First Significant Genetic Finding In Severe PMS, Or PMDD

Previously, researchers have shown that women with PMDD have an abnormal response to normal hormone levels and, thus, are differentially sensitive to their own hormone changes. Huo and colleagues now report their new findings, which link PMDD with common variants in the estrogen receptor alpha gene, in an article scheduled for publication in Biological Psychiatry.

Huo and colleagues performed genetic testing and analyses on women diagnosed with PMDD and healthy control subjects to investigate possible sources of the genetic susceptibility to experience PMDD, and found variants in the estrogen receptor alpha gene that are associated with PMDD. In other words, women with these particular genetic variants were more likely to suffer from PMDD.

Importantly, the authors also discovered that this association is seen only in women with a variant form of another gene, catechol -- o -- methyltransferase (COMT), which is involved in regulating the function of the prefrontal cortex, a critical regulator of mood. David Rubinow, M.D., lead author on this project, notes that these findings "may help fill in the picture of how changes in ovarian hormones can lead to depression and why they do so only in a small subset of women."

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, comments, "We have been waiting for molecular genetics to provide some insights into the neurobiology of PMDD and this report from Huo et al. provides a welcome starting point for this research area." He adds, "In the case of PMDD, we are interested in the internal, hormonal environment as well as external environmental factors, such as stress. This report suggests that genetic factors may influence both dimensions of PMDD vulnerability."

Although this is a preliminary report and further research, including replication of this finding, is needed, it represents an important advance in the genetic understanding of PMDD. As Dr. Rubinow explains, "The more that we can learn about how cyclical depressions get triggered in women with PMDD and why, the better will be our understanding of non hormone-related depression as well as the normal regulation of mood."

The article is "Risk for Premenstrual Dysphoric Disorder Is Associated with Genetic Variation in ESR1, the Estrogen Receptor Alpha Gene" by Liang Huo, Richard E. Straub, Peter J. Schmidt, Kai Shi, Radhakrishna Vakkalanka, Daniel R. Weinberger and David R. Rubinow. Drs. Huo, Schmidt, Shi, and Rubinow are affiliated with the Behavioral Endocrinology Branch, while Drs. Straub, Vakkalanka, and Weinberger are with the Program on Genes, Cognition, and Psychosis, of the National Institute of Mental Health (NIMH) at the National Institutes of Health (NIH) in Bethesda, Maryland. The article appears in Biological Psychiatry, Volume 62, Issue 8 (October 15, 2007), published by Elsevier.