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

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 hormoneand 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, proand 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 beta 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.

Automated summary

The study indicates that higher levels of sex hormones in the post-partum period are associated with greater severity of depressive symptoms during pregnancy. Estrogen is correlated with pro-inflammatory characteristics and neurotoxic kynurenine metabolites, while progesterone is linked to anti-inflammatory features in the post-partum period.