New research shows significant variations in B-cells in women with PPD

Jerry Guintivano, PhD, of the University of North Carolina School of Medicine, led an exclusive transcriptome-wide association research that showed substantial changes in B-cells in women with postpartum depression, with pathway observations indicating modified B-cell activation and insulin resistance.

New research shows significant variations in B-cells in women with PPD
Jerry Guintivano, PhD. Image Credit: UNC School of Medicine

The first research to look at various levels of biology in women with postpartum depression (PPD) to examine how they differ from those who do not, has been published in Molecular Psychiatry. PPD affects one out of every seven women and has adverse mental health implications for both the mother and the child. The exact biochemical pathways behind the illness, however, are uncertain.

We don’t have PPD figured out. A lot of biological research focuses on candidate genes and hormones, and we do have a lead on some PPD-specific medications, but it’s important to take multiple avenues to target this condition. Not every manifestation of PPD is the same.”

Jerry Guintivano, PhD, Study Lead Author and Assistant Professor, Department of Psychiatry, UNC School of Medicine

This is why Guintivano led a group of UNC School of Medicine scientists to perform the world’s biggest transcriptome-wide association analysis for PPD. Previous research has only looked at entire blood samples.

This research looked into the various components of blood in greater depth. They collected blood samples from 1,500 racially and culturally diverse women across North Carolina who had delivered a baby in the previous six weeks, with 482 of them being diagnosed with PPD.

Researchers looked for changes in components of blood samples from women with PPD versus those without PPD using RNA sequencing, DNA genotyping, and DNA methylation assessment—a total of three levels of fundamental biology evaluation.

They discovered that B-cells in women with PPD differed significantly. B-cells are a crucial component of the immune system. When their receptor identifies and attaches to an antigen, they become activated. B-cells that have been activated create antibodies as well as pro- and anti-inflammatory substances.

There’s a really delicate interplay of the immune system during pregnancy. It has to prevent infection from a cold, and it also has to finely tune itself so it doesn’t recognize the fetus as a foreign body and attack it. Then in the postpartum period, all these hormones and pathways reset to get back to pre-pregnancy."

Jerry Guintivano, PhD, Study Lead Author and Assistant Professor, Department of Psychiatry, UNC School of Medicine

Thousands of unique B-cell transcripts were discovered to be varied in women with PPD than in women without PPD, controlled in part by genetic variations and DNA methylation, according to the UNC researchers. They used pathway analysis to verify their findings, which revealed that altered B-cell activation and insulin resistance were involved.

This is really just the first step in a long line of research that now needs to be done. This is the biggest study of its type but we still don’t know why B-cells are changing. Are they reflecting another change in the body that is caused by or causes PPD? What is driving this B-cell behavior?”

Jerry Guintivano, PhD, Study Lead Author and Assistant Professor, Department of Psychiatry, UNC School of Medicine

The next step, according to Guintivano, is to undertake a longitudinal research that follows women over a longer length of time to see how B-cells evolve during pregnancy and after delivery. He claims that none of this study would be feasible without the dedication of many women to PPD research.

The women who participated in this study are new moms who came in during a very critical time when their babies are weeks old to participate in research to help other women, I want to thank them for that. We want to do their contributions justice with our research,” Guintivano added.

Source:
Journal reference:

Guintivano, J., et al. (2022) Transcriptome-wide association study for postpartum depression implicates altered B-cell activation and insulin resistance. Molecular Psychiatry. doi.org/10.1038/s41380-022-01525-7.

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