Could a Blood Test Help Predict the Risk of Postpartum Depression?

Women who develop postpartum depression (PPD) after giving birth may have characteristic levels of neuroactive steroids, molecules derived from the hormone progesterone, in their blood during the third trimester of pregnancy, according to a new study by researchers at Weill Cornell Medicine and the University of Virginia. These molecules affect the brain’s stress response and emotional regulation. The findings, recently published in Neuropsychopharmacology, suggest that this could provide a way to identify women at risk for PPD before symptoms arise, allowing doctors to intervene earlier.

Postpartum Depression Severely Impacts Quality of Life

Postpartum depression, a severe depression that occurs after childbirth, affects 10-15% of new mothers and causes emotional problems that can affect both the parent and the child for years. Symptoms include difficulty bonding with the baby, feelings of hopelessness and sadness, fatigue, loss of appetite and sleep disturbances, to name a few. “Postpartum is the only time in a person’s life that we know of that has a biological trigger that ensures a certain percentage of people will get sick,” said Dr. Lauren Osborne, associate professor of obstetrics and gynecology and of psychiatry at Weill Cornell Medicine, who co-led the study. “If we can unravel this biology and find predictors for it, we will not only help women, but we may also find predictors for other psychiatric illnesses.”

Co-leader of this research, Dr. Jennifer Payne, professor and associate research director of psychiatry and neurobehavioral sciences at the University of Virginia, has also spent years searching for the biological underpinnings that lead to major clinical depression. “Studying postpartum depression gives us the opportunity to identify biological changes that occur before someone gets depressed, because postpartum depression is a predictable time point,” she added.

The Role of Progesterone in Disease Development

Many studies have compared average neuroactive steroid levels with average mood levels over time, but this does not help researchers clinically. To address this gap, they limited their study to 136 women who were not depressed during pregnancy and measured neuroactive steroid levels in their blood samples at specific times during the second and third trimesters. They also followed up on clinical data for up to nine months postpartum. 33 participants developed symptoms of depression in the postpartum period. While depression can manifest at various times during and after pregnancy, this early onset, which begins 4–6 weeks postpartum, is a biologically distinct entity.

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

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

Towards Preventive Treatment

Although it is not clear why some women develop such depression, these results suggest that there may be an imbalance in the metabolism of progesterone. If this resulted in either too much progesterone or a preferential conversion to isoallopregnanolone instead of positive metabolites, these women were four times more likely to develop PPD. This could be related to the relative activity of two enzymes (3α-HSD and 3β-HSD) that help convert progesterone into pregnanolone and isoallopregnanolone.

The study results pave the way for a potential preventive treatment for pregnant women whose blood tests show neuroactive steroid levels associated with an increased risk of postpartum depression. The researchers plan to verify their findings in a larger, more diverse group of patients. In addition, Dr. Osborne, Dr. Payne and their teams will determine what happens in the progesterone pathway prior to the development of postpartum depression by directly measuring the levels of the two enzymes that convert progesterone to its metabolites.

Postpartum Basics

Postpartum Depression