These molecules influence the brain’s stress response and emotional regulation.

The findings, published Jan. 30 in Neuropsychopharmacology, suggest that this may provide a way to identify women at risk of PPD before symptoms start, allowing doctors to intervene earlier. Postpartum depression, severe depression that happens after giving birth, affects 10%-15% of new mothers, causing emotional struggles that can impact both the parent and child for years. Symptoms include difficulty bonding with the baby, feelings of hopelessness and sadness, fatigue, loss of appetite and difficulty sleeping, to name a few.

“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, M.D. ’09, associate professor of obstetrics and gynecology and of psychiatry at Weill Cornell Medicine, who co-led the study. “If we can untangle this biology and find predictors for it, not only will we be helping women, but it may give us a step up in trying to find predictors for other psychiatric illnesses also.”

Co-lead on this research, Dr. Jennifer Payne, professor and vice chair of research in psychiatry and neurobehavioral sciences at the University of Virginia School of Medicine and UVA Health, has also spent years searching for the biological basis that leads to major clinical depression.

“Studying postpartum depression gives us a way to identify biological changes that occur before someone becomes depressed because the timing of postpartum depression is predictable,” she said.

“Many papers have compared averages of neuroactive steroid levels with averages of mood across time, which just tells us there is some biological correlation but doesn’t help us clinically,” Osborne said.

To address this gap, the researchers restricted their study to 136 women who were not depressed during pregnancy and measured neuroactive steroid levels in their blood samples at specific timepoints during the second and third trimesters. They also followed up with clinical data for up to nine months after birth. Thirty-three participants developed symptoms of depression in the postpartum period.

“While depression can manifest at different times throughout and after pregnancy, that early-on, four-to-six-weeks onset is a biologically distinct entity,” Osborne said.

The study focused on the hormone progesterone and its metabolic pathway as potential suspects in postpartum depression. Two neuroactive steroids derived from progesterone that seem to affect the risk of developing PPD are pregnanolone and isoallopregnanolone. Pregnanolone acts on the GABA-A receptor to provide calming effects and decrease stress. Conversely, isoallopregnanolone interacts with the GABA-A receptor to increase stress.

The study determined that in the third trimester, individuals who developed PPD had a lower pregnanolone/progesterone ratio and a higher isoallopregnanolone/pregnanolone ratio compared with those who did not. Elevated progesterone levels in late pregnancy were also associated with a higher risk of PPD, pointing to decreased metabolism of progesterone into its beneficial downstream products.

Source: https://news.cornell.edu/stories/2025/02/hormone-levels-may-predict-risk-postpartum-depression