'Extreme PMT' gene not all the rage
that makes women more likely to suffer from the most extreme form
of premenstrual tension or syndrome (PMT, PMS).
A team of scientists at the US National Institutes of Health (NIH) have carried out genetic tests on women who suffer from premenstrual dysphoric disorder (PMDD) - sometimes referred to as severe or extreme PMT. They discovered the women had mutations in hormone receptor genes and also a gene that regulates the part of the brain responsible for mood. Researchers already knew that PMDD is caused by an abnormal response to normal hormone levels, which leaves women unusually sensitive to their own hormone changes. The symptoms, such as severe depression, irritability and anger, severely impact quality of life, both for the women and arguably their loved ones. These latest results could help scientists develop a diagnostic test or even potentially enable them to potentially discover drugs to combat PMDD, a breakthrough that would be warmly welcomed. Dr David Rubinow and his colleagues found that women who had four different single nucleotide polymorphisms (SNPs) in the oestrogen receptor alpha (ESR1) gene were more likely to suffer from PMDD. However, intriguingly, this was only true for those women who also had a variant form of another gene - catechol-O-methyltransferase (COMT). This enzyme product of this second gene is involved in oestrogen metabolism and prefrontal cortical activation, a critical part of the brain for mood regulation. However, the research is still at a very early stage - only 91 women who suffer from PMDD were tested, alongside 56 women who don't, and the findings need to be replicated in more patients before any definite conclusions can be drawn. The study will be published in the October 15 edition of the Biological Psychiatry. "We have been waiting for molecular genetics to provide some insights into the neurobiology of PMDD and this report provides a welcome starting point for this research area." said Dr John Krystal, the journal's editor. "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," he added. Rubinow said the study "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." "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," he added. Even if no new drugs result from this study, the results could have important implications for existing PMDD therapy. Women who suffer from the condition often take selective serotonin reuptake inhibitors (SSRIs). At least some of the effects of these drugs are mediated by serotonin 1A receptors, which are in turn upregulated by ESR1, through nuclear factor kappa B (NF-kB). The upshot is that the genetic mutations described by Rubinow could very well change how effective SSRI drugs are in women with PMDD.
