, 62 (33 males and 29 females met Autism Diagnostic Interview-Revised (ADI-R cut-off criteria for autism in childhood and were included in all subsequent analyses. The severity of childhood core autism symptoms did not differ between the sexes. Males and females also did not differ in self-reported empathy, systemizing, anxiety, depression, and obsessive-compulsive traits/symptoms or mentalizing performance. However, adult females with ASC showed more lifetime sensory symptoms (p = 0.036, fewer current socio-communication difficulties (p = 0.001, and more self-reported autistic traits (p = 0.012 than males. In addition, females with ASC who also had developmental language delay had lower current performance IQ than those without developmental language delay (p<0.001, a pattern not seen in males. The absence of typical sex differences in empathizing-systemizing profiles within the autism spectrum confirms a prediction from the extreme male brain theory. Behavioral sex differences within ASC may also reflect different developmental mechanisms between males and females with ASC. We discuss the importance of the superficially better socio-communication ability in adult females with ASC in terms of why females with ASC may more often go under-recognized, and receive their diagnosis later, than males.

[An approach to the executive functions in autism spectrum disorder].

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Martos-Pérez, Juan; Paula-Pérez, Isabel

2011-03-01

The psychological hypothesis of executive dysfunction plays a crucial role in explaining the behavioural phenotype of persons with autism spectrum disorders (ASD), along with other hypotheses such as the deficit in the theory of mind or the weak central coherence hypothesis. Yet, none of these hypotheses are mutually exclusive and behaviours that have their origins in one of these three hypotheses are also shaped and upheld by other processes and factors. This article reviews the behavioural manifestation and current state of research on the executive functions in persons with ASD. It also examines its impact on planning, mental flexibility and cognitive skills, generativity, response inhibition, mentalist skills and sense of activity. Although executive dysfunction has become more significant as a hypothesis explaining persons with ASD, there remain some important difficulties in need of further, more detailed research. Moreover, very few intervention programmes have been proved to be effective in minimising the effects of executive dysfunction in autism.

Social visual engagement in infants and toddlers with autism: early developmental transitions and a model of pathogenesis.

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Klin, Ami; Shultz, Sarah; Jones, Warren

2015-03-01

Efforts to determine and understand the causes of autism are currently hampered by a large disconnect between recent molecular genetics findings that are associated with the condition and the core behavioral symptoms that define the condition. In this perspective piece, we propose a systems biology framework to bridge that gap between genes and symptoms. The framework focuses on basic mechanisms of socialization that are highly-conserved in evolution and are early-emerging in development. By conceiving of these basic mechanisms of socialization as quantitative endophenotypes, we hope to connect genes and behavior in autism through integrative studies of neurodevelopmental, behavioral, and epigenetic changes. These changes both lead to and are led by the accomplishment of specific social adaptive tasks in a typical infant's life. However, based on recent research that indicates that infants later diagnosed with autism fail to accomplish at least some of these tasks, we suggest that a narrow developmental period, spanning critical transitions from reflexive, subcortically-controlled visual behavior to interactional, cortically-controlled and social visual behavior be prioritized for future study. Mapping epigenetic, neural, and behavioral changes that both drive and are driven by these early transitions may shed a bright light on the pathogenesis of autism. Copyright © 2014 Elsevier Ltd. All rights reserved.

Configuring the autism epidemic

DEFF Research Database (Denmark)

Seeberg, Jens; Christensen, Fie Lund Lindegaard

2017-01-01

Autism has been described as an epidemic, but this claim is contested and may point to an awareness epidemic, i.e. changes in the definition of what autism is and more attention being invested in diagnosis leading to a rise in registered cases. The sex ratio of children diagnosed with autism...... is skewed in favour of boys, and girls with autism tend to be diagnosed much later than boys. Building and further developing the notion of ‘configuration’ of epidemics, this article explores the configuration of autism in Denmark, with a particular focus on the health system and social support to families...... with children diagnosed with autism, seen from a parental perspective. The article points to diagnostic dynamics that contribute to explaining why girls with autism are not diagnosed as easily as boys. We unfold these dynamics through the analysis of a case of a Danish family with autism....

Epilepsy and Other Neurological Diseases in the Parents of Children with Infantile Autism. A Case Control Study

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Mouridsen, Svend Erik; Rich, Bente; Isager, Torben

2008-01-01

In order to study the broader phenotype of infantile autism (IA) we compared the rates and types of epilepsy and other neurological diseases in the parents of 111 consecutively admitted patients with IA with a matched control group of parents of 330 children from the general population. All participants were screened through the nationwide Danish…

A Causal and Mediation Analysis of the Comorbidity Between Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD)

NARCIS (Netherlands)

Sokolova, Elena; Oerlemans, Anoek M.; Rommelse, Nanda; Groot, Perry; Hartman, Catharina A.; Glennon, Jeffrey C; Claassen, Tom; Heskes, Tom; Buitelaar, Jan K.

Autism spectrum disorder (ASD) and Attention-deficit/hyperactivity disorder (ADHD) are often comorbid. The purpose of this study is to explore the relationships between ASD and ADHD symptoms by applying causal modeling. We used a large phenotypic data set of 417 children with ASD and/or ADHD, 562

Sera from Children with Autism Induce Autistic Features Which Can Be Rescued with a CNTF Small Peptide Mimetic in Rats

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Kazim, Syed Faraz; Cardenas-Aguayo, Maria del Carmen; Arif, Mohammad; Blanchard, Julie; Fayyaz, Fatima; Grundke-Iqbal, Inge; Iqbal, Khalid

2015-01-01

Autism is a neurodevelopmental disorder characterized clinically by impairments in social interaction and verbal and non-verbal communication skills as well as restricted interests and repetitive behavior. It has been hypothesized that altered brain environment including an imbalance in neurotrophic support during early development contributes to the pathophysiology of autism. Here we report that sera from children with autism which exhibited abnormal levels of various neurotrophic factors induced cell death and oxidative stress in mouse primary cultured cortical neurons. The effects of sera from autistic children were rescued by pre-treatment with a ciliary neurotrophic factor (CNTF) small peptide mimetic, Peptide 6 (P6), which was previously shown to exert its neuroprotective effect by modulating CNTF/JAK/STAT pathway and LIF signaling and by enhancing brain derived neurotrophic factor (BDNF) expression. Similar neurotoxic effects and neuroinflammation were observed in young Wistar rats injected intracerebroventricularly with autism sera within hours after birth. The autism sera injected rats demonstrated developmental delay and deficits in social communication, interaction, and novelty. Both the neurobiological changes and the behavioral autistic phenotype were ameliorated by P6 treatment. These findings implicate the involvement of neurotrophic imbalance during early brain development in the pathophysiology of autism and a proof of principle of P6 as a potential therapeutic strategy for autism. PMID:25769033

Transmission disequilibrium of small CNVs in simplex autism.

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Krumm, Niklas; O'Roak, Brian J; Karakoc, Emre; Mohajeri, Kiana; Nelson, Ben; Vives, Laura; Jacquemont, Sebastien; Munson, Jeff; Bernier, Raphe; Eichler, Evan E

2013-10-03

We searched for disruptive, genic rare copy-number variants (CNVs) among 411 families affected by sporadic autism spectrum disorder (ASD) from the Simons Simplex Collection by using available exome sequence data and CoNIFER (Copy Number Inference from Exome Reads). Compared to high-density SNP microarrays, our approach yielded ∼2× more smaller genic rare CNVs. We found that affected probands inherited more CNVs than did their siblings (453 versus 394, p = 0.004; odds ratio [OR] = 1.19) and that the probands' CNVs affected more genes (921 versus 726, p = 0.02; OR = 1.30). These smaller CNVs (median size 18 kb) were transmitted preferentially from the mother (136 maternal versus 100 paternal, p = 0.02), although this bias occurred irrespective of affected status. The excess burden of inherited CNVs among probands was driven primarily by sibling pairs with discordant social-behavior phenotypes (p 0.5). Finally, we found enrichment of brain-expressed genes unique to probands, especially in the SRS-discordant group (p = 0.0035). In a combined model, our inherited CNVs, de novo CNVs, and de novo single-nucleotide variants all independently contributed to the risk of autism (p role in the etiology of simplex autism. Importantly, the small size of these variants aids in the identification of specific genes as additional risk factors associated with ASD. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Asthma and Allergies in Children With Autism Spectrum Disorders: Results From the CHARGE Study.

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Lyall, Kristen; Van de Water, Judy; Ashwood, Paul; Hertz-Picciotto, Irva

2015-10-01

Immune aberrations are often noted in children with autism spectrum disorder (ASD), but whether asthma and allergy are related to ASD is not well defined. This study examined asthma and allergies in association with ASD and phenotypic subsets. Participants were 560 children with confirmed ASD and 391 typically developing children from the CHildhood Autism Risks from Genetics and the Environment study. Maternally reported child asthma and allergy was compared between cases and controls, and in association with cognitive and behavioral test scores. Prevalence of asthma and overall allergies did not differ between cases and controls, but overall allergy in children with ASD was associated with higher stereotypy scores as measured by the Aberrant Behavior Checklist. In addition, reported food allergies were significantly associated with ASD (adjusted odds ratio = 2.23, 95% confidence interval 1.28, 3.89). Our results suggest food allergies and sensitivities may be more common in children with ASD, and that these issues may correlate with other behaviors. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Enhanced polyubiquitination of Shank3 and NMDA receptor in a mouse model of autism.

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Bangash, M Ali; Park, Joo Min; Melnikova, Tatiana; Wang, Dehua; Jeon, Soo Kyeong; Lee, Deidre; Syeda, Sbaa; Kim, Juno; Kouser, Mehreen; Schwartz, Joshua; Cui, Yiyuan; Zhao, Xia; Speed, Haley E; Kee, Sara E; Tu, Jian Cheng; Hu, Jia-Hua; Petralia, Ronald S; Linden, David J; Powell, Craig M; Savonenko, Alena; Xiao, Bo; Worley, Paul F

2011-05-27

We have created a mouse genetic model that mimics a human mutation of Shank3 that deletes the C terminus and is associated with autism. Expressed as a single copy [Shank3(+/ΔC) mice], Shank3ΔC protein interacts with the wild-type (WT) gene product and results in >90% reduction of Shank3 at synapses. This "gain-of-function" phenotype is linked to increased polyubiquitination of WT Shank3 and its redistribution into proteasomes. Similarly, the NR1 subunit of the NMDA receptor is reduced at synapses with increased polyubiquitination. Assays of postsynaptic density proteins, spine morphology, and synapse number are unchanged in Shank3(+/ΔC) mice, but the amplitude of NMDAR responses is reduced together with reduced NMDAR-dependent LTP and LTD. Reciprocally, mGluR-dependent LTD is markedly enhanced. Shank3(+/ΔC) mice show behavioral deficits suggestive of autism and reduced NMDA receptor function. These studies reveal a mechanism distinct from haploinsufficiency by which mutations of Shank3 can evoke an autism-like disorder. Copyright © 2011 Elsevier Inc. All rights reserved.

Adult Autism Subthreshold Spectrum (AdAS Spectrum) in parents of pediatric patients with epilepsy: Correlations with post-traumatic stress symptoms.

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Dell'Osso, L; Corsi, M; Gesi, C; Bertelloni, C A; Massimetti, G; Peroni, D; Bonuccelli, A; Orsini, A; Carmassi, C

2018-05-01

Increasing literature has shown the usefulness of a dimensional approach to mental disorders, particularly when exploring subjects exposed to traumatic experiences such as a severe illness in one's child. Recent evidence suggests an increased vulnerability in subjects with autism spectrum symptoms to develop post-traumatic stress symptoms. The aim of the present study was to evaluate the presence of adult autism subthreshold spectrum in a sample of parents of children with epilepsy and its impact on post-traumatic stress spectrum symptoms in the same study sample. Results revealed noteworthy correlations between post-traumatic stress symptoms and adult autism subthreshold spectrum (AdAS Spectrum) only in the subgroup of the fathers. In particular, were evidenced correlations between AdAS Spectrum domain of rumination and narrow interests and some TALS-SR nuclear domains: reaction to traumatic events, reexperiencing and arousal. These findings corroborate the hypothesis that subthreshold autistic features may influence the possible psychopathological reaction to trauma. Copyright © 2018 Elsevier Inc. All rights reserved.

Brief Report: Sensorimotor Gating in Idiopathic Autism and Autism Associated with Fragile X Syndrome

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Yuhas, Jennifer; Cordeiro, Lisa; Tassone, Flora; Ballinger, Elizabeth; Schneider, Andrea; Long, James M.; Ornitz, Edward M.; Hessl, David

2011-01-01

Prepulse inhibition (PPI) may useful for exploring the proposed shared neurobiology between idiopathic autism and autism caused by FXS. We compared PPI in four groups: typically developing controls (n = 18), FXS and autism (FXS+A; n = 15), FXS without autism spectrum disorder (FXS-A; n = 17), and idiopathic autism (IA; n = 15). Relative to…

The relationship between tics, OC, ADHD and autism symptoms: A cross-disorder symptom analysis in Gilles de la Tourette syndrome patients and their family members

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Huisman-van Dijk, Hilde M.; van de Schoot, Rens; Rijkeboer, Marleen M.; Mathews, Carol A; Cath, Dainelle C

2016-01-01

Gilles de la Tourette’s syndrome (GTS) is a disorder in which co-morbid obsessive-compulsive (OC), Attention Deficit Hyperactivity Disorder (ADHD) and autism symptoms occur in up to 60% of patients, suggesting shared etiology. We aimed to explore the phenotypic structure underlying GTS, taking tic, OC, ADHD, and autism symptoms into account as measured by various symptom scales (YGTSS, Y-BOCS, CAARS and AQ) in 225 GTS patients and 371 family members. First, Confirmatory Factor Analyses (CFA) were performed on the symptom structure of each separate symptom scale. Second, the symptom dimensions derived from each scale were combined in one model, and correlations between them were calculated. Using the correlation matrix, Exploratory Factor Analyses (EFA) were performed on the symptom dimensions across the scales. EFA revealed a five factor structure: tic/aggression/symmetry; OC symptoms/compulsive tics/numbers and patterns; ADHD symptoms; autism symptoms; and hoarding/inattention symptoms. The symptom factors found in this study are partly in line with the traditional categorical boundaries of the symptom scales used, and partly reveal a symptom structure that cuts through the diagnostic categories. This phenotypic structure might more closely reflect underlying etiologies than a structure that classically describes GTS patients according to absence or presence of comorbid OCD, ADHD and autism, and might inform both future genetic and treatment studies. PMID:26826899

Identifying autism early: The Toddlers at Risk of Autism Clinic model.

Science.gov (United States)

Davis, Tessa; Clifton, Deirdre; Papadopoulos, Con

2015-07-01

This paper describes the Toddlers at Risk of Autism Clinic (TRAC), which utilises the Social Attention and Communication Study (SACS) and/or Autism Detection in Early Childhood (ADEC) play-based assessments to facilitate the early diagnosis of autism. A retrospective audit was conducted of all 42 children assessed over a 3-year period in the TRAC. A semi-structured interview and play-based assessment (SACS and ADEC) were used to aid experienced clinicians in diagnosing autism. Intervention was recommended, and families were routinely followed up. Analysis was conducted on the tools used, the outcomes of assessment, diagnosis and stability of diagnosis on follow-up. During this period, 35 boys and 7 girls were assessed, with a mean age of 25 months. The average waiting time for clinic was 11.6 weeks. Twenty-five patients were diagnosed with autism; 90.5% of toddlers given an initial diagnosis retained that diagnosis at follow-up. Out of the 17 children who were not diagnosed with autism in the TRAC, one child was later diagnosed with autism. Experienced clinicians can use the SACS and/or ADEC to assist with a Diagnostic and Statistical Manual diagnosis of autism in toddlers. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Which terms should be used to describe autism? Perspectives from the UK autism community.

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Kenny, Lorcan; Hattersley, Caroline; Molins, Bonnie; Buckley, Carole; Povey, Carol; Pellicano, Elizabeth

2016-05-01

Recent public discussions suggest that there is much disagreement about the way autism is and should be described. This study sought to elicit the views and preferences of UK autism community members - autistic people, parents and their broader support network - about the terms they use to describe autism. In all, 3470 UK residents responded to an online survey on their preferred ways of describing autism and their rationale for such preferences. The results clearly show that people use many terms to describe autism. The most highly endorsed terms were 'autism' and 'on the autism spectrum', and to a lesser extent, 'autism spectrum disorder', for which there was consensus across community groups. The groups disagreed, however, on the use of several terms. The term 'autistic' was endorsed by a large percentage of autistic adults, family members/friends and parents but by considerably fewer professionals; 'person with autism' was endorsed by almost half of professionals but by fewer autistic adults and parents. Qualitative analysis of an open-ended question revealed the reasons underlying respondents' preferences. These findings demonstrate that there is no single way of describing autism that is universally accepted and preferred by the UK's autism community and that some disagreements appear deeply entrenched. © The Author(s) 2015.

A Rorschach investigation of Autism Spectrum Disorders in Adulthood:

Directory of Open Access Journals (Sweden)

Manuela Crucitti

2015-12-01

Full Text Available Autism is a pervasive developmental disorder characterized by deficits in the areas of communication, socialization and behavior. Current diagnostic criteria have been modified in a restrictive sense, thus the possibility that individuals with milder impairments may not reach the diagnostic threshold is concrete. Furthermore, heterogeneity in phenotypic expression and the high rate of comorbidity with other psychiatric disorders would make even more difficult the diagnostic classification in individuals with autism spectrum disorder (ASD. The present study was a Rorschach investigation aimed to identify specific psychopathological elements to properly orient the diagnosis of ASD in adulthood. Results have shown that the examined subjects were characterized by pragmatism, documented by the presence of details and little details, falls in formal thinking, thought inflexibility, lack of answers with human content, and the prevalence of particular phenomena (denial, perseveration. Data obtained in the study showed a specific pattern of psychopathological signs in adults with ASD, thus suggesting the importance of projective methods for a better understanding of the clinical features of avoidance behaviors and relationships.

Annual Research Review: Reaction time variability in ADHD and autism spectrum disorders: measurement and mechanisms of a proposed trans-diagnostic phenotype

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Karalunas, Sarah L.; Geurts, Hilde M.; Konrad, Kerstin; Bender, Stephan; Nigg, Joel T.

2014-01-01

Background Intraindividual variability in reaction time (RT) has received extensive discussion as an indicator of cognitive performance, a putative intermediate phenotype of many clinical disorders, and a possible trans-diagnostic phenotype that may elucidate shared risk factors for mechanisms of psychiatric illnesses. Scope and Methodology Using the examples of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD), we discuss RT variability. We first present a new meta-analysis of RT variability in ASD with and without comorbid ADHD. We then discuss potential mechanisms that may account for RT variability and statistical models that disentangle the cognitive processes affecting RTs. We then report a second meta-analysis comparing ADHD and non-ADHD children on diffusion model parameters. We consider how findings inform the search for neural correlates of RT variability. Findings Results suggest that RT variability is increased in ASD only when children with comorbid ADHD are included in the sample. Furthermore, RT variability in ADHD is explained by moderate to large increases (d = 0.63–0.99) in the ex-Gaussian parameter τ and the diffusion parameter drift rate, as well as by smaller differences (d = 0.32) in the diffusion parameter of nondecision time. The former may suggest problems in state regulation or arousal and difficulty detecting signal from noise, whereas the latter may reflect contributions from deficits in motor organization or output. The neuroimaging literature converges with this multicomponent interpretation and also highlights the role of top-down control circuits. Conclusion We underscore the importance of considering the interactions between top-down control, state regulation (e.g. arousal), and motor preparation when interpreting RT variability and conclude that decomposition of the RT signal provides superior interpretive power and suggests mechanisms convergent with those implicated using other cognitive

Roses for Autism

Science.gov (United States)

Tomaino, Robert

2011-01-01

This article discusses Roses for Autism, a program that provides training, guidance and employment opportunities for older students and adults on the autistic spectrum. Roses for Autism tackles one of the biggest challenges currently facing the autism community--a disproportionally high unemployment rate that hovers around 88 percent. Although a…

Epilepsy and other neurological diseases in the parents of children with infantile autism. A case control study

DEFF Research Database (Denmark)

Mouridsen, S.E.; Rich, B.; Isager, T.

2008-01-01

In order to study the broader phenotype of infantile autism (IA) we compared the rates and types of epilepsy and other neurological diseases in the parents of 111 consecutively admitted patients with IA with a matched control group of parents of 330 children from the general population. All parti...... fathers the proportion was 5.7% vs 9.7%. No single neurological disease was significantly more frequent among parents of persons with IA. Our study lent support to the notion that epilepsy and other neurological diseases are not part of the broader IA phenotype Udgivelsesdato: 2008/3...

The interaction between the immune system and epigenetics in the etiology of autism spectrum disorders

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Stefano Nardone

2016-07-01

Full Text Available Recent studies have firmly established that the etiology of autism includes both genetic and environmental components. However, we are only just beginning to elucidate the environmental factors that might be involved in the development of autism, as well as the molecular mechanisms through which they function. Mounting epidemiological and biological evidence suggest that prenatal factors that induce a more activated immune state in the mother are involved in the development of autism. In parallel, molecular studies have highlighted the role of epigenetics in brain development as process susceptible to environmental influences and potentially causative of ASD. In this review, we will discuss converging evidence for a multidirectional interaction between immune system activation in the mother during pregnancy and epigenetic regulation in the brain of the fetus that may cooperate to produce an autistic phenotype. This interaction includes immune factor-induced changes in epigenetic signatures in the brain, dysregulation of epigenetic modifications specifically in genomic regions that encode immune functions, and aberrant epigenetic regulation of microglia. Overall, the interaction between immune system activation in the mother and the subsequent epigenetic dysregulation in the developing fetal brain may be a main consideration for the environmental factors that cause autism.

Social anxiety and autism spectrum traits among adult FMR1 premutation carriers.

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López-Mourelo, O; Mur, E; Madrigal, I; Alvarez-Mora, M I; Gómez-Ansón, B; Pagonabarraga, J; Rodriguez-Revenga, L; Milà, M

2017-01-01

Behavioral symptoms and traits have been proposed as early markers in neurodegenerative diseases. The aim of this study was to evaluate social anxiety and autism in FMR1 premutation carriers using the Social Phobia Inventory (SPIN) and the Autism-Spectrum Quotient (AQ) questionnaires. Fifty-nine premutation carriers were compared with 50 controls. The SPIN test showed statistically significant differences between female but not male carriers. The AQ questionnaire found statistically significant differences between premutation carriers and controls in the total AQ as well as in the social skills and attention switching subdomains. A gender effect was only observed for the social skills subdomain. Spearman's correlation analysis revealed a moderately positive correlation with the total AQ scores as well as the social skills and communication subdomains. Our results show that fragile X-associated tremor/ataxia syndrome (FXTAS) patients have higher AQ scores. Moreover, this is the first study to find statistically significant differences between FXTAS and no-FXTAS premutation carriers in the communication and the imagination subdomains, suggesting that FXTAS patients present a broader autistic phenotype than premutation carriers without FXTAS. Based on our results, a wide range of behavioral/psychiatric traits should be included within the broader phenotypic presentation of individuals with the FMR1 premutation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Whole Exome Sequencing in Females with Autism Implicates Novel and Candidate Genes

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Merlin G. Butler

2015-01-01

Full Text Available Classical autism or autistic disorder belongs to a group of genetically heterogeneous conditions known as Autism Spectrum Disorders (ASD. Heritability is estimated as high as 90% for ASD with a recently reported compilation of 629 clinically relevant candidate and known genes. We chose to undertake a descriptive next generation whole exome sequencing case study of 30 well-characterized Caucasian females with autism (average age, 7.7 ± 2.6 years; age range, 5 to 16 years from multiplex families. Genomic DNA was used for whole exome sequencing via paired-end next generation sequencing approach and X chromosome inactivation status. The list of putative disease causing genes was developed from primary selection criteria using machine learning-derived classification score and other predictive parameters (GERP2, PolyPhen2, and SIFT. We narrowed the variant list to 10 to 20 genes and screened for biological significance including neural development, function and known neurological disorders. Seventy-eight genes identified met selection criteria ranging from 1 to 9 filtered variants per female. Five females presented with functional variants of X-linked genes (IL1RAPL1, PIR, GABRQ, GPRASP2, SYTL4 with cadherin, protocadherin and ankyrin repeat gene families most commonly altered (e.g., CDH6, FAT2, PCDH8, CTNNA3, ANKRD11. Other genes related to neurogenesis and neuronal migration (e.g., SEMA3F, MIDN, were also identified.

Autism.

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Parr, Jeremy

2010-01-07

Evidence for the efficacy of treatments for autism has improved in recent years. In this systematic review the evidence for both drug and non-drug treatments is appraised and clinical guidance is provided for their use. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of early intensive multidisciplinary intervention programmes in children with autism? What are the effects of dietary interventions in children with autism? What are the effects of drug treatments in children with autism? What are the effects of non-drug treatments in children with autism? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2009 (Clinical evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 30 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: applied behavioural analysis; auditory integration training; Autism Preschool Programme; casein-free diet; chelation; Child's Talk programme; cognitive behavioural therapy; digestive enzymes; EarlyBird programme; facilitated communication; Floortime therapy; gluten-free diet; immunoglobulins; melatonin; memantine; methylphenidate; More Than Words programme; music therapy; olanzapine; omega-3 fish oil; picture exchange communication system; Portage scheme; probiotics; relationship development interventions; risperidone; secretin; selective serotonin reuptake inhibitors (SSRIs); sensory integration training; social stories; social skills training; Son-Rise programme; TEACCH

The Pleiotropic MET Receptor Network: Circuit Development and the Neural-Medical Interface of Autism.

