Significant change in B cells in women with postpartum depression





Summary: Researchers found significant differences in B cells in women with postpartum depression. B cells are important components of the immune system that help produce antibodies and secrete pro and anti-inflammatory factors.

Source: UNC Health Care

A study published in Molecular psychiatry is the first to examine multiple levels of biology in women with postpartum depression (PPD) to see how women with the condition differ from those without. PPD affects 1 in 7 women and has negative consequences on the mental health of both mother and child. However, the precise biological mechanisms behind the disease are unknown.

“We didn’t understand the PPD,” said lead author Jerry Guintivano, Ph.D., assistant professor in the UNC Department of Psychiatry.

“A lot of biological research is focusing on candidate genes and hormones, and we have a head start on some PPD-specific drugs, but it’s important to take multiple avenues to target this condition. Not all manifestations of PPD are the same.

That’s why Guintivano led a team of researchers from the UNC School of Medicine to conduct the largest transcriptome-wide association study for PPD to date. Previous studies have only analyzed whole blood samples.

This study delved into and examined the different components of blood. They took blood samples from 1,500 women of various races and ethnicities across North Carolina who had given birth in the past six weeks, 482 of whom were diagnosed with PPD.

The researchers used RNA sequencing, DNA genotyping and DNA methylation assessment – representing three basic biological assessment levels – to look for differences in components of blood samples of women with PPD compared to women without PPD.

They found that B cells showed significant differences in women with PPD. B cells are an important part of the immune system. They activate when their receptor recognizes an antigen and binds to it. Activated B lymphocytes then produce antibodies and also secrete pro- and anti-inflammatory factors.

“There’s a really tricky interaction of the immune system during pregnancy,” Guintivano said. “He has to prevent infection from a cold, and he also has to adjust himself finely so that he doesn’t recognize the fetus as a foreign body and attack it. Then, in the postpartum period, all of those hormones and pathways reset back to pre-pregnancy.

In women with PPD, UNC researchers found thousands of individual B cell transcripts different from those in women without PPD, regulated in part by genetic variants and DNA methylation. To confirm these results, they performed pathway analysis, which involved altered B-cell activation and insulin resistance.

This shows a 3D rendering of a B cell
3D rendering of a B cell. Credit: Blausen.com staff (CC BY-SA 4.0)

“This is really just the first step in a long series of research that now needs to be done,” Guintivano said.

“This is the largest study of its kind, but we still don’t know why B cells change. Do they reflect another change in the body that is caused by or causes PPD? What drives this B cell behavior? »

Guintivano says their next step is to conduct a longitudinal study that follows women over a longer period of time to see how B cells change during pregnancy and in the postpartum period. He says that none of this research would be possible without many women dedicating themselves to PPD research.

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

About this PPD Research News

Author: Press office
Source: UNC Health Care
Contact: Press Office – UNC Health Care
Picture: Image is credited to Blausen.com staff (CC BY-SA 4.0)

Original research: Free access.
“A transcriptome-wide association study for postpartum depression involves altered B-cell activation and insulin resistance” by Jerry Guintivano et al. Molecular psychiatry


Abstract

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Transcriptome-wide association study for postpartum depression involves altered B-cell activation and insulin resistance

Postpartum depression (PPD) affects 1 in 7 women and has negative consequences on the mental health of both mother and child. However, the precise biological mechanisms behind the disease are unknown.

Therefore, we performed the largest transcriptome-wide association study (TWAS) for PPD (482 cases, 859 controls) to date using RNA sequencing in whole blood and types of deconvoluted cells.

No transcriptional changes were observed in whole blood. B cells showed a majority of significant findings at the transcriptome scale (891 transcripts representing 789 genes) with pathway analyzes involving impaired B cell activation and insulin resistance.

Integration of other types of data revealed that cell type-specific DNA methylation loci and disease-associated eQTLs (deQTLs), but not hormones/neuropeptides (estradiol, progesterone, oxytocin, BDNF), serve as regulators for some of the transcriptional differences between cases and controls. Additionally, deQTLs were enriched for several brain region-specific eQTLs, but no overlap with MDD risk loci was observed.

Overall, our results constitute a convergence of evidence for the most affected pathways in PPD with data on different biological mechanisms.




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