Impaired cell-cleanup is a predictor of postpartum depression

Autophagy, the process by which the body recycles damaged cell parts into fully functioning cell parts, may be dampened in women with postpartum depression, according to a recent Cornell Weill study done in collaboration with John Hopkins University School of Medicine and the University of Virginia Health.

Old cell components such as mitochondria and ribosomes often function inefficiently, and may end up developing defects that require removal while new parts are made.

“This same process has been implicated in things like Alzheimer’s disease and neurodegenerative disorders. Plaques form, and the process of autophagy is unable to get rid of the misfolded proteins,” said Sarven Sabunciyan, assistant professor at Johns Hopkins University.

Up to 70 percent of new mothers face the “baby blues,” a temporary condition experienced one to two weeks after childbirth. If symptoms of true postpartum depression arise toward the end of pregnancy or within four weeks after giving birth, the condition is normally diagnosed and treated with a combination of psychotherapy or antidepressants.

“Hormonal shifts happen at childbirth, but only some women are vulnerable to those shifts,” said Dr. Lauren Osborne, Vice Chair of clinical research for Obstetrics and Gynecology at Weill Cornell.

These hormonal shifts are due to change in relationship with a partner in becoming a mother along with enormous sleep deprivation.

One in eight women experience postpartum depression. Osborne’s research in the field focuses on determining the biological link in the hormonal system that makes certain women vulnerable to these hormonal changes that all women experience.

“Our theory is that not being able to use this essentially cellular recycling system made women somehow more vulnerable to developing postpartum depression, connected with hormonal shifts or other immune system changes throughout pregnancy and postpartum,” Osborne said.

Her previous research found that extracellular RNA communication is heavily involved in several biological processes, pregnancy included. The study looked at extracellular vesicles in the blood and how the mRNA communication differs between women who do and do not become ill postpartum.

Extracellular vesicles are lipid-bound vesicles in the membrane that are released to transport “cargo” such as DNA and RNA. This is a form of communication within the cell, and it is increased during pregnancy. According to the study, mRNA associated with autophagy were reduced in patients with postpartum depression, establishing a connection between the lack of “cell cleanup” and postpartum depression.

Prior research also identifies that antidepressants play a role in increasing autophagy. However, many women with pre-existing depression will unnecessarily stop taking their medication while pregnant, creating a large group of people who are significantly vulnerable to a relapse of symptoms such as depressed mood or fatigue. There is about a 65 to 75 percent chance these women will relapse during pregnancy, according to Osborne.

“So many women are reluctant about taking medication during pregnancy and postpartum, and because lots of doctors aren’t educated on the safety of those medications, we have a really vulnerable group of women who don’t get identified and treated,” she said.

Osborne’s research is working to identify these women to provide doctors with a test to diagnose vulnerability to postpartum depression in its early stages. Her team is looking to develop a test that can be easily implemented in the clinic such as a blood test that can identify the vulnerable group of women at risk of becoming ill. This will allow physicians to get sick patients access to care early.

“We have some very good results… [but] we want to look at more people, a diverse group of women from different ethnicities and races,” Sabunciyan said. “It’s not going to be in the next week, but we’re hoping, within a decade or so, we’re going to be having a test available.”

SourceWeill Cornell Medicine

Osborne LM, Payne JL, Sherer ML, Sabunciyan S. (2022) Altered extracellular mRNA communication in postpartum depression is associated with decreased autophagy. Mol Psychiatry [Epub ahead of print]. [abstract]

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