Researchers Target Biomarker for Postpartum Depression

Date: March 1, 2014

We’d like to say that new mothers who suffer from depression have it for a straightforward reason,” says psychiatrist Jennifer Payne. “Estrogen drops suddenly postpartum, and there you are.”

But that’s not the case. “Estrogen is involved,” Payne adds, “but not in the way we thought.”

A new study sheds light on what happens to many with postpartum depression (PPD). More than that, it brings hope of a reliable biomarker—one that could be flagged by a routine blood test to predict a pregnant woman’s risk of slipping into the condition.

Payne, who heads Johns Hopkins’ Women’s Mood Disorders Center, wants to end the mystery of the disorder, which affects some 10 percent of new mothers in the general population and a third of those with a previous mood disorder. Postpartum depression can overwhelm women, and its harm to their children isn’t trivial. Physical abuse—even murder—can occur. Studies also confirm risks of low self-esteem and behavioral problems in children.

The new work from the research team, led by molecular biologist Zachary Kaminsky, confirms that lowered estrogen isn’t a sufficient cause of depression. “Postpartum depression does appear after estrogen bottoms out,” he says, “but all women experience a postpartum drop, and most aren’t clinically depressed.” Instead, Kaminsky believes that estrogen’s effects vary. “Women with true PPD are apparently more sensitive to it than others.” 

To find out why, the team compared genes of pregnant women who developed PPD with those who didn’t. Because differences between the two groups are subtle, Kaminsky and Payne were scrupulous with study criteria.

One of Payne’s benchmarks for identifying women with PPD was ultra-tight: women who had a clear episode starting within a month of giving birth. “The literature is messy,” she explains. “People call a lot of things PPD, even depression that starts during pregnancy.”

Kaminsky’s focus wasn’t on genes, per se, but on genes’ epigenetic “marks”—added-on molecular tags that can override a gene’s basic programming. In the end, pregnant women not destined for PPD showed little change in epigenetic marks of key genes. In “sensitive” women who got depressed, those same genes gained or lost marks.

“How the altered marking pattern could lead to depression is something we’re eager to uncover,” says Kaminsky. In the postpartum depression group, two genes stood out as especially changed by estrogen, he found. Those genes are now looking like a PPD biomarker. “I jumped up and punched air when we confirmed that they could predict PPD 85 percent of the time.” New patient groups support the very promising results, Kaminsky adds.

Fortunately, blood cell DNA seems to be as good as brain DNA in predicting the condition. And while it’s early days in ushering the markers into a useful clinical test, “We’re already figuring out what we might do to block PPD in mothers at risk,” says Payne. One possibility is use of intermittent antidepressants after delivery, a successful tactic she uses for women with premenstrual mood symptoms. “In that case, women who wake up with a low mood take a single Prozac, for example, and feel better by evening.” The bump in serotonin works, Payne explains.

“Because PPD doesn’t just affect the mother,” she adds, “it’s incredibly important for us to identify and intervene early.”

—Marjorie Centofanti

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Top Four Signs of Postpartum Depression

1. Low or irritable mood that lasts two weeks or longer.

2. Not feeling attached to the baby.

3. Frequently feeling anxious or panicky.

4. Having trouble sleeping, even when the baby is sleeping.