Are alterations in estradiol, cortisol, and inflammatory cytokines associated with depression during pregnancy and postpartum? An exploratory study

Background: Pregnant veterans are a subpopulation known to be at elevated risk of developing mental health symptoms, such as depression and suicidal ideation. Inflammation has been associated with depression, specifically during the perinatal period. Critical changes in estradiol, cortisol, and inflammatory cytokines are necessary for the progression of a healthy pregnancy, which are then rapidly altered in the postpartum period. We explored changes in estradiol, cortisol, and pro-inflammatory cytokines relative to depressive symptoms and suicidal thoughts across pregnancy and postpartum in this pilot and feasibility study. Methods: We measured estradiol, cortisol, and the inflammatory cytokines IL-1β, IL-6, IL-8, IFN-γ, and TNF-α in 18 pregnant veterans and analyzed the data using descriptive statistics, dependent t-tests, and correlation analyses. We assessed depression severity with the Edinburgh Postnatal Depression Scale and suicidality with the Columbia-Suicide Severity Rating Scale. Thirteen of the women repeated assessments in the early postpartum period at an average of 6.7 weeks after birth. Results: As anticipated, estradiol (t(12) ​= ​12.47, p ​< ​.001) and cortisol (t(12) ​= ​9.43, p ​< ​.001) significantly decreased from pregnancy to postpartum. There were no differences in the means of gestational and postpartum IL-1β, IL-6, TNF-α, or IFN-γ, but IL-8 was significantly increased from pregnancy to postpartum (t(12) ​= ​−4.60, p ​= ​.001). Estradiol during pregnancy was positively correlated with IL-6 levels both during pregnancy (rp ​= ​.656, p ​= ​.008) and postpartum (r ​= ​0.648, p ​= ​.023). Elevated IL-1β was associated with suicidal thoughts during pregnancy (r ​= ​0.529, p ​= ​.029). Although not statistically significant, depressive symptom severity trended towards a positive association with larger increases in IL-1β (r ​= ​0.535, p ​= ​.09) and TNF-α (r ​= ​0.501, p ​= ​.08) from pregnancy to postpartum. Conclusion: This preliminary study suggests the feasibility of our approach for exploring a complex interplay between hormonal and pro-inflammatory changes from pregnancy to postpartum, and their relationship with depressive symptoms. Given our small sample and the relatively exploratory nature of our analyses, additional investigation focusing on hormonal and inflammatory changes and their potential associations with perinatal mental health is necessary to confirm and extend our preliminary findings and examine additional potential covariates