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Eagleson, Kathie L; Xie, Zhihui; Levitt, Pat

2017-03-01

People with autism spectrum disorder and other neurodevelopmental disorders (NDDs) are behaviorally and medically heterogeneous. The combination of polygenicity and gene pleiotropy-the influence of one gene on distinct phenotypes-raises questions of how specific genes and their protein products interact to contribute to NDDs. A preponderance of evidence supports developmental and pathophysiological roles for the MET receptor tyrosine kinase, a multifunctional receptor that mediates distinct biological responses depending upon cell context. MET influences neuron architecture and synapse maturation in the forebrain and regulates homeostasis in gastrointestinal and immune systems, both commonly disrupted in NDDs. Peak expression of synapse-enriched MET is conserved across rodent and primate forebrain, yet regional differences in primate neocortex are pronounced, with enrichment in circuits that participate in social information processing. A functional risk allele in the MET promoter, enriched in subgroups of children with autism spectrum disorder, reduces transcription and disrupts socially relevant neural circuits structurally and functionally. In mice, circuit-specific deletion of Met causes distinct atypical behaviors. MET activation increases dendritic complexity and nascent synapse number, but synapse maturation requires reductions in MET. MET mediates its specific biological effects through different intracellular signaling pathways and has a complex protein interactome that is enriched in autism spectrum disorder and other NDD candidates. The interactome is coregulated in developing human neocortex. We suggest that a gene as pleiotropic and highly regulated as MET, together with its interactome, is biologically relevant in normal and pathophysiological contexts, affecting central and peripheral phenotypes that contribute to NDD risk and clinical symptoms. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Aging with autism spectrum disorder: an emerging public health problem.

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Hategan, Ana; Bourgeois, James A; Goldberg, Jeremy

2017-04-01

From 1943, when Leo Kanner originally described autism, and to the first objective criteria for "infantile autism" in DSM-III and the inclusion of Asperger's disorder in DSM-IV, the subsequent classification scheme for autistic disorders has led to a substantial change with the 2013 issuance of the DSM-5 by including subcategories into one umbrella diagnosis of autism spectrum disorder (ASD) (Baker, 2013). ASD is a lifelong neurodevelopmental disorder, characterized by social and communication impairments and restricted, stereotypical patterns of behavior (Baker, 2013). It is currently expected that most, or all of the actual cases of ASD, are identified in a timely way (i.e. in early childhood). However, there are many undiagnosed older adults who may have met the current diagnostic criteria for ASD as children, but never received such a diagnosis due to the fact it had yet to be established. In addition, some patients with relatively less impairing phenotypes may escape formal diagnosis in childhood, only to later be diagnosed in adulthood. Nevertheless, the first generation of diagnosed patients with ASD is now in old age. Many such ASD patients have needed family and institutional support for their lives subsequent to childhood diagnosis. Due to aging and death of their parents and other supportive figures leading to a loss of social structures, there is no better time than now for the medical community to act.

Exploring Anxiety Symptoms in a Large-Scale Twin Study of Children with Autism Spectrum Disorders, Their Co-Twins and Controls

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Hallett, Victoria; Ronald, Angelica; Colvert, Emma; Ames, Catherine; Woodhouse, Emma; Lietz, Stephanie; Garnett, Tracy; Gillan, Nicola; Rijsdijk, Fruhling; Scahill, Lawrence; Bolton, Patrick; Happé, Francesca

2013-01-01

Background: Although many children with autism spectrum disorders (ASDs) experience difficulties with anxiety, the manifestation of these difficulties remains unresolved. The current study assessed anxiety in a large population-based twin sample, aged 10-15 years. Phenotypic analyses were used to explore anxiety symptoms in children with ASDs,…

Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders.

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Katherine M Ku

Full Text Available The laboratory rat is emerging as an attractive preclinical animal model of autism spectrum disorder (ASD, allowing investigators to explore genetic, environmental and pharmacological manipulations in a species exhibiting complex, reciprocal social behavior. The present study was carried out to compare two commonly used strains of laboratory rats, Sprague-Dawley (SD and Long-Evans (LE, between the ages of postnatal day (PND 26-56 using high-throughput behavioral phenotyping tools commonly used in mouse models of ASD that we have adapted for use in rats. We detected few differences between young SD and LE strains on standard assays of exploration, sensorimotor gating, anxiety, repetitive behaviors, and learning. Both SD and LE strains also demonstrated sociability in the 3-chamber social approach test as indexed by spending more time in the social chamber with a constrained age/strain/sex matched novel partner than in an identical chamber without a partner. Pronounced differences between the two strains were, however, detected when the rats were allowed to freely interact with a novel partner in the social dyad paradigm. The SD rats in this particular testing paradigm engaged in play more frequently and for longer durations than the LE rats at both juvenile and young adult developmental time points. Results from this study that are particularly relevant for developing preclinical ASD models in rats are threefold: (i commonly utilized strains exhibit unique patterns of social interactions, including strain-specific play behaviors, (ii the testing environment may profoundly influence the expression of strain-specific social behavior and (iii simple, automated measures of sociability may not capture the complexities of rat social interactions.

Juvenile manifestation of ultrasound communication deficits in the neuroligin-4 null mutant mouse model of autism.

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Ju, Anes; Hammerschmidt, Kurt; Tantra, Martesa; Krueger, Dilja; Brose, Nils; Ehrenreich, Hannelore

2014-08-15

Neuroligin-4 (Nlgn4) is a member of the neuroligin family of postsynaptic cell adhesion molecules. Loss-of-function mutations of NLGN4 are among the most frequent, known genetic causes of heritable autism. Adult Nlgn4 null mutant (Nlgn4(-/-)) mice are a construct valid model of human autism, with both genders displaying a remarkable autistic phenotype, including deficits in social interaction and communication as well as restricted and repetitive behaviors. In contrast to adults, autism-related abnormalities in neonatal and juvenile Nlgn4(-/-) mice have not been reported yet. The present study has been designed to systematically investigate in male and female Nlgn4(-/-) pups versus wildtype littermates (WT, Nlgn4(+/+)) developmental milestones and stimulus-induced ultrasound vocalization (USV). Neonatal development, followed daily from postnatal days (PND) 4 to 21, including physical development, neurological reflexes and neuromotor coordination, did not yield any differences between Nlgn4(-/-) and their WT littermates. USV in pups (PND8-9) in response to brief separation from their mothers revealed remarkable gender effects, and a genotype influence in females regarding latency to first call. In juveniles (PND22-23), USV monitoring upon exposure to an anesthetized female intruder mouse uncovered a clear genotype effect with reduced USV in Nlgn4(-/-) mice, and again a more prominent phenotype in females. Together, these data support an early manifestation of communication deficits in Nlgn4(-/-) mice that appear more pronounced in immature females with their overall stronger USV as compared to males. Copyright © 2014 Elsevier B.V. All rights reserved.

Cognitive-behavioral phenotypes of Williams syndrome are associated with genetic variation in the GTF2I gene, in a healthy population.

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Crespi, Bernard J; Hurd, Peter L

2014-11-28

Individuals with Williams syndrome, a neurogenetic condition caused by deletion of a set of genes at chromosomal location 7q11.23, exhibit a remarkable suite of traits including hypersociality with high, nonselective friendliness and low social anxiety, expressive language relatively well-developed but under-developed social-communication skills overall, and reduced visual-spatial abilities. Deletions and duplications of the Williams-syndrome region have also been associated with autism, and with schizophrenia, two disorders centrally involving social cognition. Several lines of evidence have linked the gene GTF2I (General Transcription Factor IIi) with the social phenotypes of Williams syndrome, but a role for this gene in sociality within healthy populations has yet to be investigated. We genotyped a large set of healthy individuals for two single-nucleotide polymorphisms in the GTF2I gene that have recently been significantly associated with autism, and thus apparently exhibit functional effects on autism-related social phenotypes. GTF2I genotypes for these SNPs showed highly significant association with low social anxiety combined with reduced social-communication abilities, which represents a metric of the Williams-syndrome cognitive profile as described from previous studies. These findings implicate the GTF2I gene in the neurogenetic basis of social communication and social anxiety, both in Williams syndrome and among individuals in healthy populations.

Stereotypes of autism.

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Draaisma, Douwe

2009-05-27

In their landmark papers, both Kanner and Asperger employed a series of case histories to shape clinical insight into autistic disorders. This way of introducing, assessing and representing disorders has disappeared from today's psychiatric practice, yet it offers a convincing model of the way stereotypes may build up as a result of representations of autism. Considering that much of what society at large learns on disorders on the autism spectrum is produced by representations of autism in novels, TV-series, movies or autobiographies, it will be of vital importance to scrutinize these representations and to check whether or not they are, in fact, misrepresenting autism. In quite a few cases, media representations of talent and special abilities can be said to have contributed to a harmful divergence between the general image of autism and the clinical reality of the autistic condition.

Neuroanatomical phenotypes in mental illness: identifying convergent and divergent cortical phenotypes across autism, ADHD and schizophrenia.

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Park, Min Tae M; Raznahan, Armin; Shaw, Philip; Gogtay, Nitin; Lerch, Jason P; Chakravarty, M Mallar

2018-05-01

There is evidence suggesting neuropsychiatric disorders share genomic, cognitive and clinical features. Here, we ask if autism-spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD) and schizophrenia share neuroanatomical variations. First, we used measures of cortical anatomy to estimate spatial overlap of neuroanatomical variation using univariate methods. Next, we developed a novel methodology to determine whether cortical deficits specifically target or are "enriched" within functional resting-state networks. We found cortical anomalies were preferentially enriched across functional networks rather than clustering spatially. Specifically, cortical thickness showed significant enrichment between patients with ASD and those with ADHD in the default mode network, between patients with ASD and those with schizophrenia in the frontoparietal and limbic networks, and between patients with ADHD and those with schizophrenia in the ventral attention network. Networks enriched in cortical thickness anomalies were also strongly represented in functional MRI results (Neurosynth; r = 0.64, p = 0.032). We did not account for variable symptom dimensions and severity in patient populations, and our cross-sectional design prevented longitudinal analyses of developmental trajectories. These findings suggest that common deficits across neuropsychiatric disorders cannot simply be characterized as arising out of local changes in cortical grey matter, but rather as entities of both local and systemic alterations targeting brain networks.

Cortical enlargement in autism is associated with a functional VNTR in the monoamine oxidase A gene.

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Davis, Lea K; Hazlett, Heather C; Librant, Amy L; Nopoulos, Peggy; Sheffield, Val C; Piven, Joesph; Wassink, Thomas H

2008-10-05

Monoamine oxidase A (MAOA) is an enzyme expressed in the brain that metabolizes dopamine, norepinephrine, epinephrine, and serotonin. Abnormalities of serotonin neurotransmission have long been implicated in the psychopathology of autism. A polymorphism exists within the promoter region of the MAOA gene that influences MAOA expression levels so that "low activity" alleles are associated with increased neurotransmitter levels in the brain. Individuals with autism often exhibit elevated serotonin levels. Additional studies indicate that the "low activity" allele may be associated with lower IQ and more severe autistic symptoms. In this study we genotyped the MAOA promoter polymorphism in a group of 29 males (age 2-3 years) with autism and a group of 39 healthy pediatric controls for whom brain MRI data was available. We found a consistent association between the "low activity" allele and larger brain volumes for regions of the cortex in children with autism but not in controls. We did not find evidence for over-transmission of the "low activity" allele in a separate sample of 114 affected sib pair families. Nor did we find any unknown SNPs in yet another sample of 96 probands. Future studies will determine if there is a more severe clinical phenotype associated with both the "low activity" genotype and the larger brain volumes in our sample.

A Causal and Mediation Analysis of the Comorbidity between Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD)

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Sokolova, Elena; Oerlemans, Anoek M.; Rommelse, Nanda N.; Groot, Perry; Hartman, Catharina A.; Glennon, Jeffrey C.; Claassen, Tom; Heskes, Tom; Buitelaar, Jan K.

2017-01-01

Autism spectrum disorder (ASD) and Attention-deficit/hyperactivity disorder (ADHD) are often comorbid. The purpose of this study is to explore the relationships between ASD and ADHD symptoms by applying causal modeling. We used a large phenotypic data set of 417 children with ASD and/or ADHD, 562 affected and unaffected siblings, and 414 controls,…

Comparison of Scores on the Checklist for Autism Spectrum Disorder, Childhood Autism Rating Scale, and Gilliam Asperger's Disorder Scale for Children with Low Functioning Autism, High Functioning Autism, Asperger's Disorder, ADHD, and Typical Development

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Mayes, Susan Dickerson; Calhoun, Susan L.; Murray, Michael J.; Morrow, Jill D.; Yurich, Kirsten K. L.; Mahr, Fauzia; Cothren, Shiyoko; Purichia, Heather; Bouder, James N.; Petersen, Christopher

2009-01-01

Reliability and validity for three autism instruments were compared for 190 children with low functioning autism (LFA), 190 children with high functioning autism or Asperger's disorder (HFA), 76 children with attention deficit hyperactivity disorder (ADHD), and 64 typical children. The instruments were the Checklist for Autism Spectrum Disorder…

Sensory perception in autism.

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Robertson, Caroline E; Baron-Cohen, Simon

2017-11-01

Autism is a complex neurodevelopmental condition, and little is known about its neurobiology. Much of autism research has focused on the social, communication and cognitive difficulties associated with the condition. However, the recent revision of the diagnostic criteria for autism has brought another key domain of autistic experience into focus: sensory processing. Here, we review the properties of sensory processing in autism and discuss recent computational and neurobiological insights arising from attention to these behaviours. We argue that sensory traits have important implications for the development of animal and computational models of the condition. Finally, we consider how difficulties in sensory processing may relate to the other domains of behaviour that characterize autism.

Robot Enhanced Therapy for Children with Autism (DREAM): A Social Model of Autism

OpenAIRE

Richardson, Kathleen; Coecklebergh, M; Wakunuma, Kutoma; Billing, Erik; Ziemke, Tom; Gomez, P; Vanderborght, Bram; Belpaeme, Tony

2017-01-01

Development of Robot-enhanced Therapy for Children with Autism Spectrum Disorders The development of social robots for children with autism has been a growth field in the last 15 years. This paper reviews studies in robots and autism as a neurodevelopmental disorder that impacts on social-communication development and the way in which social robots could help children with autism develop social skills. Drawing on the ethics research from the EU funded DREAM project (framework 7), based on ...

A Clinical Translation of the Article Titled "Evidence for the Implementation of the Early Start Denver Model for Young Children With Autism Spectrum Disorder".

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Shannon, Robin Adair

2015-01-01

The purpose of this article is to offer a clinical translation of a literature review titled "Evidence for the Implementation of the Early Start Denver Model for Young Children With Autism Spectrum Disorder" by Ryberg (2015). The literature review was conducted to determine the strength of the research evidence regarding the effectiveness of the Early Start Denver Model in improving cognitive, language, and behavioral functioning of children with autism spectrum disorder. In an effort to narrow the gap between evidence and practice, this clinical translation will discuss the components of the literature review in terms of its rationale for and objectives, methods, results, and implications for evidence-based nursing practice. © The Author(s) 2015.

Autism Spectrum Disorder, Developmental and Psychiatric Features in 16p11.2 Duplication.

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Green Snyder, LeeAnne; D'Angelo, Debra; Chen, Qixuan; Bernier, Raphael; Goin-Kochel, Robin P; Wallace, Arianne Stevens; Gerdts, Jennifer; Kanne, Stephen; Berry, Leandra; Blaskey, Lisa; Kuschner, Emily; Roberts, Timothy; Sherr, Elliot; Martin, Christa L; Ledbetter, David H; Spiro, John E; Chung, Wendy K; Hanson, Ellen

2016-08-01

The 16p11.2 duplication (BP4-BP5) is associated with Autism Spectrum Disorder (ASD), although significant heterogeneity exists. Quantitative ASD, behavioral and neuropsychological measures and DSM-IV diagnoses in child and adult carriers were compared with familial non-carrier controls, and to published results from deletion carriers. The 16p11.2 duplication phenotype ranges widely from asymptomatic presentation to significant disability. The most common diagnoses were intellectual disability, motor delays and Attention Deficit Hyperactivity Disorder in children, and anxiety in adults. ASD occurred in nearly 20 % of child cases, but a majority of carriers did not show the unique social features of ASD. The 16p11.2 duplication phenotype is characterized by wider variability than the reciprocal deletion, likely reflecting contributions from additional risk factors.

"Frank" presentations as a novel research construct and element of diagnostic decision-making in autism spectrum disorder.

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de Marchena, Ashley; Miller, Judith

2017-04-01

Many individuals with ASD have a distinctive behavioral presentation that is recognizable within moments, a phenomenon we call "frank" ASD. This phenomenon has been discussed informally for decades, perhaps as "classic" ASD; however, there is no unitary "classic" presentation, and classic autism does not seem to correspond to level of functioning. Thus, neither "frank" nor "classic" autism has been delineated or studied as a research construct. To initiate the empirical study of frank ASD, we surveyed 151 clinicians, from a range of disciplines that diagnose ASD, about this phenomenon. Respondents completed a 13-item questionnaire about frank ASD, which was analyzed using a mixed-methods approach. Ninety-seven percentage of respondents were familiar with the phenomenon. Respondents estimated that 40% of the ASD population has a frank presentation. Respondents reported the most highly specific behaviors associated with frank presentations were a general sense of impaired reciprocity, quality of eye contact, atypical vocal prosody, presence of motor mannerisms, and atypical gait or posture. In general, respondents reported detecting frank features rapidly, with the majority forming their impressions within the first ten minutes of interaction or observation. Although unstudied empirically, "frank" presentations of ASD are familiar to diagnosing clinicians, and appear to be based on behaviors both central to ASD diagnostic criteria (e.g., impaired reciprocity), and absent from diagnostic criteria (e.g., atypical gait or posture). We discuss these findings within the context of diagnostic decision-making and behavioral phenotyping of ASD. Autism Res 2016,. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 653-662. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Maternal Inflammation Contributes to Brain Overgrowth and Autism-Associated Behaviors through Altered Redox Signaling in Stem and Progenitor Cells

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Janel E. Le Belle

2014-11-01

Full Text Available A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.

[Autism spectrum syndrome replaces Asperger syndrome and autism].

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Bejerot, Susanne; Nordin, Viviann

2014-09-23

Autism spectrum disorder describes a behaviourally defined impairment in social interaction and communication, along with the presence of restricted interests and repetitive behaviours. Although the etiology is mostly unknown, it is evident that biological factors affect the brain and result in the autistic clinical presentation. Assessment for diagnosing autism spectrum disorder should be comprehensive in order to cover all sorts of problems related to the disorder. Knowledge and experience from working with neurological and psychiatric disorders are a prerequisite for quality in the examination. Up to now, there is no cure for autism spectrum disorder, but support and adaptations in education are nevertheless important for obtaining sufficient life quality for the patients and the family.

Social attention in a virtual public speaking task in higher functioning children with autism.

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Jarrold, William; Mundy, Peter; Gwaltney, Mary; Bailenson, Jeremy; Hatt, Naomi; McIntyre, Nancy; Kim, Kwanguk; Solomon, Marjorie; Novotny, Stephanie; Swain, Lindsay

2013-10-01

Impairments in social attention play a major role in autism, but little is known about their role in development after preschool. In this study, a public speaking task was used to study social attention, its moderators, and its association with classroom learning in elementary and secondary students with higher functioning autism spectrum disorder (HFASD). Thirty-seven students with HFASD and 54 age- and intelligence quotient (IQ)-matched peers without symptoms of ASD were assessed in a virtual classroom public speaking paradigm. This paradigm assessed the ability to attend to nine avatar peers seated at a table, while simultaneously answering self-referenced questions. Students with HFASD looked less frequently to avatar peers in the classroom while talking. However, social attention was moderated in the HFASD sample such that students with lower IQ, and/or more symptoms of social anxiety, and/or more attention deficit/hyperactivity disorder inattentive symptoms, displayed more atypical social attention. Group differences were more pronounced when the classroom contained social avatars versus nonsocial targets. Moreover, measures of social attention rather than nonsocial attention were significantly associated with parent report and objective measures of learning in the classroom. The data in this study support the hypothesis of the Social Attention Model of ASD that social attention disturbance remains part of the school-aged phenotype of autism that is related to syndrome-specific problems in social learning. More research of this kind would likely contribute to advances in the understanding of the development of the spectrum of autism and educational intervention approaches for affected school-aged children. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Pre- and postnatal exposure to low dose glufosinate ammonium induces autism-like phenotypes in mice.

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Laugeray, Anthony; Herzine, Ameziane; Perche, Olivier; Hébert, Betty; Aguillon-Naury, Marine; Richard, Olivier; Menuet, Arnaud; Mazaud-Guittot, Séverine; Lesné, Laurianne; Briault, Sylvain; Jegou, Bernard; Pichon, Jacques; Montécot-Dubourg, Céline; Mortaud, Stéphane

2014-01-01

Glufosinate ammonium (GLA) is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here, we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in relative brain weight of the offspring. In addition, reduced expression of Pten and Peg3 - two genes implicated in autism-like deficits - was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between pre- and postnatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods.

Narrow, duplicated internal auditory canal

Energy Technology Data Exchange (ETDEWEB)

Ferreira, T. [Servico de Neurorradiologia, Hospital Garcia de Orta, Avenida Torrado da Silva, 2801-951, Almada (Portugal); Shayestehfar, B. [Department of Radiology, UCLA Oliveview School of Medicine, Los Angeles, California (United States); Lufkin, R. [Department of Radiology, UCLA School of Medicine, Los Angeles, California (United States)

2003-05-01

A narrow internal auditory canal (IAC) constitutes a relative contraindication to cochlear implantation because it is associated with aplasia or hypoplasia of the vestibulocochlear nerve or its cochlear branch. We report an unusual case of a narrow, duplicated IAC, divided by a bony septum into a superior relatively large portion and an inferior stenotic portion, in which we could identify only the facial nerve. This case adds support to the association between a narrow IAC and aplasia or hypoplasia of the vestibulocochlear nerve. The normal facial nerve argues against the hypothesis that the narrow IAC is the result of a primary bony defect which inhibits the growth of the vestibulocochlear nerve. (orig.)

Flooding correlations in narrow channel

International Nuclear Information System (INIS)

Kim, S. H.; Baek, W. P.; Chang, S. H.

1999-01-01

Heat transfer in narrow gap is considered as important phenomena in severe accidents in nuclear power plants. Also in heat removal of electric chip. Critical heat flux(CHF) in narrow gap limits the maximum heat transfer rate in narrow channel. In case of closed bottom channel, flooding limited CHF occurrence is observed. Flooding correlations will be helpful to predict the CHF in closed bottom channel. In present study, flooding data for narrow channel geometry were collected and the work to recognize the effect of the span, w and gap size, s were performed. And new flooding correlations were suggested for high-aspect-ratio geometry. Also, flooding correlation was applied to flooding limited CHF data

Autism spectrum disorder model mice: Focus on copy number variation and epigenetics.

Science.gov (United States)

Nakai, Nobuhiro; Otsuka, Susumu; Myung, Jihwan; Takumi, Toru

2015-10-01

Autism spectrum disorder (ASD) is gathering concerns in socially developed countries. ASD is a neuropsychiatric disorder of genetic origin with high prevalence of 1%-2%. The patients with ASD characteristically show impaired social skills. Today, many genetic studies identify numerous susceptible genes and genetic loci associated with ASD. Although some genetic factors can lead to abnormal brain function linked to ASD phenotypes, the pathogenic mechanism of ASD is still unclear. Here, we discuss a new mouse model for ASD as an advanced tool to understand the mechanism of ASD.

Are endocrine disrupting compounds environmental risk factors for autism spectrum disorder?

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Moosa, Amer; Shu, Henry; Sarachana, Tewarit; Hu, Valerie W

2017-10-23

Recent research on the etiology of autism spectrum disorder (ASD) has shifted in part from a singular focus on genetic causes to the involvement of environmental factors and their gene interactions. This shift in focus is a result of the rapidly increasing prevalence of ASD coupled with the incomplete penetrance of this disorder in monozygotic twins. One such area of environmentally focused research is the association of exposures to endocrine disrupting compounds (EDCs) with elevated risk for ASD. EDCs are exogenous chemicals that can alter endogenous hormone activity and homeostasis, thus potentially disrupting the action of sex and other natural hormones at all stages of human development. Inasmuch as sex hormones play a fundamental role in brain development and sexual differentiation, exposure to EDCs in utero during critical stages of development can have lasting neurological and other physiological influences on the developing fetus and, ultimately, the child as well as adult. This review will focus on the possible contributions of EDCs to autism risk and pathogenesis by first discussing the influence of endogenous sex hormones on the autistic phenotype, followed by a review of documented human exposures to EDCs and associations with behaviors relevant to ASD. Mechanistic links between EDC exposures and aberrant neurodevelopment and behaviors are then considered, with emphasis on EDC-induced transcriptional profiles derived from animal and cellular studies. Finally, this review will discuss possible mechanisms through which EDC exposure can lead to persistent changes in gene expression and phenotype, which may in turn contribute to transgenerational inheritance of ASD. Copyright © 2017 Elsevier Inc. All rights reserved.

