Cellular communication indicates risk of postpartum depression

A team led by Johns Hopkins Medicine researchers has found that communication among cells is altered in pregnant women who go on to develop postpartum depression (PPD) after giving birth. The findings of their study have been published in the journal Molecular Psychiatry.

One in nine new mothers has PPD, a condition marked by periods of sadness, loneliness and inability to care for their newborns that last longer than two weeks. Efforts have been underway for decades to identify genetic or other biological markers for PPD, so that doctors can identify mothers who may be more at risk and work to prevent these adverse events.

The research team investigated the messenger RNA (mRNA) content of extracellular vesicles (EVs) — fatty sacs of genetic material that are essential to communication among cells. During pregnancy, this communication system ramps up to address needs for embryo implantation and growth; a mother’s placenta also releases RNA vital for immune system development that protects the growing foetus from viruses. Changes in extracellular RNA communication have already been linked to premature births, gestational diabetes, toxic maternal high blood pressure and other pregnancy-related events. Leaders of the new study examined blood samples from 42 pregnant women and sought to determine if there were distinct changes in the extracellular communications system during PPD.

Newly developed sequencing and computational analysis methods were used to measure the level of thousands of different mRNAs that are packaged into EVs in the blood of 14 participants during the second and third trimester of pregnancy and up to six months after giving birth. Seven of the participants were diagnosed with postpartum depression after childbirth, receiving a score of 13 or above on the Edinburgh Postnatal Depression Scale. None of these women had signs of depression during pregnancy. The mRNA levels identified to change the most robustly in participants who had PPD using this analysis were then measured in the blood of an additional 28 women during pregnancy. 14 of these women were diagnosed with PPD and five of them exhibited signs of depression during pregnancy. The changes in mRNA levels identified in those who developed PPD in the first set of 14 participants were replicated in the second group of 28 women, confirming the validity of the sequencing findings.

The researchers said this analysis revealed that extracellular RNA communication levels during pregnancy and the postpartum period were extensively altered in women who developed PPD. The researchers found that the level of 2449 mRNAs changed (1010 increased and 1439 decreased) between those who went on to develop PPD compared with those who did not. On average, there was nearly a twofold difference in individual mRNA levels between the two groups. The vast majority of these changes occurred during the pregnancy instead of the postpartum period.

The researchers also discovered that EV mRNA levels associated with autophagy were decreased in women who later developed PPD, meaning the cells were not cleaning out excessive, damaged or defective parts; this process is also known to malfunction in the brain of patients with Alzheimer’s and Parkinson’s disease. In addition, they found that EV mRNAs associated with PPD originated from white blood cells known as monocytes and macrophages.

The researchers cautioned that their study was limited by small numbers and a lack of racial diversity. If further studies confirm the findings, they could potentially develop a blood test that can identify women who are pregnant who are at risk for developing PPD after delivery. The research may also advance development of therapies for PPD, with the potential for the condition to be treated using Alzheimer’s and Parkinson’s disease medications that induce autophagy.

Image credit: iStock.com/globalmoments

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