Depression is the leading cause of disability in the United States and represents a major public health burden. The proposed research focuses on epigenetic markers of depression because these are potential mechanisms by which environmental exposures during critical periods of development alter the expression of genes related to behaviors, affective states, and cognitions that increase vulnerability for depression. We aim to identify epigenetic correlates of depression symptom trajectories that are predicted to vary in terms of their severity and course across adolescence and to test whether these epigenetic differences partly explain emerging sex differences in the prevalence of depression in adolescence. Moving beyond a candidate gene, cross-sectional approach, we propose to prospectively examine the extent to which DNA methylation profiles at two sensitive points in development – birth and adolescence – are associated with trajectories of depression symptoms from early to late adolescence.