Gene-brain-environment interactions: Predicting social skill heterogeneity in ASD

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DESCRIPTION (provided by applicant): While autism spectrum disorders (ASDs) are characterized by significant impairments in social-communication, there is tremendous heterogeneity in the severity of these impairments. Very little is still known about the genetic, neurobiological, and environmental predictors of this heterogeneity. Emerging research suggests that all three of these factors relate separately to social development in ASD, but the lack of integrative research leaves many questions unanswered about how and why children with ASD differ so greatly in developmental course and quality of social skills. A better understanding of how these predictors interact is crucial to 1) understand risk and protective factors in the social development of children with ASD; 2) determine prognosis for young children with ASD; 3) select optimal treatments based on individual characteristics; and 4) develop early interventions to improve social development. The proposed study takes an interdisciplinary approach to examine how genetic risk and early parenting interact to predict later heterogeneity in brain and behavioral markers of social functioning in children with ASD. Participants will be 25 children with ASD and 25 age- and IQ-matched typically developing (TD) controls, ages 7-9 years. All children previously participated in a high-risk infant study at ages , 12, 18, and 24 months and have agreed to return for ongoing imaging studies at the UCLA Brain Mapping Center. The proposed study will examine group differences in trajectories of child social attention and maternal synchrony during early parent-child interactions, as well as how these trajectories predict social functioning in school-age. Additionally, the study will test whether brain connectivity in social brain networks during 1) social reward learning and 2) resting state mediates the relationship between early social interactions and later social functioning. Finally, this study will examine the early social interactions as mediators of the relationship between genetic risk (presence of oxytocin receptor gene OXTR) risk alleles and reduced connectivity in social brain networks. This work will contribute to the field by facilitatig an interdisciplinary understanding of the nature and development of social heterogeneity in ASD with implications for improvement of early prediction and intervention. These aims are consistent with the National Institute of Mental Health's strategic plan to link studies of genes with brain and behavioral development to understand atypical functioning as a transactional developmental process.