Postpartum depression is thought to affect around 15 percent of women after childbirth – and can have a negative effect on kids too – but we still don't entirely understand why it happens in the first place. A new study has now uncovered a potential link with the person's immune system.

A team co-led by researchers from Virginia Commonwealth University looked at multiple characteristics of blood samples from 482 women with postpartum depression (PPD for short), finding significant differences in B-cells compared to those without the condition.

B-cells are a key part of the body's immune system, activated when the body identifies foreign objects; in response, these cells are one of the key antibody producers. B-cells also send out both pro- and anti-inflammatory signals.

"There's a really delicate interplay of the immune system during pregnancy," says geneticist Jerry Guintivano, from the University of North Carolina.

"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."

Guintivano and his colleagues used three types of biological analysis to identify the B-cell variations, namely RNA sequencing, DNA genotyping, and DNA methylation assessment – all designed to measure cell composition and activity.

In women with PPD, the researchers found thousands of individual B-cell transcripts – coding sequences for synthesizing proteins – that weren't seen in women without PPD. These differences were shown to be partly down to DNA variants and genetic regulation.

A fourth genetic technique called pathway analysis, which links coding sequences to possible physiological pathways the resulting proteins interact with, also highlighted altered B-cell activation between those with PPD and those without. At this stage though it's not clear exactly what's behind the variations or how they might play into the condition.

"This is the biggest study of its type but we still don't know why B-cells are changing," says Guintivano. "Are they reflecting another change in the body that is caused by or causes PPD? What is driving this B-cell behavior?"

That's where further studies will have to carry the work. Previous research has looked closely at genes and hormones and how they relate to PPD, but the team says that "multiple avenues" will need to be explored to fully understand the condition.

What the current study does provide is a large and diverse sample size – the largest ever in a study of this kind into postpartum depression – and a few possible clues as to how the immune system could be the cause and potential fix for what new mothers are experiencing.

PPD can be a devastating condition for both parents of a child, leading to anxiety, low energy, extreme sadness, eating and sleeping issues, and even suicidal thoughts. The researchers were keen to praise the women who came forward for the research.

"The women who participated in this study are new moms who came in during a very critical time when their babies were weeks old to participate in research to help other women," says Guintivano.

"I want to thank them for that. We want to do their contributions justice with our research."

The research has been published in Molecular Psychiatry.