PROJECT SUMMARY Borderline Personality Disorder (BPD) is a prominent contributor to disability, burden, and increased mortality. Although impairments in self (RDoC Systems for Social Processes: Perception and understanding of self) and interpersonal (RDoC Systems for Social Processes: Affiliation) functioning originate in early childhood, little is known about the developmental psychopathology of these core features in BPD, as opposed to a related psychiatric disorder that often precedes and co-develops with BPD: Major Depressive Disorder (MDD). The current proposal will establish developmental trajectories of interpersonal and self dysfunction from early childhood into young adulthood, examining interactions with environmental factors and associations with aberrant neural circuitry, to predict onset of BPD in early adulthood. In this renewal, we leverage 17 years of previously collected longitudinal data (R01 MH090786) from 348 young children enriched for emotional dysregulation. Now young adults (19-25 years), 36% exhibit BPD above diagnostic threshold. This sample offers an unparalleled opportunity to understand specific developmental precursors for BPD onset. Rich phenotyping, including over a decade of clinical interviews, narratives, questionnaires, observations, and repeated MRI and EEG assessments make this the ideal and highly cost-effective dataset to investigate impairments in self and interpersonal functioning that lead to BPD versus MDD. New data collection in young adulthood includes multi-method assessments of interpersonal and self functioning alongside psychiatric diagnostic interviews. Our motivating hypothesis is that in the context of emotion dysregulation, peer acceptance and aggression (interpersonal dysfunction) from preschool through middle childhood, interacts with self-functioning (unstable, incoherent self-worth and self- concept) in adolescence to uniquely predict BPD onset in adulthood versus MDD. We will examine: (1) how specific aspects of these constructs prospectively relate to adult BPD, as opposed to continuation of MDD; (2) during which developmental periods these constructs provide the most predictive utility, including the moderating effect of specific environmental factors; and (3) assess the predictive and mechanistic role of neural correlates of these constructs in forecasting BPD versus MDD. Findings will inform the optimal timing and content-focus (i.e., specific neural/behavioral self and interpersonal targets) of novel early-intervention for preventing BPD during the earliest developmental periods. This longitudinal research will be able to identify risk factors for the persistence or worsening of interpersonal and self dysfunction and BPD onset, offering the best starting point toward developing a prevention strategy for BPD.