The study identifies a potential biological marker for diagnosing postpartum depression

The study identifies a potential biological marker for diagnosing postpartum depression

A federally funded study led by researchers at Johns Hopkins Medicine has found that communication between cells is altered in pregnant women who develop postpartum depression (PPD) after giving birth.

Changes in extracellular RNA communication, a recently discovered cell signaling method, have already been linked to preterm birth, gestational diabetes, toxic maternal hypertension, and other pregnancy-related events. The leaders of the new study examined maternal blood and wanted to find out whether there were significant changes in this extracellular communication system during PPD. The changes in extracellular RNA communication identified in the study suggest that women who develop PPD are unable to efficiently remove aging and defective cellular components. This process, called autophagy, is also known to be defective in the brains of patients with Alzheimer's and Parkinson's diseases.

Possibly postpartum depression could be treated with certain Alzheimer's and Parkinson's disease medications that trigger autophagy.

Sarven Sabunciyan, Ph.D., assistant professor of pediatrics at Johns Hopkins University School of Medicine and senior author of paper

The results of the study were published September 22 in Molecular Psychiatry.

One in nine new mothers suffers from postpartum depression, a condition characterized by periods of sadness, loneliness and inability to care for their newborn that lasts longer than two weeks. “With postpartum depression, there are many possible negative consequences, such as a high rate of maternal suicide or impaired cognitive, emotional and social development of the baby,” says Sabunciyan. “If we could identify mothers who may be at higher risk before birth, we could prevent these adverse events.”

Attempts have been made to identify genetic or other biological markers for PPD for decades.

In the new study, the research team specifically looked at the levels of messenger RNA (mRNA) in extracellular vesicles (EVs) – fatty sacs of genetic material that are essential for communication between cells. During pregnancy, Sabunciyan says, this communication system is intensified to meet the need for embryo implantation and growth. A mother's placenta also releases RNA, which is important for the development of the immune system and protects the growing fetus from viruses.

Sabunciyan, a neuroscientist at Johns Hopkins Children's Center whose work focuses on the root causes of psychiatric disorders, says the research team collected blood samples from 42 pregnant women being examined at Johns Hopkins Hospital.

Newly developed sequencing and computational analysis methods were used to measure the levels of thousands of different mRNAs packaged in EVs in the blood of 14 participants during the second and third trimesters of pregnancy and up to six months after birth. Seven of the participants were diagnosed with postnatal depression after birth and scored 13 or higher on the Edinburgh Postnatal Depression Scale (a standard tool for identifying women with the condition). None of these women had any signs of depression during pregnancy. The mRNA levels that were found to change most in participants with PPD using this analysis were then measured in the blood of an additional 28 women during pregnancy. Fourteen of these women were diagnosed with PPD and five of them showed signs of depression during pregnancy. The changes in mRNA levels found in those who developed PPD in the first group of 14 participants replicated in the second group of 28 women, confirming the validity of the sequencing results. Of the 42 women in the study, 34 were white, four were Asian or Pacific Islander, two were black and two were of another race. All were in their late 20s or early 30s and had live births.

The research team says this analysis found that extracellular RNA communication levels were "significantly altered" during pregnancy and the postpartum period in women who developed postpartum depression. The researchers found that the levels of 2,449 mRNAs changed (1,010 increased and 1,439 decreased) between those who later developed PPD and those who did not. On average, there was an almost two-fold difference in individual mRNA levels between the two groups. The vast majority of these changes occurred during pregnancy and not in the postpartum period.

The researchers also found that EV mRNA levels linked to autophagy were reduced in women who later developed PPD - meaning the cells did not remove excess, damaged or defective parts. In addition, they found that EV mRNAs associated with PPD come from white blood cells known as monocytes and macrophages.

The researchers note that their study was limited due to small numbers and lack of racial diversity. But they say if further studies confirm the results, they may be able to develop a blood test that can identify pregnant women who are at risk of developing PPD after delivery. The research could also advance the development of treatments for PPD.

“If we can identify those at risk early and treat them appropriately, we can probably prevent many serious effects of postpartum depression,” says Sabunciyan.

In addition to Sabunciyan, authors include Morgan Sherer of Johns Hopkins, Jennifer Payne of the University of Virginia and Lauren Osborne, formerly of Johns Hopkins and now at Weill Cornell Medicine.

Source:

Johns Hopkins Medicine

Reference:

Osborne, L.M., et al. (2022) Altered extracellular mRNA communication in postpartum depression is associated with reduced autophagy. Molecular Psychiatry. doi.org/10.1038/s41380-022-01794-2.

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