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Deficits in mesolimbic reward pathway underlie social interaction impairments in children with autism.

ABSTRACT: Lack of interest in social interaction is a hallmark of autism spectrum disorder. Animal studies have implicated the mesolimbic reward pathway in driving and reinforcing social behaviour, but little is known about the integrity of this pathway and its behavioural consequences in children with autism spectrum disorder. Here we test the hypothesis that the structural and functional integrity of the mesolimbic reward pathway is aberrant in children with autism spectrum disorder, and these aberrancies contribute to the social interaction impairments. We examine structural and functional connectivity of the mesolimbic reward pathway in two independent cohorts totalling 82 children aged 7-13 years with autism spectrum disorder and age-, gender-, and intelligence quotient-matched typically developing children (primary cohort: children with autism spectrum disorder n = 24, typically developing children n = 24; replication cohort: children with autism spectrum disorder n = 17, typically developing children n = 17), using high angular resolution diffusion-weighted imaging and functional MRI data. We reliably identify white matter tracts linking-the nucleus accumbens and the ventral tegmental area-key subcortical nodes of the mesolimbic reward pathway, and provide reproducible evidence for structural aberrations in these tracts in children with autism spectrum disorder. Further, we show that structural aberrations are accompanied by aberrant functional interactions between nucleus accumbens and ventral tegmental area in response to social stimuli. Crucially, we demonstrate that both structural and functional circuit aberrations in the mesolimbic reward pathway are related to parent-report measures of social interaction impairments in affected children. Our findings, replicated across two independent cohorts, reveal that deficits in the mesolimbic reward pathway contribute to impaired social skills in childhood autism, and provide fundamental insights into neurobiological mechanisms underlying reduced social interest in humans.

SUBMITTER: Supekar K

PROVIDER: S-EPMC6113649 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Deficits in mesolimbic reward pathway underlie social interaction impairments in children with autism.

Supekar Kaustubh K Kochalka John J Schaer Marie M Wakeman Holly H Qin Shaozheng S Padmanabhan Aarthi A Menon Vinod V

Brain : a journal of neurology 20180901 9

Lack of interest in social interaction is a hallmark of autism spectrum disorder. Animal studies have implicated the mesolimbic reward pathway in driving and reinforcing social behaviour, but little is known about the integrity of this pathway and its behavioural consequences in children with autism spectrum disorder. Here we test the hypothesis that the structural and functional integrity of the mesolimbic reward pathway is aberrant in children with autism spectrum disorder, and these aberranci ...[more]

PMID: 30016410

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Project description:BackgroundRecognition of symptoms of Social anxiety (SA) may be difficult among individuals with Autism Spectrum Disorders (ASD) because of overlap between social anxiety and autistic symptomatology. The main aim of our study was thus to explore the association between symptoms of social anxiety and clinical characteristics of ASD in order to identify individuals experiencing concomitant ASD and social anxiety disorder. We also described the prevalence of SA in a sample of children and adolescents with ASD.Method79 children and adolescents with ASD (with and without intellectual disability) and 28-matched control participants were recruited in two French Expert Centers for ASD, coordinated by the Fundation FondaMental. Psychiatric comorbidities, anxiety disorders and depression were screened with standard tools (Liebowitz social anxiety scale, Hamilton Depression and Anxiety Rating Scale) and correlated to autistic features and social skills assessed with the social responsiveness scale 2 (SRS-2) and the repetitive behavior scale (RBS-R). We performed bivariate analysis between the social anxiety level and the scores measured with different clinical scales. We then adjusted the observed relationships with the alterations of SRS-2 and RBS-R scores.ResultsAfter adjustment, the level of social anxiety appeared as significantly associated with alterations in social reciprocity and particularly with the SRS-2 "social communication" and "social motivation" sub-scores, but not with RBS-R score.ConclusionsWe confirm previous reports showing that individuals with ASD are at high risk for specific anxiety disorders. In particular, high levels of impairments in social motivation and social communication (SRS-2) are indicative of comorbid disorders namely, social anxiety and ASD. Our findings clearly inform diagnostic assessment in ASD and stress the need to take comorbid anxiety disorders into consideration to improve treatment of ASD. To further clarify the impact of social anxiety on social competences and socio-adaptive handicap, longitudinal studies and cluster analysis will be needed in the future.

Dataset Information

Deficits in mesolimbic reward pathway underlie social interaction impairments in children with autism.

Publications

Deficits in mesolimbic reward pathway underlie social interaction impairments in children with autism.

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