Kids' Quest: Autism

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... I Have Information For… Parents / Educators What is autism and how do I recognize a kid who might be diagnosed as having an autism spectrum disorder? Recommend on Facebook Tweet Share Compartir ...

Increased glutamate/GABA+ ratio in a shared autistic and schizotypal trait phenotype termed Social Disorganisation.

Science.gov (United States)

Ford, Talitha C; Nibbs, Richard; Crewther, David P

2017-01-01

Autism and schizophrenia are multi-dimensional spectrum disorders that have substantial phenotypic overlap. This overlap is readily identified in the non-clinical population, and has been conceptualised as Social Disorganisation (SD). This study investigates the balance of excitatory glutamate and inhibitory γ -aminobutyric acid (GABA) concentrations in a non-clinical sample with high and low trait SD, as glutamate and GABA abnormalities are reported across the autism and schizophrenia spectrum disorders. Participants were 18 low (10 females) and 19 high (9 females) SD scorers aged 18 to 40 years who underwent 1 H-MRS for glutamate and GABA+macromolecule (GABA+) concentrations in right and left hemisphere superior temporal (ST) voxels. Reduced GABA+ concentration ( p  = 0.03) and increased glutamate/GABA+ ratio ( p  = 0.003) in the right ST voxel for the high SD group was found, and there was increased GABA+ concentration in the left compared to right ST voxel ( p  = 0.047). Bilateral glutamate concentration was increased for the high SD group ( p  = 0.006); there was no hemisphere by group interaction ( p  = 0.772). Results suggest that a higher expression of the SD phenotype may be associated with increased glutamate/GABA+ ratio in the right ST region, which may affect speech prosody processing, and lead behavioural characteristics that are shared within the autistic and schizotypal spectra.

Differential sensory fMRI signatures in autism and schizophrenia: Analysis of amplitude and trial-to-trial variability.

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Haigh, Sarah M; Gupta, Akshat; Barb, Scott M; Glass, Summer A F; Minshew, Nancy J; Dinstein, Ilan; Heeger, David J; Eack, Shaun M; Behrmann, Marlene

2016-08-01

Autism and schizophrenia share multiple phenotypic and genotypic markers, and there is ongoing debate regarding the relationship of these two disorders. To examine whether cortical dynamics are similar across these disorders, we directly compared fMRI responses to visual, somatosensory and auditory stimuli in adults with autism (N=15), with schizophrenia (N=15), and matched controls (N=15). All participants completed a one-back letter detection task presented at fixation (to control attention) while task-irrelevant sensory stimulation was delivered to the different modalities. We focused specifically on the response amplitudes and the variability in sensory fMRI responses of the two groups, given the evidence of greater trial-to-trial variability in adults with autism. Both autism and schizophrenia individuals showed weaker signal-to-noise ratios (SNR) in sensory-evoked responses compared to controls (d>0.42), but for different reasons. For the autism group, the fMRI response amplitudes were indistinguishable from controls but were more variable trial-to-trial (d=0.47). For the schizophrenia group, response amplitudes were smaller compared to autism (d=0.44) and control groups (d=0.74), but were not significantly more variable (dautism and is not a defining characteristic of schizophrenia, and (2) that blunted response amplitudes may be characteristic of schizophrenia. The relationship between the amplitude and the variability of cortical activity might serve as a specific signature differentiating these neurodevelopmental disorders. Identifying the neural basis of these responses and their relationship to the underlying genetic bases may substantially enlighten the understanding of both disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

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…

A genome-wide scan for common alleles affecting risk for autism.

LENUS (Irish Health Repository)

Anney, Richard

2010-10-15

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner\\'s curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.

A genome-wide scan for common alleles affecting risk for autism.

Science.gov (United States)

Anney, Richard; Klei, Lambertus; Pinto, Dalila; Regan, Regina; Conroy, Judith; Magalhaes, Tiago R; Correia, Catarina; Abrahams, Brett S; Sykes, Nuala; Pagnamenta, Alistair T; Almeida, Joana; Bacchelli, Elena; Bailey, Anthony J; Baird, Gillian; Battaglia, Agatino; Berney, Tom; Bolshakova, Nadia; Bölte, Sven; Bolton, Patrick F; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Carson, Andrew R; Casallo, Guillermo; Casey, Jillian; Chu, Su H; Cochrane, Lynne; Corsello, Christina; Crawford, Emily L; Crossett, Andrew; Dawson, Geraldine; de Jonge, Maretha; Delorme, Richard; Drmic, Irene; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A; Folstein, Susan E; Fombonne, Eric; Freitag, Christine M; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T; Goldberg, Jeremy; Green, Jonathan; Guter, Stephen J; Hakonarson, Hakon; Heron, Elizabeth A; Hill, Matthew; Holt, Richard; Howe, Jennifer L; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Kim, Cecilia; Klauck, Sabine M; Kolevzon, Alexander; Korvatska, Olena; Kustanovich, Vlad; Lajonchere, Clara M; Lamb, Janine A; Laskawiec, Magdalena; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L; Lionel, Anath C; Liu, Xiao-Qing; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C; Maestrini, Elena; Mahoney, William; Mantoulan, Carine; Marshall, Christian R; McConachie, Helen; McDougle, Christopher J; McGrath, Jane; McMahon, William M; Melhem, Nadine M; Merikangas, Alison; Migita, Ohsuke; Minshew, Nancy J; Mirza, Ghazala K; Munson, Jeff; Nelson, Stanley F; Noakes, Carolyn; Noor, Abdul; Nygren, Gudrun; Oliveira, Guiomar; Papanikolaou, Katerina; Parr, Jeremy R; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Piven, Joseph; Posey, David J; Poustka, Annemarie; Poustka, Fritz; Prasad, Aparna; Ragoussis, Jiannis; Renshaw, Katy; Rickaby, Jessica; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L; Bierut, Laura J; Rice, John P; Salt, Jeff; Sansom, Katherine; Sato, Daisuke; Segurado, Ricardo; Senman, Lili; Shah, Naisha; Sheffield, Val C; Soorya, Latha; Sousa, Inês; Stoppioni, Vera; Strawbridge, Christina; Tancredi, Raffaella; Tansey, Katherine; Thiruvahindrapduram, Bhooma; Thompson, Ann P; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; Van Engeland, Herman; Vincent, John B; Volkmar, Fred; Wallace, Simon; Wang, Kai; Wang, Zhouzhi; Wassink, Thomas H; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Yaspan, Brian L; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Betancur, Catalina; Buxbaum, Joseph D; Cantor, Rita M; Cook, Edwin H; Coon, Hilary; Cuccaro, Michael L; Gallagher, Louise; Geschwind, Daniel H; Gill, Michael; Haines, Jonathan L; Miller, Judith; Monaco, Anthony P; Nurnberger, John I; Paterson, Andrew D; Pericak-Vance, Margaret A; Schellenberg, Gerard D; Scherer, Stephen W; Sutcliffe, James S; Szatmari, Peter; Vicente, Astrid M; Vieland, Veronica J; Wijsman, Ellen M; Devlin, Bernie; Ennis, Sean; Hallmayer, Joachim

2010-10-15

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.

Phelan-McDermid syndrome in two adult brothers: atypical bipolar disorder as its psychopathological phenotype?

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Verhoeven WMA

2012-04-01

Full Text Available Willem MA Verhoeven1,2, Jos IM Egger1,3,4, Marjolein H Willemsen5, Gert JM de Leijer6, Tjitske Kleefstra51Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, 2Erasmus University Medical Centre, Department of Psychiatry, Rotterdam, 3Donders Centre for Cognition, Radboud University Nijmegen, Nijmegen, 4Behavioural Science Institute, Radboud University Nijmegen, Nijmegen, 5Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, 6Dichterbij, Institutes for Intellectual Disabilities, Gennep, The NetherlandsAbstract: The 22q13.3 deletion, or Phelan-McDermid syndrome, is characterized by global intellectual disability, generalized hypotonia, severely delayed or absent speech associated with features of autism spectrum disorder, and minor dysmorphisms. Its behavioral phenotype comprises sleep disturbances, communication deficits, and motor perseverations. Data on psychological dysfunctions are so far not available. Previous studies have suggested that the loss of one copy of the gene SH3 and multiple ankyrin repeat domains 3 (SHANK3 is related to the neurobehavioral phenotype. Additional genes proximal to SHANK3 are also likely to play a role in the phenotype of patients with larger deletions. The present paper describes two adult brothers with an identical 2.15 Mb 22qter (22q13.32q13.33 deletion, of whom the youngest was referred for evaluation of recurrent mood changes. In both patients, magnetic resonance imaging of the brain showed hypoplasia of the vermis cerebelli. Extensive clinical examinations led to a final diagnosis of atypical bipolar disorder, of which symptoms fully remitted during treatment with a mood stabilizer. In the older brother, a similar psychopathological picture appeared to be present, although less severe and with a later onset. It is concluded that the behavioral phenotype of the 22q13.3 deletion syndrome comprises absent or delayed speech and perseverations

Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A): implications for autism

LENUS (Irish Health Repository)

Tansey, Katherine E

2011-03-31

Abstract Background Arginine vasopressin (AVP) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. The arginine vasopressin receptor 1A gene (AVPR1A) is widely expressed in the brain and is considered to be a key receptor for regulation of social behaviour. Moreover, genetic variation at AVPR1A has been reported to be associated with autism. Evidence from non-human mammals implicates variation in the 5\\'-flanking region of AVPR1A in variable gene expression and social behaviour. Methods We examined four tagging single nucleotide polymorphisms (SNPs) (rs3803107, rs1042615, rs3741865, rs11174815) and three microsatellites (RS3, RS1 and AVR) at the AVPR1A gene for association in an autism cohort from Ireland. Two 5\\'-flanking region polymorphisms in the human AVPR1A, RS3 and RS1, were also tested for their effect on relative promoter activity. Results The short alleles of RS1 and the SNP rs11174815 show weak association with autism in the Irish population (P = 0.036 and P = 0.008, respectively). Both RS1 and RS3 showed differences in relative promoter activity by length. Shorter repeat alleles of RS1 and RS3 decreased relative promoter activity in the human neuroblastoma cell line SH-SY5Y. Conclusions These aligning results can be interpreted as a functional route for this association, namely that shorter alleles of RS1 lead to decreased AVPR1A transcription, which may proffer increased susceptibility to the autism phenotype.

Autism Spectrum Disorders (ASD) and Diet

Science.gov (United States)

... Conditions Autism Autism Spectrum Disorders (ASD) and Diet Autism Spectrum Disorders (ASD) and Diet By Karen Ansel, MS, RDN, CDN Published April 2, 2018 nambitomo/iStock/Thinkstock Autism Spectrum Disorder, or ASD, is a complex developmental and neurological ...

Neuronal glucose transporter isoform 3 deficient mice demonstrate features of autism spectrum disorders.

Science.gov (United States)

Zhao, Y; Fung, C; Shin, D; Shin, B-C; Thamotharan, S; Sankar, R; Ehninger, D; Silva, A; Devaskar, S U

2010-03-01

Neuronal glucose transporter (GLUT) isoform 3 deficiency in null heterozygous mice led to abnormal spatial learning and working memory but normal acquisition and retrieval during contextual conditioning, abnormal cognitive flexibility with intact gross motor ability, electroencephalographic seizures, perturbed social behavior with reduced vocalization and stereotypies at low frequency. This phenotypic expression is unique as it combines the neurobehavioral with the epileptiform characteristics of autism spectrum disorders. This clinical presentation occurred despite metabolic adaptations consisting of an increase in microvascular/glial GLUT1, neuronal GLUT8 and monocarboxylate transporter isoform 2 concentrations, with minimal to no change in brain glucose uptake but an increase in lactate uptake. Neuron-specific glucose deficiency has a negative impact on neurodevelopment interfering with functional competence. This is the first description of GLUT3 deficiency that forms a possible novel genetic mechanism for pervasive developmental disorders, such as the neuropsychiatric autism spectrum disorders, requiring further investigation in humans.

Demographic and clinical correlates of autism symptom domains and autism spectrum diagnosis

OpenAIRE

Frazier, Thomas W; Youngstrom, Eric A; Embacher, Rebecca; Hardan, Antonio Y; Constantino, John N; Law, Paul; Findling, Robert L; Eng, Charis

2013-01-01

Demographic and clinical factors may influence assessment of autism symptoms. This study evaluated these correlates and also examined whether social communication and interaction and restricted/repetitive behavior provided unique prediction of autism spectrum disorder diagnosis. We analyzed data from 7352 siblings included in the Interactive Autism Network registry. Social communication and interaction and restricted/repetitive behavior symptoms were obtained using caregiver-reports on the So...

Defining Autism: Variability in State Education Agency Definitions of and Evaluations for Autism Spectrum Disorders

Directory of Open Access Journals (Sweden)

Malinda L. Pennington

2014-01-01

Full Text Available In light of the steady rise in the prevalence of students with autism, this study examined the definition of autism published by state education agencies (SEAs, as well as SEA-indicated evaluation procedures for determining student qualification for autism. We compared components of each SEA definition to aspects of autism from two authoritative sources: Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR and Individuals with Disabilities Education Improvement Act (IDEA-2004. We also compared SEA-indicated evaluation procedures across SEAs to evaluation procedures noted in IDEA-2004. Results indicated that many more SEA definitions incorporate IDEA-2004 features than DSM-IV-TR features. However, despite similar foundations, SEA definitions of autism displayed considerable variability. Evaluation procedures were found to vary even more across SEAs. Moreover, within any particular SEA there often was little concordance between the definition (what autism is and evaluation procedures (how autism is recognized. Recommendations for state and federal policy changes are discussed.

Autism Narratives in Media Coverage of the MMR Vaccine-Autism Controversy under a Crip Futurism Framework.

Science.gov (United States)

Mann, Benjamin W

2018-03-09

While previous studies in health communication have examined online news media regarding autism, there is a lack of research that critically examines how such media representations may stigmatize autism and seeks to eliminate the condition, particularly in the context of the resurging measles, mumps, and rubella (MMR) vaccine-autism controversy. To address this gap in the literature, this study analyzes 153 articles that engage the MMR vaccine-autism controversy from the top 10 online news sources in the U.S. from September 2015 through July 2017. It draws from Kafer's (2013) work in Feminist, Crip, Queer, using a lens of crip futurism to interpret three major narrative themes: a death and survival narrative that purports autism as a worst-case scenario, a societal problem narrative, and a preventative narrative that seeks to eliminate the condition. These themes suggest that online news media narratives about autism surrounding the autism-MMR controversy play into stereotypes about autism, including stigmatization and prioritization of preventive behaviors and cures over supporting the lived experiences of autistic individuals. Continued research on the impact of online media portrayals of autism specifically, and disability in health contexts generally, is called for.

A Comparison of the Autism Treatment Evaluation Checklist (ATEC) and the Childhood Autism Rating Scale (CARS) for the Quantitative Evaluation of Autism

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Geier, David A.; Kern, Janet K.; Geier, Mark R.

2013-01-01

The purpose of this study was to evaluate scores generated from the Autism Treatment Evaluation Checklist (ATEC), a parent-rated measure, and those derived from professionally completed Childhood Autism Rating Scale (CARS) evaluations. A cohort of 56 participants diagnosed with an autism spectrum disorder was used for the study, and each child was…

Autism Spectrum Disorder

Science.gov (United States)

... Caregiver Education » Fact Sheets Autism Spectrum Disorder Fact Sheet What is autism spectrum disorder? What are some ... of mutations in individual genes but rather spontaneous coding mutations across many genes. De novo mutations may ...

Increasing autism prevalence in metropolitan New Jersey.

Science.gov (United States)

Zahorodny, Walter; Shenouda, Josephine; Howell, Sandra; Rosato, Nancy Scotto; Peng, Bo; Mehta, Uday

2014-02-01

High baseline autism spectrum disorder prevalence estimates in New Jersey led to a follow-up surveillance. The objectives were to determine autism spectrum disorder prevalence in the year 2006 in New Jersey and to identify changes in the prevalence of autism spectrum disorder or in the characteristics of the children with autism spectrum disorder, between 2002 and 2006. The cohorts included 30,570 children, born in 1998 and 28,936 children, born in 1994, residing in Hudson, Union, and Ocean counties, New Jersey. Point prevalence estimates by sex, ethnicity, autism spectrum disorder subtype, and previous autism spectrum disorder diagnosis were determined. For 2006, a total of 533 children with autism spectrum disorder were identified, consistent with prevalence of 17.4 per 1000 (95% confidence interval = 15.9-18.9), indicating a significant increase in the autism spectrum disorder prevalence (p autism spectrum disorder was broad, affecting major demographic groups and subtypes. Boys with autism spectrum disorder outnumbered girls by nearly 5:1. Autism spectrum disorder prevalence was higher among White children than children of other ethnicities. Additional studies are needed to specify the influence of better awareness of autism spectrum disorder prevalence estimates and to identify possible autism spectrum disorder risk factors. More resources are necessary to address the needs of individuals affected by autism spectrum disorder.

Prevalence of Autism Spectrum Disorder in Children Referred for Diagnostic Autism Evaluation.

Science.gov (United States)

Monteiro, Sonia A; Spinks-Franklin, Adiaha; Treadwell-Deering, Diane; Berry, Leandra; Sellers-Vinson, Sherry; Smith, Eboni; Proud, Monica; Voigt, Robert G

2015-12-01

Increased public awareness of autism spectrum disorders (ASD) and routine screening in primary care have contributed to increased requests for diagnostic ASD evaluations. However, given the scarcity of subspecialty autism diagnostic resources, overreferral of children suspected of having ASD may be contributing to long waiting lists at tertiary care autism centers and delaying diagnosis for those children who truly have ASD. To determine whether children are being excessively referred to ASD-specific diagnostic clinics, our objective was to determine the prevalence of true ASD diagnoses in children referred for diagnostic ASD evaluation. Charts of all patients referred to a regional autism center between April 2011 and August 2012 for suspicion of a possible ASD were retrospectively reviewed and demographic and clinical diagnoses abstracted. Only 214 of 348 patients evaluated (61%) received an ASD diagnosis. Thus, concerns about autism are not confirmed by an ASD diagnosis in a significant number of children. © The Author(s) 2015.

Reflections on Autism : Ethical Perspectives on Autism Spectrum Disorder in Health Care and Education

OpenAIRE

Jaarsma, Pier

2014-01-01

In the four papers presented in this dissertation I analyze and discuss various value statements and moral stances, which I regard as unjustifiably harmful for persons with Autism and obstacles for the creation of an Autism-friendly society. In the papers I try to show that the positions underpinning the Autism-phobic moral stances are not warranted and cannot be defended in a good way. In doing so, I hope to transform the harmful moral intuitions underlying these positions into autism-friend...

Diagnosis of autism

OpenAIRE

Baird, Gillian; Cass, Hilary; Slonims, Vicky

2003-01-01

Parents want autism to be diagnosed as early as possible, and early intervention may improve long term outcomes. The authors of this review discuss the identification and assessment process for children with autism and autistic spectrum disorder

Language abilities in preschool-aged siblings of children with autism spectrum disorders – preliminary report

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Ewa Pisula

2015-01-01

Full Text Available Background The characteristics of autism spectrum disorders (ASD observed among relatives of people affected with autism are referred to as broader autism phenotype (BAP. Among the components of BAP are language and communication skills. Research to date on these skills amongst the relatives of individuals with ASD is inconclusive. Furthermore, limited data are available about preschool-aged siblings of children with ASD. Participants and procedure Eighty-six children aged 4 years and 6 months – 6 years and 11 months took part in the study (32 girls and 54 boys. They were divided into four groups: siblings of children with autism (S/ASD, high-functioning children diagnosed with autism spectrum disorders (HF/ASD, siblings of children with Down syndrome (S/DS and siblings of typically developing children (Controls, C. Communication and language skills were tested using the Vocabulary Test for Children (TSD. It was used to assess two kinds of verbal skills: receptive language (passive and expressive language (active. Results No differences were observed in expressive lanquage or receptive language between siblings of children with ASD and siblings of children with DS as well as typically developing children. In terms of receptive language and general communication skills, siblings of children with ASD scored higher than high functioning children with ASD. High functioning children with ASD displayed difficulties with receptive language, expressive language, general language and communication skills. Conclusions The results suggest that siblings of children with ASD do not display deficits in communication and language skills. It is however important to note that due to a small sample size this study should be considered as preliminary.

Language and Speech in Autism.

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Gernsbacher, Morton Ann; Morson, Emily M; Grace, Elizabeth J

2016-01-01

Autism is a developmental disability characterized by atypical social interaction, interests or body movements, and communication. Our review examines the empirical status of three communication phenomena believed to be unique to autism: pronoun reversal (using the pronoun you when the pronoun I is intended, and vice versa), echolalia (repeating what someone has said), and a reduced or even reversed production-comprehension lag (a reduction or reversal of the well-established finding that speakers produce less sophisticated language than they can comprehend). Each of these three phenomena has been claimed to be unique to autism; therefore, each has been proposed to be diagnostic of autism, and each has been interpreted in autism-centric ways (psychoanalytic interpretations of pronoun reversal, behaviorist interpretations of echolalia, and clinical lore about the production-comprehension lag). However, as our review demonstrates, none of these three phenomena is in fact unique to autism; none can or should serve as diagnostic of autism, and all call into question unwarranted assumptions about autistic persons and their language development and use.

Overlap of autistic and schizotypal traits in adolescents with Autism Spectrum Disorders.

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Barneveld, Petra S; Pieterse, Jolijn; de Sonneville, Leo; van Rijn, Sophie; Lahuis, Bertine; van Engeland, Herman; Swaab, Hanna

2011-03-01

This study addresses the unraveling of the relationship between autism spectrum and schizophrenia spectrum traits in a population of adolescents with Autism Spectrum Disorders (ASD). Recent studies comparing isolated symptoms of both spectrum disorders as well as diagnostic criteria for each (DSM-IV-TR) suggest resemblances in the clinical phenotype. A group of 27 adolescents with ASD (11 to 18 years) and 30 typically developing adolescents, matched for age and gender, participated in this study. Within the ASD group 11 adolescents satisfied DSM-IV-TR criteria for schizotypal personality disorders. Autistic and schizotypal traits were identified by means of well validated questionnaires (Autism Questionnaire, AQ and Schizotypal Personality Questionnaire-Revised, SPQ). Significantly more schizotypal traits in adolescents with ASD were found than in typically developing controls. Besides high levels of negative symptoms, adolescents with ASD also displayed high levels of positive and disorganized symptoms. There appeared to be a relationship between the mean level of autistic symptoms and schizotypal traits, as well as specific associations between autistic symptoms and negative, disorganized and positive schizotypal symptoms within individuals. Schizotypal symptomatology in all sub dimensions that are reflected by the SPQ scores, was most prominently associated with attention switching problems of the autism symptoms from the AQ. These findings indicate that patients diagnosed with an ASD show schizophrenia spectrum traits in adolescence. Although other studies have provided empirical support for this overlap in diagnostic criteria between both spectrum disorders, the present findings add to the literature that behavioral overlap is not limited to negative schizotypal symptoms, but extends to disorganized and positive symptoms as well. Copyright © 2010 Elsevier B.V. All rights reserved.

Biological sex affects the neurobiology of autism

Science.gov (United States)

Lombardo, Michael V.; Suckling, John; Ruigrok, Amber N. V.; Chakrabarti, Bhismadev; Ecker, Christine; Deoni, Sean C. L.; Craig, Michael C.; Murphy, Declan G. M.; Bullmore, Edward T.; Baron-Cohen, Simon

2013-01-01

In autism, heterogeneity is the rule rather than the exception. One obvious source of heterogeneity is biological sex. Since autism was first recognized, males with autism have disproportionately skewed research. Females with autism have thus been relatively overlooked, and have generally been assumed to have the same underlying neurobiology as males with autism. Growing evidence, however, suggests that this is an oversimplification that risks obscuring the biological base of autism. This study seeks to answer two questions about how autism is modulated by biological sex at the level of the brain: (i) is the neuroanatomy of autism different in males and females? and (ii) does the neuroanatomy of autism fit predictions from the ‘extreme male brain’ theory of autism, in males and/or in females? Neuroanatomical features derived from voxel-based morphometry were compared in a sample of equal-sized high-functioning male and female adults with and without autism (n = 120, n = 30/group). The first question was investigated using a 2 × 2 factorial design, and by spatial overlap analyses of the neuroanatomy of autism in males and females. The second question was tested through spatial overlap analyses of specific patterns predicted by the extreme male brain theory. We found that the neuroanatomy of autism differed between adult males and females, evidenced by minimal spatial overlap (not different from that occurred under random condition) in both grey and white matter, and substantially large white matter regions showing significant sex × diagnosis interactions in the 2 × 2 factorial design. These suggest that autism manifests differently by biological sex. Furthermore, atypical brain areas in females with autism substantially and non-randomly (P males with autism. How differences in neuroanatomy relate to the similarities in cognition between males and females with autism remains to be understood. Future research should stratify by biological sex to reduce

Music therapy for children with autism

OpenAIRE

Thálová, Kateřina

2012-01-01

Music Therapy and Children with Autism Abstract The thesis entitled Music Therapy and Children with Autism deals with the characteristics of childhood autism and introduces music therapy as one of the possible forms of therapies, by means of which the development of children with autism can be positively influenced. The objective of the thesis is to record and organize theoretical knowledge regarding therapeutic effect of music on children with autism. The practical, empiric, part of the thes...

