Abstract: A marked increase in suicidal thoughts and behaviors (STB) among pre-pubertal children over the last decade has been reported by the CDC. Death by suicide in children ages 10-14 more than doubled between 2007 and 2014 with rates of non-lethal self-inflicted injuries doubling during the same period. Despite these dramatic rises in STB rates, there has been little investigation of the prevalence, timing of onset, or correlates and causes of STB or non-suicidal self-injury (NSSI) in pre-pubertal children. In a longitudinal study of preschool depression, we reported that preschool-onset STB shows stability across childhood. Outside of case reports, there are no other published data on STB or NSSI in early childhood. Our findings, taken together with the CDC data, support the critical need for studies of STB and NSSI that start in early childhood to identify the predictors of STB and NSSI in middle childhood and adolescence. In a sample of 3-7 year olds screened for a treatment study of depression we again found alarmingly high rates of NSSI (21.3%) and STB (19.4%) at baseline. Supplemental NIMH funding was awarded to investigate the characteristics and neural and behavioral correlates of STB and NSSI in this depressed sample, and to add age matched healthy controls. We found both common and unique risk factors for STB and NSSI in young children, consistent with the extant adolescent literature. Building on these findings, we propose to follow this well characterized sample into school age and early adolescence to test developmental models of these phenomena. We will investigate the longitudinal course, mediators and moderators, and neural correlates of early onset STB and NSSI. We will conduct behavioral and ERP assessments at two time points, 18-months apart in our sample of N=314 who have data from the preschool period. We will also sample the frequency, intensity, and proximal precipitants of STB/NSSI using weekly mini-assessments (WMA). Building on preliminary findings, we will use ERPs to test hypotheses about RDoC constructs that map to the risk factors that may contribute to STB and NSSI, including responses to negative and positive feedback to reward, errors, and peer rejection. We will test specific hypotheses about both shared risk factors for NSSI and STB (greater depression, peer rejection, adverse life events, and harsh parenting, as well as stronger ERP responses to loss and peer rejection, and blunted ERP responses to wins and social acceptance) as well as risk factors that may be more selective for NSSI (greater shame, irritability, self-criticism and higher pain tolerance) versus STB (reduced belongingness, greater hopelessness and a family history of suicide). Given the young age of the ascertained sample at baseline, we also have the opportunity to investigate differences in risk as a function of developmental stage. The proposed study provides an unprecedented opportunity to follow the largest ever sample of young children with STB and NSSI to investigate developmental trajectories into school age and early adolescence, potentially identifying early developmental targets for earlier intervention.