Illuminating the complex interplay of risk factors for depression within a large-scale US longitudinal cohort

A thorough understanding of depression susceptibility requires research to comprehensively assimilate a vast and complex array of risk factors. We leverage data from the National Longitudinal Study of Adolescent to Adult Health to integrate factors spanning biological (genetic data), psychological (health, personality, positive cognition, and self-worth), social (family, peers, school, and neighbourhood experiences), built (geo-coded healthcare, education, labour force, religion, crime, poverty, political climate), and natural (geo-coded population density, rainfall, and urban distances) systems and their contribution to depression symptoms in adolescence and adulthood using relatedness-based linear mixed models (N=5,030). First, a subset of 81 individual-level factors explained 83-86% of the variance in adolescence and 14% in adulthood symptoms. Positive cognition (feeling accepted and loved) contributed the most in adolescence (15%, SE=4%), and factors contributed relatively equally in adulthood. Second, all 162 factors capturing interconnected genetic, psychological, social, built, and natural systems explained 82-86% of the variance in adolescence and 32% in adulthood. The psychological system (adolescence 41-42% SE=5%, adulthood 6% SE=1%), psychological-genetic interaction (adolescence 26-28% SE=5%, adulthood 15% SE=3%), social-genetic interaction (adolescence 6-8% SE=2%) contributed most to depression symptoms. We provide a holistic understanding of depression risk and emphasise feeling supported and accepted as crucial for early detection.