Air pollution exposure and emerging depression risk: Testing the role of peripheral inflammatory cytokines during adolescence

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Project Summary Depression is a prevalent, recurrent, and frequently chronic disorder that affects approximately 21% of individuals in their lifetime and is associated with significant impairment and considerable public health burden. To elucidate factors that contribute to the onset and development of depressive symptoms, the current project seeks to test the role of alterations in peripheral cytokines as a biological mediator of associations between air pollution exposure and depressive symptoms in adolescents. Specifically, the current project will utilize a prospective longitudinal study of 120 adolescents to examine associations between air pollution exposure and subsequent trajectories of depressive symptoms and immune markers. Through the direct assessment of theorized biological mediators, use of repeated assessments, and creation of sophisticated air pollution exposure estimates, we will overcome past roadblocks to progress and rigorously test a putative mediator of risk. Leveraging stored blood samples collected as part of an ongoing parent study of social contributors to depression during adolescence, this work will characterize air pollution exposure for study participants across multiple timescales (Aim 1), which will then be utilized to determine dose-response associations between air pollution and trajectories of depressive symptoms across a 6-month period (Aim 2). Lastly, it will probe peripheral immune markers as putative mediations between air pollution and depressive symptoms, testing competing models of cytokines (e.g., proinflammatory, Th-1, and Th-2) to determine the specificity of the immune markers in relation to risk. Through this methodologically rigorous approach, we will be poised to conduct strong tests of directional associations between air pollution exposure and depressive symptoms and to identify immunological parameters that may mediate risk. In doing so, insights from this project will critically inform future hypotheses to elucidate biological and psychological cascades that contribute to the adverse effects of air pollution exposure on mental health to identify novel targets for intervention efforts and ultimately reduce the significant burdens associated with depression.