A Family-Genetic Study of Language in Autism

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Project Summary Differences in pragmatic (i.e., social) language are the language deficit most robustly associated with Autism Spectrum Disorder (ASD) and the Broad Autism Phenotype (BAP, a constellation of subclinical features in relatives that parallel in quality the defining characteristics of ASD and are believed to reflect genetic liability in clinically unaffected relatives). Findings from the initial award period indicate that retrospective, longitudinal measures of childhood language and cognitive development in parents, together with our battery of psycholinguistic and computational linguistic measures of pragmatic ability, measurable in individuals with ASD and their parents, are highly promising markers of ASD endophenotypes that can be targeted in genetic, neurobiological and treatment studies. This competing renewal builds significantly on these findings and our related work, in three important ways. First, given striking findings that parents' early rates of language and cognitive growth in childhood predict the BAP in adulthood, and ASD severity in the next generation (i.e., their children), we expand our study design and methods significantly, to investigate a unique and more expansive archival database of retrospective developmental, cognitive, social, behavior and personality measures available on a cohort of grandparents and parents of individuals with ASD, from high school through young adult years. These rich resources, together with our existing longitudinal data on parents' grade school testing records (which we will continue to collect), will afford an unprecedented look at developmental profiles through childhood and young adulthood (prior to having a child with ASD) that may predict genetic risk of ASD. We also further investigate the biological basis of our candidate pragmatic language endophenotypes through analysis of auditory brainstem response related to an expanded battery of pragmatic language in ASD families. Finally, we investigate the molecular basis of these candidate endophenotypes in families of individuals with ASD through measurement of the Fragile X Mental Retardation Protein, which is the protein product of FMR1 (implicated in ASD symptomatology), with strong connections to the auditory brainstem, and which preliminary data show may relate to pragmatic language features in family members of individuals with ASD.