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This project will provide prospective clinical and MRI data that will allow us to make causal predictions on data derived from an extensive survey of religion/spirituality (R/S) that was recently supported by the John Templeton Foundation (#54679, PI Weissman) in the same sample. Previously, in this longitudinal, 3-generation family study of individuals at high and low risk for major depressive disorder, we found single-item R/S measures (i.e., personal R/S importance, service attendance) to predict clinical and biological outcomes associated with resilience against depression. At Year 35 of the study, we further collected data on an extended full R/S survey to better understand our previous findings based on the single-item R/S measures. We found retrospective associations between depression and some R/S measures (i.e., religious commitment), but not others (e.g., altruism, meditation, spirituality in nature). With new incoming data at Year 40, the two aims of the proposed project are to (1) examine the pattern of relationships between the extensive R/S survey and clinical outcomes (e.g., depression, anxiety, substance abuse, suicidal behavior), as well as various medical outcomes (e.g., diabetes, cardiac functioning) prospectively, and (2) to use the R/S survey to make predictions in terms of health and its associated neurobiological outcomes. As most studies of religion and health are cross-sectional, this longitudinal data will provide us with the opportunity to gain a deeper understanding into the mechanisms underlying the association between various facets of R/S and health.