Project Summary/Abstract Preschool anxiety, while prevalent and impairing, is an imperfect predictor of future outcomes. For example, longitudinal data suggest that anxiety disorders in preschool predict not just future anxiety but also other internalizing disorders and comorbid disruptive behavior in adolescence. Similarly, early adversity increases risk for many forms of adolescent psychopathology. Using our current methods we cannot identify which preschool children will go on to acquire which disorders in adolescence. This is in part because most models focus primarily on continuity within diagnoses as opposed to transdiagnostic risk factors and in the case of adversity, on the number rather than character of adverse childhood experiences. The current proposal tests a novel conceptual model focused on the type of adverse exposure, which differentiates two primary dimensions of experience underlying multiple forms of adversity: deprivation and threat. Interpersonal violence or threat and decreased cognitive and social inputs or deprivation are differentiated by the kind of experiences children have and by the impact of those experiences on neural and cognitive function. Thus, this model of adversity allows a focus on transdiagnostic risk factors. Importantly, the neural pathways linked to deprivation and threat are the same neural circuits known to be disrupted in early anxiety disorders. Given this shared neural risk we expect that early adversity and anxiety will interact to increase risk for psychopathology in adolescence. We also expect further moderation by other preschool diagnoses (e.g., ODD, ADHD). These neural pathways may be the ‘missing link’ between preschool anxiety and adolescent psychopathology. To address this knowledge gap, we propose following a group of adolescents (now aged 15-17 years; N=502) who were first assessed in preschool (ages 2–5 years). A subsample of these children (N=93) underwent structural and functional imaging up to 3 times between 5-10 years of age. This innovative, cost-effective proposal will provide an unparalleled opportunity to answer central questions about the trajectory of neurodevelopmental processes linking early risk to specific forms of adolescent psychopathology in a highly vulnerable population. The proposed research directly addresses Objectives 1 and 2 of the NIMH strategic plan.