Associations between prenatal inflammation and dimensions of depressive symptoms across the perinatal period

The perinatal period is characterized by physiological changes, including fluctuations in inflammation, and an increased risk for depression. However, the timing and cytokine-specific relations to depressive symptoms during and after pregnancy are unclear. In this study, we examined the relationships between four cytokines (IL-6, IL-8, IL-10, and TNF-α) and depression at multiple time points throughout the perinatal period and investigated the role of different dimensions of depressive symptoms in these associations.

We used longitudinal data from 314 mothers (M_age = 29.25, M_INR = 2.78, 56.6 % Black/African American) in the Early Life Adversity and Biological Embedding Study from the first trimester of pregnancy to the early postnatal period. Multiple linear regressions examined the relationships between cytokines and maternal depressive symptoms. Specifically, we investigated these relationships throughout pregnancy, using cytokine slopes, third-trimester levels, and changes late in pregnancy, from the second to third trimester. Then, we investigated whether cytokines levels predicted depressive symptoms at future time points, including postnatally. Analyses with the same model structure, looking at different symptom dimensions, were adjusted using multiple comparison procedures (Bonferroni).

Cytokine levels were not associated with total depression scores at any time point. IL-6 levels and anhedonia symptoms were positively associated in the third trimester (β = 0.13, p = 0.01, q = 0.04). More positive IL-6 and TNF-α slopes across pregnancy, indicating increasing levels of TNF-α over time, were associated with greater average prenatal anhedonia symptoms (β = 0.91, p = 0.01, q = 0.04 and β = 0.92, p = 0.01, q = 0.03, respectively). Increases in IL-6 from the second to third trimester predicted less postnatal anxiety (β = -0.15, p = 0.01, q = 0.02), whereas increases in TNF-α from the second to third trimester predicted greater third-trimester anxiety and sad mood (β = 0.08, p = 0.03, q = 0.05, β = 0.09, p = 0.01, q = 0.03). None of the depressive symptoms were associated with IL-8 or IL-10 at any time point (ps = 0.05-0.96).

Findings provide additional evidence for the role of IL-6 and TNF-α in perinatal depressive symptoms. Anhedonia symptoms and third-trimester inflammation may be particularly important. Future work focusing on dimensions of depressive symptoms and inflammatory processes across the perinatal period is key to elucidating specific temporal associations. Further investigation of how changes in inflammation across pregnancy relate to specific types of depressive symptoms could inform and improve perinatal care and intervention.