UVA Researcher Discovers What Might Cause Postpartum Depression

A mother cradles a swaddled baby, surrounded by dark clouds and radiating lines

Postpartum depression affects as many as one in five new mothers. UVA research is unraveling the cause. (Illustration by Emily Faith Morgan, University Communications)

October 4, 2022

Newly discovered biological changes in mothers who suffer postpartum depression may help explain the condition, yield long-sought treatments and let doctors identify those at risk even before their babies are born.

The discovery suggests that some mothers’ bodies don’t do well in cleaning up old genetic material and other cellular debris, and that could trigger the debilitating condition. It also means medicine that assists in the cellular clean-up might help.

“The finding that cells aren’t cleaning out old proteins and cellular debris, called autophagy, occurs before women develop depression symptoms, indicating that it could be part of the disease process,” said Dr. Jennifer L. Payne, director of the Reproductive Psychiatry Research Program at the University of Virginia School of Medicine. “There are several medications that promote autophagy in cells, so this finding might open the door to new treatments and to identification of women at risk of postpartum depression before they become ill.”

Jennifer Payne poses for a portrait, smiling at the camera

UVA Researcher Jennifer L. Payne has zeroed in on a possible biological cause for postpartum depression. The discovery could make treatment better. (Contributed photo)

As many as one in five new mothers suffer postpartum depression, a condition that can affect a mother’s ability to think, sleep and eat. It can also cause anxiety and irritability, and may lead to suicide. Newborns whose mothers have postpartum depression can experience problems with cognitive, emotional and social development.

Payne and colleagues from John Hopkins Medicine and Weill Cornell Medicine wanted to determine if a recently discovered form of communication among cells, called “extracellular RNA communication,” might contribute to postpartum depression. This form of cellular communication is heightened during pregnancy and is critical in the implantation of the fertilized embryo and in the body’s inflammatory response afterward, among other roles.

The researchers analyzed blood plasma samples collected from 14 research participants during and after their pregnancies, including women who suffered postpartum depression and those who did not. The researchers found that extracellular RNA communication in immune cells was altered extensively in women who suffered postpartum depression. Further, they determined that this “large and consistent” change significantly limited the women’s bodies’ ability to perform important cellular cleanup – suggesting a potential biological cause for their depression.

“Deficits in autophagy are thought to cause toxicity that may lead to the changes in the brain and body associated with depression,” Payne said. “We have never fully understood the biological basis for postpartum depression, and this finding gets us closer to an understanding.”

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Now that this biological issue has been identified, researchers may be able to target it to develop treatments for postpartum depression. They also may be able to use the finding to develop a blood test that can identify those at risk, even before their babies are born. That could help doctors intervene earlier and make life easier and better for new moms.

“I hope very much this finding leads to better treatments for postpartum depression,” Payne said. “Our goal is to one day prevent (postpartum depression) in women at risk.”

The researchers published their findings in the scientific journal Nature Molecular Psychiatry. The team consisted of Lauren M. Osborne, Payne, Morgan L. Sherer and Sarven Sabunciyan.

Payne has served as a consultant for SAGE Therapeutics, Brii Biosciences and Pure Tech Health; has received a speaking honorarium from Karuna Therapeutics; and holds a patent titled “Epigenetic Biomarkers of Postpartum Depression.”

The work was supported by the National Institutes of Health’s National Institute of Mental Health, grants R01 MH112704 and 1K23 MH110607, and the NIH’s National Institute of Allergy and Infectious Diseases, grant T32 AI007417.

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Josh Barney

UVA Health