This is a competitive renewal of "Course and Outcome of Bipolar Disorder in Youth (COBY)," a collaborative undertaking by University of Pittsburgh, Brown, and UCLA to collect long-term prospective data on children and adolescents with Bipolar-Spectrum Disorders (BP) across psychiatric (categorical and dimensional), familial, psychosocial, cognitive, and naturalistic treatment domains using state-of-the-art instruments. COBY successfully enrolled a total of 446 youth (197 children and 249 adolescents) with BP, the largest cohort of rigorously defined cases of early-onset BP described to date. Since 100% of subjects will be older than 18 years and 65% will exceed age 24 by the end the proposed extension, COBY now seeks 5 more years of follow-up in order to comprehensively describe, for the first time, the prospective course of pediatric BP into young adulthood. In accord with the current NIMH Strategic Plan, 5 more years of observation data across multiple disease-specific and functional domains will address fundamental gaps in our knowledge of this poorly understood childhood condition by: (a) identifying the differential long-term course trajectories extending from childhood/adolescence into young adulthood, and their predictors;(b) describing changes in clinical phenotypes that coincide with transitions across developmental periods;(c) determining the long-term developmental course of psychosocial functioning from intake into young adulthood;(d) documenting the prevalence and predictors of new psychiatric comorbidities shown to accentuate risk of treatment non- response in adult studies;(e) identifying risk and predictors of suicidality, smoking, and substance use disorder as subjects enter the peak risk period of young adulthood;(f) evaluating long-term bi-directional effects of BP and neurocognition from childhood into young adulthood;and (g) evaluating how naturalistic psychosocial and pharmacological treatments affect course and psychosocial outcomes, and determining how these effects change with age. In addition, two novel aims are proposed in this renewal. First, given overlap between BP and Borderline Personality Disorder and the risk of mistreatment that results from diagnostic error, COBY will prospectively evaluate the temporal relationship between these phenotypes. Second, reflecting mounting evidence linking BP to elevated risk of cardiovascular disease (CVD) and mortality, COBY will examine risk for CVD by prospectively assessing physical activity and diet, metabolic syndrome and its components (central obesity, hyperglycemia, hypertension, and dyslipidemia), and the presence of inflammatory markers associated with risk for CVD (interleukin-6, tumor necrosis factor-alpha and C-reactive protein). These data will be compared to a demographically matched sample of young adults reported in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Findings from this effort will inform unanswered questions concerning long-term, cumulative, developmental effects of pediatric BP on adult psychiatric, functional, and health status, as well as the development of novel preventive strategies to enhance long-term management. PUBLIC HEALTH RELEVANCE: The Course and Outcome of Bipolar Youth (COBY) study has been interviewing children and adolescents with Bipolar Disorder (BP), every 6 months, for almost a decade, and COBY is proposing to continue the study for 5 more years to determine the impact of pediatric BP on adulthood. Since all of these youth will become young adults during the proposed project period, the results of this study will help us to better understand the clinical characteristics and the persistence of BP symptoms over time, the persistence or development of other psychiatric conditions (substance abuse, suicidal behaviors, personality problems), the risk for cardiovascular illnesses, and the social consequences of BP from childhood to adolescence and into young adulthood.