Blood Test Could Predict Risk of Postpartum Depression

It leads to emotional struggles that can have long-lasting effects on both the mother and child. Symptoms include difficulty bonding with the baby, feelings of hopelessness, sadness, fatigue, loss of appetite, and trouble sleeping. Understanding the biological mechanisms behind PPD and identifying potential predictors could not only aid women suffering from this condition but may also help identify risk factors for other psychiatric disorders. Now, a new study has found that women who develop PPD may exhibit specific levels of neuroactive steroids, which are molecules derived from the hormone progesterone, during the third trimester of pregnancy. These steroids influence the brain’s stress response and emotional regulation. The study, published in the journal Neuropsychopharmacology, suggests that monitoring these levels could help identify women at risk of PPD before symptoms appear, enabling earlier intervention.

While many studies have looked at average neuroactive steroid levels and mood fluctuations over time, they haven’t led to clinical applications. To bridge this gap, researchers at Weill Cornell Medicine (New York, NY, USA) and the University of Virginia (Charlottesville, VA, USA) conducted a study involving 136 women who were not depressed during pregnancy. They measured neuroactive steroid levels in the women’s blood at specific time points during their second and third trimesters and followed up with clinical data up to nine months after delivery. Thirty-three of the participants developed postpartum depression. The study focused on progesterone and its metabolic pathways as possible contributors to PPD. Two neuroactive steroids derived from progesterone—pregnanolone and isoallopregnanolone—were found to affect the risk of developing PPD. Pregnanolone acts on the GABA-A receptor, producing calming effects and reducing stress, while isoallopregnanolone interacts with the same receptor to increase stress.

The study revealed that during the third trimester, women who developed PPD had a lower pregnanolone/progesterone ratio and a higher isoallopregnanolone/pregnanolone ratio compared to those who did not develop PPD. Additionally, higher progesterone levels late in pregnancy were linked to an increased risk of PPD, indicating a reduced metabolism of progesterone into its beneficial metabolites. Although the exact cause of PPD remains unclear, these findings suggest that an imbalance in progesterone metabolism may play a role. Women with an excess of progesterone or who metabolize it preferentially into isoallopregnanolone instead of positive metabolites were found to be four times more likely to develop PPD. This imbalance may be related to the activity of two enzymes, 3α-HSD and 3β-HSD, that convert progesterone into pregnanolone and isoallopregnanolone. Currently, treatments like brexanolone and zuranolone are available once PPD is diagnosed, but these findings could lead to preventive treatments for pregnant women whose blood tests show neuroactive steroid levels associated with a higher risk of PPD.

“Postpartum is the only time in people’s lifespans when we know there is a biological trigger which guarantees that a certain percentage of people will become ill,” said Dr. Lauren Osborne, associate professor of obstetrics and gynecology and of psychiatry at Weill Cornell Medicine, who co-led the study. “If we were able to replicate these results, then this could reasonably become a clinical test that could predict the development of future illness.”