Project Summary This application is a competing continuation of an Autism Centers of Excellence (ACE) Network entitled, “A Longitudinal Brain and Behavior Study of Autism from Infancy through Adolescence”. Prior funding supported a prospective, longitudinal study that has collected high quality brain imaging and behavior assessments in children at high- and low- familial risk (HR, LR) for autism spectrum disorder (ASD), starting in infancy, and at various points at 3-6-9-12-15-24-36 months to 7-11 years of age. Key findings from this network have revealed that: (1) early brain features of ASD are detectable by 6 months of age, well before diagnosis is possible; (2) ASD-specific brain and behavior features change substantially throughout early childhood, as ASD emerges; and (3) brain features in the first year of life are associated with later ASD behaviors and accurately predict ASD diagnosis in individuals at 24 months of age. The overarching goal of this ACE Network proposal is to extend into adolescence the follow-up of a prospective cohort of 400 subjects (300 HR; 100 LR) with detailed brain and behavior assessment between 13-16 years of age. Adolescence is a time of substantial challenges to autistic individuals. It is the time of peak onset of psychiatric disorders, rates of which are considerably higher in ASD than in the general population, with particular vulnerabilities in ASD females. Adolescence sets the stage for transition to early adulthood, a time when decline in daily living skills and worsening outcomes in ASD are commonly reported. In this application we therefore propose to: (Aim 1) characterize brain and brain-behavior trajectories in those with ASD, from infancy through adolescence, to gain insights into developmental mechanisms that inform the timing and targets of intervention; (Aim 2) identify infant-to-school-age brain and behavior features in those at elevated ASD familial risk, that predict clinically-relevant outcomes in adolescence and, (3) define the expression of familial ASD risk in adolescent females, identify early childhood markers of adolescent clinical impairment and, characterize patterns of infant-to-adolescent brain development, in adolescent females at high familial risk for ASD. This study would be the first prospective examination of brain and behavior features associated with ASD risk, in the same individuals, from infancy through adolescence. It has the potential to: (1) inform about the nature and timing of underlying mechanisms and targets of intervention; (2) elucidate childhood brain and behavior features that predict individual-level, adolescent dysfunction, related to familial ASD risk; and (3) to provide new insights regarding the expression of ASD risk in adolescent females, their identification earlier in childhood and associated patterns of brain development. This proposal addresses “areas of interest” specified in the ACE RFA, including: (1) a focus on under-studied subgroups e.g., individu...