Study links neuroactive steroids to postpartum depression risk

Study links neuroactive steroids to postpartum depression risk | Image Credit: © Pixel-Shot - © Pixel-Shot - stock.adobe.com.

During the third trimester of pregnancy, women may present with characteristic levels of neuroactive steroids indicating an increased risk of postpartum depression (PPD), according to a recent study published in Neuropsychopharmacology.¹

Neuroactive steroids are molecules derived from progesterone that influence stress response and emotional regulation in the brain. The findings indicate that by identifying these molecules, doctors can assess PPD risk in pregnant patients before symptoms begin and provide earlier intervention.

“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 Lauren Osborne, MD, associate professor of obstetrics and gynecology and psychiatry at Weill Cornell Medicine.

“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,” added Osborne.

Ten percent to 15% of new mothers experience PPD, leading to symptoms such as difficulty bonding with the baby, feeling hopeless and sad, loss of appetite, trouble sleeping, and fatigue. These symptoms may cause emotional struggles that impact mothers and their children for years after birth.

The study was conducted to determine the link between neuroactive steroid levels during pregnancy and PPD risk. Women without depression during pregnancy were selected for participation, with neuroactive steroid levels in blood samples being measured during the second and third trimester.

Follow-up lasted for up to 9 months following delivery. During this period, depression symptoms were reported in 33 of 136 participants. Pregnanolone and isoallopregnanolone were identified as neuroactive steroids derived from progesterone that impacted PPD risk.

A lower pregnanolone/progesterone ratio and a higher isoallopregnanolone/pregnanolone ratio was reported in PPD patients during the third trimester vs non-PPD patients. The risk of PPD was also increased in patients with higher levels of progesterone during late pregnancy.

These results indicated an imbalance in the metabolism of progesterone. Investigators hypothesized a relation to the relative activity of the 3α-HSD and 3β-HSD enzymes responsible for conversion of progesterone into pregnanolone and isoallopregnanolone.

Brexanolone and zuranolone are 2 new treatment doctors can prescribe to their patients diagnosed with PPD. According to investigators, the study’s findings highlight an opportunity for preventive treatment in pregnant women with blood tests indicating neuroactive steroid levels linked to increased PPD risk.

“We don’t know if these drugs would work as a preventive measure for people who are at risk of developing postpartum depression, but based on our findings, they have the potential to prevent the development of postpartum depression,” said Osborne.

The team plans to conduct additional research in a larger and more diverse population. Additionally, Osborne plans to research the processes that occur in the progesterone metabolic pathway before PPD incidence.

Additional methods are also being investigated for predicting PPD risk, including the evaluation of electronic health records (EHRs).² A diagnostic study was conducted in 2024 to assess the efficacy of prognostic models for PPD with psychometric screening as the target variable.

The primary model displayed an area under the receiver operating curve ranging from 0.610 to 0.635, compared to prior models ranging from 0.602 to 0.635. This highlighted modest performance from the model, providing additional options to predict PPD in pregnant individuals.

Reference

1. Findings may lead to blood test to predict risk of postpartum depression. Weill Cornell Medicine. January 30, 2025. Accessed February 19, 2025. https://www.eurekalert.org/news-releases/1071826
2. Krewson C. EHR-based models show promise in predicting postpartum depression. Contemporary OB/GYN. December 24, 2024. Accessed February 19, 2025. https://www.contemporaryobgyn.net/view/ehr-based-models-show-promise-in-predicting-postpartum-depression