Comparing the use of the Childhood Autism Rating Scale and the Autism Behavior Checklist protocols to identify and characterize autistic individuals.

Science.gov (United States)

Santos, Thaís Helena Ferreira; Barbosa, Milene Rossi Pereira; Pimentel, Ana Gabriela Lopes; Lacerda, Camila Andrioli; Balestro, Juliana Izidro; Amato, Cibelle Albuquerque de la Higuera; Fernandes, Fernanda Dreux Miranda

2012-01-01

To compare the results obtained in the Autism Behavior Checklist with those obtained in the Childhood Autism Rating Scale to identify and characterize children with Autism Spectrum Disorders. Participants were 28 children with psychiatric diagnosis within the autism spectrum that were enrolled in language therapy in a specialized service. These children were assessed according to the Autism Behavior Checklist and Childhood Autism Rating Scale criteria, based on information obtained with parents and therapists, respectively. Data were statistically analyzed regarding the agreement between responses. Results indicating high or moderate probability of autism in the Autism Behavior Checklist were considered concordant with the results indicating mild-to-moderate or severe autism in the Childhood Autism Rating Scale. Results indicating low probability of autism in the Autism Behavior Checklist and without autism in the Childhood Autism Rating Scale were also considered concordant. There was agreement on most of the responses. Cases in which there was disagreement between results obtained on both protocols corroborate literature data, showing that the instruments may not be sufficient, if applied alone, to define the diagnosis. The Childhood Autism Rating Scale may not effectively diagnose autistic children, while the Autism Behavior Checklist may result in over- diagnose, including within the autism spectrum children with other disorders. Therefore, the associated use of both protocols is recommended.

The Diagnosis of Autism and Autism Spectrum Disorder in Low- and Middle-Income Countries: Experience from Jamaica

Science.gov (United States)

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

2017-01-01

The administration requirements of the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised, widely used in high-income countries, make them less feasible for diagnosis of autism spectrum disorder in low- and middle-income countries. The flexible administration requirements of the Childhood Autism Rating Scale have…

Autism-Like Behavior and Epigenetic Changes Associated with Autism as Consequences of In Utero Exposure to Environmental Pollutants in a Mouse Model

Directory of Open Access Journals (Sweden)

Denise S. Hill

2015-01-01

Full Text Available We tested the hypothesis that in utero exposure to heavy metals increases autism-like behavioral phenotypes in adult animals and induces epigenetic changes in genes that have roles in the etiology of autism. Mouse dams were treated with cadmium, lead, arsenate, manganese, and mercury via drinking water from gestational days (E 1–10. Valproic acid (VPA injected intraperitoneally once on (E 8.5 served as a positive control. Young male offspring were tested for behavioral deficits using four standardized behavioral assays. In this study, in utero exposure to heavy metals resulted in multiple behavioral abnormalities that persisted into adulthood. VPA and manganese induced changes in perseverative/impulsive behavior and social dominance behavior, arsenic caused changes only in perseverative/impulsive behavior, and lead induced abnormalities in social interaction in comparison to the control animals. Brain samples from Mn, Pb, and VPA treated and control animals were evaluated for changes in CpG island methylation in promoter regions and associated changes in gene expression. The Chd7 gene, essential for neural crest cell migration and patterning, was found to be hypomethylated in each experimental animal tested compared to water-treated controls. Furthermore, distinct patterns of CpG island methylation yielded novel candidate genes for further investigation.

Individuals with autism have higher 8-Iso-PGF2α levels than controls, but no correlation with quantitative assay of Paraoxonase 1 serum levels.

Science.gov (United States)

Pop, Bianca; Niculae, Alexandru-Ștefan; Pop, Tudor Lucian; Răchișan, Andreea Liana

2017-12-01

Autism spectrum disorder (ASD) represents a very large set of neurodevelopmental issues with diverse clinical outcomes. Various hypotheses have been put forth for the etiology of autism spectrum disorder, including issues pertaining to oxidative stress. In this study, we conducted measurements of serum 8-Iso-Prostaglanding F2 α (8-iso-PGF2α, which is the results of non-enzimatically mediated polyunsaturated fatty acid oxidation) in a population of individuals with autism and a control group of age and sex matched controls. A quantitative assay of Paraoxonase 1 (PON1) was conducted. Data regarding comorbidities, structural MRI scans, medication, intelligence quotient (IQ) and Childhood Autism Rating Scale scores (CARS) were also included in our study. Our results show that patients diagnosed with autism have higher levels of 8-iso-PGF2α than their neurotypical counterparts. Levels of this particular metabolite, however, do not correlate with quantitative serum levels of Paraoxonase 1, which has been shown to be altered in individuals with autism. Neither 8-iso-PGF2α nor quantitative levels of PON1 provide any meaningful correlation with clinical or neuroimaging data in this study group. Future research should focus on providing data regarding PON 1 phenotype, in addition to standard quantitative measurements, in relation to 8-iso-PGF2α as well as other clinical and structural brain findings.

Autism from a cognitive-pragmatic perspective

OpenAIRE

Reboul , Anne; Manificat , Sabine; Foudon , Nadège

2012-01-01

International audience; Autism is one of a group of three neuro-developmental disorders including, in addition to autism itself, Asperger Syndrome and a fairly heterogeneous group of patients who present some but not all of the symptoms of autism (see below, section 2.2). Asperger Syndrome and autism being the best described pathologies, notably in terms of language and language development, they will be the focus of our attention in what follows. Autism has been described as being to pragmat...

Green Space and Childhood Autism

Science.gov (United States)

Autism, a group of complex neurodevelopmental disorders typically identified in early childhood, affects more than 3 million people in the U.S. To date, the cause of autism is unclear. It is believed that autism results from a combination of genetic and environmental factors incl...

Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits.

Science.gov (United States)

Wong, C C Y; Meaburn, E L; Ronald, A; Price, T S; Jeffries, A R; Schalkwyk, L C; Plomin, R; Mill, J

2014-04-01

Autism spectrum disorder (ASD) defines a group of common, complex neurodevelopmental disorders. Although the aetiology of ASD has a strong genetic component, there is considerable monozygotic (MZ) twin discordance indicating a role for non-genetic factors. Because MZ twins share an identical DNA sequence, disease-discordant MZ twin pairs provide an ideal model for examining the contribution of environmentally driven epigenetic factors in disease. We performed a genome-wide analysis of DNA methylation in a sample of 50 MZ twin pairs (100 individuals) sampled from a representative population cohort that included twins discordant and concordant for ASD, ASD-associated traits and no autistic phenotype. Within-twin and between-group analyses identified numerous differentially methylated regions associated with ASD. In addition, we report significant correlations between DNA methylation and quantitatively measured autistic trait scores across our sample cohort. This study represents the first systematic epigenomic analyses of MZ twins discordant for ASD and implicates a role for altered DNA methylation in autism.

SAP SE: Autism at Work

DEFF Research Database (Denmark)

Pisano, Gary P.; Austin, Robert D.

2016-01-01

This case describes SAP's 'Autism at Work' program, which integrates people with autism into the company's workforce. The company has a stated objective of making 1% o its workforce people with autism by 2020. SAP's rationale for the program is based on the belief that 'neurodiversity' contributes...

The Broader Cognitive Phenotype of Autism in Parents: How Specific Is the Tendency for Local Processing and Executive Dysfunction?

Science.gov (United States)

Bolte, Sven; Poustka, Fritz

2006-01-01

Background: The objective of this study was to investigate the tendency for local processing style ("weak central coherence") and executive dysfunction in parents of subjects with an autism spectrum disorder (ASD) compared with parents of individuals with early onset schizophrenia (EOS) and mental retardation (MR). Method: Sixty-two…

Two phenotypes of arthropathy in long-term controlled acromegaly? A comparison between patients with and without joint space narrowing (JSN)

NARCIS (Netherlands)

Claessen, K. M. J. A.; Kloppenburg, M.; Kroon, H. M.; Romijn, J. A.; Pereira, A. M.; Biermasz, N. R.

2013-01-01

Arthropathy is an invalidating complication of acromegaly, also in long-term controlled patients, and is radiographically characterized by osteophytes and preserved joint spaces. However, joint space narrowing (JSN) is observed in the minority of patients. It is unknown whether JSN is the end-stage

A comprehensive review of the 1H-MRS metabolite spectrum in autism spectrum disorder.

Directory of Open Access Journals (Sweden)

Talitha eFord

2016-03-01

Full Text Available Neuroimaging studies of neuropsychiatric behaviour biomarkers across spectrum disorders are typically based on diagnosis, thus failing to account for the heterogeneity of multi-dimensional spectrum disorders such as autism (ASD. Control group trait phenotypes are also seldom reported. Proton magnetic resonance spectroscopy (1H-MRS measures the abundance of neurochemicals such as neurotransmitters and metabolites and hence can probe disorder phenotypes at clinical and sub-clinical levels. This detailed review summarises and critiques the current 1H-MRS research in ASD. The literature reports reduced N-acetylaspartate (NAA, glutamate and glutamine (Glx, gamma-aminobutyric acid (GABA, creatine and choline, and increased glutamate for children with ASD. Adult studies are few and results are inconclusive. Overall, the literature has several limitations arising from differences in 1H-MRS methodology and sample demographics. We argue that more consistent methods and greater emphasis on phenotype studies will advance understanding of underlying cortical metabolite disturbance in ASD, and the detection, diagnosis and treatment of ASD and other multi-dimensional psychiatric disorders.

Which Terms Should Be Used to Describe Autism? Perspectives from the UK Autism Community

Science.gov (United States)

Kenny, Lorcan; Hattersley, Caroline; Molins, Bonnie; Buckley, Carole; Povey, Carol; Pellicano, Elizabeth

2016-01-01

Recent public discussions suggest that there is much disagreement about the way autism is and should be described. This study sought to elicit the views and preferences of UK autism community members--autistic people, parents and their broader support network--about the terms they use to describe autism. In all, 3470 UK residents responded to an…

Distinct phenotype of PHF6 deletions in females.

Science.gov (United States)

Di Donato, N; Isidor, B; Lopez Cazaux, S; Le Caignec, C; Klink, B; Kraus, C; Schrock, E; Hackmann, K

2014-02-01

We report on two female patients carrying small overlapping Xq26.2 deletions of 100 kb and 270 kb involving the PHF6 gene. Mutations in PHF6 have been reported in individuals with Borjeson-Forssman-Lehmann syndrome, a condition present almost exclusively in males. Two very recent papers revealed de novo PHF6 defects in seven female patients with intellectual disability and a phenotype resembling Coffin-Siris syndrome (sparse hair, bitemporal narrowing, arched eyebrows, synophrys, high nasal root, bulbous nasal tip, marked clinodactyly with the hypoplastic terminal phalanges of the fifth fingers and cutaneous syndactyly of the toes, Blaschkoid linear skin hyperpigmentation, dental anomalies and occasional major malformations). The clinical presentation of these patients overlaps completely with our first patient, who carries a germline deletion involving PHF6. The second patient has a mosaic deletion and presented with a very mild phenotype of PHF6 loss in females. Our report confirms that PHF6 loss in females results in a recognizable phenotype overlapping with Coffin-Siris syndrome and distinct from Borjeson-Forssman-Lehmann syndrome. We expand the clinical spectrum and provide the first summary of the recommended medical evaluation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Morphological analysis and DNA methylation in Conyza bonariensis L. cronquist (Asteraceae phenotypes

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Juliana Maria de Paula

2017-08-01

Full Text Available ABSTRACT The species Conyza bonariensis (L. cause losses in agriculture due to their invasive capacity and resistance to herbicides like glyphosate. The species of this genus exhibit phenotypic plasticity, which complicates their identification and characterization. Thus, experiments were performed with 2 extreme C. bonariensis phenotypes (called broad leaf and narrow leaf in greenhouse conditions and in the laboratory, in order to verify if the morphological differences among these phenotypes are a genetic character or result from environmental effects. In addition to the comparative morphological analysis, assessment of DNA methylation profile was performed to detect the occurrence, or not, of differences in the epigenetic level. The morphological characteristics evaluated were length, width, shape, margin and leaves indument; plant height and stem indument; the number of capitula, flowers and seeds. The Methylation Sensitive Amplified Polymorphism technique was used to investigate the methylation levels. The morphological differences of phenotypes supposed to be C. bonariensis are probably genetic in origin and not the result of environmental effects, since, after 6 crop cycles in a greenhouse under the same environmental conditions, these phenotypes remained with the same morphological characteristics and seed production in relation to the original phenotypes found in the collection site. The different phenotypes did not show differences corresponding to DNA methylation patterns that could indicate an epigenetic effect as the cause of the differences between the 2 phenotypes. The results of morphological analysis and methylation probably indicate that maybe they are individuals of populations from different taxa not registered yet in the literature.

Influence of children's formed beliefs about characheristic of autism on acceptance of peers with autism spectrum disorder

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Čolić Marija

2015-01-01

Full Text Available The aim of this study was to determine the influence of formed beliefs about autism of students in fourth and seventh grade of primary school on acceptance of peers with autism. Belief about autism was formed using the vignettes which were constructed with the aim to explain autism as a disorder in communication, socialization and restrictive/repetitive interests. After the students read a vignette they were expected to fill out The Shared Activities Questionnaire. The mean scores indicate moderate positive behavioral intentions within three domains (Social, Academic and Recreational. The students rather participated in activities within the social domain than in academic and recreational domains. The girls expressed more positive behavioral intention within all three domains towards a peer with autism than the boys. The boys were more willing to participate in activities with a peer with autism when they were told that autism is a disorder in socialization. Although our sample on the whole reported moderate positive attitude towards peers with autism, when isolated items are observed, it is clear that one third of the students would not participate in certain activities with a peer with autism, which indicates the necessity for intervention in order to create a more positive attitude.

Autism: A “Critical Period” Disorder?

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Jocelyn J. LeBlanc

2011-01-01

Full Text Available Cortical circuits in the brain are refined by experience during critical periods early in postnatal life. Critical periods are regulated by the balance of excitatory and inhibitory (E/I neurotransmission in the brain during development. There is now increasing evidence of E/I imbalance in autism, a complex genetic neurodevelopmental disorder diagnosed by abnormal socialization, impaired communication, and repetitive behaviors or restricted interests. The underlying cause is still largely unknown and there is no fully effective treatment or cure. We propose that alteration of the expression and/or timing of critical period circuit refinement in primary sensory brain areas may significantly contribute to autistic phenotypes, including cognitive and behavioral impairments. Dissection of the cellular and molecular mechanisms governing well-established critical periods represents a powerful tool to identify new potential therapeutic targets to restore normal plasticity and function in affected neuronal circuits.

Random Number Generation in Autism.

Science.gov (United States)

Williams, Mark A.; Moss, Simon A.; Bradshaw, John L.; Rinehart, Nicole J.

2002-01-01

This study explored the ability of 14 individuals with autism to generate a unique series of digits. Individuals with autism were more likely to repeat previous digits than comparison individuals, suggesting they may exhibit a shortfall in response inhibition. Results support the executive dysfunction theory of autism. (Contains references.)…

Neurodiversity: Autism Pride among Mothers of Children with Autism Spectrum Disorders

Science.gov (United States)

Cascio, M. Ariel

2012-01-01

The neurodiversity movement takes an identity politics approach to autism spectrum disorders, proposing autism spectrum disorders as a positive "neuro-variation" to be approached only with interventions that assist individuals without changing them. This article explicates the concept of "neurodiversity" and places it within…

The "Reading the Mind in the Eyes" Test: Complete Absence of Typical Sex Difference in ~400 Men and Women with Autism.

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Simon Baron-Cohen

Full Text Available The "Reading the Mind in the Eyes" test (Eyes test is an advanced test of theory of mind. Typical sex difference has been reported (i.e., female advantage. Individuals with autism show more difficulty than do typically developing individuals, yet it remains unclear how this is modulated by sex, as females with autism have been under-represented. Here in a large, non-male-biased sample we test for the effects of sex, diagnosis, and their interaction. The Eyes test (revised version was administered online to 395 adults with autism (178 males, 217 females and 320 control adults (152 males, 168 females. Two-way ANOVA showed a significant sex-by-diagnosis interaction in total correct score (F(1,711 = 5.090, p = 0.024, ηp2 = 0.007 arising from a significant sex difference between control males and females (p < 0.001, Cohen's d = 0.47, and an absence of a sex difference between males and females with autism (p = 0.907, d = 0.01; significant case-control differences were observed across sexes, with effect sizes of d = 0.35 in males and d = 0.69 in females. Group-difference patterns fit with the extreme-male-brain (EMB theory predictions. Eyes test-Empathy Quotient and Eyes test-Autism Spectrum Quotient correlations were significant only in females with autism (r = 0.35, r = -0.32, respectively, but not in the other 3 groups. Support vector machine (SVM classification based on response pattern across all 36 items classified autism diagnosis with a relatively higher accuracy for females (72.2% than males (65.8%. Nevertheless, an SVM model trained within one sex generalized equally well when applied to the other sex. Performance on the Eyes test is a sex-independent phenotypic characteristic of adults with autism, reflecting sex-common social difficulties, and provides support for the EMB theory predictions for both males and females. Performance of females with autism differed from same-sex controls more than did that of males with autism. Females with

Neuropsychological phenotype of a patient with a de novo 970 kb interstitial deletion in the distal 16p11.2 region

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Egger JI

2014-03-01

Full Text Available Jos I M Egger,1–3 Willem M A Verhoeven,1,4 Wim Verbeeck,5 Nicole de Leeuw61Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, the Netherlands; 2Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, the Netherlands; 3Behavioural Science Institute, Radboud University Nijmegen, Nijmegen, the Netherlands; 4Erasmus University Medical Centre, Department of Psychiatry, Rotterdam, the Netherlands; 5Vincent van Gogh Institute for Psychiatry, Centre for Autism and ADHD, Venray, the Netherlands; 6Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the NetherlandsAbstract: The 16p11.2 microdeletion syndrome is characterized by a wide range of phenotypic expressions and is frequently associated with developmental delay, symptoms from the autism spectrum, epilepsy, congenital anomalies, and obesity. These phenotypes are often related to a proximal 16p11.2 deletion of approximately 600 kb (BP4–BP5 that includes the SH2B1 gene that is reported to be causative for morbid obesity. This more centromeric deletion is most strongly related to autism spectrum susceptibility and is functionally different from the more distal 16p12.2p11.2 region, which includes the so-called atypical 16p11.2 BP2–BP3 deletion (approximately 220 kb presenting with developmental delay, behavioral problems and mild facial dysmorphisms. Here, an adult male with a long history of maladaptive behaviors is described who was referred for diagnostic assessment of his amotivational features. Extensive neuropsychological examination demonstrated rigid thinking, anxious beliefs, and ideas of reference in the presence of normal intelligence. Microarray analysis demonstrated a de novo 970 kb 16p11.2 BP1–BP4 microdeletion that can be regarded as explanatory for his behavioral profile. It is concluded that microdeletion syndromes are not exclusively related to intellectual disabilities and

Demographic profile of families and children in the Study to Explore Early Development (SEED): Case-control study of autism spectrum disorder.

Science.gov (United States)

DiGuiseppi, Carolyn G; Daniels, Julie L; Fallin, Daniele M; Rosenberg, Steven A; Schieve, Laura A; Thomas, Kathleen C; Windham, Gayle C; Goss, Cynthia W; Soke, Gnakub N; Currie, Dustin W; Singer, Alison B; Lee, Li-Ching; Bernal, Pilar; Croen, Lisa A; Miller, Lisa A; Pinto-Martin, Jennifer A; Young, Lisa M; Schendel, Diana E

2016-07-01

The Study to Explore Early Development (SEED) is designed to enhance knowledge of autism spectrum disorder characteristics and etiologies. This paper describes the demographic profile of enrolled families and examines sociodemographic differences between children with autism spectrum disorder and children with other developmental problems or who are typically developing. This multi-site case-control study used health, education, and birth certificate records to identify and enroll children aged 2-5 years into one of three groups: 1) cases (children with autism spectrum disorder), 2) developmental delay or disorder controls, or 3) general population controls. Study group classification was based on sampling source, prior diagnoses, and study screening tests and developmental evaluations. The child's primary caregiver provided demographic characteristics through a telephone (or occasionally face-to-face) interview. Groups were compared using ANOVA, chi-squared test, or multinomial logistic regression as appropriate. Of 2768 study children, sizeable proportions were born to mothers of non-White race (31.7%), Hispanic ethnicity (11.4%), and foreign birth (17.6%); 33.0% of households had incomes below the US median. The autism spectrum disorder and population control groups differed significantly on nearly all sociodemographic parameters. In contrast, the autism spectrum disorder and developmental delay or disorder groups had generally similar sociodemographic characteristics. SEED enrolled a sociodemographically diverse sample, which will allow further, in-depth exploration of sociodemographic differences between study groups and provide novel opportunities to explore sociodemographic influences on etiologic risk factor associations with autism spectrum disorder and phenotypic subtypes. Copyright © 2016 Elsevier Inc. All rights reserved.

Autism: Collaborative Perspektives in Education

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Imanuel Hitipeuw

2016-02-01

Full Text Available Autism is the continuum of impairments. Children with autism show intellectual, social, emotional, and language or communication disorder. Collaboration is an important aspect in delivering education/intervention for children. Professionals have to have knowledge and skill related to autism and have to team up with parent in dealing with the disorder. The unique profile of the individual with autism calls for emphasis in the areas of communication skills, social-emotional, behavioral, and sensory regulation, and communication. Pre-identification of the children may help teachers and parents to make decisions whether the child needs a referral or not. In this case, Indonesia needs to make more political will in order to implement autism education in various setting to address immediate needs of the children before the problem becomes more complicated

Enhanced Polyubiquitination of Shank3 and NMDA receptor in a mouse model of Autism

OpenAIRE

Bangash, M Ali; Park, Joo Min; Melnikova, Tatiana; Wang, Dehua; Jeon, Soo Kyeong; Lee, Deidre; Syeda, Sbaa; Kim, Juno; Kouser, Mehreen; Schwartz, Joshua; Cui, Yiyuan; Zhao, Xia; Speed, Haley E.; Kee, Sara E.; Tu, Jian Cheng

2011-01-01

We have created a mouse genetic model that mimics a human mutation of Shank3 that deletes the C-terminus and is associated with autism. Expressed as a single copy [Shank3(+/ΔC) mice], Shank3ΔC protein interacts with the WT gene product and results in >90 % reduction of Shank3 at synapses. This “gain of function” phenotype is linked to increased polyubiquitination of WT Shank3 and its redistribution into proteasomes. Similarly, the NR1 subunit of the NMDA receptor is reduced at synapses with i...

Chromosomal abnormalities and autism

African Journals Online (AJOL)

Farida El-Baz

2015-06-19

Jun 19, 2015 ... Abstract Background: Autism is a neurodevelopmental disorder characterized by clinical, etio- logic and ... twin and family studies provide evidence for strong genetic ..... adolescents rats: relevant to autism spectrum disorders.

Strabismus in Autism Spectrum Disorder.

Science.gov (United States)

Kaplan, Melvin; Edelson, Stephen M.; Rimland, Bernard

1999-01-01

Two studies of strabismus ("crossed eyes") in children with autism are reported. A clinical optometric evaluation of 34 individuals with autism, ages 7 to 19 years, found a strabismus rate of 50% and a parent survey of 7,640 families of children with autism found an incidence of 18% (compared to 2-4% in the general population). (Author/DB)

Autism Overview: What We Know

Science.gov (United States)

US Department of Health and Human Services, 2005

2005-01-01

The National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health (NIH), within the U.S. Department of Health and Human Services, is one of many federal agencies working to understand autism. The NICHD supports and conducts research on what causes autism, how many people have autism, how best to treat…

A genome-wide scan for common alleles affecting risk for autism

Science.gov (United States)

Anney, Richard; Klei, Lambertus; Pinto, Dalila; Regan, Regina; Conroy, Judith; Magalhaes, Tiago R.; Correia, Catarina; Abrahams, Brett S.; Sykes, Nuala; Pagnamenta, Alistair T.; Almeida, Joana; Bacchelli, Elena; Bailey, Anthony J.; Baird, Gillian; Battaglia, Agatino; Berney, Tom; Bolshakova, Nadia; Bölte, Sven; Bolton, Patrick F.; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Carson, Andrew R.; Casallo, Guillermo; Casey, Jillian; Chu, Su H.; Cochrane, Lynne; Corsello, Christina; Crawford, Emily L.; Crossett, Andrew; Dawson, Geraldine; de Jonge, Maretha; Delorme, Richard; Drmic, Irene; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A.; Folstein, Susan E.; Fombonne, Eric; Freitag, Christine M.; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T.; Goldberg, Jeremy; Green, Jonathan; Guter, Stephen J.; Hakonarson, Hakon; Heron, Elizabeth A.; Hill, Matthew; Holt, Richard; Howe, Jennifer L.; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Kim, Cecilia; Klauck, Sabine M.; Kolevzon, Alexander; Korvatska, Olena; Kustanovich, Vlad; Lajonchere, Clara M.; Lamb, Janine A.; Laskawiec, Magdalena; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L.; Lionel, Anath C.; Liu, Xiao-Qing; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C.; Maestrini, Elena; Mahoney, William; Mantoulan, Carine; Marshall, Christian R.; McConachie, Helen; McDougle, Christopher J.; McGrath, Jane; McMahon, William M.; Melhem, Nadine M.; Merikangas, Alison; Migita, Ohsuke; Minshew, Nancy J.; Mirza, Ghazala K.; Munson, Jeff; Nelson, Stanley F.; Noakes, Carolyn; Noor, Abdul; Nygren, Gudrun; Oliveira, Guiomar; Papanikolaou, Katerina; Parr, Jeremy R.; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Piven, Joseph; Posey, David J; Poustka, Annemarie; Poustka, Fritz; Prasad, Aparna; Ragoussis, Jiannis; Renshaw, Katy; Rickaby, Jessica; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L.; Bierut, Laura J.; Rice, John P.; Salt, Jeff; Sansom, Katherine; Sato, Daisuke; Segurado, Ricardo; Senman, Lili; Shah, Naisha; Sheffield, Val C.; Soorya, Latha; Sousa, Inês; Stoppioni, Vera; Strawbridge, Christina; Tancredi, Raffaella; Tansey, Katherine; Thiruvahindrapduram, Bhooma; Thompson, Ann P.; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; Van Engeland, Herman; Vincent, John B.; Volkmar, Fred; Wallace, Simon; Wang, Kai; Wang, Zhouzhi; Wassink, Thomas H.; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Yaspan, Brian L.; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Betancur, Catalina; Buxbaum, Joseph D.; Cantor, Rita M.; Cook, Edwin H.; Coon, Hilary; Cuccaro, Michael L.; Gallagher, Louise; Geschwind, Daniel H.; Gill, Michael; Haines, Jonathan L.; Miller, Judith; Monaco, Anthony P.; Nurnberger, John I.; Paterson, Andrew D.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Sutcliffe, James S.; Szatmari, Peter; Vicente, Astrid M.; Vieland, Veronica J.; Wijsman, Ellen M.; Devlin, Bernie; Ennis, Sean; Hallmayer, Joachim

2010-01-01

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C. PMID:20663923

Evaluation of Pax6 mutant rat as a model for autism.

