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

J Affect Disord. 2021 Feb 15:281:9-12. doi: 10.1016/j.jad.2020.10.052. Epub 2020 Oct 29.

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-1β 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.

Keywords: Cytokine; Depression; Estrogen; Kynurenine; Post-partum; Progesterone.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Depression, Postpartum*
  • Estrogens
  • Female
  • Humans
  • Inflammation
  • Kynurenine*
  • Postpartum Period
  • Pregnancy
  • Progesterone
  • Retrospective Studies

Substances

  • Estrogens
  • Kynurenine
  • Progesterone