A federally funded study by researchers at Johns Hopkins Medicine found that communication between cells is impaired in pregnant women who develop postpartum depression (PPD) after childbirth.
Changes in extracellular RNA communication, a recently discovered cell signaling method, have previously been linked to preterm birth, gestational diabetes, toxic maternal hypertension, and other pregnancy-related events. pregnancy. The new study examined maternal blood and sought to determine if there were any distinct changes in this extracellular communication system during PPD. The extracellular RNA communication changes identified in the study suggest that women who develop PPD are unable to effectively eliminate aging and defective cellular components. This process, called autophagy, is also known to malfunction in the brains of patients with Alzheimer’s and Parkinson’s disease.
Potentially, postpartum depression could be treated with certain Alzheimer’s disease and Parkinson’s disease drugs that induce autophagy. »
Sarven Sabunciyan, Ph.D., assistant professor of pediatrics at Johns Hopkins University School of Medicine and senior author of the article.
The results of the study were published on September 22 in the journal Molecular Psychiatry.
One in nine new mothers suffer from postpartum depression, a condition marked by periods of sadness, loneliness and inability to care for their newborn that last for more than two weeks. “With postpartum depression, there are many potential negative outcomes, such as a high rate of suicide in mothers or disruption of the baby’s cognitive, emotional, and social development,” says Sabunciyan. “If we could identify mothers who may be at higher risk before giving birth, we could prevent these adverse events. »
Efforts have been underway for decades to identify genetic or other biological markers of PPD.
In the new study, the research team specifically looked at the messenger RNA (mRNA) content of extracellular vesicles (EVs) – fatty sacs containing genetic material essential for communication between cells. According to Ms. Sabunciyan, during pregnancy, this communication system speeds up to meet the needs of implantation and the growth of the embryo. The mother’s placenta also releases an RNA essential for the development of the immune system that protects the growing fetus against virus.
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 women who were pregnant and were seen at Johns Hospital. Hopkins.
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 trimesters of pregnancy and up to six months after childbirth. Seven of the participants were diagnosed with postpartum depression after giving birth, with a score of 13 or more on the Edinburgh Postpartum Depression Scale (a standard tool for identifying women with the condition). None of these women showed signs of depression during pregnancy. The mRNA levels identified as changing most dramatically in participants with PPD through this analysis were then measured in the blood of 28 additional 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 identified in those who developed PPD in the first group of 14 participants were 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 identified as another race. All were between 20 and 30 years old and had had live births.
According to the research team, this analysis revealed that extracellular RNA communication levels during pregnancy and the postpartum period were “largely impaired” in women who developed postpartum depression. The researchers found that the level of 2,449 mRNAs changed (1,010 increased and 1,439 decreased) between those who developed PPD and those who did not. On average, individual mRNA levels were almost doubled between the two groups. The vast majority of these changes occurred during pregnancy and not during the postpartum period.
The researchers also found that autophagy-associated EV mRNA levels were reduced in women who later developed PPD – meaning the cells did not clean up excess, damaged or defective parts. In addition, they found that DPP-associated EV mRNAs originated from white blood cells called monocytes and macrophages.
The researchers caution that their study is limited by small numbers and a lack of racial diversity. But they say that if further studies confirm the findings, they may eventually develop a blood test to identify pregnant women who are at risk of developing PPD after giving birth. This research could also advance the development of therapies for PPD.
“If we can identify those at risk early on and get them on appropriate treatment, we can likely prevent many of the serious effects of postpartum depression,” says Sabunciyan.
Along with Sabunciyan, the authors are Morgan Sherer of Johns Hopkins, Jennifer Payne of the University of Virginia, and Lauren Osborne, formerly of Johns Hopkins and now of Weill Cornell Medicine.
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Journal reference:
Osborne, L.M., et al. (2022) Impaired extracellular mRNA communication in postpartum depression is associated with decreased autophagy. Molecular psychiatry. doi.org/10.1038/s41380-022-01794-2.