PROJECT SUMMARY Suicide is a leading cause of death for adolescents worldwide, and rates have increased over the past decade. Yet, we lack reliable predictors of suicidal behavior (SB) due in part to a need to consider a broader range of risk processes and methods of assessment. There is a particularly critical and urgent need for research on objective, prospective predictors of SB to identify youth at greatest risk and elucidate novel targets for intervention. The goal of this study is to characterize alterations in RDoC’s Positive Valence Systems, particularly neural processes involve in reward valuation, in a large, high-risk sample of adolescents in acute psychiatric treatment for self-injurious thoughts and behaviors (SITBs) who will be followed for 6 months following discharge—a period of high risk for SB. Our preliminary data and theories of SB highlight a key role of reward valuation in that SB partly reflects a choice between immediate relief from emotional pain rather than waiting for potential future rewards that come from continuing to live through difficult times. Consistent with this, rigorous cross-sectional research has linked SB to greater discounting of the value of delayed monetary rewards, and our preliminary data indicate enhanced neural responsiveness to immediate relative to delayed rewards in youth with recent SB. Importantly, preferences for immediate rather than delayed reinforcers are known to increase in times of high stress, and acute interpersonal stress is associated with elevated risk for SB in adolescents, while social support tends to be protective. This multi-method, prospective study will test an innovative conceptual model of SB by which youth with enhanced neural reactivity to immediate reinforcers and blunted reactivity to delayed rewards are more likely to engage in SB, particularly in times of acute interpersonal stress, and social support buffers effects of reward valuation on SB. We will recruit a transdiagnostic sample of adolescents (ages 13-17 years; N=300) in acute psychiatric treatment for SITBs. Participants will complete clinical assessments and behavioral and neural measures of reward valuation in the hospital to capture a high-risk state and minimize participant burden. Following discharge, participants will complete a brief daily survey of interpersonal stress, social support, and SITBs for 90 days. Finally, participants will complete follow-up interviews of SITBs 6 months after discharge to test prospective predictors of SB. This study will characterize patterns of reward valuation associated with SB histories in high-risk youth (Aim 1), examine neural measures of reward valuation as prospective predictors of SB following hospital discharge (Aim 2), and examine the interplay between neural reward valuation and interpersonal factors in the proximal prediction of SB (Aim 3). This study directly addresses NIMH priorities and will be the first to examine neural predictors of future SB in a large, ...