What Causes Postpartum Depression? Missing Brain Protein May Boost Stress

Scientists have found a stress-related malfunction in new mothers that could be at the root of postpartum depression.

A study conducted with mice suggested that moms with the mental health condition may not have enough of a brain protein whose absence has been associated with stress. The researchers said the findings could lead to a new way to treat postpartum depression, which affects hundreds of thousands of women every year in the United States.

At the center of the new research is the hypothalamic-pituitary-adrenal axis. Also called the HPA axis, it describes a set of interactions in the body’s hormonal system that has been associated with stress and responses to that stress, such as the mechanism known as fight-or-flight. Although stress is a key that turns on the system, “during and after pregnancy such activation is normally blunted — helping to insulate developing offspring from stress,” according to Tufts University. “Dysregulation of the HPA axis has been suggested as playing a role in the physiology of postpartum depression.”

Another factor at play is a protein the brain, KCC2. It has a role in regulating a hormone in the brain that, in turn, lights up the axis to create a stress response.

Under normal conditions, groups of virgin, pregnant and postpartum mice showed the researchers that although KCC2 is lower in the absence of a baby, to allow for a stress response, mice that are pregnant or recently gave birth have higher levels of the protein.

The team also bred mice that didn’t have the KCC2 protein at all, then watched the activity in their HPA axis. Their study, in the journal Psychoneuroendocrinology, says those deficient mice could not suppress the stress activation system while pregnant and showed “abnormal postpartum behaviors.”

Those behaviors were mouse equivalents to the kind seen in mothers with postpartum depression. In addition to standard depression symptoms like extreme sadness and anxiety, mothers with postpartum depression have difficulty bonding with their newborns.

“Pregnancy obviously involves great changes to a woman’s body, but we’re only now beginning to understand the significant unseen adaptations occurring at the neurochemical and circuitry level that may be important to maintaining mental health and maternal behavior in the first few weeks to months following delivery,” first study author Laverne Camille Melón said in the Tufts statement. “We hope we have identified a potential molecular target for the development of a new class of compounds that are more effective for women suffering from postpartum depression and anxiety.”

There could, however, be other things causing the conditions. Scientists have previously found links between postpartum depression and factors as varied as the amount of pain a woman experiences during labor and the season in which the baby was born.

“Many psychiatric and neurological disorders are a constellation of symptoms and represent an unfortunate synergy of heterogeneous maladaptations,” Melón said. “The mechanisms underlying one woman’s postpartum depression may differ from another’s.”