The autism spectrum disorders (ASDs) are a heterogeneous group of developmental disorders with specific core features, including impaired social interaction and abnormal repetitive behavior. Several ongoing studies, including our own, are assessing the use of the drug oxytocin to ameliorate social deficits in individuals with ASDs and other psychosocial disorders. We hypothesize that behavioral response to oxytocin treatment is mediated by genetic and epigenetic factors and that these factors, particularly epigenetic mediators of gene expression, may be pivotal to baseline response and/or may change during oxytocin exposure. This proposal will explore the role of the epigenome and genetic predisposition to oxytocin treatment response in longitudinal samples that have already been collected as part of an ongoing clinical trial in high and low functioning children with ASDs; we will investigate the transcriptome and epigenome (5mC and 5hmC) in regions of the brain and periphery of a mouse model of ASD known to have positive response to oxytocin treatment; we will also examine novel regulatory mechanisms of oxytocin's receptor OXTR via 5-hydroxy methyl cytosine. The data generated by these aims will not only serve to develop (epi)genetic predictors of oxytocin response, but they will inform other trials using oxytocin to treat psychosocial disorders.