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Toshiko Umeda

Full Text Available Autism is a highly variable brain developmental disorder and has a strong genetic basis. Pax6 is a pivotal player in brain development and maintenance. It is expressed in embryonic and adult neural stem cells, in astrocytes in the entire central nervous system, and in neurons in the olfactory bulb, amygdala, thalamus, and cerebellum, functioning in highly context-dependent manners. We have recently reported that Pax6 heterozygous mutant (rSey(2/+ rats with a spontaneous mutation in the Pax6 gene, show impaired prepulse inhibition (PPI. In the present study, we further examined behaviors of rSey(2/+ rats and revealed that they exhibited abnormality in social interaction (more aggression and withdrawal in addition to impairment in rearing activity and in fear-conditioned memory. Ultrasonic vocalization (USV in rSey(2+ rat pups was normal in male but abnormal in female. Moreover, treatment with clozapine successfully recovered the defects in sensorimotor gating function, but not in fear-conditioned memory. Taken together with our prior human genetic data and results in other literatures, rSey(2/+ rats likely have some phenotypic components of autism.

Rhythm, movement, and autism: Using rhythmic rehabilitation research as a model for autism

Directory of Open Access Journals (Sweden)

A. Blythe eLaGasse

2013-03-01

Full Text Available Recently, there has been increased focus on movement and sensory abnormalities in autism spectrum disorders (ASD. This has come from research demonstrating cortical and cerebellar difference in autism, with suggestion of early cerebellar dysfunction. As evidence for an extended profile of ASD grows, there are vast implications for treatment and therapy for individuals with autism. Persons with autism are often provided behavioral or cognitive strategies for navigating their environment; however, these strategies do not consider differences in motor functioning. One accommodation that has not yet been explored in the literature is the use of auditory rhythmic cueing to improve motor functioning in ASD. The purpose of this paper is to illustrate the potential impact of auditory rhythmic cueing for motor functioning in persons with ASD. To this effect, we review research on rhythm in motor rehabilitation, draw parallels to motor dysfunction in ASD, and propose a rationale for how rhythmic input can improve sensorimotor functioning, thereby allowing individuals with autism to demonstrate their full cognitive, behavioral, social, and communicative potential.

[Genetics and epigenetics in autism].

Science.gov (United States)

Nakayama, Atsuo; Masaki, Shiego; Aoki, Eiko

2006-11-01

Autism is a behaviorally defined syndrome characterized by impaired social interaction and communication, and restricted, stereotyped interests and behaviors. Several lines of evidence support the contention that genetic factors are a large component to autism etiology. However, in spite of vigorous genetic studies, no single causative or susceptibility gene common in autism has been identified. Thus multiple susceptibility genes in interaction are considered to account for the disorder. Furthermore, environmental risk factors can accelerate the autism development of. Recent advances in understanding the epigenetic regulation may shed light on the interaction among multiple genetic factors and environmental factors.

Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European Multi-Site Sample of Individuals with Autism Spectrum Disorder

Science.gov (United States)

Tillmann, J.; Ashwood, K.; Absoud, M.; Bölte, S.; Bonnet-Brilhault, F.; Buitelaar, J. K.; Calderoni, S.; Calvo, R.; Canal-Bedia, R.; Canitano, R.; De Bildt, A.; Gomot, M.; Hoekstra, P. J.; Kaale, A.; McConachie, H.; Murphy, D. G.; Narzisi, A.; Oosterling, I.; Pejovic-Milovancevic, M.; Persico, A. M.; Puig, O.; Roeyers, H.; Rommelse, N.; Sacco, R.; Scandurra, V.; Stanfield, A. C.; Zander, E.; Charman, T.

2018-01-01

Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and…

Implicit and Explicit Memory in Autism: Is Autism an Amnesic Disorder?

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Renner, Peggy; Klinger, Laura Grofer; Klinger, Mark R.

2000-01-01

This study examined whether children with high-functioning autism have a dissociation between explicit and implicit memory abilities characteristic of medial temporal lobe amnesic disorder. Children (N=14 and ages 6-14) with autism showed intact implicit and explicit memory abilities but did not show typical memory patterns, suggesting they used…

Epigenetics of autism-related impairment: copy number variation and maternal infection.

Science.gov (United States)

Mazina, Varvara; Gerdts, Jennifer; Trinh, Sandy; Ankenman, Katy; Ward, Tracey; Dennis, Megan Y; Girirajan, Santhosh; Eichler, Evan E; Bernier, Raphael

2015-01-01

Epidemiological data have suggested maternal infection and fever to be associated with increased risk of autism spectrum disorder (ASD). Animal studies show that gestational infections perturb fetal brain development and result in offspring with the core features of autism and have demonstrated that behavioral effects of maternal immune activation are dependent on genetic susceptibility. The goal of this study was to explore the impact of ASD-associated copy number variants (CNVs) and prenatal maternal infection on clinical severity of ASD within a dataset of prenatal history and complete genetic and phenotypic findings. We analyzed data from the Simons Simplex Collection sample including 1971 children with a diagnosis of ASD aged 4 to 18 years who underwent array comparative genomic hybridization screening. Information on infection and febrile episodes during pregnancy was collected through parent interview. ASD severity was clinically measured through parent-reported interview and questionnaires. We found significant interactive effects between the presence of CNVs and maternal infection during pregnancy on autistic symptomatology, such that individuals with CNVs and history of maternal infection demonstrated increased rates of social communicative impairments and repetitive/restricted behaviors. In contrast, no significant interactions were found between presence of CNVs and prenatal infections on cognitive and adaptive functioning of individuals with ASD. Our findings support a gene-environment interaction model of autism impairment, in that individuals with ASD-associated CNVs are more susceptible to the effects of maternal infection and febrile episodes in pregnancy on behavioral outcomes and suggest that these effects are specific to ASD rather than to global neurodevelopment.

Autism and primary care dentistry: parents' experiences of taking children with autism or working diagnosis of autism for dental examinations.

Science.gov (United States)

Thomas, Nicole; Blake, Sharon; Morris, Christopher; Moles, David R

2018-03-01

Accessing and receiving preventative dental treatment can be difficult for children with autism due to sensory processing disorders and/or challenging behaviours coupled with a reported reluctance by dentists to treat these children. To gather dental experiences of UK parents of children with autism or working diagnosis of autism and explore how they feel primary care dental services can be improved. A total of 17 parents of children with a diagnosis or working diagnosis of autism took part in semi-structured interviews. Data were analysed thematically. Key themes identified were flexibility of the dental team and environment, confidence of the parents to advocate for their children's needs, continuity of services and clear referral pathways to specialist services. Cross-cutting all themes was the value of clear communication. The experiences provide greater understanding of issues such as hyper-empathy, the dental chair, challenges of the waiting room, perceived medical authority, and the importance of continuation of care. In line with previous research about the importance of family-centred care, a strong relationship between parents and the whole dental team is essential for children with autism to access dental examinations and have satisfactory experience of care. © 2017 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Overlapping Phenotypes in Autism Spectrum Disorder and Developmental Coordination Disorder: A Cross-Syndrome Comparison of Motor and Social Skills

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Sumner, Emma; Leonard, Hayley C.; Hill, Elisabeth L.

2016-01-01

Motor and social difficulties are often found in children with an autism spectrum disorder (ASD) and with developmental coordination disorder (DCD), to varying degrees. This study investigated the extent of overlap of these problems in children aged 7-10 years who had a diagnosis of either ASD or DCD, compared to typically-developing controls.…

Paracentric inversion of chromosome 2 associated with cryptic duplication of 2q14 and deletion of 2q37 in a patient with autism.

Science.gov (United States)

Devillard, Françoise; Guinchat, Vincent; Moreno-De-Luca, Daniel; Tabet, Anne-Claude; Gruchy, Nicolas; Guillem, Pascale; Nguyen Morel, Marie-Ange; Leporrier, Nathalie; Leboyer, Marion; Jouk, Pierre-Simon; Lespinasse, James; Betancur, Catalina

2010-09-01

We describe a patient with autism and a paracentric inversion of chromosome 2q14.2q37.3, with a concurrent duplication of the proximal breakpoint at 2q14.1q14.2 and a deletion of the distal breakpoint at 2q37.3. The abnormality was derived from his mother with a balanced paracentric inversion. The inversion in the child appeared to be cytogenetically balanced but subtelomere FISH revealed a cryptic deletion at the 2q37.3 breakpoint. High-resolution single nucleotide polymorphism array confirmed the presence of a 3.5 Mb deletion that extended to the telomere, and showed a 4.2 Mb duplication at 2q14.1q14.2. FISH studies using a 2q14.2 probe showed that the duplicated segment was located at the telomeric end of chromosome 2q. This recombinant probably resulted from breakage of a dicentric chromosome. The child had autism, mental retardation, speech and language delay, hyperactivity, growth retardation with growth hormone deficiency, insulin-dependent diabetes, and mild facial dysmorphism. Most of these features have been previously described in individuals with simple terminal deletion of 2q37. Pure duplications of the proximal chromosome 2q are rare and no specific syndrome has been defined yet, so the contribution of the 2q14.1q14.2 duplication to the phenotype of the patient is unknown. These findings underscore the need to explore apparently balanced chromosomal rearrangements inherited from a phenotypically normal parent in subjects with autism and/or developmental delay. In addition, they provide further evidence indicating that chromosome 2q terminal deletions are among the most frequently reported cytogenetic abnormalities in individuals with autism.

SNORD116 deletions cause Prader-Willi syndrome with a mild phenotype and macrocephaly.

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Fontana, P; Grasso, M; Acquaviva, F; Gennaro, E; Galli, M L; Falco, M; Scarano, F; Scarano, G; Lonardo, F

2017-10-01

Prader-Willi syndrome is a complex condition caused by lack of expression of imprinted genes in the paternally derived region of chromosome 15 (15q11q13). A small number of patients with Prader-Willi phenotype have been discovered to have narrow deletions, not encompassing the whole critical region, but only the SNORD116 cluster, which includes genes codifying for small nucleolar RNAs. This kind of deletion usually is not detected by the classic DNA methylation analysis test. We present the case of a male patient with a mild Prader-Willi phenotype and a small deletion including SNORD116, diagnosed by methylation-sensitive multiplex ligation-dependent probe amplification (MLPA. The patient showed neonatal hypotonia, hyperphagia, obesity, central hypogonadism, hypothyroidism, strabismus. Stature and intellectual development are within the normal range. The presence of macrocephaly, observed in other cases of SNORD116 deletions as well, is uncommon for the classic phenotype of the syndrome. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Issues in Identification and Assessment of Children with Autism and a Proposed Resource Toolkit for Speech-Language Pathologists.

Science.gov (United States)

Hus, Yvette

2017-01-01

The prevalence of autism spectrum disorder (ASD) has increased significantly in the last decade as have treatment choices. Nonetheless, the vastly diverse autism topic includes issues related to naming, description, iden-tification, assessment, and differentiation from other neu-rodevelopmental conditions. ASD issues directly impact speech-language pathologists (SLPs) who often see these children as the second contact, after pediatric medical practitioners. Because of shared symptomology, differentiation among neurodevelopmental disorders is crucial as it impacts treatment, educational choices, and the performance trajectory of affected children. To highlight issues in: identification and differentiation of ASD from other communication and language challenges, the prevalence differences between ASD gender phenotypes, and the insufficient consideration of cultural factors in evaluating ASD in children. A second objective was to propose a tool to assist SLPs in the management of autism in children. A universal resource toolkit development project for SLP communities at large is proposed. The resource is comprised of research-based observation and screening tools for caregivers and educators, as well as parent questionnaires for portraying the children's function in the family, cultural com-munity, and educational setting. © 2017 S. Karger AG, Basel.

Autism Spectrum Disorder (ASD)

Science.gov (United States)

... within the category. These were autistic disorder ("classic" autism), Asperger syndrome (which usually involved milder symptoms, mostly related ... but not all, of the features of classic autism or Asperger syndrome). 2 Health care providers no longer use ...

Demographic and Clinical Correlates of Autism Symptom Domains and Autism Spectrum Diagnosis

Science.gov (United States)

Frazier, Thomas W.; Youngstrom, Eric A.; Embacher, Rebecca; Hardan, Antonio Y.; Constantino, John N.; Law, Paul; Findling, Robert L.; Eng, Charis

2014-01-01

Demographic and clinical factors may influence assessment of autism symptoms. This study evaluated these correlates and also examined whether social communication and interaction and restricted/repetitive behavior provided unique prediction of autism spectrum disorder diagnosis. We analyzed data from 7352 siblings included in the Interactive…

The social brain network and autism.

Science.gov (United States)

Misra, Vivek

2014-04-01

Available research data in Autism suggests the role of a network of brain areas, often known as the 'social brain'. Recent studies highlight the role of genetic mutations as underlying patho-mechanism in Autism. This mini review, discusses the basic concepts behind social brain networks, theory of mind and genetic factors associated with Autism. It critically evaluates and explores the relationship between the behavioral outcomes and genetic factors providing a conceptual framework for understanding of autism.

The genetic basis of hair whorl, handedness, and other phenotypes

Science.gov (United States)

Hatfield, J.S.

2006-01-01

Evidence is presented that RHO, RHCE, and other RH genes, may be interesting candidates to consider when searching for the genetic basis of hair whorl rotation (i.e., clockwise or counterclockwise), handedness (i.e., right handed, left handed or ambidextrous), speech laterality (i.e., right brained or left brained), speech dyslexia (e.g., stuttering), sexual orientation (i.e., heterosexual, homosexual, bisexual, or transsexual), schizophrenia, bipolar disorder, and autism spectrum disorder. Such evidence involves the need for a genetic model that includes maternal immunization to explain some of the empirical results reported in the literature. The complex polymorphisms present among the maternally immunizing RH genes can then be used to explain other empirical results. Easily tested hypotheses are suggested, based upon genotypic (but not phenotypic) frequencies of the RH genes. In particular, homozygous dominant individuals are expected to be less common or lacking entirely among the alternative phenotypes. If it is proven that RH genes are involved in brain architecture, it will have a profound effect upon our understanding of the development and organization of the asymmetrical vertebrate brain and may eventually lead to a better understanding of the developmental processes which occur to produce the various alternative phenotypes discussed here. In addition, if RH genes are shown to be involved in the production of these phenotypes, then the evolutionary studies can be performed to demonstrate the beneficial effect of the recessive alleles of RHO and RHCE, and why human evolution appears to be selecting for the recessive alleles even though an increase in the frequency of such alleles may imply lower average fecundity among some individuals possessing them.

Increasing Autism Prevalence in Metropolitan New Jersey

Science.gov (United States)

Zahorodny, Walter; Shenouda, Josephine; Howell, Sandra; Rosato, Nancy Scotto; Peng, Bo; Mehta, Uday

2014-01-01

High baseline autism spectrum disorder prevalence estimates in New Jersey led to a follow-up surveillance. The objectives were to determine autism spectrum disorder prevalence in the year 2006 in New Jersey and to identify changes in the prevalence of autism spectrum disorder or in the characteristics of the children with autism spectrum disorder,…

Low Endogenous Neural Noise in Autism

Science.gov (United States)

Davis, Greg; Plaisted-Grant, Kate

2015-01-01

"Heuristic" theories of autism postulate that a single mechanism or process underpins the diverse psychological features of autism spectrum disorder. Although no such theory can offer a comprehensive account, the parsimonious descriptions they provide are powerful catalysts to autism research. One recent proposal holds that…

Verification of Parent-Report of Child Autism Spectrum Disorder Diagnosis to a Web-Based Autism Registry

Science.gov (United States)

Daniels, Amy M.; Rosenberg, Rebecca E.; Anderson, Connie; Law, J. Kiely; Marvin, Alison R.; Law, Paul A.

2012-01-01

Growing interest in autism spectrum disorder (ASD) research requires increasingly large samples to uncover epidemiologic trends; such a large dataset is available in a national, web-based autism registry, the Interactive Autism Network (IAN). The objective of this study was to verify parent-report of professional ASD diagnosis to the registry's…

Symptoms of Autism Among Children with Congenital Deafblindness

DEFF Research Database (Denmark)

Dammeyer, Jesper Herup

2014-01-01

concerning individuals with congenital deafblindness. This study examines symptoms of autism among 71 children with congenital deafblindness using the Autism Behavior Checklist. The cohort of children with congenital deafblindness was found to have symptoms of autism on a level similar to children......Associations between congenital deafness or blindness and autism have been found. The main consequences of congenital sensory impairment, being barriers for communication, language and social interaction development, may lead to symptoms of autism. To date only few studies have been reported...... with another developmental disorder than autism for example intellectual disability. No association was found between severity of congenital sensory impairment and severity or type of symptoms of autism....

Autism As a Disorder of High Intelligence

Science.gov (United States)

Crespi, Bernard J.

2016-01-01

A suite of recent studies has reported positive genetic correlations between autism risk and measures of mental ability. These findings indicate that alleles for autism overlap broadly with alleles for high intelligence, which appears paradoxical given that autism is characterized, overall, by below-average IQ. This paradox can be resolved under the hypothesis that autism etiology commonly involves enhanced, but imbalanced, components of intelligence. This hypothesis is supported by convergent evidence showing that autism and high IQ share a diverse set of convergent correlates, including large brain size, fast brain growth, increased sensory and visual-spatial abilities, enhanced synaptic functions, increased attentional focus, high socioeconomic status, more deliberative decision-making, profession and occupational interests in engineering and physical sciences, and high levels of positive assortative mating. These findings help to provide an evolutionary basis to understanding autism risk as underlain in part by dysregulation of intelligence, a core human-specific adaptation. In turn, integration of studies on intelligence with studies of autism should provide novel insights into the neurological and genetic causes of high mental abilities, with important implications for cognitive enhancement, artificial intelligence, the relationship of autism with schizophrenia, and the treatment of both autism and intellectual disability. PMID:27445671

Update on the implication of potassium channels in autism: K+ channelautism spectrum disorder

Directory of Open Access Journals (Sweden)

Luca eGuglielmi

2015-03-01

Full Text Available Autism spectrum disorders (ASDs are characterized by impaired ability to properly implement environmental stimuli that are essential to achieve a state of social and cultural exchange. Indeed, the main features of ASD are impairments of interpersonal relationships, verbal and non-verbal communication and restricted and repetitive behaviors. These aspects are often accompanied by several comorbidities such as motor delay, praxis impairment, gait abnormalities, insomnia and above all epilepsy. Genetic analyses of autistic individuals uncovered deleterious mutations in several K+ channel types strengthening the notion that their intrinsic dysfunction may play a central etiologic role in ASD. However, indirect implication of K+ channels in ASD has been also reported. For instance, loss of fragile X mental retardation protein (FMRP results in K+ channels deregulation, network dysfunction and ASD-like cognitive and behavioral symptoms. Therefore, this review provides an update on direct and indirect implications of K+ channels in ASDs. Owing to a mounting body of evidence associating a channelopathy pathogenesis to autism and that nearly 500 ion channel proteins are encoded by the human genome, we also propose to classify ASDs − whose susceptibility is significantly enhanced by ion channels defects, either in a monogenic or multigenic condition − in a new category named channelAutism Spectrum Disorder (channelASD; cASD and introduce a new taxonomy (e.g.: Kvx.y-channelASD and likewise Navx.y-channelASD, Cavx.y-channelASD; etc.. This review also highlights some degree of clinical and genetic overlap between K+ channelASDs and K+ channelepsies, whereby such correlation suggests that a subcategory characterized by a channelASD-channelepsy phenotype may be distinguished. Ultimately, this overview aims to further understand the different clinical subgroups and help parse out the distinct biological basis of autism that are essential to establish patient

Motor skills and calibrated autism severity in young children with autism spectrum disorder.

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MacDonald, Megan; Lord, Catherine; Ulrich, Dale A

2014-04-01

In addition to the core characteristics of autism spectrum disorder (ASD), motor skill deficits are present, persistent, and pervasive across age. Although motor skill deficits have been indicated in young children with autism, they have not been included in the primary discussion of early intervention content. One hundred fifty-nine young children with a confirmed diagnosis of ASD (n = 110), PDD-NOS (n = 26), and non-ASD (n = 23) between the ages of 14-33 months participated in this study.1 The univariate general linear model tested the relationship of fine and gross motor skills and social communicative skills (using calibrated autism severity scores). Fine motor and gross motor skills significantly predicted calibrated autism severity (p motor skills have greater social communicative skill deficits. Future directions and the role of motor skills in early intervention are discussed.

Jihadism, Narrow and Wide

DEFF Research Database (Denmark)

Sedgwick, Mark

2015-01-01

The term “jihadism” is popular, but difficult. It has narrow senses, which are generally valuable, and wide senses, which may be misleading. This article looks at the derivation and use of “jihadism” and of related terms, at definitions provided by a number of leading scholars, and at media usage....... It distinguishes two main groups of scholarly definitions, some careful and narrow, and some appearing to match loose media usage. However, it shows that even these scholarly definitions actually make important distinctions between jihadism and associated political and theological ideology. The article closes...

Resources available for autism research in the big data era: a systematic review

Directory of Open Access Journals (Sweden)

Reem Al-jawahiri

2017-01-01

Full Text Available Recently, there has been a move encouraged by many stakeholders towards generating big, open data in many areas of research. One area where big, open data is particularly valuable is in research relating to complex heterogeneous disorders such as Autism Spectrum Disorder (ASD. The inconsistencies of findings and the great heterogeneity of ASD necessitate the use of big and open data to tackle important challenges such as understanding and defining the heterogeneity and potential subtypes of ASD. To this end, a number of initiatives have been established that aim to develop big and/or open data resources for autism research. In order to provide a useful data reference for autism researchers, a systematic search for ASD data resources was conducted using the Scopus database, the Google search engine, and the pages on ‘recommended repositories’ by key journals, and the findings were translated into a comprehensive list focused on ASD data. The aim of this review is to systematically search for all available ASD data resources providing the following data types: phenotypic, neuroimaging, human brain connectivity matrices, human brain statistical maps, biospecimens, and ASD participant recruitment. A total of 33 resources were found containing different types of data from varying numbers of participants. Description of the data available from each data resource, and links to each resource is provided. Moreover, key implications are addressed and underrepresented areas of data are identified.

Stoppage in Autism Spectrum Disorders

DEFF Research Database (Denmark)

Grønborg, Therese Koops; Hansen, Stefan Nygaard; Nielsen, Svend V

2015-01-01

of bias in sibling recurrence risk estimation. This study investigated whether stoppage occurs in Danish families with a firstborn child diagnosed with autism spectrum disorders, and if stoppage was differential. We found that stoppage occurs moderately in Danish families affected by autism spectrum...... disorders, and that stoppage is differential. However, differential stoppage is a minor source of estimation bias in Danish sibling recurrence risk studies of autism spectrum disorders....

Novel Probiotic Therapies for Autism

Science.gov (United States)

2013-09-01

1 AD_________________ Award Number: W81XWH-11-1-0515 TITLE: Novel Probiotic Therapies for Autism PRINCIPAL...August 2012 – 21 August 2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Novel Probiotic Therapies for Autism 5b. GRANT NUMBER W81XWH-11-0515...suggest a gut-microbiome-brain connection in autism, and identify a potential probiotic therapy for ASD. We have now developed assays for some of

Device Physics of Narrow Gap Semiconductors

CERN Document Server

Chu, Junhao

2010-01-01

Narrow gap semiconductors obey the general rules of semiconductor science, but often exhibit extreme features of these rules because of the same properties that produce their narrow gaps. Consequently these materials provide sensitive tests of theory, and the opportunity for the design of innovative devices. Narrow gap semiconductors are the most important materials for the preparation of advanced modern infrared systems. Device Physics of Narrow Gap Semiconductors offers descriptions of the materials science and device physics of these unique materials. Topics covered include impurities and defects, recombination mechanisms, surface and interface properties, and the properties of low dimensional systems for infrared applications. This book will help readers to understand not only the semiconductor physics and materials science, but also how they relate to advanced opto-electronic devices. The last chapter applies the understanding of device physics to photoconductive detectors, photovoltaic infrared detector...

