Pro-inflammatory factors and neuroactive tryptophan metabolites in an expecting mother may influence symptoms of peripartum depression according to a study published in Translational Psychiatry.

To learn more about the biological underpinnings of peripartum depression, researchers looked at the kynurenine pathway, an enzymatic pathway highly expressed in placenta. Increased pathway activity may affect serotonin levels. To learn more, the researchers enrolled 113 women in their first trimester and evaluated them in each trimester to follow via psychiatric assessments and blood samples.

The researchers found higher levels of the inflammatory cytokine IL-6 biomarker were associated with increased depression severity throughout pregnancy. In addition, as cytokine IL-1β increased, depression symptoms worsened. Overall, IL-6, rKT (kynurenine/tryptophan), QUIN (quinolinic acid), and KYN (kynurenine) measured in the second trimester have strong evidence (>95% chance) of being positively associated with both depression severity and risk for significant depressive symptoms (EPDS (Edinburgh Postnatal Depression Rating Scale) ≥ 13) in the third trimester, the researchers reported. Also, TNF (tumor necrosis factor) and rQK (quinolinic acid/kynaurenic acid) in the second trimester were strongly associated with depression severity in the third trimester.

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The various immune function fluctuations and fluctuation in inflammatory factors are important for fetal development, the researchers state, but they also affect mood. Extreme fluctuations or fluctuations in women vulnerable to depression trigger the depression.

The study was conducted at 1 health center, however, which could reduce generalizability. They also analyzed a small number of samples — 350 total samples among 4 time points. 

Randomized controlled studies would help confirm or deny the researchers’ findings and may point to treating inflammation to control peripartum depression. Future researchers must take caution, they add, “due to the involvement of these factors in fetal development,” they state.

“Importantly, our study showed that a set of biomarkers was able to predict the future development of depression during pregnancy, and steps could be taken to move these markers into clinical risk assessments.”


Sha Q, Madaj Z, Keaton S, et al. Cytokines and tryptophan metabolites can predict depressive symptoms in pregnancy. Transl Psychiatry. 2022 Jan 26;12(1):35. doi:10.1038/s41398-022-01801-8

This article originally appeared on Psychiatry Advisor