The objective of this study is to identify contributing genetic factors for abnormal repetitive behavior (such as flapping arms, lining up objects, peculiar fascination with odd objects, a very narrow restricted interest, and intolerance to changes of routines) among children with autism spectrum disorders (ASDs). As one of the core features of ASDs, restricted repetitive behavior (RRB) frequently dominates the daily activities of affected children, interferes with opportunities to develop functional behaviors, and requires intervention and treatment. Despite the clinical significance of RRB, little is known about underlying genetic mechanisms. In this study, we propose to investigate whether genetic variations within the GABA and glutamate neurotransmission system play a role in the pathogenesis of RRB in children with ASDs, based on prior studies implicating abnormal GABA and glutamate neurotransmission in the pathogeneses of RRB as well as ASDs. We will identify children between ages of 6 and 18 through a community-based support organization for schools and families with children with ASDs. The primary caregivers of the identified children will be asked to complete a battery of rating scales including the social communication questionnaire (SCQ), social responsiveness scale (SRS), the repetitive behavior scale-revised (RBS-R), the Vineland Adaptive Behavior Scale-II (parent/caregiver rating form) and a questionnaire for medication, family psychiatric history and past medical history. Consenting children will be asked to donate either saliva or buccal swab samples for genotyping. A total of ~750 single nucleotide polymorphisms (SNPs) from the GABA and glutamate system related genes will be genotyped and analyzed for quantitative association between specific genetic variants and specific forms of RRB. In addition, we will identify loci contributing epistatically to quantitative traits of RRB among the GABA and glutamate system related genes as a secondary aim. If genetic underpinnings of RRB are identified, this will lead to new insight as to early detection and treatment of this chronic and devastating condition.
Our goal is to find contributing genetic factors for abnormal repetitive behavior among children with autism spectrum disorders. We hypothesize that genes related to the GABA and glutamate neurotransmission system may play a key role in the development of the maladaptive repetitive behavior. Positive findings may lead to a new insight as to early detection and treatment of this chronic and disabling condition.
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