Shared and unique lifetime stressor characteristics and brain networks predict adolescent anxiety and depression

Exposure to major life stressors and aberrant brain functioning have been linked to anxiety and depression, especially during periods of heighted functional brain plasticity, such as adolescence. However, it remains unclear if specific characteristics of major life stressors and functional network disruptions differentially predict anxiety and depression symptoms over time and, if so, whether they act independently or jointly. We collected baseline lifetime stressor exposure data and resting-state functional magnetic resonance imaging data in a longitudinal sample of 107 adolescents enriched for anxiety and depressive disorders. We examined five stressor characteristics: physical danger, interpersonal loss, humiliation, entrapment, and role change/disruption. Anxiety and depression symptoms were assessed at baseline, 6-month and 12-month follow-ups. Linear mixed effect models tested if these stressor characteristics, functional connectivity within and between frontoparietal, default, and ventral attention networks, and their interactions differentially predicted anxiety and depression symptoms at 6-month and 12-month follow-ups. Greater lifetime severity of physical danger and humiliation prospectively predicted increased anxiety symptoms at both follow-ups, whereas greater lifetime entrapment severity prospectively predicted higher anxiety and depression symptoms. Only the effects of lifetime entrapment severity were robust to including within- and between-network functional connectivity metrics and other significantly predictive stressor characteristics. Lifetime entrapment severity more strongly predicted anxiety symptoms in youth with higher default network connectivity. Greater functional connectivity between frontoparietal and default networks prospectively predicted increased depression symptoms. Taken together, these results underscore the critical importance of using stressor characteristics and functional connectivity jointly to study predictors for adolescent anxiety and depression.