The team discovered four specific genetic variants, called single nucleotide polymorphisms, in one of the two genes that encode the estrogen receptor. The variants, which are differences in strings of DNA nucleotides A, G, C, or T, were identified in the estrogen receptor alpha gene, ESR1.
Compared to the control group, women with PMDD were significantly more likely to have the ESR1 gene variants, the study found.
"While these are preliminary findings that require replication in larger studies, we would argue that this may explain part of the variance among women in the susceptibility to developing this mood disorder," Rubinow said. "Studies have shown that PMDD is characterized by abnormal sensitivity to reproductive steroids like estrogen. As a receptor for the hormone that can trigger the onset of PMDD symptoms, ESR1 has clear physiologic relevance for this disorder."
The authors acknowledge that as with other complex genetic disorders, the contribution to PMDD of polymorphisms in a single gene may not be large. In addition, they also noted that the findings may be telling us more about the control group.
These women, who have no history of psychiatric problems or menstrual cycle-related symptoms, may have gene variants that protect against PMDD. According to Rubinow, "this is equally interesting because it may help us to understand resilience and protection, which are also very important."
Dr. Susan S. Girdler, professor of psychiatry and director of the UNC Psychiatry Stress and Health Research Program, pointed out that the severity of PMDD symptoms are as great or can be as great as those of women with full-blown major depression or major anxiety disorder. "But what makes them different is that the symptoms are very time-limited and linked strongly with the women's menstrual cycle."
Girdler emphasizes that to qualify for PMDD, symptoms
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Contact: Les Lang
llang@med.unc.edu
919-843-9687
University of North Carolina School of Medicine
17-Jul-2007