PROJECT SUMMARY/ABSTRACT Depression is a leading cause of disability in adolescents worldwide and is a major risk factor for suicide. Ninety percent of the world’s adolescents live in low- and middle-income countries (LMIC), yet the majority of research on adolescent depression has been conducted in high-income countries (HIC). This leaves a significant gap in our knowledge of the psychosocial predictors and neurodevelopmental mechanisms of adolescent depression in low resource settings. Our team, an established global interdisciplinary consortium: Identifying Depression Early in Adolescence (IDEA), is uniquely positioned to successfully conduct large scale longitudinal research in LMIC settings to address these gaps. The long-term goal of the research team is to develop a cross-culturally valid risk calculator for depression that could identify adolescents at high risk for depression to guide research, prevention, and treatment based on knowledge of the neural networks driving depression risk. The objective for this R21 is to test the predictive utility of a risk calculator for depression in a middle-income country and determine whether this risk calculator predicts altered neural development within hypothesized neural networks. In addition, the team will build capacity for adolescent neuroscience research in LMIC. The IDEA research consortium has generated a composite risk score for the development of depression using sociodemographic variables collected directly from the adolescent. Using this risk score, the team recruited a baseline sample of 150 adolescents (ages 14 to 16 years, 50% female, 44% African descent) in Porto Alegre, Brazil, who were classified into one of three groups at baseline: 50 “high-risk” participants without current or prior depression, 50 “low-risk” participants without current or prior depression, and 50 participants with current untreated depression. During their baseline assessment, participants completed an fMRI scan with tasks that elicited threat and reward network activity and completed measures of depression symptoms. For this R21, they will be invited back 3 years after the baseline assessment to complete the same measures. The research team will complete three specific aims. First, the team will test whether risk group classification at baseline predicts changes in depression symptom severity three years later, and whether altered development of the threat and reward brain networks explains this association. Second, in line with the Research Domain Criteria (RDoC) framework, the team will examine whether changes in the threat and reward networks predict behaviors and depression symptoms associated with negative affect and anhedonia, respectively. Third, the research team will build capacity in Brazil to conduct interdisciplinary neuroscience research through a constellation of training programs. This research will advance NIMH Strategic Objective 2 by characterizing developmental trajectories of brain function associated with the development of depression and identifying clinically useful biomarkers and behavioral indicators that predict risk for depression during adolescence.

PROJECT NARRATIVE The research team proposes to test the predictive utility of a risk calculator for depression in adolescents in Brazil, test whether specific brain networks explain depression risk, and increase capacity for neuroscience research in Brazil. Results from this research will lay the foundation for developing a cross-culturally and cross- contextually valid risk calculator that could be used to identify adolescents at high risk for depression across different settings. This research will also inform the design of personalized interventions for adolescents at high risk for depression based on knowledge of how differences in brain function and patterns of thinking contribute to depression risk.