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The researchers hope they can use the findings to develop a blood test that could help spot pregnant women who are vulnerable to postpartum depression, which affects around 15 percent of new mothers.
Their study, reported in the May 21 issue of the journal Molecular Psychiatry, uncovered specific chemical changes in two genes that predicted which women would develop postpartum depression with 85 percent accuracy.
Little is known about the genes, called TTC9B and HP1BP3, but they are somehow involved in activity in the brain's hippocampus, which regulates mood. Based on animal research, both genes seem to be "reactive to estrogen," said Zachary Kaminsky, a researcher at Johns Hopkins University School of Medicine in Baltimore who worked on the study.
The findings offer clues as to what makes some women susceptible to postpartum depression. But there is still a lot of work to be done before a screening test becomes available, according to an expert not involved in the research.
"This is a first step, but I think we're pretty far off from having a blood test," said Dr. Kimberly Yonkers, a professor of psychiatry and obstetrics and gynecology at Yale School of Medicine in New Haven, Conn.
She said the study was small -- involving only 51 women, about a dozen of whom developed depression within a month of giving birth -- so the results need to be validated in larger studies.
But beyond that, Yonkers said, there's the larger, "dicey" issue of how much benefit there would be from telling pregnant women their genes put them at heightened risk of postpartum depression.
"You may unnecessarily worry some women," Yonkers said.
"Information is power," Kaminsky said, and for some women, knowing they are at risk of postpartum depression can offer a chance to minimize that risk: Their partner, family or friends could be especially attentive and step in to ease some of the stress of being a new mom, for example.
Kaminsky acknowledged that if a blood test result actually caused distress for an expectant mom, it would not be good. But, he said, having a blood test as an option for women who want an idea of their risk could be valuable.
Kaminsky and two of his co-researchers have filed for a patent on testing for the genetic markers.
The findings are based on 51 pregnant women with a history of depression or bipolar disorder, which raises the risk of suffering depression during or after pregnancy. One group of 19 women had major depression during their pregnancies, and 12 continued to have symptoms in the first month after giving birth.
Another 32 women were depression-free during pregnancy, but 11 developed postpartum depression.
Based on research with mice, Kaminsky's team suspected that estrogen triggers so-called epigenetic changes in genes in the brain's hippocampus. With epigenetic changes, there is no defect in the underlying DNA, but a gene's activity is altered. The results of research conducted in mice, however, often are not able to be replicated in humans.
The researchers found that epigenetic changes in the TTC9B and HP1BP3 genes were predictive of a woman's risk of postpartum depression.
Yonkers said one theory has been that women who develop postpartum depression may respond differently to the big shifts in estrogen and other hormones that happen during pregnancy and after childbirth.
Kaminsky said the new findings give some insight into that hormonal response. But he said more research is needed to really understand what's going on.
The results also need to be confirmed in a larger, more diverse group of women, Kaminsky said. "The women in this study all had been previously diagnosed with depression or bipolar disorder," he said. "We really need to look at this in a general population of women too."
In general, experts suspect that many factors come together to cause postpartum depression, including a woman's particular circumstances, such as whether she has a good "support network," if she has other major stressors in her life or whether the pregnancy was planned or not.
So no blood test would tell the whole story.
Right now, doctors may diagnose postpartum depression either because a woman complains of symptoms, or through a screening questionnaire. Yonkers said experts differ on whether new mothers should be routinely screened; the American Academy of Pediatrics, for example, says pediatricians should screen moms for depression during newborn checkups.
Other groups, including the American College of Obstetricians and Gynecologists, do not advise routine screening, but say doctors and women should consider it.
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