Postpartum Depression: How Antidepressants May Treat PPD

Most new mothers know the feeling. People call it the "Baby Blues," and for a lot of women it shows up in the first days after giving birth: mood swings, bouts of crying, anxiety, irritability, sadness, trouble concentrating, poor sleep. Usually it fades within a few days or a couple of weeks. When those same feelings dig in harder and refuse to lift, something else may be going on. Postpartum depression (PPD) starts to get in the way of caring for the baby and of ordinary daily tasks. Left alone, it can stretch on for months and becomes a genuine health risk to mother and child alike.

The warning signs tend to be heavier than the Baby Blues. Intense irritability and anger. A struggle to bond with the baby. Pulling away from family and friends. Thoughts of harming yourself, or harming your infant.

Scientists at Ohio State University reported findings that point toward restoring the connections between brain cells in regions that chronic stress during pregnancy appears to damage. The hope is that repairing those connections could ease the crushing depression some new mothers feel and help them return to their lives and their children. In the study, rats that had been chronically stressed while pregnant showed depression-like behavior after they gave birth, which the team treated as a stand-in for PPD. Brain structures in particular regions of those rats were also less complex than in rats that had not been stressed.

The researchers gave the affected rats Citalopram, the drug sold under the brand name Celexa. It belongs to the class called selective serotonin reuptake inhibitors, or SSRIs. Citalopram carries no FDA indication for postpartum depression, yet doctors prescribe it for that purpose fairly often.

The stressed mother rats behaved a lot like humans with PPD. They showed shifts in mood and depression, and their caregiving dropped off. They stopped showing pleasure, a state called anhedonia, and during a water test they floated more than the unstressed rats did. When an animal floats instead of swimming, researchers read that as a depressive sign.

To deliver the drug, the team implanted small pumps under the skin of the mother rats that were showing depressive symptoms, dosing them daily with Citalopram for three weeks. By the end, the neurons in their brains had shifted back toward normal structural complexity. In the water test they swam hard again, and the depressive behavior was gone.

Achikam Haim, a student in the Neuroscience Graduate Program at Ohio State and one of the study's authors, presented the work at Neuroscience 2014, the Society for Neuroscience's annual meeting. "We saw that Citalopram was effective in improving mood in stressed mothers and completely reversed the stress effects in areas of the brain that our lab has shown are altered by stress during pregnancy," Haim said. Earlier research had already flagged a long list of possible contributors to PPD, spanning physical, emotional, and lifestyle factors.

Part of what happens is hormonal. After childbirth, estrogen and progesterone drop sharply, and that plunge may feed postpartum depression. Thyroid hormones can fall too, which leaves a woman worn out, slowed down, and low. Shifts in blood volume, blood pressure, immune function, and metabolism add to the fatigue and push mood swings further. A new mother is also sleep-deprived and stretched thin, so even small problems can feel unmanageable. Worry about whether she can care for the baby creeps in. Some women lose their sense of who they are and watch their self-esteem slide.

Stack other pressures on top of all that: a baby who demands constant attention, other children at home, trouble with breast-feeding, money worries, and little support from a partner or anyone else. The clinical picture of PPD is clear enough, and these factors clearly matter, but what actually goes on inside the brain during this period is still being worked out.

Benedetta Leuner, an assistant professor of psychology and neuroscience at Ohio State and the study's senior author, built the rat model to get at those brain changes. Her lab produces depression-like symptoms by putting pregnant rats under chronic stress, a condition known to predict PPD in people. "We have a suspicion that stress during pregnancy is somehow altering the reward system in the brain, producing anhedonia and making these depressed mothers less rewarded by their offspring and less motivated to care for them," Leuner said. "It's possible that the effects of stress on the brain circuit regulating reward can lead to these symptoms."

In the reward center of the stressed rats' brains, a region called the nucleus accumbens, the team counted fewer dendritic spines than in the unstressed animals. Human research lines up with that: in mothers with PPD, the brain's reward center doesn't light up the way it should when they hear a recording of their own baby crying. "The structural data from our work in rats can at least partially explain that, because neurons with fewer spines, and therefore less input, arguably have lower activation levels," Haim said.

Anyone who has lived through PPD knows how brutal it is, with damage that shows up in both the short and long term. The possibility that an SSRI can blunt those symptoms is encouraging. Still, there's a catch. These antidepressants usually take two to four weeks to start working, and that is far too long a wait for a mother who is suffering now, with a baby who needs her. The findings have turned attention toward other chemical systems in the brain that might respond faster. "Fixing that impaired maternal functioning is really what's critical in moving forward and developing better treatment options," Leuner said.

For now, SSRIs look like one tool that may help treat postpartum depression. (Laura Wells. Sources: Mayo Clinic Staff, "Postpartum depression," September 11, 2012; Ohio State University, "Why antidepressant may be effective in postpartum depression," ScienceDaily, November 19, 2014.)