PROJECT SUMMARY Major depressive disorder (MDD) is a common, often recurrent mental health problem associated with an increased likelihood for several common physical health problems and a decreased lifespan. A history of experiencing childhood maltreatment is considered a major risk factor for the development of MDD in adulthood, as well as an overall worse course of illness. Dysregulation of the immune system and associated inflammation has emerged as a leading theory in helping to explain the association between childhood maltreatment and MDD in adulthood. Unfortunately, two pressing problems have persisted throughout this field. First, studies are highly heterogeneous in their designs or are not representative of the U.S., despite the U.S. having the highest incidence of MDD among all high-income nations. Second, many studies poorly assess the role of sex, implementing it as a covariate despite recognition that sex affects the associations between childhood maltreatment, inflammation, and MDD systemically. Even fewer studies account for the roles of both sex and gender. The research agenda outlined in this F31 proposal will utilize data from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative U.S. sample following adolescents to midlife. Aim 1 will model the associations between different types of childhood maltreatment, inflammation, and MDD symptoms in the U.S. using a multi-wave design. Aim 2 will explore how both sex and gender may affect the associations between childhood maltreatment, inflammation, and MDD symptoms. During the completion of these outlined aims the applicant will achieve three training goals. Training Goal 1 will focus on developing the applicant’s abilities in conducting longitudinal path modeling with large multi-wave data sets. Training Goal 2 will focus on developing the applicant’s ability to explore sex-differences as they pertain to MDD, childhood maltreatment, and inflammation, while also gaining experience with propensity score matching. Training Goal 3 will focus on professional development through readings, lab meetings, peer review trainings, and presenting at several academic venues.