Project Summary/Abstract Depression is a leading cause of psychosocial impairment, poor academic performance, increased risk of school dropout, and a greater likelihood of self-harm, suicide, and medical illness over the lifespan. Moreover, a striking 30% of college students experience clinical levels of depression, making this is a critical period to identify intervention targets to mitigate risk for this burdensome disorder. Although research has evaluated psychological and immunological mechanisms of depression, these factors are typically studied in isolation. Social Safety Theory is a compelling, integrated framework that hypothesizes that social stressors are uniquely predictive of increases in depression because social stress has a greater biological impact compared to other stressors. Further, this pathway can be amplified by negative social safety schemas characterized by interpretating social situations as conflictual, unreliable, and dangerous. This proposal seeks to test this integrated, multi-level model of depression etiology using the transition from high school to college as a quasi-experimental social stressor and an intensive longitudinal design. Briefly, self-report data collected daily and inflammatory data collected every three days over a 24-day period will be used to evaluate how trajectories of perceived stress, inflammatory proteins, and depression symptom change as a function of transitioning to college (Aim 1), test if negative social schemas predict individual differences in trajectories of perceived stress, inflammatory proteins, and depression symptoms (Aim 2), and investigate the extent to which changes in inflammatory proteins mediate the association between changes in stress and depression symptoms during this period and whether this indirect relation is moderated by negative social safety schemas (Aim 3). To test if these interrelations between stress, social safety schemas, and inflammation predict long-term depression outcomes, Aims 2 and 3 will be re-tested predicting depression diagnoses across the entire freshman year (Exploratory Aim). Participants will be 112 healthy, incoming UCLA freshmen will be recruited via e-mails from the Registrar’s Office. Starting seven days before moving onto campus, participants will complete daily self-report measures (stress and depression symptoms, n = 2,688) and blood draws every three days (n = 896). Trait social safety schemas will be measured on the first day and a diagnostic interview will be completed before the study and again at the end of the year. Consistent with the NIMH Strategic Objectives (SO), this multi-method study will define biological mechanisms of mental illness (SO 1); provide insight into how mental illness trajectories change during developmental transitions (SO 2); highlight three, multi-domain targets for prevention and intervention (SO 3); and contribute to the public health impact of NIMH by reducing rates of depression on college campuses (SO 4)....