Autism spectrum disorder - Asperger syndrome

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... part of the larger developmental disorder category of autism spectrum disorder . ... American Psychiatric Association. Autism spectrum disorder. ... VA: American Psychiatric Publishing: 2013;50-59. Raviola GJ, ...

Epilepsy and Autism: Is there a special relationship?

Science.gov (United States)

Berg, Anne T.; Plioplys, Sigita

2012-01-01

Increasingly, there has been an interest in the association between epilepsy and autism. The high frequency of autism in some of the early-onset developmental encephalopathic epilepsies is frequently cited as evidence of the relationship between autism and epilepsy. While these specific forms of epilepsy carry a higher than expected risk of autism, most if not all of the association may be due to intellectual disability (ID). The high prevalence of interictal EEG discharges in children with autism is also cited as further evidence although errors in the diagnosis of epilepsy seem to account for at least part of those findings. The prevalence of ID is substantially elevated in children with either epilepsy or autism. In the absence of ID, there is little evidence of a substantial, if any, increased risk of autism in children with epilepsy. Further, although the reported prevalence of autism has increased over the last several years, much of this increase may be attributable to changes in diagnostic practices, conceptualization of autism in the presence of ID, and laws requiring provision of services for children with autism. In the context of these temporal trends, any further efforts to tease apart the relationships between epilepsy, ID, and autism will have to address head-on the accuracy of diagnosis of all three conditions before we can determine whether there is indeed a special relationship between autism and epilepsy. PMID:22381386

Proteomic explorations of autism spectrum disorder.

Science.gov (United States)

Szoko, Nicholas; McShane, Adam J; Natowicz, Marvin R

2017-09-01

Proteomics, the large-scale study of protein expression in cells and tissues, is a powerful tool to study the biology of clinical conditions and has provided significant insights in many experimental systems. Herein, we review the basics of proteomic methodology and discuss challenges in using proteomic approaches to study autism. Unlike other experimental approaches, such as genomic approaches, there have been few large-scale studies of proteins in tissues from persons with autism. Most of the proteomic studies on autism used blood or other peripheral tissues; few studies used brain tissue. Some studies found dysregulation of aspects of the immune system or of aspects of lipid metabolism, but no consistent findings were noted. Based on the challenges in using proteomics to study autism, we discuss considerations for future studies. Apart from the complex technical considerations implicit in any proteomic analysis, key nontechnical matters include attention to subject and specimen inclusion/exclusion criteria, having adequate sample size to ensure appropriate powering of the study, attention to the state of specimens prior to proteomic analysis, and the use of a replicate set of specimens, when possible. We conclude by discussing some potentially productive uses of proteomics, potentially coupled with other approaches, for future autism research including: (1) proteomic analysis of banked human brain specimens; (2) proteomic analysis of tissues from animal models of autism; and (3) proteomic analysis of induced pluripotent stem cells that are differentiated into various types of brain cells and neural organoids. Autism Res 2017, 10: 1460-1469. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Disruption of the ASTN2/TRIM32 locus at 9q33.1 is a risk factor in males for autism spectrum disorders, ADHD and other neurodevelopmental phenotypes

Science.gov (United States)

Lionel, Anath C.; Tammimies, Kristiina; Vaags, Andrea K.; Rosenfeld, Jill A.; Ahn, Joo Wook; Merico, Daniele; Noor, Abdul; Runke, Cassandra K.; Pillalamarri, Vamsee K.; Carter, Melissa T.; Gazzellone, Matthew J.; Thiruvahindrapuram, Bhooma; Fagerberg, Christina; Laulund, Lone W.; Pellecchia, Giovanna; Lamoureux, Sylvia; Deshpande, Charu; Clayton-Smith, Jill; White, Ann C.; Leather, Susan; Trounce, John; Melanie Bedford, H.; Hatchwell, Eli; Eis, Peggy S.; Yuen, Ryan K.C.; Walker, Susan; Uddin, Mohammed; Geraghty, Michael T.; Nikkel, Sarah M.; Tomiak, Eva M.; Fernandez, Bridget A.; Soreni, Noam; Crosbie, Jennifer; Arnold, Paul D.; Schachar, Russell J.; Roberts, Wendy; Paterson, Andrew D.; So, Joyce; Szatmari, Peter; Chrysler, Christina; Woodbury-Smith, Marc; Brian Lowry, R.; Zwaigenbaum, Lonnie; Mandyam, Divya; Wei, John; MacDonald, Jeffrey R.; Howe, Jennifer L.; Nalpathamkalam, Thomas; Wang, Zhuozhi; Tolson, Daniel; Cobb, David S.; Wilks, Timothy M.; Sorensen, Mark J.; Bader, Patricia I.; An, Yu; Wu, Bai-Lin; Musumeci, Sebastiano Antonino; Romano, Corrado; Postorivo, Diana; Nardone, Anna M.; Monica, Matteo Della; Scarano, Gioacchino; Zoccante, Leonardo; Novara, Francesca; Zuffardi, Orsetta; Ciccone, Roberto; Antona, Vincenzo; Carella, Massimo; Zelante, Leopoldo; Cavalli, Pietro; Poggiani, Carlo; Cavallari, Ugo; Argiropoulos, Bob; Chernos, Judy; Brasch-Andersen, Charlotte; Speevak, Marsha; Fichera, Marco; Ogilvie, Caroline Mackie; Shen, Yiping; Hodge, Jennelle C.; Talkowski, Michael E.; Stavropoulos, Dimitri J.; Marshall, Christian R.; Scherer, Stephen W.

2014-01-01

Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration 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 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3′ terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (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 NDDs, 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 near the 3′ end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment. PMID:24381304

Long-term exposure to intranasal oxytocin in a mouse autism model.

Science.gov (United States)

Bales, K L; Solomon, M; Jacob, S; Crawley, J N; Silverman, J L; Larke, R H; Sahagun, E; Puhger, K R; Pride, M C; Mendoza, S P

2014-11-11

Oxytocin (OT) is a neuropeptide involved in mammalian social behavior. It is currently in clinical trials for the treatment of autism spectrum disorder (ASD). Previous studies in healthy rodents (prairie voles and C57BL/6J mice) have shown that there may be detrimental effects of long-term intranasal administration, raising the questions about safety and efficacy. To investigate the effects of OT on the aspects of ASD phenotype, we conducted the first study of chronic intranasal OT in a well-validated mouse model of autism, the BTBR T+ Itpr3tf/J inbred strain (BTBR), which displays low sociability and high repetitive behaviors. BTBR and C57BL/6J (B6) mice (N=94) were administered 0.8  IU/kg of OT intranasally, daily for 30 days, starting on day 21. We ran a well-characterized set of behavioral tasks relevant to diagnostic and associated symptoms of autism, including juvenile reciprocal social interactions, three-chambered social approach, open-field exploratory activity, repetitive self-grooming and fear-conditioned learning and memory, some during and some post treatment. Intranasal OT did not improve autism-relevant behaviors in BTBR, except for female sniffing in the three-chambered social interaction test. Male saline-treated BTBR mice showed increased interest in a novel mouse, both in chamber time and sniffing time, whereas OT-treated male BTBR mice showed a preference for the novel mouse in sniffing time only. No deleterious effects of OT were detected in either B6 or BTBR mice, except possibly for the lack of a preference for the novel mouse's chamber in OT-treated male BTBR mice. These results highlight the complexity inherent in understanding the effects of OT on behavior. Future investigations of chronic intranasal OT should include a wider dose range and early developmental time points in both healthy rodents and ASD models to affirm the efficacy and safety of OT.

Translation and validation of Autism Diagnostic Interview-Revised (ADI-R for autism diagnosis in Brazil

Directory of Open Access Journals (Sweden)

Michele M. Becker

2012-03-01

Full Text Available OBJECTIVE: To translate into Brazilian Portuguese the Autism Diagnostic Interview-Revised (ADI-R, an extremely useful diagnostic tool in autism. METHODS: A case-control study was done to validate the ADI-R. After being translated, the interview was applied in a sample of 20 patients with autism and 20 patients with intellectual disability without autism, in order to obtain the initial psychometric properties. RESULTS: The internal consistency was high, with a of Crombach of 0.967. The validity of criterion had sensitivity and specificity of 100%, having as a gold standard the DSM-IV diagnostic criteria. The interview had high discriminant validity, with higher scores in the group of patients with autism, as well as high interobserver consistency, with median kappa of 0.824. CONCLUSION: The final version of ADI-R had satisfactory psychometric characteristics, indicating good preliminary validation properties. The instrument needs to be applied in bigger samples in other areas of the country.

Myths about autism: An exploratory study using focus groups.

Science.gov (United States)

John, Rachael Ps; Knott, Fiona J; Harvey, Kate N

2017-08-01

Individuals with autism are often stigmatised and isolated by their typically developing peers according to parental, teacher and self-reports. While quantitative studies often report negative attitudes towards individuals with autism, it is still unclear how understandings of autism influence attitudes. In this exploratory study, misconceptions or myths about autism, that is, the cognitive component of attitudes, were examined using focus groups. Purposive sampling was used to recruit undergraduate and postgraduate students, and adults with and without experience of autism, to one of the five focus groups (n = 37). Content analysis was used to identify emergent themes. The data identified seven commonly held beliefs about individuals with autism. The first four were related to social interaction, such as that people with autism do not like to be touched. The fifth reflected the view that all individuals with autism have a special talent, and the final two concerned beliefs that people with autism are dangerous. The findings from this study demonstrate that people with varying experience or knowledge of autism often hold inaccurate beliefs about autism. These findings improve our understandings of lay beliefs about autism and will aid the development and implementation of interventions designed to improve lay knowledge of autism.

Autism spectrum disorder in the scope of tactile processing

Directory of Open Access Journals (Sweden)

Mark Mikkelsen

2018-01-01

Full Text Available Sensory processing abnormalities are among the most common behavioral phenotypes seen in autism spectrum disorder (ASD, typically characterized by either over- or under-responsiveness to stimulation. In this review, we focus on tactile processing dysfunction in ASD. We firstly review clinical studies wherein sensitivity to tactile stimuli has traditionally been assessed by self-, parent- and experimenter-reports. We also discuss recent investigations using psychophysical paradigms that gauge individual tactile thresholds. These more experimentally rigorous studies allow for more objective assessments of tactile abnormalities in ASD. However, little is understood about the neurobiological mechanisms underlying these abnormalities, or the link between tactile abnormalities and ASD symptoms. Neurobiological research that has been conducted has pointed toward dysfunction in the excitation/inhibition balance of the central nervous system of those with ASD. This review covers recent efforts that have investigated tactile dysfunction in ASD from clinical and behavioral perspectives, and some of the efforts to link these to neurobiology. On the whole, findings are inconsistent, which can be ascribed to the subjectivity of clinical assessments, the heterogeneity of ASD cohorts, and the diversity of tactile sensitivity measures. Future endeavors into understanding tactile processing differences in ASD will greatly benefit from controlled experiments driven by neurobiological hypotheses. Keywords: Autism spectrum disorder, Psychophysics, Review, Touch, Somatosensory, Tactile processing

Williams syndrome deletions and duplications: Genetic windows to understanding anxiety, sociality, autism, and schizophrenia.

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Crespi, Bernard J; Procyshyn, Tanya L

2017-08-01

We describe and evaluate an integrative hypothesis for helping to explain the major neurocognitive features of individuals with Williams syndrome region deletions and duplications. First, we demonstrate how the cognitive differences between Williams syndrome individuals, individuals with duplications of this region, and healthy individuals parallel the differences between individuals subject to effects of increased or decreased oxytocin. Second, we synthesize evidence showing that variation in expression of the gene GTF2I (General Transcription Factor II-I) underlies the primary social phenotypes of Williams syndrome and that common genetic variation in GTF2I mediates oxytocin reactivity, and its correlates, in healthy populations. Third, we describe findings relevant to the hypothesis that the GTF2I gene is subject to parent of origin effects whose behavioral expression fits with predictions from the kinship theory of genomic imprinting. Fourth, we describe how Williams syndrome can be considered, in part, as an autistic syndrome of Lorna Wing's 'active-but-odd' autism subtype, in contrast to associations of duplications with both schizophrenia and autism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gastrointestinal microbiota in children with autism in Slovakia.

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Tomova, Aleksandra; Husarova, Veronika; Lakatosova, Silvia; Bakos, Jan; Vlkova, Barbora; Babinska, Katarina; Ostatnikova, Daniela

2015-01-01

Development of Autism Spectrum Disorders (ASD), including autism, is based on a combination of genetic predisposition and environmental factors. Recent data propose the etiopathogenetic role of intestinal microflora in autism. The aim of this study was to elucidate changes in fecal microbiota in children with autism and determine its role in the development of often present gastrointestinal (GI) disorders and possibly other manifestations of autism in Slovakia. The fecal microflora of 10 children with autism, 9 siblings and 10 healthy children was investigated by real-time PCR. The fecal microbiota of autistic children showed a significant decrease of the Bacteroidetes/Firmicutes ratio and elevation of the amount of Lactobacillus spp. Our results also showed a trend in the incidence of elevated Desulfovibrio spp. in children with autism reaffirmed by a very strong association of the amount of Desulfovibrio spp. with the severity of autism in the Autism Diagnostic Interview (ADI) restricted/repetitive behavior subscale score. The participants in our study demonstrated strong positive correlation of autism severity with the severity of GI dysfunction. Probiotic diet supplementation normalized the Bacteroidetes/Firmicutes ratio, Desulfovibrio spp. and the amount of Bifidobacterium spp. in feces of autistic children. We did not find any correlation between plasma levels of oxytocin, testosterone, DHEA-S and fecal microbiota, which would suggest their combined influence on autism development. This pilot study suggests the role of gut microbiota in autism as a part of the "gut-brain" axis and it is a basis for further investigation of the combined effect of microbial, genetic, and hormonal changes for development and clinical manifestation of autism. Copyright © 2014 Elsevier Inc. All rights reserved.

Identifying autism from neural representations of social interactions: neurocognitive markers of autism.

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Just, Marcel Adam; Cherkassky, Vladimir L; Buchweitz, Augusto; Keller, Timothy A; Mitchell, Tom M

2014-01-01

Autism is a psychiatric/neurological condition in which alterations in social interaction (among other symptoms) are diagnosed by behavioral psychiatric methods. The main goal of this study was to determine how the neural representations and meanings of social concepts (such as to insult) are altered in autism. A second goal was to determine whether these alterations can serve as neurocognitive markers of autism. The approach is based on previous advances in fMRI analysis methods that permit (a) the identification of a concept, such as the thought of a physical object, from its fMRI pattern, and (b) the ability to assess the semantic content of a concept from its fMRI pattern. These factor analysis and machine learning methods were applied to the fMRI activation patterns of 17 adults with high-functioning autism and matched controls, scanned while thinking about 16 social interactions. One prominent neural representation factor that emerged (manifested mainly in posterior midline regions) was related to self-representation, but this factor was present only for the control participants, and was near-absent in the autism group. Moreover, machine learning algorithms classified individuals as autistic or control with 97% accuracy from their fMRI neurocognitive markers. The findings suggest that psychiatric alterations of thought can begin to be biologically understood by assessing the form and content of the altered thought's underlying brain activation patterns.

GENETIC ASPECTS OF AUTISM

Directory of Open Access Journals (Sweden)

Anastas LAKOSKI

1997-06-01

Full Text Available In the first paper on the syndrome of autism, Kanner described it as innate and inborn. He drew attention to the abnormalities in infancy without evidence of prior normal development and the intellectual, non emotional qualities shown by many of the parents and grandparents. Subsequently, the supposed lack of parental warmth led many clinicians to abandon the notions of constitutional deficit in the child and instead to postulate a psychogenic origin etiology was likely, genetic factors probably did not play a major role. Attention was draw to the low rate of autism in siblings, the lack of chromosome anomalies, and the similarities with syndromes associated with known brain trauma. Although the rate of autism in siblings was indeed low, it was much higher than in the general population rate providing a strong pointer to the genetic factors. The recognition that this was so, associated with the parallel finding of apparently high familiar loading for language delay, stimulated the first, systematic, twin study of autism, which suggested a strong genetic component. Subsequent research has produced findings in the same direction, although many questions remain unanswered. In this paper the evidence that has accumulated on genetic influences on autism is summarized and the remained dilemmas on this field are discussed.

Microglia M2A Polarization as Potential Link between Food Allergy and Autism Spectrum Disorders

Directory of Open Access Journals (Sweden)

Hans O. Kalkman

2017-12-01

Full Text Available Atopic diseases are frequently co-morbid with autism spectrum disorders (ASD. Allergic responses are associated with an activation of mast cells, innate lymphoid cells, and Th2 cells. These cells produce type-2 cytokines (IL4 and IL13, which stimulate microglia and macrophages to adopt a phenotype referred to as ‘alternative activation’ or ‘M2A’. M2A-polarized macrophages and microglia play a physiological role in tissue repair by secreting growth factors such as brain-derived neurotrophic factor (BDNF and insulin-like growth factor-1. In ASD there is evidence for increased type-2 cytokines, microglia activation, M2A polarization, and increased levels of growth factors. In neurons, these growth factors drive a signal transduction pathway that leads to activation of the enzyme mammalian Target of Rapamycin (mTOR, and thereby to the inhibition of autophagy. Activation of mTOR is an effect that is also common to several of the genetic forms of autism. In the central nervous system, redundant synapses are removed via an autophagic process. Activation of mTOR would diminish the pruning of redundant synapses, which in the context of ASD is likely to be undesired. Based on this line of reasoning, atopic diseases like food allergy, eczema or asthma would represent risk factors for autism spectrum disorders.

A novel 3q29 deletion associated with autism, intellectual disability, psychiatric disorders, and obesity.

Science.gov (United States)

Biamino, Elisa; Di Gregorio, Eleonora; Belligni, Elga Fabia; Keller, Roberto; Riberi, Evelise; Gandione, Marina; Calcia, Alessandro; Mancini, Cecilia; Giorgio, Elisa; Cavalieri, Simona; Pappi, Patrizia; Talarico, Flavia; Fea, Antonio M; De Rubeis, Silvia; Cirillo Silengo, Margherita; Ferrero, Giovanni Battista; Brusco, Alfredo

2016-03-01

Copy number variation (CNV) has been associated with a variety of neuropsychiatric disorders, including intellectual disability/developmental delay (ID/DD), autism spectrum disorder (ASD), and schizophrenia (SCZ). Often, individuals carrying the same pathogenic CNV display high clinical variability. By array-CGH analysis, we identified a novel familial 3q29 deletion (1.36 Mb), centromeric to the 3q29 deletion region, which manifests with variable expressivity. The deletion was identified in a 3-year-old girl diagnosed with ID/DD and autism and segregated in six family members, all affected by severe psychiatric disorders including schizophrenia, major depression, anxiety disorder, and personality disorder. All individuals carrying the deletion were overweight or obese, and anomalies compatible with optic atrophy were observed in three out of four cases examined. Amongst the 10 genes encompassed by the deletion, the haploinsufficiency of Optic Atrophy 1 (OPA1), associated with autosomal dominant optic atrophy, is likely responsible for the ophthalmological anomalies. We hypothesize that the haploinsufficiency of ATPase type 13A4 (ATP13A4) and/or Hairy/Enhancer of Split Drosophila homolog 1 (HES1) contribute to the neuropsychiatric phenotype, while HES1 deletion might underlie the overweight/obesity. In conclusion, we propose a novel contiguous gene syndrome due to a proximal 3q29 deletion variably associated with autism, ID/DD, psychiatric traits and overweight/obesity. © 2015 Wiley Periodicals, Inc.

Pulih Dari Autisme

OpenAIRE

Hidayat, Meilinah

2003-01-01

Autisme adalah gangguan perkembangan pervasif pada anak yang umumnya muncul sebelum usia 3 tahun. Autisme bukan gangguan perilaku semata, tapi ada sebab-sebab fisik yang mendasarinya. Jadi pengobatannya selain untuk terapi mental, juga diperlukan intervensi biomedis untuk terapi fisik sesuai penyebab gejalanya. Dipaparkan kasus Alan yang didiagnosis sebagai ADD (Attention Deficit Disorder) / ADHD (Attention Deficit Disorder + Hiperactivity) dan Taylor yang didiagnosis sebagai Late onset infan...

Color Perception in Children with Autism

Science.gov (United States)

Franklin, Anna; Sowden, Paul; Burley, Rachel; Notman, Leslie; Alder, Elizabeth

2008-01-01

This study examined whether color perception is atypical in children with autism. In experiment 1, accuracy of color memory and search was compared for children with autism and typically developing children matched on age and non-verbal cognitive ability. Children with autism were significantly less accurate at color memory and search than…

Setting the Standard for Autism Treatments: National Autism Center Releases Groundbreaking Report

Science.gov (United States)

Wilczynski, Susan M.; Pollack, Eileen G.

2009-01-01

In the United States and throughout the world, one's understanding of autism and other related disorders continues to evolve. Parents, educators, and health professionals today benefit from significant advancements in both the diagnosis and treatment of autism. However, the need to evaluate and select from a list of treatment options can be…

Diagnosis, Disclosure, and Having Autism: An Interpretative Phenomenological Analysis of the Perceptions of Young People with Autism

Science.gov (United States)

Huws, Jaci C.; Jones, Robert S. P.

2008-01-01

Background: Although there is extensive research examining parental experiences of assessment and diagnosis of autism, there is a paucity of research from the perspective of individuals with autism. Method: Semi-structured interviews were conducted with nine young people with high functioning autism who were capable of providing a verbal account…

Phenotypic diagnosis of dwarfism in six Friesian horses.

Science.gov (United States)

Back, W; van der Lugt, J J; Nikkels, P G J; van den Belt, A J M; van der Kolk, J H; Stout, T A E

2008-05-01

An extreme form of abnormal development, dwarfism, is common in man and some animals, but has not been officially reported in horses. Within the Friesian horse breed, congenital dwarfism has been recognised for many years, but no detailed report exists on its phenotype. The most salient feature of the dwarf syndrome is the physeal growth retardation in both limbs and ribs. Affected animals have approximately 25% shorter fore- and hindlimbs and approximately 50% reduced bodyweight. Postnatal growth is still possible in these animals, albeit at a slower rate: the head and back grow faster than the limbs and ribs leading to the characteristic disproportional growth disturbance. Thus, adult dwarfs exhibit a normal, but a relatively larger head conformation, a broader chest with narrowing at the costochondral junction, a disproportionally long back, abnormally short limbs, hyperextension of the fetlocks and narrow long-toed hooves. Furthermore, a dysplastic metaphysis of the distal metacarpus and metatarsus is radiographically evident. Microscopic analysis of the growth plates at the costochondral junction shows an irregular transition from cartilage to bone, and thickening and disturbed formation of chondrocyte columns, which is similar to findings in osteochondrodysplasia.

Occupational Therapy's Role with Autism

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Fact Sheet Occupational Therapy’s Role with Autism Autism is a lifelong condition associated with a varied course from early childhood through adulthood. Occupational therapy practitioners are distinctly qualified to ...

Brief Report: Trends in U.S. National Autism Awareness from 2004 to 2014: The Impact of National Autism Awareness Month

Science.gov (United States)

DeVilbiss, Elizabeth A.; Lee, Brian K.

2014-01-01

We sought to evaluate the potential for using historical web search data on autism spectrum disorders (ASD)-related topics as an indicator of ASD awareness. Analysis of Google Trend data suggested that National Autism Awareness Month and televised reports concerning autism are an effective method of promoting online search interest in autism.

Challenging situations when teaching children with autism spectrum disorders in general physical education.

Science.gov (United States)

Obrusnikova, Iva; Dillon, Suzanna R

2011-04-01

As the first step of an instrument development, teaching challenges that occur when students with autism spectrum disorders are educated in general physical education were elicited using Goldfried and D'Zurilla's (1969) behavioral-analytic model. Data were collected from a convenience sample of 43 certified physical educators (29 women and 14 men) using a demographic questionnaire and an elicitation questionnaire. Participants listed 225 teaching challenges, 46% related to cooperative, 31% to competitive, and 24% to individualistic learning situations. Teaching challenges were categorized into nine themes: inattentive and hyperactive behaviors, social impairment, emotional regulation difficulties, difficulties understanding and performing tasks, narrow focus and inflexible adherence to routines and structure, isolation by classmates, negative effects on classmates' learning, and need for support.

