Associations between estrogen and progesterone, the kynurenine pathway, and inflammation in the post-partum

Abstract Background: Depression during and after pregnancy is common, affecting at least 15% of women. Features of depression in pregnancy range from mild symptoms of disrupted mood and interest to severe depression and suicidal behavior. Previous studies suggest hormone- and immune dysregulations might contribute to post-partum depression, but consistent evidence is lacking. Methods: A total of 163 women were included in the study in the post-partum. Peri-partum depression (PPD) was diagnosed using SCID interviews and depressive symptoms were quantified using the Edinburgh Perinatal Depression Rating Scale (EPDS), retrospectively long-term, as well as acutely. Plasma estrogen, progesterone, pro- and anti-inflammatory cytokines and kynurenine metabolites were measured in the post-partum. Results: Higher estrogen and progesterone in the post-partum were linked to more severe depressive symptoms over pregnancy. In the post-partum, estrogen was positively correlated with the pro-inflammatory cytokine IL-6 and negatively correlated with kynurenine and picolinic acid. Conversely, progesterone was negatively correlated with IL-1 β , and several metabolites in the kynurenine pathway, including quinolinic acid. Limitations: Associative study design, did not attempt to assess causality. Did not adjust hormone levels for medication effects. Conclusions: Our study suggests that higher sex hormones in the post-partum are linked to depression severity over pregnancy. Estrogen was coupled with a pro-inflammatory profile and neurotoxic kynurenine metabolites, whereas progesterone was linked to an anti-inflammatory profile in the post-partum.