Project Summary/Abstract Adolescence, the developmental transition of juvenile social and cognitive processes to their adult forms, is a period of remarkable physiological, psychological, and social changes. During adolescence there is a significant increase in the risk for psychiatric disorders such that half of people who will suffer from mental illness have their onset by 14 years of age. Early research suggests that it is a pivotal transition for youth with autism spectrum disorder (ASD), a condition characterized by difficulty with social competence and change including developmental transitions. During the initial phase of the longitudinal study (MH111599), significant, clinically meaningful findings regarding autistic youth were revealed including: 1) dynamic and significant developmental effects of age on biobehavioral profiles, 2) advanced pubertal onset especially in autistic females, #3) elevated risk for depression emerging in early adolescence, 4) physiological dysregulation increasing with age and symptom severity and associated with depression, and 5) unique and complex profiles of sex and gender. These studies have provided the foundation and data for our competing renewal application, which is aligned with the NIMH Strategic Plan Goal 2 “…to examine mental illness trajectories to determine when, where, and how to intervene.” The overarching goal is on mental health risk (e.g., depression) and resiliency (e.g., coping) and potential moderating factors that may impact individual outcomes including diagnosis (autistic, neurotypical), development (age, puberty), sex (female, male) and gender (binary, non-binary) over adolescence. This research will help identify sensitive periods to reduce risk and prevent the onset of mental illnesses. Due to advanced pubertal timing in ASD and a significant rise in mental illness (e.g., depression) in early adolescence, studying the prepubescent period is essential. To examine developmental changes, the study will use a rigorous accelerated longitudinal design (ALD) corresponding with pre-, peri-, and pubertal development. Three cohorts will be enrolled at ages 8-9 (N=80), 10-11 (N=80) and 12-13 (N=80) followed over a four-year study period. Additionally, the previous cohort ages 15-17 (ASD N=64; TD N=60) will be followed providing a broad age span (8-17 years). The aims will address three areas. Aim 1: When: will examine the impact and unique contributions of adolescence and puberty on mental health profile based on diagnosis (ASD vs. TD) and Sex (Females vs. Males). Aim 2. Where: will examine social and emotional functioning during naturalistic interactions with peers. Aim 3. How: will examine physiological responses at the level of the central nervous system (event related potential), HPA axis (cortisol), and peripheral nervous system (heart rate variability) as plausible biobehavioral targets that predict risk and resiliency. An exploratory aim, Why: to explore key risk factors that impact ment...