Neuroimaging of autism

Energy Technology Data Exchange (ETDEWEB)

Verhoeven, Judith S; Cock, Paul de; Lagae, Lieven [University Hospitals of the Catholic University of Leuven, Department of Pediatrics, Leuven (Belgium); Sunaert, Stefan [University Hospitals of the Catholic University of Leuven, Department of Radiology, Leuven (Belgium)

2010-01-15

Neuroimaging studies done by means of magnetic resonance imaging (MRI) have provided important insights into the neurobiological basis for autism. The aim of this article is to review the current state of knowledge regarding brain abnormalities in autism. Results of structural MRI studies dealing with total brain volume, the volume of the cerebellum, caudate nucleus, thalamus, amygdala and the area of the corpus callosum are summarised. In the past 5 years also new MRI applications as functional MRI and diffusion tensor imaging brought considerable new insights in the pathophysiological mechanisms of autism. Dysfunctional activation in key areas of verbal and non-verbal communication, social interaction, and executive functions are revised. Finally, we also discuss white matter alterations in important communication pathways in the brain of autistic patients. (orig.)

Neuroimaging of autism

International Nuclear Information System (INIS)

Verhoeven, Judith S.; Cock, Paul de; Lagae, Lieven; Sunaert, Stefan

2010-01-01

Neuroimaging studies done by means of magnetic resonance imaging (MRI) have provided important insights into the neurobiological basis for autism. The aim of this article is to review the current state of knowledge regarding brain abnormalities in autism. Results of structural MRI studies dealing with total brain volume, the volume of the cerebellum, caudate nucleus, thalamus, amygdala and the area of the corpus callosum are summarised. In the past 5 years also new MRI applications as functional MRI and diffusion tensor imaging brought considerable new insights in the pathophysiological mechanisms of autism. Dysfunctional activation in key areas of verbal and non-verbal communication, social interaction, and executive functions are revised. Finally, we also discuss white matter alterations in important communication pathways in the brain of autistic patients. (orig.)

Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus.

Science.gov (United States)

Zhang, Ying; Cao, Shu-Xia; Sun, Peng; He, Hai-Yang; Yang, Ci-Hang; Chen, Xiao-Juan; Shen, Chen-Jie; Wang, Xiao-Dong; Chen, Zhong; Berg, Darwin K; Duan, Shumin; Li, Xiao-Ming

2016-06-01

Mutations in the X-linked MECP2 gene cause Rett syndrome (RTT), an autism spectrum disorder characterized by impaired social interactions, motor abnormalities, cognitive defects and a high risk of epilepsy. Here, we showed that conditional deletion of Mecp2 in cholinergic neurons caused part of RTT-like phenotypes, which could be rescued by re-expressing Mecp2 in the basal forebrain (BF) cholinergic neurons rather than in the caudate putamen of conditional knockout (Chat-Mecp2(-/y)) mice. We found that choline acetyltransferase expression was decreased in the BF and that α7 nicotine acetylcholine receptor signaling was strongly impaired in the hippocampus of Chat-Mecp2(-/y) mice, which is sufficient to produce neuronal hyperexcitation and increase seizure susceptibility. Application of PNU282987 or nicotine in the hippocampus rescued these phenotypes in Chat-Mecp2(-/y) mice. Taken together, our findings suggest that MeCP2 is critical for normal function of cholinergic neurons and dysfunction of cholinergic neurons can contribute to numerous neuropsychiatric phenotypes.

Narrow dibaryon resonances

International Nuclear Information System (INIS)

Kajdalov, A.B.

1986-01-01

Experimental data on np interactions indicating to existence of narrow resonances in pp-system are discussed. Possible theoretical interpretations of these resonances are given. Experimental characteristics of the dibaryon resonances with isospin I=2 are considered

Test Review: Autism Spectrum Rating Scales

Science.gov (United States)

Simek, Amber N.; Wahlberg, Andrea C.

2011-01-01

This article reviews Autism Spectrum Rating Scales (ASRS) which are designed to measure behaviors in children between the ages of 2 and 18 that are associated with disorders on the autism spectrum as rated by parents/caregivers and/or teachers. The rating scales include items related to behaviors associated with Autism, Asperger's Disorder, and…

Autism: the quest for the genes.

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Sykes, Nuala H; Lamb, Janine A

2007-09-03

Autism, at its most extreme, is a severe neurodevelopmental disorder, and recent studies have indicated that autism spectrum disorders are considerably more common than previously supposed. However, although one of the most heritable neuropsychiatric syndromes, autism has so far eluded attempts to discover its genetic origins in the majority of cases. Several whole-genome scans for autism-susceptibility loci have identified specific chromosomal regions, but the results have been inconclusive and fine mapping and association studies have failed to identify the underlying genes. Recent advances in knowledge from the Human Genome and HapMap Projects, and progress in technology and bioinformatic resources, have aided study design and made data generation more efficient and cost-effective. Broadening horizons about the landscape of structural genetic variation and the field of epigenetics are indicating new possible mechanisms underlying autism aetiology, while endophenotypes are being used in an attempt to break down the complexity of the syndrome and refine genetic data. Although the genetic variants underlying idiopathic autism have proven elusive so far, the future for this field looks promising.

Non-ASD outcomes at 36 months in siblings at familial risk for autism spectrum disorder (ASD): A baby siblings research consortium (BSRC) study.

Science.gov (United States)

Charman, Tony; Young, Gregory S; Brian, Jessica; Carter, Alice; Carver, Leslie J; Chawarska, Katarzyna; Curtin, Suzanne; Dobkins, Karen; Elsabbagh, Mayada; Georgiades, Stelios; Hertz-Picciotto, Irva; Hutman, Ted; Iverson, Jana M; Jones, Emily J; Landa, Rebecca; Macari, Suzanne; Messinger, Daniel S; Nelson, Charles A; Ozonoff, Sally; Saulnier, Celine; Stone, Wendy L; Tager-Flusberg, Helen; Webb, Sara Jane; Yirmiya, Nurit; Zwaigenbaum, Lonnie

2017-01-01

We characterized developmental outcomes of a large sample of siblings at familial high-risk of autism spectrum disorder (ASD), who themselves did not have ASD (n = 859), and low-risk controls with no family history of ASD (n = 473). We report outcomes at age 3 years using the Mullen Scales of Early Learning, the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview-Revised (ADI-R) and adaptive functioning on the Vineland Adaptive Behavior Scales. Around 11% of high-risk siblings had mild-to-moderate levels of developmental delay, a rate higher than the low-risk controls. The groups did not differ in the proportion of toddlers with mild-to-moderate language delay. Thirty percent of high-risk siblings had elevated scores on the ADOS, double the rate seen in the low-risk controls. High-risk siblings also had higher parent reported levels of ASD symptoms on the ADI-R and lower adaptive functioning on the Vineland. Males were more likely to show higher levels of ASD symptoms and lower levels of developmental ability and adaptive behavior than females across most measures but not mild-to-moderate language delay. Lower maternal education was associated with lower developmental and adaptive behavior outcomes. These findings are evidence for early emerging characteristics related to the "broader autism phenotype" (BAP) previously described in older family members of individuals with ASD. There is a need for ongoing clinical monitoring of high-risk siblings who do not have an ASD by age 3 years, as well as continued follow-up into school age to determine their developmental and behavioral outcomes. Autism Res 2017, 10: 169-178. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

76 FR 19265 - World Autism Awareness Day, 2011

Science.gov (United States)

2011-04-07

... America A Proclamation With autism spectrum disorders (ASDs) affecting nearly one percent of children in... autism spectrum and provide necessary resources for their families, we must also remember that young... about autism and what they can do to support individuals on the autism spectrum and their families...

Developmental Trajectories in Siblings of Children with Autism: Cognition and Language from 4 Months to 7 Years

OpenAIRE

Gamliel, Ifat; Yirmiya, Nurit; Jaffe, Dena H.; Manor, Orly; Sigman, Marian

2009-01-01

We compared the cognitive and language development at 4, 14, 24, 36, 54 months, and 7 years of siblings of children with autism (SIBS-A) to that of siblings of children with typical development (SIBS-TD) using growth curve analyses. At 7 years, 40% of the SIBS-A, compared to 16% of SIBS-TD, were identified with cognitive, language and/or academic difficulties, identified using direct tests and/or parental reports. This sub-group was identified as SIBS-A-broad phenotype (BP). Results indicated...

Autism-specific copy number variants further implicate the phosphatidylinositol signaling pathway and the glutamatergic synapse in the etiology of the disorder.

Science.gov (United States)

Cuscó, Ivon; Medrano, Andrés; Gener, Blanca; Vilardell, Mireia; Gallastegui, Fátima; Villa, Olaya; González, Eva; Rodríguez-Santiago, Benjamín; Vilella, Elisabet; Del Campo, Miguel; Pérez-Jurado, Luis A

2009-05-15

Autism spectrum disorders (ASDs) constitute a group of severe neurodevelopmental conditions with complex multifactorial etiology. In order to explore the hypothesis that submicroscopic genomic rearrangements underlie some ASD cases, we have analyzed 96 Spanish patients with idiopathic ASD after extensive clinical and laboratory screening, by array comparative genomic hybridization (aCGH) using a homemade bacterial artificial chromosome (BAC) array. Only 13 of the 238 detected copy number alterations, ranging in size from 89 kb to 2.4 Mb, were present specifically in the autistic population (12 out of 96 individuals, 12.5%). Following validation by additional molecular techniques, we have characterized these novel candidate regions containing 24 different genes including alterations in two previously reported regions of chromosome 7 associated with the ASD phenotype. Some of the genes located in ASD-specific copy number variants act in common pathways, most notably the phosphatidylinositol signaling and the glutamatergic synapse, both known to be affected in several genetic syndromes related with autism and previously associated with ASD. Our work supports the idea that the functional alteration of genes in related neuronal networks is involved in the etiology of the ASD phenotype and confirms a significant diagnostic yield for aCGH, which should probably be included in the diagnostic workup of idiopathic ASD.

Reciprocal deletion and duplication at 2q23.1 indicates a role for MBD5 in autism spectrum disorder.

Science.gov (United States)

Mullegama, Sureni V; Rosenfeld, Jill A; Orellana, Carmen; van Bon, Bregje W M; Halbach, Sara; Repnikova, Elena A; Brick, Lauren; Li, Chumei; Dupuis, Lucie; Rosello, Monica; Aradhya, Swaroop; Stavropoulos, D James; Manickam, Kandamurugu; Mitchell, Elyse; Hodge, Jennelle C; Talkowski, Michael E; Gusella, James F; Keller, Kory; Zonana, Jonathan; Schwartz, Stuart; Pyatt, Robert E; Waggoner, Darrel J; Shaffer, Lisa G; Lin, Angela E; de Vries, Bert B A; Mendoza-Londono, Roberto; Elsea, Sarah H

2014-01-01

Copy number variations associated with abnormal gene dosage have an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID) and autism. We hypothesize that the chromosome 2q23.1 region encompassing MBD5 is a dosage-dependent region, wherein deletion or duplication results in altered gene dosage. We previously established the 2q23.1 microdeletion syndrome and report herein 23 individuals with 2q23.1 duplications, thus establishing a complementary duplication syndrome. The observed phenotype includes ID, language impairments, infantile hypotonia and gross motor delay, behavioral problems, autistic features, dysmorphic facial features (pinnae anomalies, arched eyebrows, prominent nose, small chin, thin upper lip), and minor digital anomalies (fifth finger clinodactyly and large broad first toe). The microduplication size varies among all cases and ranges from 68 kb to 53.7 Mb, encompassing a region that includes MBD5, an important factor in methylation patterning and epigenetic regulation. We previously reported that haploinsufficiency of MBD5 is the primary causal factor in 2q23.1 microdeletion syndrome and that mutations in MBD5 are associated with autism. In this study, we demonstrate that MBD5 is the only gene in common among all duplication cases and that overexpression of MBD5 is likely responsible for the core clinical features present in 2q23.1 microduplication syndrome. Phenotypic analyses suggest that 2q23.1 duplication results in a slightly less severe phenotype than the reciprocal deletion. The features associated with a deletion, mutation or duplication of MBD5 and the gene expression changes observed support MBD5 as a dosage-sensitive gene critical for normal development.

Variable sensory perception in autism.

Science.gov (United States)

Haigh, Sarah M

2018-03-01

Autism is associated with sensory and cognitive abnormalities. Individuals with autism generally show normal or superior early sensory processing abilities compared to healthy controls, but deficits in complex sensory processing. In the current opinion paper, it will be argued that sensory abnormalities impact cognition by limiting the amount of signal that can be used to interpret and interact with environment. There is a growing body of literature showing that individuals with autism exhibit greater trial-to-trial variability in behavioural and cortical sensory responses. If multiple sensory signals that are highly variable are added together to process more complex sensory stimuli, then this might destabilise later perception and impair cognition. Methods to improve sensory processing have shown improvements in more general cognition. Studies that specifically investigate differences in sensory trial-to-trial variability in autism, and the potential changes in variability before and after treatment, could ascertain if trial-to-trial variability is a good mechanism to target for treatment in autism. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Autism counts. Stereological studies on human postmortem brains and a mouse model for autism

NARCIS (Netherlands)

van Kooten, I.A.J.

2008-01-01

Autism is a neurodevelopmental disorder with a strong genetic component and several known environmental risk factors. Classical neuropathology studies have reported consistent findings in the limbic system, cerebellum and cerebral cortex of patients with autism. However, the neurobiological

Autism Spectrum Disorder and Fragile X Syndrome

Science.gov (United States)

... only after another family member has been diagnosed. Autism Spectrum Disorder and Fragile X Syndrome Fragile X syndrome is ... gene cause of ASD What Is Autism Spectrum Disorder? Autism spectrum disorder (ASD) is a behavioral diagnosis. The range ...

Therapies for Children With Autism Spectrum Disorder

Science.gov (United States)

... With Autism Spectrum Disorder Therapies for Children With Autism Spectrum Disorder Consumer Summary September 23, 2014 Download PDF 692. ... Web page Understanding Your Child's Condition What is autism spectrum disorder (ASD)? ASD includes a range of behavioral symptoms. ...

Genetics and epigenetics of autism: A Review.

Science.gov (United States)

Waye, Mary M Y; Cheng, Ho Yu

2018-04-01

Autism is a developmental disorder that starts before age 3 years, and children with autism have impairment in both social interaction and communication, and have restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. There is a strong heritable component of autism and autism spectrum disorder (ASD) as studies have shown that parents who have a child with ASD have a 2-18% chance of having a second child with ASD. The prevalence of autism and ASD have been increasing during the last 3 decades and much research has been carried out to understand the etiology, so as to develop novel preventive and treatment strategies. This review aims at summarizing the latest research studies related to autism and ASD, focusing not only on the genetics but also some epigenetic findings of autism/ASD. Some promising areas of research using transgenic/knockout animals and some ideas related to potential novel treatment and prevention strategies will be discussed. © 2017 The Chinese University of Hong Kong. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

[The neurobiology of autism].

Science.gov (United States)

Kotsopoulos, S

2007-07-01

The research effort on autism has for several years been intensive. Recent progress in this field is due mainly to the development of increasingly sophisticated visualizing assessment methods of the brain. Most of the evidence reported in this review requires further replication and elaboration by ongoing research. Evidence from volumetric studies indicates that the brain of the child with autism deviates from normal paths at the early stages of development showing excessive growth during the first year and a half involving the hemispheres and the cerebellum. Post mortem studies have shown neuron abnormalities in the frontal and temporal cortex and the cerebellum. Studies using diffusion tensor imaging, an fMRI based method, have shown disruptions between white and grey matter in several areas of the hemispheres. Other studies investigating activation of the cortex showed lack of synchrony and coordination between anterior and posterior areas of the hemispheres. It has been suggested that the deviation in brain development in autism consists of excessive numbers of neurons which cause the cytoarchitectural deviation. A theory suggesting that the basic deficit in autism is due to dysfunction of the "mirror neuron system" requires further substantiation. The aetiology of autism is not known although risk factors have been identified. Predominant among them are genetic influences. The search is currently intensive for an understanding of the pathogenesis of the pathological deviation in the development of the brain in autism. Neurotrophic factors which determine the developmental steps of the brain are examined such as serotonin, brain-derived neurotrophic factor (BDNF), the neuropeptide reelin, neuroligines and others. There is evidence of some involvement of these factors with autism but it is still far from clear how they do interact with one another and how they lead to the pathological deviations observed in autism. The neurotrophic factors are evidently coded by

Parental Attributions for the Behavior Problems of Children and Adolescents With Autism Spectrum Disorders

Science.gov (United States)

Hartley, Sigan L.; Schaidle, Emily M.; Burnson, Cynthia F.

2014-01-01

Objective The authors examined parental attributions for child behavior problems in 63 married couples of children and adolescents (aged 3–20 years) with autism spectrum disorders (ASDs). Both child-referent attributions (i.e., beliefs about causes related to the child or adolescent) and parent-referent attributions (i.e., beliefs about causes related to the parent) were examined along the dimensions of locus, stability, and controllability. Parent and child/adolescent factors related to parental attributions were identified, and the associations between parental attributions and parenting burden were explored. Method Mothers and fathers independently completed self-reported measures of parental attributions, parenting burden, and child behavior problems. Couples jointly reported on their son or daughter’s severity of autism symptoms, intellectual disability status, age, and gender. Results Parents tended to attribute the behavior problems of their child/adolescent with an ASD to characteristics that were not only internal to and stable in the child/adolescent but also controllable by the child/adolescent. Mothers were more likely to attribute their son or daughter’s behavior problems to characteristics that were less internal to and less stable in the child/adolescent with an ASD than were fathers. In addition, parents with a higher level of symptoms of the broader autism phenotype, parents of younger children, and parents of children/adolescents with intellectual disability, a higher severity of autism symptoms, and a higher severity of overall behavior problems were more likely to attribute their son or daughter’s behavior problems to characteristics that were more internal to and stable in the child/adolescent and factors that were less controllable by the child/adolescent. Parental attributions were related to parents’ level of parenting burden. Implications Findings have implications for designing appropriate interventions and services for families

Parental attributions for the behavior problems of children and adolescents with autism spectrum disorders.

Science.gov (United States)

Hartley, Sigan L; Schaidle, Emily M; Burnson, Cynthia F

2013-01-01

The authors examined parental attributions for child behavior problems in 63 married couples of children and adolescents (aged 3-20 years) with autism spectrum disorders (ASDs). Both child-referent attributions (i.e., beliefs about causes related to the child or adolescent) and parent-referent attributions (i.e., beliefs about causes related to the parent) were examined along the dimensions of locus, stability, and controllability. Parent and child/adolescent factors related to parental attributions were identified, and the associations between parental attributions and parenting burden were explored. Mothers and fathers independently completed self-reported measures of parental attributions, parenting burden, and child behavior problems. Couples jointly reported on their son or daughter's severity of autism symptoms, intellectual disability status, age, and gender. Parents tended to attribute the behavior problems of their child/adolescent with an ASD to characteristics that were not only internal to and stable in the child/adolescent but also controllable by the child/adolescent. Mothers were more likely to attribute their son or daughter's behavior problems to characteristics that were less internal to and less stable in the child/adolescent with an ASD than were fathers. In addition, parents with a higher level of symptoms of the broader autism phenotype, parents of younger children, and parents of children/adolescents with intellectual disability, a higher severity of autism symptoms, and a higher severity of overall behavior problems were more likely to attribute their son or daughter's behavior problems to characteristics that were more internal to and stable in the child/adolescent and factors that were less controllable by the child/adolescent. Parental attributions were related to parents' level of parenting burden. Findings have implications for designing appropriate interventions and services for families of children and adolescents with ASDs.

Ubiquinol Improves Symptoms in Children with Autism

NARCIS (Netherlands)

Gvozdjakova, Anna; Kucharska, Jarmila; Ostatnikova, Daniela; Babinska, Katarina; Nakladal, Dalibor; Crane, Fred L.

2014-01-01

Background. Autism is a spectrum of neurodevelopmental disorders with manifestation within 3 years after birth. Manifestations of autism include behavior problems (hyperactivity, toys destruction, self-harm, and agression) and sleep and eating disorders. Etiology of autism is poorly understood.

Children with Autism: Sleep Problems and Symptom Severity

Science.gov (United States)

Tudor, Megan E.; Hoffman, Charles D.; Sweeney, Dwight P.

2012-01-01

Relationships between the specific sleep problems and specific behavioral problems of children with autism were evaluated. Mothers' reports of sleep habits and autism symptoms were collected for 109 children with autism. Unlike previous research in this area, only children diagnosed with autism without any commonly comorbid diagnoses (e.g.,…

Signs and Symptoms of Autism

Science.gov (United States)

... Search Form Controls Cancel Submit Search the CDC Autism Spectrum Disorder (ASD) Note: Javascript is disabled or ... Mitochondrial Disease FAQs Data & Statistics New Data on Autism Research & Tracking ADDM Community Report CADDRE SEED Frequently ...

Consensus Paper: Pathological Role of the Cerebellum in Autism

Science.gov (United States)

Fatemi, S. Hossein; Aldinger, Kimberly A.; Ashwood, Paul; Bauman, Margaret L.; Blaha, Charles D.; Blatt, Gene J.; Chauhan, Abha; Chauhan, Ved; Dager, Stephen R.; Dickson, Price E.; Estes, Annette M.; Goldowitz, Dan; Heck, Detlef H.; Kemper, Thomas L.; King, Bryan H.; Martin, Loren A.; Millen, Kathleen J.; Mittleman, Guy; Mosconi, Matthew W.; Persico, Antonio M.; Sweeney, John A.; Webb, Sara J.; Welsh, John P.

2013-01-01

There has been significant advancement in various aspects of scientific knowledge concerning the role of cerebellum in the etiopathogenesis of autism. In the current consensus paper, we will observe the diversity of opinions regarding the involvement of this important site in the pathology of autism. Recent emergent findings in literature related to cerebellar involvement in autism are discussed, including: cerebellar pathology, cerebellar imaging and symptom expression in autism, cerebellar genetics, cerebellar immune function, oxidative stress and mitochondrial dysfunction, GABAergic and glutamatergic systems, cholinergic, dopaminergic, serotonergic, and oxytocin related changes in autism, motor control and cognitive deficits, cerebellar coordination of movements and cognition, gene-environment interactions, therapeutics in autism and relevant animal models of autism. Points of consensus include presence of abnormal cerebellar anatomy, abnormal neurotransmitter systems, oxidative stress, cerebellar motor and cognitive deficits, and neuroinflammation in subjects with autism. Undefined areas or areas requiring further investigation include lack of treatment options for core symptoms of autism, vermal hypoplasia and other vermal abnormalities as a consistent feature of autism, mechanisms underlying cerebellar contributions to cognition, and unknown mechanisms underlying neuroinflammation. PMID:22370873

Consensus paper: pathological role of the cerebellum in autism.

Science.gov (United States)

Fatemi, S Hossein; Aldinger, Kimberly A; Ashwood, Paul; Bauman, Margaret L; Blaha, Charles D; Blatt, Gene J; Chauhan, Abha; Chauhan, Ved; Dager, Stephen R; Dickson, Price E; Estes, Annette M; Goldowitz, Dan; Heck, Detlef H; Kemper, Thomas L; King, Bryan H; Martin, Loren A; Millen, Kathleen J; Mittleman, Guy; Mosconi, Matthew W; Persico, Antonio M; Sweeney, John A; Webb, Sara J; Welsh, John P

2012-09-01

There has been significant advancement in various aspects of scientific knowledge concerning the role of cerebellum in the etiopathogenesis of autism. In the current consensus paper, we will observe the diversity of opinions regarding the involvement of this important site in the pathology of autism. Recent emergent findings in literature related to cerebellar involvement in autism are discussed, including: cerebellar pathology, cerebellar imaging and symptom expression in autism, cerebellar genetics, cerebellar immune function, oxidative stress and mitochondrial dysfunction, GABAergic and glutamatergic systems, cholinergic, dopaminergic, serotonergic, and oxytocin-related changes in autism, motor control and cognitive deficits, cerebellar coordination of movements and cognition, gene-environment interactions, therapeutics in autism, and relevant animal models of autism. Points of consensus include presence of abnormal cerebellar anatomy, abnormal neurotransmitter systems, oxidative stress, cerebellar motor and cognitive deficits, and neuroinflammation in subjects with autism. Undefined areas or areas requiring further investigation include lack of treatment options for core symptoms of autism, vermal hypoplasia, and other vermal abnormalities as a consistent feature of autism, mechanisms underlying cerebellar contributions to cognition, and unknown mechanisms underlying neuroinflammation.

IMUNODIAGNOSTIC AND IMMUNOTHERAPY OF AUTISM

Directory of Open Access Journals (Sweden)

Vladimir TRAJKOVSKI

2000-06-01

Full Text Available Infantile autism is one of the most disabling illnesses of neurological, emotional and intellectual development. The cause of autism remains unknown. However, recent investigations suggest that this disorder shares several features of established autoimmune disorders.The aim of this article is to describe the news of imunodiagnostic and immunotherapy in autism. Interpretation of data is made by conceptual and methodological differences between studies. The autoimmune response is most likely directed against the brain myelin, perhaps secondary to a viral infection. The idea that autism is an autoimmune disorder is further strengthened by the fact that autistic patients respond well to treatment with immune modulating drugs. Immune interventions can produce immune modulation-state of suppression or stimulation. Immune therapy should always be done in consultation with physicians.

Epigenetics and autism.

