Inflammatory trajectories across pregnancy: Investigating novel markers of risk for postpartum depression

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Project Summary Postpartum depression (PPD) is the most common form of psychiatric illness occurring after childbirth, affecting nearly 18% of women globally and contributing to suffering and impaired functioning in both mothers and their children. To elucidate factors that contribute to PPD risk, the current project seeks to test the role of inflammatory markers across pregnancy in the prediction of postpartum depressive symptoms. Specifically, reflecting recent theoretical work on the complex and shifting role of the immune system during pregnancy, the current project will utilize a prospective longitudinal design of 165 pregnant women to examine dynamic trajectories of inflammatory markers across pregnancy in the prediction of PPD symptoms and diagnosis at one- and two- months postpartum. Through repeated assessments across the prenatal and postpartum periods, by considering potentially curvilinear trajectories of inflammatory markers instead of single assessments, and by examining a range of immunological markers simultaneously, we will overcome past roadblocks to progress and more closely mirror the alternating immunological priorities of pregnancy. Leveraging stored plasma samples collected prior to the COVID-19 pandemic as part of a parent R01 study of depressive symptoms during pregnancy (MH109662), this work will characterize trajectories of key depression-relevant inflammatory markers across each trimester of pregnancy in women with and without elevated prenatal depressive symptoms (Aim 1) and examine whether inflammatory trajectories prospectively predict depressive symptoms and PPD diagnosis at one- and two-months postpartum (Aim 2). As well, it will probe the predictive specificity of depression-relevant inflammatory markers (versus shifts in Th1 and Th2 cytokines or inflammatory markers implicated in other psychiatric disorders) and will explore whether inflammatory profiles in pregnancy differentially relate to certain PPD symptoms (Aim 3). Through this methodologically rigorous approach, we will be poised to conduct strong tests of directional associations between prenatal inflammation and postpartum depressive symptoms and to identify inflammatory parameters that may serve as risk biomarkers. In doing so, insights from this project will be critical for advancing future hypotheses to elucidate the precise neurobiological cascades that account for links between inflammation and postpartum depressive symptoms, with the ultimate goal to identify novel factors to target in the prevention or treatment of postpartum depression.