While fodder for too many jokes about women's behavior during that "certain time of the month," premenstrual dysphoric disorder (PMDD) is a very real and disabling condition. While as many as 75 percent of women suffer in some ways from the monthly irritability, anxiety, depression, mood swings that are commonly referred to as premenstrual disorder (PMS), for an estimated 3 to 9 percent of women these symptoms are so severe that they interfere with their normal lives. But why are some women more vulnerable than others? A new study that looks at brain receptors during the ovarian cycle in female mice may provide some clues for their larger, primate sisters.

What the researchers wanted to know: Researchers have looked at the way that GABAA receptors, receptors that exist throughout our brain and control the reactivity of neurons in the brain react to hormonal fluctuations during the menstrual cycle. Lots of the research has focused on the way they react to various neurotransmitters and hormones. But when looking at hormones, all the research has been done on males to avoid the complications caused by the ovarian cycles. How does the ovarian cycle affect the GABAA receptors in the brain?

What they did: The best way to determine what was going on with these receptors was basically to throw them completely out of whack by a seizure and in this extreme state examine how they behaved when different hormones were present. So researchers induced seizures in mice and then examined their brains. But first researchers determined that there were two stages of the mouse estrous cycle: the estrus phase when estrogen levels are high and progesterone levels are low during the day and the late diestrus phase when progesterone levels peak and estrogen levels are low. After injecting kainic acid, which causes seizures that are similar to epileptic seizures, in female mice at various stages of their cycle, researchers recorded the electrical activity in their brains on an EEG. They then killed the mice and examined cross sections of the brains to see how the GABAA receptors had changed in the wake of the seizures.

What they found: Mice that were in the estrus phase, or premenstrual in the human version, spent significantly more time in a seizure than did mice in the later phase. Moreover, they also exhibited greater anxiety during the earlier phase than in the later phase. After looking at the GABAA receptors in the hippocampus, they found that these receptors, which are so crucial to modulating and inhibiting anxiety responses, were less resilient during the time that was analagous to the premenstrual period. They were more compromised by the seizure that occurred during the estrus stage than the one that occurred during the late diestrus phase, and the changes occurred in the GABAA receptors that exist on the part of the brain where progesterone-derived neurosteroids are active. That activity changes the way nerve cells act and increases the vulnerability of the mouse to seizures and to anxiety.

What this study means to you: By seeing how the changes in the brain receptors during the menstrual cycle affect seizures and anxiety, researchers are hoping to find novel therapies that could treat PMDD and other symptoms associated with the menstrual cycle. Today, PMDD is often treated with antidepressants, which work on the serotonin neurotransmitters in the brain. But if these findings hold up in women, then new drugs can be targeted specifically for the GABAA receptors. Researchers also believe that this may have implications for postpartum depression and mood swings during pregnancy and may even explain how stress hormones affect the brain.

Caveats: Mice are not women.

Find out more: The American Psychiatric Association offers a brief article outlining the disorder. In addition, factsforhealth.org and apa.org provide both support for women with PMDD and further information.

Read the article: Mody I. et al. "Ovarian Cycle-Linked Changes in GABAA Receptors Mediating Tonic Inhibition Alter Seizure Susceptibility and Anxiety." Nature Neuroscience Advance Online Publication, May 15, 2005.

Abstract online: http://www.nature.com