Science.gov (United States)

Mbadiwe, Tafari; Millis, Richard M

2013-01-01

This review identifies mechanisms for altering DNA-histone interactions of cell chromatin to upregulate or downregulate gene expression that could serve as epigenetic targets for therapeutic interventions in autism. DNA methyltransferases (DNMTs) can phosphorylate histone H3 at T6. Aided by protein kinase C β 1, the DNMT lysine-specific demethylase-1 prevents demethylation of H3 at K4. During androgen-receptor-(AR-) dependent gene activation, this sequence may produce AR-dependent gene overactivation which may partly explain the male predominance of autism. AR-dependent gene overactivation in conjunction with a DNMT mechanism for methylating oxytocin receptors could produce high arousal inputs to the amygdala resulting in aberrant socialization, a prime characteristic of autism. Dysregulation of histone methyltransferases and histone deacetylases (HDACs) associated with low activity of methyl CpG binding protein-2 at cytosine-guanine sites in genes may reduce the capacity for condensing chromatin and silencing genes in frontal cortex, a site characterized by decreased cortical interconnectivity in autistic subjects. HDAC1 inhibition can overactivate mRNA transcription, a putative mechanism for the increased number of cerebral cortical columns and local frontal cortex hyperactivity in autistic individuals. These epigenetic mechanisms underlying male predominance, aberrant social interaction, and low functioning frontal cortex may be novel targets for autism prevention and treatment strategies.

Deficit in visual temporal integration in autism spectrum disorders.

Science.gov (United States)

Nakano, Tamami; Ota, Haruhisa; Kato, Nobumasa; Kitazawa, Shigeru

2010-04-07

Individuals with autism spectrum disorders (ASD) are superior in processing local features. Frith and Happe conceptualize this cognitive bias as 'weak central coherence', implying that a local enhancement derives from a weakness in integrating local elements into a coherent whole. The suggested deficit has been challenged, however, because individuals with ASD were not found to be inferior to normal controls in holistic perception. In these opposing studies, however, subjects were encouraged to ignore local features and attend to the whole. Therefore, no one has directly tested whether individuals with ASD are able to integrate local elements over time into a whole image. Here, we report a weakness of individuals with ASD in naming familiar objects moved behind a narrow slit, which was worsened by the absence of local salient features. The results indicate that individuals with ASD have a clear deficit in integrating local visual information over time into a global whole, providing direct evidence for the weak central coherence hypothesis.

mGluR5-antagonist mediated reversal of elevated stereotyped, repetitive behaviors in the VPA model of autism.

Directory of Open Access Journals (Sweden)

Mili V Mehta

Full Text Available Autism spectrum disorders (ASD are highly disabling developmental disorders with a population prevalence of 1-3%. Despite a strong genetic etiology, there are no current therapeutic options that target the core symptoms of ASD. Emerging evidence suggests that dysfunction of glutamatergic signaling, in particular through metabotropic glutamate receptor 5 (mGluR5 receptors, may contribute to phenotypic deficits and may be appropriate targets for pharmacologic intervention. This study assessed the therapeutic potential of 2-methyl-6-phenylethyl-pyrididine (MPEP, an mGluR5-receptor antagonist, on repetitive and anxiety-like behaviors in the valproic acid (VPA mouse model of autism. Mice were exposed prenatally on day E13 to VPA and assessed for repetitive self-grooming and marble burying behaviors as adults. Anxiety-like behavior and locomotor activity were measured in an open-field. VPA-exposed mice displayed increased repetitive and anxiety-like behaviors, consistent with previously published results. Across both marble burying and self-grooming assays, MPEP significantly reduced repetitive behaviors in VPA-treated mice, but had no effect on locomotor activity. These results are consistent with emerging preclinical literature that mGluR5-antagonists may have therapeutic efficacy for core symptoms of autism.

Sex differences in the reciprocal behaviour of children with autism.

Science.gov (United States)

Backer van Ommeren, Tineke; Koot, Hans M; Scheeren, Anke M; Begeer, Sander

2017-08-01

Differences in the social limitations of girls compared to boys on the autism spectrum are still poorly understood. Impaired social-emotional reciprocity is a core diagnostic criterion for an autism spectrum disorder. This study compares sex differences in reciprocal behaviour in children with autism spectrum disorder (32 girls, 114 boys) and in typically developing children (24 girls, 55 boys). While children with autism spectrum disorder showed clear limitations in reciprocal behaviour compared to typically developing children, sex differences were found only in the autism spectrum disorder group: girls with autism spectrum disorder had higher reciprocity scores than boys with autism spectrum disorder. However, compared to typically developing girls, girls with autism spectrum disorder showed subtle differences in reciprocal behaviour. The sex-specific response patterns in autism spectrum disorder can inform and improve the diagnostic assessment of autism in females.

Default mode network in young male adults with autism spectrum disorder: Relationship with autism spectrum traits

OpenAIRE

Jung, Minyoung; Kosaka, Hirotaka; Saito, Daisuke N; Ishitobi, Makoto; Morita, Tomoyo; Inohara, Keisuke; Asano, Mizuki; Arai, Sumiyoshi; Munesue, Toshio; Tomoda, Akemi; Wada, Yuji; Sadato, Norihiro; Okazawa, Hidehiko; Iidaka, Tetsuya

2014-01-01

Background: Autism spectrum traits are postulated to lie on a continuum that extends between individuals with autism and individuals with typical development (TD). Social cognition properties that are deeply associated with autism spectrum traits have been linked to functional connectivity between regions within the brain's default mode network (DMN). Previous studies have shown that the resting-state functional connectivities (rs-FCs) of DMN are low and show negative correlation with the lev...

Selective Disruption of Metabotropic Glutamate Receptor 5-Homer Interactions Mimics Phenotypes of Fragile X Syndrome in Mice.

Science.gov (United States)

Guo, Weirui; Molinaro, Gemma; Collins, Katie A; Hays, Seth A; Paylor, Richard; Worley, Paul F; Szumlinski, Karen K; Huber, Kimberly M

2016-02-17

Altered function of the Gq-coupled, Group 1 metabotropic glutamate receptors, specifically mGlu5, is implicated in multiple mouse models of autism and intellectual disability. mGlu5 dysfunction has been most well characterized in the fragile X syndrome mouse model, the Fmr1 knock-out (KO) mouse, where pharmacological and genetic reduction of mGlu5 reverses many phenotypes. mGlu5 is less associated with its scaffolding protein Homer in Fmr1 KO mice, and restoration of mGlu5-Homer interactions by genetic deletion of a short, dominant negative of Homer, H1a, rescues many phenotypes of Fmr1 KO mice. These results suggested that disruption of mGlu5-Homer leads to phenotypes of FXS. To test this idea, we examined mice with a knockin mutation of mGlu5 (F1128R; mGlu5(R/R)) that abrogates binding to Homer. Although FMRP levels were normal, mGlu5(R/R) mice mimicked multiple phenotypes of Fmr1 KO mice, including reduced mGlu5 association with the postsynaptic density, enhanced constitutive mGlu5 signaling to protein synthesis, deficits in agonist-induced translational control, protein synthesis-independent LTD, neocortical hyperexcitability, audiogenic seizures, and altered behaviors, including anxiety and sensorimotor gating. These results reveal new roles for the Homer scaffolds in regulation of mGlu5 function and implicate a specific molecular mechanism in a complex brain disease. Abnormal function of the metabotropic, or Gq-coupled, glutamate receptor 5 (mGlu5) has been implicated in neurodevelopmental disorders, including a genetic cause of intellectual disability and autism called fragile X syndrome. In brains of a mouse model of fragile X, mGlu5 is less associated with its binding partner Homer, a scaffolding protein that regulates mGlu5 localization to synapses and its ability to activate biochemical signaling pathways. Here we show that a mouse expressing a mutant mGlu5 that cannot bind to Homer is sufficient to mimic many of the biochemical, neurophysiological, and

Randomized Controlled Trial for Early Intervention for Autism: A Pilot Study of the Autism 1-2-3 Project

Science.gov (United States)

Wong, Virginia C. N.; Kwan, Queenie K.

2010-01-01

We piloted a 2-week "Autism-1-2-3" early intervention for children with autism and their parents immediately after diagnosis that targeted at (1) eye contact, (2) gesture and (3) vocalization/words. Seventeen children were randomized into the Intervention (n = 9) and Control (n = 8) groups. Outcome measures included the Autism Diagnostic…

The Autism-Spectrum Quotient (AQ)-Adolescent Version

OpenAIRE

Baron-Cohen, Simon; Hoekstra, Rosa A.; Knickmeyer, Rebecca; Wheelwright, Sally

2006-01-01

The Autism Spectrum Quotient (AQ) quantifies autistic traits in adults. This paper adapted the AQ for children (age 9.8-15.4 years). Three groups of participants were assessed: Group 1: n=52 adolescents with Asperger Syndrome (AS) or high-functioning autism (HFA); Group 2: n=79 adolescents with classic autism; and Group 3, n=50 controls. The adolescents with AS/ HFA did not differ significantly from the adolescents with autism but both clinical groups scored higher than controls. Approximatel...

Functional neuroimaging and childhood autism

Energy Technology Data Exchange (ETDEWEB)

Boddaert, Nathalie [Service de Radiologie Pediatrique, Necker-Enfants Malades Hospital, Paris (France); Service Hospitalier Frederic Joliot, DRM, DSV, CEA, Orsay (France); Zilbovicius, Monica [Service Hospitalier Frederic Joliot, DRM, DSV, CEA, Orsay (France); INSERM, Tours [France

2002-01-01

Childhood autism is now widely viewed as being of developmental neurobiological origin. Yet, localised structural and functional brain correlates of autism have to be established. Structural brain-imaging studies performed in autistic patients have reported abnormalities such as increased total brain volume and cerebellar abnormalities. However, none of these abnormalities fully account for the full range of autistic symptoms. Functional brain imaging, such as positron emission tomography (PET), single photon emission computed tomography (SPECT) and functional MRI (fMRI) have added a new perspective to the study of normal and pathological brain functions. In autism, functional studies have been performed at rest or during activation. However, first-generation functional imaging devices were not sensitive enough to detect any consistent dysfunction. Recently, with improved technology, two independent groups have reported bilateral hypoperfusion of the temporal lobes in autistic children. In addition, activation studies, using perceptive and cognitive paradigms, have shown an abnormal pattern of cortical activation in autistic patients. These results suggest that different connections between particular cortical regions could exist in autism. The purpose of this review is to present the main results of rest and activation studies performed in autism. (orig.)

[Infantile autism and mirror neurons].

Science.gov (United States)

Cornelio-Nieto, J O

2009-02-27

Infantile autism is a disorder that is characterised by alterations affecting reciprocal social interactions, abnormal verbal and non-verbal communication, poor imaginative activity and a restricted repertoire of activities and interests. The causes of autism remain unknown, but there are a number of different approaches that attempt to explain the neurobiological causes of the syndrome. A recent theory that has been considered is that of a dysfunction in the mirror neuron system (MNS). The MNS is a neuronal complex, originally described in monkeys and also found in humans, that is related with our movements and which offers specific responses to the movements and intended movements of other subjects. This system is believed to underlie processes of imitation and our capacity to learn by imitation. It is also thought to play a role in language acquisition, in expressing the emotions, in understanding what is happening to others and in empathy. Because these functions are altered in children with autism, it has been suggested that there is some dysfunction present in the MNS of those with autism. Dysfunction of the MNS could account for the symptoms that are observed in children with autism.

Social demographic change and autism.

Science.gov (United States)

Liu, Kayuet; Zerubavel, Noam; Bearman, Peter

2010-05-01

Parental age at child's birth--which has increased for U.S. children in the 1992-2000 birth cohorts--is strongly associated with an increased risk of autism. By turning a social demographic lens on the historical patterning of concordance among twin pairs, we identify a central mechanism for this association: de novo mutations, which are deletions, insertions, and duplications of DNA in the germ cells that are not present in the parents' DNA. Along the way, we show that a demographic eye on the rising prevalence of autism leads to three major discoveries. First, the estimated heritability of autism has been dramatically overstated. Second, heritability estimates can change over remarkably short periods of time because of increases in germ cell mutations. Third, social demographic change can yield genetic changes that, at the population level, combine to contribute to the increased prevalence of autism.

Large-amplitude and narrow-band vibration phenomenon of a foursquare fix-supported flexible plate in a rigid narrow channel

Energy Technology Data Exchange (ETDEWEB)

Liu Lifang, E-mail: liu_lifang1106@yahoo.cn [School of Nuclear Science and Engineering, North China Electric Power University, Zhuxinzhuang, Dewai, Beijing 102206 (China); Lu Daogang, E-mail: ludaogang@ncepu.edu.cn [School of Nuclear Science and Engineering, North China Electric Power University, Zhuxinzhuang, Dewai, Beijing 102206 (China); Li Yang, E-mail: qinxiuyi@sina.com [School of Nuclear Science and Engineering, North China Electric Power University, Zhuxinzhuang, Dewai, Beijing 102206 (China); Zhang Pan, E-mail: zhangpan@ncepu.edu.cn [School of Nuclear Science and Engineering, North China Electric Power University, Zhuxinzhuang, Dewai, Beijing 102206 (China); Niu Fenglei, E-mail: niufenglei@ncepu.edu.cn [School of Nuclear Science and Engineering, North China Electric Power University, Zhuxinzhuang, Dewai, Beijing 102206 (China)

2011-08-15

Highlights: > FIV of a foursquare fix-supported flexible plate exposed to axial flow was studied. > Special designed test section and advanced measuring equipments were adopted. > The narrow-band vibration phenomenon with large amplitude was observed. > Line of plate's vibration amplitude and flow rate was investigated. > The phenomenon and the measurement error were analyzed. - Abstract: An experiment was performed to analyze the flow-induced vibration behavior of a foursquare fix-supported flexible plate exposed to the axial flow within a rigid narrow channel. The large-amplitude and narrow-band vibration phenomenon was observed in the experiment when the flow velocity varied with the range of 0-5 m/s. The occurring condition and some characteristics of the large-amplitude and narrow-band vibrations were investigated.

Temporal context memory in high-functioning autism.

Science.gov (United States)

Gras-Vincendon, Agnès; Mottron, Laurent; Salamé, Pierre; Bursztejn, Claude; Danion, Jean-Marie

2007-11-01

Episodic memory, i.e. memory for specific episodes situated in space and time, seems impaired in individuals with autism. According to weak central coherence theory, individuals with autism have general difficulty connecting contextual and item information which then impairs their capacity to memorize information in context. This study investigated temporal context memory for visual information in individuals with autism. Eighteen adolescents and adults with high-functioning autism (HFA) or Asperger syndrome (AS) and age- and IQ-matched typically developing participants were tested using a recency judgement task. The performance of the autistic group did not differ from that of the control group, nor did the performance between the AS and HFA groups. We conclude that autism in high-functioning individuals does not impair temporal context memory as assessed on this task. We suggest that individuals with autism are as efficient on this task as typically developing subjects because contextual memory performance here involves more automatic than organizational processing.

Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disorders.

LENUS (Irish Health Repository)

Anney, Richard J L

2012-02-01

Recent genome-wide association studies (GWAS) have implicated a range of genes from discrete biological pathways in the aetiology of autism. However, despite the strong influence of genetic factors, association studies have yet to identify statistically robust, replicated major effect genes or SNPs. We apply the principle of the SNP ratio test methodology described by O\\'Dushlaine et al to over 2100 families from the Autism Genome Project (AGP). Using a two-stage design we examine association enrichment in 5955 unique gene-ontology classifications across four groupings based on two phenotypic and two ancestral classifications. Based on estimates from simulation we identify excess of association enrichment across all analyses. We observe enrichment in association for sets of genes involved in diverse biological processes, including pyruvate metabolism, transcription factor activation, cell-signalling and cell-cycle regulation. Both genes and processes that show enrichment have previously been examined in autistic disorders and offer biologically plausibility to these findings.

Depression symptoms in boys with autism spectrum disorder and comparison samples.

Science.gov (United States)

Gadow, Kenneth D; Guttmann-Steinmetz, Sarit; Rieffe, Carolien; Devincent, Carla J

2012-07-01

This study compares severity of specific depression symptoms in boys with autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), or chronic multiple tic disorder (CMTD) and typically developing boys (Controls). Children were evaluated with parent and teacher versions of the Child Symptom Inventory-4 (CSI-4) and a demographic questionnaire. Mothers' and teachers' ratings generally indicated the most severe symptoms in boys with ASD ± ADHD. Associations of depression with ASD severity and IQ varied considerably for specific symptoms of depression, ASD functional domain, and informant. Findings provide additional support for the differential influence of neurobehavioral syndromes on co-occurring symptom severity and illustrate how more fine-grained analyses of clinical phenotypes may contribute to a better understanding of etiology and current nosology.

AUTISM. Unraveling a pathway to autism

NARCIS (Netherlands)

Burbach, J Peter H

2016-01-01

Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders with shared symptoms in the area of communication and language, restricted interests, and stereotyped and social behaviors. Causes lie in perturbations of brain development, which can be manifold, but genetic

Gaze Perception Develops Atypically in Children with Autism

Directory of Open Access Journals (Sweden)

Simon Webster

2011-01-01

Full Text Available The Mindblindness model is the main model of social cognitive development in autism. This model assumes that eye direction detection and eye contact detection develop typically in autism (Baron-Cohen, 1995. The model's assumption of maturational development implies that when these skills are abnormal, they must either be absent or developmentally delayed. In contrast, the atypical modularisation hypothesis predicts that these skills can develop deviantly—successfully but atypically—in children with autism. Two computer-based tasks were used to assess eye direction detection and eye contact detection in children with autism and in typically developing children. These skills were developmentally deviant in children with autism. The findings support a model of social cognition in autism that accounts for developmental processes.

Olfactory functions are not associated with autism severity in autism spectrum disorders

Directory of Open Access Journals (Sweden)

Dudova I

2013-11-01

Full Text Available Iva Dudova, Michal HrdlickaDepartment of Child Psychiatry, University Hospital Motol, Prague, Czech RepublicBackground: Changes in olfactory functions have been found in many neurodegenerative and psychiatric disorders, including autism spectrum disorders (ASDs. The aim of the present study was to evaluate the relationship between olfactory functions (odor-detection thresholds, odor identification, and odor preference and autism severity and sensory-related behavior in children and adolescents with ASD.Subjects and methods: Our sample consisted of 35 high-functioning patients with ASD (mean age 10.8±3.6 years, 31 boys. Olfactory testing (threshold and identification used the Sniffin' Sticks test. Odor pleasantness was assessed on a 5-point scale using the Identification part of the Sniffin’ Sticks test. The severity of autistic psychopathology was measured using the Childhood Autism Rating Scale (CARS.Results: Using Spearman’s correlation, we found no significant correlations between autism severity (as expressed by total CARS score and odor-detection thresholds (R=0.144, P=0.409, odor identification (R=0.07, P=0.966, or odor pleasantness (R=-0.046, P=0.794. There was also no significant relationship between CARS item 9 (“Taste, smell, and touch response and use” and odor-detection thresholds (R=0.170, P=0.330, odor identification (R=0.282, P=0.100, or odor pleasantness (R=0.017, P=0.923.Conclusion: We did not find any significant relationship between the severity of autistic psychopathology and olfactory functions.Keywords: autism spectrum disorders, psychopathology, Sniffin’ Sticks, odor threshold, odor identification, odor pleasantness

Evolution of deformation velocity in narrowing for Zircaloy 2

Energy Technology Data Exchange (ETDEWEB)

Cetlin, P R [Minas Gerais Univ., Belo Horizonte (Brazil). Dept. de Engenharia Metalurgica; Okuda, M Y [Goias Univ., Goiania (Brazil). Inst. de Matematica e Fisica

1980-09-01

Some studies on the deformation instability in strain shows that the differences in this instability may lead to localized narrowing or elongated narrowing, for Zircaloy-2. The variation of velocity deformation with the narrowing evolution is expected to be different for these two cases. The mentioned variation is discussed, a great difference in behavior having been observed for the case of localized narrowing.

45 CFR 1308.15 - Eligibility criteria: Autism.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Eligibility criteria: Autism. 1308.15 Section 1308... Services Performance Standards § 1308.15 Eligibility criteria: Autism. A child is classified as having autism when the child has a developmental disability that significantly affects verbal and non-verbal...

Developing Undergraduate Coursework in Autism Spectrum Disorders

Science.gov (United States)

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

2014-01-01

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

The Autism Parent Screen for Infants: Predicting risk of autism spectrum disorder based on parent-reported behavior observed at 6-24 months of age.

Science.gov (United States)

Sacrey, Lori-Ann R; Bryson, Susan; Zwaigenbaum, Lonnie; Brian, Jessica; Smith, Isabel M; Roberts, Wendy; Szatmari, Peter; Vaillancourt, Tracy; Roncadin, Caroline; Garon, Nancy

2018-04-01

This study examined whether a novel parent-report questionnaire, the Autism Parent Screen for Infants, could differentiate infants subsequently diagnosed with autism spectrum disorder from a high-risk cohort (siblings of children diagnosed with autism spectrum disorder (n = 66)) from high-risk and low-risk comparison infants (no family history of autism spectrum disorder) who did not develop autism spectrum disorder (n = 138 and 79, respectively). Participants were assessed prospectively at 6, 9, 12, 15, 18, and 24 months of age. At 36 months, a blind independent diagnostic assessment for autism spectrum disorder was completed. Parent report on the Autism Parent Screen for Infants was examined in relation to diagnostic outcome and risk status (i.e. high-risk sibling with autism spectrum disorder, high-risk sibling without autism spectrum disorder, and low-risk control). The results indicated that from 6 months of age, total score on the Autism Parent Screen for Infants differentiated between the siblings with autism spectrum disorder and the other two groups. The sensitivity, specificity, and positive and negative predictive validity of the Autism Parent Screen for Infants highlight its potential for the early screening of autism spectrum disorder in high-risk cohorts.

Genetic modifications associated with ketogenic diet treatment in the BTBRT+Tf/J mouse model of autism spectrum disorder.

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Mychasiuk, Richelle; Rho, Jong M

2017-03-01

Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder characterized by hallmark behavioral features. The spectrum of disorders that fall within the ASD umbrella encompass a distinct but overlapping symptom complex that likely results from an array of molecular and genetic aberrations rather than a single genetic mutation. The ketogenic diet (KD) is a high-fat low-carbohydrate anti-seizure and neuroprotective diet that has demonstrated efficacy in the treatment of ASD-like behaviors in animal and human studies. We investigated changes in mRNA and gene expression in the BTBR mouse model of ASD that may contribute to the behavioral phenotype. In addition, we sought to examine changes in gene expression following KD treatment in BTBR mice. Despite significant behavioral abnormalities, expression changes in BTBR mice did not differ substantially from controls; only 33 genes were differentially expressed in the temporal cortex, and 48 in the hippocampus. Examination of these differentially expressed genes suggested deficits in the stress response and in neuronal signaling/communication. After treatment with the KD, both brain regions demonstrated improvements in ASD deficits associated with myelin formation and white matter development. Although our study supports many of the previously known impairments associated with ASD, such as excessive myelin formation and impaired GABAergic transmission, the RNAseq data and pathway analysis utilized here identified new therapeutic targets for analysis, such as Vitamin D pathways and cAMP signaling. Autism Res 2017, 10: 456-471. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Autism spectrum disorder - childhood disintegrative disorder

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... part of the larger developmental disorder category of autism spectrum disorder . ... American Psychiatric Association. Autism spectrum disorder. ... VA: American Psychiatric Publishing: 2013;50-59. Raviola GJ, ...

Brief Report: Checklist for Autism Spectrum Disorder--Most Discriminating Items for Diagnosing Autism

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Mayes, Susan D.

2018-01-01

The smallest subset of items from the 30-item Checklist for Autism Spectrum Disorder (CASD) that differentiated 607 referred children (3-17 years) with and without autism with 100% accuracy was identified. This 6-item subset (CASD-Short Form) was cross-validated on an independent sample of 397 referred children (1-18 years) with and without autism…

Survey of Bilingualism in Autism Spectrum Disorders

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Kay-Raining Bird, Elizabeth; Lamond, Erin; Holden, Jeanette

2012-01-01

This survey study investigates issues related to bilingualism and autism. Bilingualism is common around the world but there is little published information to guide professionals and parents in making decisions about bilingualism for children with autism. Participants were 49 parents or guardians of children with autism who were members of a…

Epigenetics and Autism

Directory of Open Access Journals (Sweden)

Tafari Mbadiwe

2013-01-01

Full Text Available This review identifies mechanisms for altering DNA-histone interactions of cell chromatin to upregulate or downregulate gene expression that could serve as epigenetic targets for therapeutic interventions in autism. DNA methyltransferases (DNMTs can phosphorylate histone H3 at T6. Aided by protein kinase Cβ1, the DNMT lysine-specific demethylase-1 prevents demethylation of H3 at K4. During androgen-receptor-(AR- dependent gene activation, this sequence may produce AR-dependent gene overactivation which may partly explain the male predominance of autism. AR-dependent gene overactivation in conjunction with a DNMT mechanism for methylating oxytocin receptors could produce high arousal inputs to the amygdala resulting in aberrant socialization, a prime characteristic of autism. Dysregulation of histone methyltransferases and histone deacetylases (HDACs associated with low activity of methyl CpG binding protein-2 at cytosine-guanine sites in genes may reduce the capacity for condensing chromatin and silencing genes in frontal cortex, a site characterized by decreased cortical interconnectivity in autistic subjects. HDAC1 inhibition can overactivate mRNA transcription, a putative mechanism for the increased number of cerebral cortical columns and local frontal cortex hyperactivity in autistic individuals. These epigenetic mechanisms underlying male predominance, aberrant social interaction, and low functioning frontal cortex may be novel targets for autism prevention and treatment strategies.