A possible predictor for PPD identified in new research

Affecting as many as 1 in 8 mothers in the U.S., postpartum depression (PPD) is a highly common condition in early motherhood. While certain factors such as history of mental illness and having pregnancy or birth complications may contribute to the development of the condition, a recent study published in the journal “Molecular Psychiatry” reports on the discovery of a potential postpartum depression predictor. 

The study authors suggest that in people with PPD, the cells’ ability to clear out cellular waste is impaired. The accumulated debris makes it difficult for cells to operate normally, causing more damage and potentially cell death. A buildup of toxins from damaged or dead cells may alter how the brain is wired. Having a biological explanation for why PPD occurs may pave the way to better treatments for PPD in the near future.

Related: When I tell you I have postpartum depression, here’s what I want you to know

The stigma around mental illness in motherhood can breed feelings of guilt and shame, making many women suffer in silence. As many as 50% of PPD cases go undiagnosed—and untreated. What’s more, the pandemic worsened the mental health of millions, and rates of PPD skyrocketed since 2020.

Despite the high incidence, there are few postpartum depression treatments. One reason is because researchers weren’t too sure what triggered it—until now. And it all started when scientists eavesdropped on a conversation between cells.

Communication between cells changes during pregnancy

Earlier this century, scientists discovered a new way cells talk to each other called extracellular RNA communication. Cells package genetic messages into sacs of fluids that serve as mail carriers. The sacs, known as vesicles, are transported to other cells all over the body. Once delivered, the RNA cargo contain a wealth of information for the recipient that can influence their cellular function.

While biologists haven’t pinned down the specifics of this complex system, they have found that extracellular RNA communication is necessary for a successful pregnancy. A February 2020 study published in the International Journal of Molecular Sciences found the vesicles carry a wealth of resources—proteins, lipids and mRNA—that help the mother’s uterus recognize the pregnancy and start the process for early embryo development. Extracellular RNA communication also regulates the body’s immune response during pregnancy, directing when to release more or less inflammation.

How cellular cleanup affects PPD

The authors sought to find whether disruptions in extracellular RNA communication are associated with PPD. They collected blood plasma samples from 14 women at six different points in their pregnancy, starting in their second trimester and up to 6 months after giving birth. They clinically diagnosed seven of the women with PPD using the Edinburgh Postnatal Depression Scale. The other seven did not have it, and served as the control group for the study.

Related: You’re not alone: Postpartum depression is common and can last longer than a year, says study

After analyzing the blood samples, the researchers found that women who developed PPD had extensive changes in their extracellular mRNA levels during pregnancy. The team then took a closer look to see what information may have not been relayed and found that the most ‘undelivered’ messages had to do with autophagy function. Autophagy is essentially the janitorial duties of the cell. It involves cleaning up or recycling any debris or junk parts cells have lying around they don’t need anymore. It’s also an important mechanism for sweeping out any damaged cells.

“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 Jennifer L. Payne, MD, the director of the reproductive psychiatry research program at the University of Virginia School of Medicine and coauthor of the study, in a press release. 

Problems with a lack of cell clean-up during pregnancy may cause a buildup of debris and damaged cell parts that affect how a cell operates. 

Research shows that reduced or impaired autophagy function is associated with several neuropsychiatric diseases, including depression. “Deficits in autophagy are thought to cause toxicity that may lead to the changes in the brain and body associated with depression,” adds Payne. “We have never fully understood the biological basis for postpartum depression, and this finding gets us closer to an understanding.”

Related: Spotting postpartum depression can be difficult. Here’s why you should enlist your partner’s help

Study inspires new treatments for postpartum depression 

Though the study is small, the findings provide a key contributor to one of the biological causes of PPD, albeit not the sole cause. Developing PPD is affected by social and psychological factors too, such as a lack of social support, prior history of mood disorders, pregnancy/birth trauma, a stressful life event, among others. However, identifying a biological marker for PPD opens up more clinical treatment options. 

For example, antidepressants are a commonly prescribed medication for PPD, and the study suggests antidepressants that stimulate autophagy function may be more effective. What’s more, blood tests could act as good screeners to identify pregnant people most at risk for developing PPD. This would help new parents take early action to protect their mental health, and allow doctors to intervene sooner with antidepressants long before the baby is born. “Our goal is to one day prevent [postpartum depression] in women at risk,” concludes Payne.

Sources

Bridi A, Perecin F, Silveira JC. Extracellular vesicles mediated early embryo–maternal interactions. International Journal of Molecular Sciences. 2020 Feb 10;21(3):1163. doi:10.3390/ijms21031163

Osborne L, Payne J, Sherer M & Sabunciyan S. Altered extracellular mRNA communication in postpartum depression is associated with decreased autophagy. Molecular Psychiatry. 2022. doi:10.1038/s41380-022-01794-2Tang M, Liu T, Jiang P, Dang R. The interaction between autophagy and neuroinflammation in major depressive disorder: from pathophysiology to therapeutic implications. Pharmacological Research. 2021 Jun 1;168:105586.