Dataset Information

Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior.

ABSTRACT: Fifty years ago, increased whole-blood serotonin levels, or hyperserotonemia, first linked disrupted 5-HT homeostasis to Autism Spectrum Disorders (ASDs). The 5-HT transporter (SERT) gene (SLC6A4) has been associated with whole blood 5-HT levels and ASD susceptibility. Previously, we identified multiple gain-of-function SERT coding variants in children with ASD. Here we establish that transgenic mice expressing the most common of these variants, SERT Ala56, exhibit elevated, p38 MAPK-dependent transporter phosphorylation, enhanced 5-HT clearance rates and hyperserotonemia. These effects are accompanied by altered basal firing of raphe 5-HT neurons, as well as 5HT(1A) and 5HT(2A) receptor hypersensitivity. Strikingly, SERT Ala56 mice display alterations in social function, communication, and repetitive behavior. Our efforts provide strong support for the hypothesis that altered 5-HT homeostasis can impact risk for ASD traits and provide a model with construct and face validity that can support further analysis of ASD mechanisms and potentially novel treatments.

SUBMITTER: Veenstra-VanderWeele J

PROVIDER: S-EPMC3325657 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior.

Veenstra-VanderWeele Jeremy J Muller Christopher L CL Iwamoto Hideki H Sauer Jennifer E JE Owens W Anthony WA Shah Charisma R CR Cohen Jordan J Mannangatti Padmanabhan P Jessen Tammy T Thompson Brent J BJ Ye Ran R Kerr Travis M TM Carneiro Ana M AM Crawley Jacqueline N JN Sanders-Bush Elaine E McMahon Douglas G DG Ramamoorthy Sammanda S Daws Lynette C LC Sutcliffe James S JS Blakely Randy D RD

Proceedings of the National Academy of Sciences of the United States of America 20120319 14

Fifty years ago, increased whole-blood serotonin levels, or hyperserotonemia, first linked disrupted 5-HT homeostasis to Autism Spectrum Disorders (ASDs). The 5-HT transporter (SERT) gene (SLC6A4) has been associated with whole blood 5-HT levels and ASD susceptibility. Previously, we identified multiple gain-of-function SERT coding variants in children with ASD. Here we establish that transgenic mice expressing the most common of these variants, SERT Ala56, exhibit elevated, p38 MAPK-dependent t ...[more]

PMID: 22431635

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Project description:Eighty-seven percent of a large sample of children with autism spectrum disorder (ASD) are at risk for motor impairment (Bhat, Physical Therapy, 2020, 100, 633-644). In spite of the high prevalence for motor impairment in children with ASD, it is not considered among the diagnostic criteria or specifiers within DSM-V. In this article, we analyzed the SPARK study dataset (n = 13,887) to examine associations between risk for motor impairment using the Developmental Coordination Disorder-Questionnaire (DCD-Q), social communication impairment using the Social Communication Questionnaire (SCQ), repetitive behavior severity using the Repetitive Behaviors Scale - Revised (RBS-R), and parent-reported categories of cognitive, functional, and language impairments. Upon including children with ASD with cognitive impairments, 88.2% of the SPARK sample was at risk for motor impairment. The relative risk ratio for motor impairment in children with ASD was 22.2 times greater compared to the general population and that risk further increased up to 6.2 with increasing social communication (5.7), functional (6.2), cognitive (3.8), and language (1.6) impairments as well as repetitive behavior severity (5.0). Additionally, the magnitude of risk for motor impairment (fine- and gross-motor) increased with increasing severity of all impairment types with medium to large effects. These findings highlight the multisystem nature of ASD, the need to recognize motor impairments as one of the diagnostic criteria or specifiers for ASD, and the need for appropriate motor screening and assessment of children with ASD. Interventions must address not only the social communication and cognitive/behavioral challenges of children with ASD but also their motor function and participation. LAY ABSTRACT: Eighty-eight percent of the SPARK sample of children with ASD were at risk for motor impairment. The relative risk for motor impairment was 22.2 times greater in children with ASD compared to the general population and the risk increased with more social communication, repetitive behavior, cognitive, and functional impairment. It is important to recognize motor impairments as one of the diagnostic criteria or specifiers for ASD and there is a need to administer appropriate motor screening, assessment, and interventions in children with ASD.

Dataset Information

Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior.

Publications

Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior.

Similar Datasets

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