This A1competitive renewal is one of four collaborative, linked R01s that proposes to examine the long-term effects of a Cognitive Behavioral Program (CBP) for preventing depression provided when adolescents were 13-17 years old. The sample is at high risk by virtue of familial (parental depression) and individual factors (past history of depression and/or current subsyndromal depressive symptoms). In the original study, we successfully enrolled 99% (N=316) of our proposed target recruitment of 320 adolescents, with equal recruitment across the 4 sites. Participants were randomized into either CBP or treatment as usual (TAU), with equally high retention (92%) in both conditions. Results through the 8-month follow-up indicated a significant prevention effect of CBP with regard to depressive episodes (HR=.60, 95% CI, .38-.96; effect size, d=.25), thus replicating and extending the earlier, single site study by Clarke et al., (2001). The aims of the current proposal are to (a) study the longer term impact of CBP on preventing depression during the critical developmental transition to early adulthood, a period of multiple new life challenges and stressors; (b) assess potential biological (e.g., genetic) and psychosocial (e.g., childhood abuse, stressful life events) moderators of response to the intervention; (c) examine the broader impact of the CBP program on sequelae of depression including other mental and medical health problems, health risk behaviors, and impairment in the attainment of developmental competencies; and (d) assess the long-term cost-efficacy of CBP, identify markers of the impact of CBP on key economic outcomes (e.g., workplace productivity), and examine the longer-term economic benefits of preventing or delaying the onset of mood disorders in adolescents with CBP. We will explore the potential role of adolescent depression in mediating these outcomes in young adulthood. These aims are consistent with the areas of highest priority for the NIMH Division of Services and Intervention Research (DSIR) insofar as this project will evaluate the durability and broader effects as well as cost-efficacy of an innovative prevention strategy, will potentially reduce the burden of suicidality by increasing depression-free days, and will both aid in the personalization of the intervention and the identification of new prevention targets through our study of biological and psychosocial moderators of treatment effects. Knowledge gained from this study will be used to identify individuals who are most and least likely to benefit from this prevention program, and will provide an empirical foundation for novel and innovative strategies for the prevention of depression. In our original study, we found that we can prevent depression among at-risk youth, but we do not yet know if this prevention lasts and whether it improves youths' schooling, employment, and relationships with others. The proposed study will be the first to examine whether depression continues to be prevented as these teens become young adults. This study also will identify youth who are most likely to benefit from this program, and will inform us about how to create future prevention programs that help those youth who did not benefit. Public Health Relevance: In our original study, we found that we can prevent depression among at-risk youth, but we do not yet know if this prevention lasts and whether it improves youths' schooling, employment, and relationships with others. The proposed study will be the first to examine whether depression continues to be prevented as these teens become young adults. This study also will identify youth who are most likely to benefit from this program, and will inform us about how to create future prevention programs that help those youth who did not benefit.