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Gene complex implicated in severe premenstrual syndrome

09 January 2017

By Sarah Gregory

Appeared in BioNews 883

Researchers in the USA have shown that a severe form of premenstrual syndrome (PMS) may be caused by irregular gene expression, which leads to atypical responses to sex hormones.

As part of a study examining how women with and without premenstrual dysphoric disorder (PMDD) respond to treatment that blocks sex hormones, researchers based at the National Institutes of Health (NIH) and the University of North Carolina found that a reduction in symptoms was linked to a particular gene complex called ESC/E(Z).

'We found dysregulated expression in a suspect gene complex which adds to evidence that PMDD is a disorder of cellular response to oestrogen and progesterone,' explained Dr Peter Schmidt of the National Institute of Mental Health's Behavioral Endocrinology Branch and one of the principal investigators on the study.

'Learning more about the role of this gene complex holds hope for improved treatment of such prevalent reproductive endocrine-related mood disorders,' he said.

PMDD affects two to five percent of women of reproductive age and is characterised by an exaggeration of the symptoms associated with PMS, including feelings of hopelessness, depression and anxiety, as well as bloating, headaches and cramps. Previous research has shown that women who regularly experience such severe symptoms are abnormally sensitive to changes in sex hormones, oestrogen and progesterone, despite normal levels.

In the current study, the researchers showed that in ten women with PMDD, blocking sex hormones eliminated PMS symptoms, which then returned once treatment ended after six months. The team then examined white blood cells from the same women with PMDD to test whether differences in gene expression might underlie the changes in responsiveness to the sex hormones.  

They showed that gene expression in a gene complex that regulates epigenetic processes, called the ESC/E(Z), differed in cells from the women with PMDD compared to those without. More than half of the ESC/E(Z) genes were over-expressed, while protein expression of four key genes was decreased in PMDD cells. Additionally, progesterone boosted expression of several of these genes in women without PMDD, while oestrogen decreased expression in those with the disorder.

'This is a big moment for women's health, because it establishes that women with PMDD have an intrinsic difference in their molecular apparatus for response to sex hormones – not just emotional behaviors they should be able to voluntarily control,' said Dr David Goldman from NIH's National Institute on Alcohol Abuse and Alcoholism, who led the study.

The study, published in the journal Molecular Psychiatry, provides the first scientific evidence that women with and without PMDD differ at a cellular level – which also suggests that the condition might be inherited. However, NHS Choices reports that the researchers do stress that the biological relevance of these findings should be interpreted with caution for now as there are 'many important elements' in the nervous system that cannot be seen in the blood cells and that 'it would only be a matter of speculation' to suggest these findings could apply to PMS.

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