Autism is a disorder that is likely caused by the interaction of genetic predispositions and environmental triggers that coalesce during a sensitive period of development to lead to the spectrum of behaviors known Autism Spectrum Disorder. Despite extensive research into the underlying causes of this disorder, the linkage between its molecular origins, gene expression, affected neural pathways, and impacted cognitive and behavioral functions remains unclear. Our proposal offers new and distinct approaches to elucidating the relations among these components of autism. Our overarching objective is to simultaneously approach the problem of autism from several new and distinct points of view, supported by a programmatic cohesiveness that compels each perspective to intimately inform the others. The common theme that connects all of the proposed experiments in the proposed TranslationalAutism Research Program (TARP) is that the identification of the biological and biochemical functions influencing gene expression in affected neural pathways is the key to developing effective therapeutic treatments for autism. Our research objectives thus span a broad inquiry, encompassing the study of altered gene expression that may permit early identification of affected or at-risk children (TARP Projectl), gene copy number analyses (TARP Project #2), the study and validation of molecular mechanisms underlying the autism (TARP Project # 3), imaging the brain as we study visual processing abilities (focusing specifically on face processing) (TARP project #4), and the testing of well controlled and standardized treatment regimens within the context of altered gene expression or neural function TARP Project #5). Each of the five Projects comprising this proposal, supported by three Cores, will provide answers to a domain-specific element of the ASDs. In aggregate, these Projects will provide the links between the molecular, genetic, cognitive, and behavioral components of autism, and we anticipate that the relations among these areas will mature through the process of discovery.
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