Genetic predictors of postpartum depression

Johns Hopkins researchers say they have discovered specific chemical alterations in two genes that, when present during pregnancy, reliably predict whether a woman will develop postpartum depression.
The epigenetic modifications, which alter the way genes function without changing the underlying DNA sequence, can apparently be detected in the blood of pregnant women during any trimester, potentially providing a simple way to foretell depression in the weeks after giving birth, and an opportunity to intervene before symptoms become debilitating.
The findings are of the small study involving 52 pregnant women.
‘Postpartum depression can be harmful to both mother and child,’ says study leader Zachary Kaminsky, Ph.D., an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. ‘But we don’t have a reliable way to screen for the condition before it causes harm, and a test like this could be that way.’
It is not clear what causes postpartum depression, a condition marked by persistent feelings of sadness, hopelessness, exhaustion and anxiety that begins within four weeks of childbirth and can last weeks, several months or up to a year. An estimated 10 to 18 percent of all new mothers develop the condition, and the rate rises to 30 to 35 percent among women with previously diagnosed mood disorders. Scientists long believed the symptoms were related to the large drop-off in the mother’s oestrogen levels following childbirth, but studies have shown that both depressed and non-depressed women have similar oestrogen levels.
By studying mice, the Johns Hopkins researchers suspected that oestrogen induced epigenetic changes in cells in the hippocampus, a part of the brain that governs mood. Kaminsky and his team then created a complicated statistical model to find the candidate genes most likely undergoing those epigenetic changes, which could be potential predictors for postpartum depression. That process resulted in the identification of two genes, known as TTC9B and HP1BP3, about which little is known save for their involvement in hippocampal activity.
Kaminsky says the genes in question may have something to do with the creation of new cells in the hippocampus and the ability of the brain to reorganise and adapt in the face of new environments — two elements important in mood. In some ways, he says, oestrogen can behave like an antidepressant, so that when inhibited, it adversely affects mood.
The researchers later confirmed their findings in humans by looking for epigenetic changes to thousands of genes in blood samples from 52 pregnant women with mood disorders. Jennifer L. Payne, M.D., director of the Johns Hopkins Women’s Mood Disorders Center, collected the blood samples. The women were followed both during and after pregnancy to see who developed postpartum depression.
The researchers noticed that women who developed postpartum depression exhibited stronger epigenetic changes in those genes that are most responsive to oestrogen, suggesting that these women are more sensitive to the hormone’s effects. Specifically, two genes were most highly correlated with the development of postpartum depression. TTC9B and HP1BP3 predicted with 85 percent certainty which women became ill. John Hopkins Medicine