Back to table of contents Previous article Next article Clinical & Research NewsFull AccessRoots of Postpartum Depression May Lie in GABA ReceptorJoan Arehart-TreichelJoan Arehart-TreichelSearch for more papers by this authorPublished Online:19 Sep 2008https://doi.org/10.1176/pn.43.18.0017aGABA neurotransmitters have long been implicated in various psychiatric disorders, say, generalized anxiety disorder, panic disorder, and posttraumatic stress disorder. Now, research suggests that a subunit of a receptor for GABA called the delta subunit of the GABAA receptor seems to play a critical role in postpartum depression—at least in an animal model.The research was conducted by Jamie Maguire, Ph.D., and Istvan Mody, Ph.D., neurology-physiology scientists at the University of California, Los Angeles. Results were published in the July 31 Neuron.Researchers had suspected that postpartum depression might stem from a rapid and dramatic decline in the reproductive hormone progesterone following pregnancy. Yet experimental manipulation of progesterone in women with and without a history of postpartum depression seemed to rule this out. So it looked as if something other than progesterone was the culprit in postpartum depression.Enter Maguire and Mody. They took brain tissue from nonpregnant mice, pregnant mice, and postpartum mice and examined the activity, in the brain tissue samples, of the delta subunit of the GABAA reception. They found that the subunit's activity differed depending on the sample from which it came. It was less active in pregnancy than in nonpregnancy, yet it was just as active postpartum as in nonpregnancy. In other words, it looked as if the subunit became less active during pregnancy, then rebounded to a normal state after birth. So Maguire and Mody suspected that the subunit might play a pivotal role in postpartum depression and tested that hypothesis.Twenty-three female mice were genetically engineered so that they did not contain the subunit. They were then bred and, after giving birth, were observed. Finally, their behaviors were compared with those of nine postpartum female mice possessing the subunit (controls). The mouse mothers lacking the subunit not only engaged in depression-like behaviors, but also in abnormal postpartum behaviors, such as not building proper nests and neglecting their pups. And significantly fewer of their 136 pups survived than did the 53 pups of the control mouse mothers. So it looked as if the subunit might truly be complicit in postpartum depression, at least in a mouse model of postpartum depression.And the case grew even stronger when the researchers gave five female mice lacking the subunit a drug known to restore its function. The drug, called THIP, is a selective GABAAR agonist. When these mice became mothers, they acted maternally, and their 32 pups experienced significantly greater survival than did the 90 pups of 15 new mouse mothers lacking the protein and not getting THIP.In an accompanying editorial, Charles Nemeroff, M.D., chair of psychiatry at Emory University, wrote, “Depression during pregnancy and in the postpartum period is common, devastating to mothers and their offspring, and poorly understood in terms of pathophysiology.... [The findings by Maguire and Mody] likely represent an incremental breakthrough in the field.”In a prepared press statement, Thomas Insel, M.D., director of the National Institute of Mental Health, said that the research “points to a specific potential new target in the brain for medications to treat [postpartum depression] ... [and] for the first time, we may have a highly useful model of postpartum depression.”As Maguire and Mody wrote in their study report, “Our data are consistent with the idea that the pathophysiology of postpartum depression may be related to the inability to properly regulate GABA ... during pregnancy and postpartum.”The research was funded by the National Institute of Mental Health, American Epilepsy Foundation, and UCLA Center for the Neurobiology of Stress.An abstract of “GABAAR Plasticity During Pregnancy: Relevance to Postpartum Depression” is posted at<www.neuron.org/content/article/abstract?uid=PIIS0896627308005370>.▪ ISSUES NewArchived
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