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Possible Cause of Postpartum Depression Pinpointed
Date:7/30/2008

y after delivery. As a result, neurosteroid levels also rise and fall.

Maguire and Mody wanted to see what happens to GABA receptors in the brains of mice undergoing the hormonal swings associated with pregnancy. By comparing virgin, pregnant and postpartum mice, the pair discovered that GABA receptor abundance (and function) falls during pregnancy and then returns to pre-pregnancy levels following birth.

That makes sense from a homeostatic point of view, Maguire explained. For the body to maintain a constant level of GABA receptor-derived inhibition, receptor abundance must stay more or less in synch with neurosteroid levels.

"If you want to maintain a constant level of inhibition, with more neurosteroids, you need fewer receptors," she explained. "After pregnancy, when hormone levels drop off, you need more receptors to maintain that level. If you cannot maintain that level after pregnancy, that's when the disorders manifest."

She and Mody reached that conclusion using mice genetically engineered to lack a particular component of the GABA receptor -- that is, mice that cannot adjust GABA receptor levels in response to changing hormone levels. By comparing these mutants to normal mice, the pair discovered that dysregulation of the normal changes in GABA receptor levels lead to mouse behaviors akin to postpartum depression, such as anxiety and depression, with a concomitant decrease in pup survival.

Treatment with THIP (Gaboxadol), a GABA receptor agonist originally intended to treat sleep disorders, ameliorated these effects in mice containing decreased levels of GABA receptors.

"Our thinking is that postpartum depression, and maybe premenstrual syndrome and premenstrual dysphoric disorder, may be due to impaired trafficking of these [GABA] receptors to the [neural] membrane," Mody said.

The next step, he said, is to determine whether human postpartum depression is caused by a similar defect.'/>"/>

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