Some risk factors for postpartum depression are well documented. They include anxiety, stress, lack of social support, low self-esteem, depression before or during pregnancy, a history of premenstrual syndrome, and a history of oral contraceptive—induced mood changes.

A biological marker for postpartum depression may now have been discovered as well. The marker is an elevated level of the hypothalamic hormone corticotropin-releasing hormone (CRH) during the 25th week of pregnancy.

The finding was reported in the February Archives of General Psychiatry. The lead investigator was Ilona Yim, Ph.D., an assistant professor of psychology and social behavior at the University of California, Irvine.

CRH is known to play an important role in the origin of depression in the non-pregnant state. CRH levels are also known to soar during pregnancy. Yim and her coworkers suspected that a surge of CRH during pregnancy might help set the stage for postpartum depression in some women, so they launched a longitudinal cohort study to test the hypothesis.

One hundred pregnant women were recruited into the study. Blood samples were obtained at 15, 19, 25, 31, and 37 weeks of pregnancy from each of the women. The blood samples were screened not just for CRH, but for the pituitary hormone adrenocorticotropic hormone (ACTH), which is regulated by CRH, and for the adrenal cortex hormone cortisol, which is regulated by ACTH. Each woman was assessed for depressive symptoms four times during pregnancy and on average nine weeks after delivery. Out of the 100 women, 16 developed postpartum depression symptoms.

After taking prenatal depressive symptoms into consideration, the researchers looked to see whether there was any link between pregnancy levels of CRH, ACTH, or cortisol and the development of postpartum depression symptoms. They found only one link, and that concerned CRH. An elevated level of CRH at 25 weeks of pregnancy was a highly significant predictor of postpartum depression—that is, it predicted postpartum depression with an accuracy of 75 percent and with a misclassification rate of 24 percent.

Although Yim and her colleagues had anticipated that CRH might predict postpartum depression, she "was surprised at how robust this finding was," Yim told Psychiatric News. "I also did not anticipate a timing effect. I would have speculated that overall CRH exposure throughout pregnancy would play a bigger role."

Yim and her group will now attempt to replicate their findings. If they manage to do so, and if other groups manage to do so as well, "it may be considered useful to implement a CRH-postpartum depression screen into standard prenatal care," they wrote in their study report." Because blood draws to screen for gestational diabetes are typically performed at 24 to 28 weeks of gestation, a potential postpartum depression screen could be completed at the same time."

Meanwhile, Yim and her colleagues will attempt to determine why a large surge in CRH around 25 weeks of pregnancy seems to predict postpartum depression. They do know that the placenta starts to churn out large amounts of CRH around this time, supplementing the amount of CRH that is already being made by the hypothalamus. But why many women who develop postpartum depression tend to produce even more CRH at 25 weeks of pregnancy than do women who do not develop postpartum depression is not clear.

"This work is an exciting contribution in the area of postpartum depression," Marlene Freeman, M.D., told Psychiatric News." It supports [the notion] that women who suffer from postpartum depression have a biological vulnerability, and that risk may be assessed during pregnancy at a specific point. It would be important to build upon this work to determine how women at risk for postpartum major depressive episodes might be clearly identified for careful monitoring, early treatment, and even prophylaxis."

Freeman is a psychiatrist with a focus on the interface between psychiatry and obstetrics. She is affiliated with the Perinatal and Reproductive Psychiatry Clinical Research Program at Massachusetts General Hospital.

The study was funded by the National Institute of Child Health and Human Development.

An abstract of "Risk of Postpartum Depressive Symptoms With Elevated Corticotropin-Releasing Hormone in Human Pregnancy" is posted at<http://archpsyc.ama-assn.org/cgi/content/abstract/66/2/162>.▪