The present application builds on recent research in our laboratory in which we collected data, beginning in the first 2 months of life, from infants at high-risk for autism spectrum disorder (ASD). Following confirmatory diagnosis at 36 months, analyses of ASD-positive infants revealed that when looking at an approaching caregiver, from at least 2 months of age, infants with ASD follow a significantly different developmental trajectory from typical peers, with decline in fixation on others'eyes and increased fixation on body and object areas. Longitudinal change in measures of their visual fixation to caregivers was highly correlated with severity of clinical outcome at 24 months. In addition, based only on data collected in the first 6 months of life, measures of their developmental rate of change in looking at others'eyes and bodies predicted diagnostic classification with high sensitivity and specificity. To our knowledge, these are the eariiest known indicators of ASD in the extant literature and mark crucial first steps in advancing our understanding of the developmental pathogenesis of ASD. They also advance our efforts to enable the eariiest possible diagnostic identification of ASD-a critical factor in promoting optimal long-term outcome. The present application will build on these findings to study developmental profiles of social visual engagement as risk indices (Aim 1);as profiles for positive outcome (Aim 2);and as predictors of treatment response in eariy intervention (Aim 3). A cohort of 330 infants will be enrolled in this project, consisting of infant siblings of children with autism who are at High Risk for developing an ASD (HR-ASD, N=230); infants at High Risk for Developmental Delays without familial history of ASD (HR-DD, N=50);and children at Low Risk of developmental delays, with Typical Development expected (LR-TDx, N=50). Data will be collected longitudinally and prospectively, beginning in the first month of life, with confirmatory diagnostic assessment at 36 months. This project directly addresses several of the aspirational goals for autism set forth by the NIH Interagency Autism Coordinating Committee, with emphasis on identification of eariy risk; measures of developmental pathogenesis;and prognostic indicators for treatment and outcome.
Project I of this Emory/Marcus ACE application will identify and refine quantitative, performance-based indices of risk and resilience for social disability, beginning in the first months of life, to test the extent to which these measures of social engagement (in tandem with Project II) predict treatment response and outcome (Project IIl). These same constructs and measures are then shared with Projects IV &V to interrogate the genetic and neurobiological underpinnings of species-typical social development.
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