Healthy Living

Hormone-Related Genes Linked To Premenstrual Dysphoric Disorder

Exciting news came from the NIMH, the National Institute of Mental Health, this past week. It’s a press release about a study on genes and PMDD, which I want to share with you as simply as possible. The report, dated January 3, 2017, announced that NIH researchers have discovered a link between a reproductive hormone-related set of genes and PMDD, or Premenstrual Dysphoric Disorder. PMDD is a disabling mood disorder causing sadness, irritability, and anxiety in the days right before a woman’s menstrual period. It affects approximately 2-5% of reproductive age women. A gene, made up of DNA and found on our chromosomes, is inherited from our parents. Genes instruct the body to make proteins and molecules necessary for the body to function properly. Reproductive hormones are estrogen and progesterone in women; these hormones rise and fall with the cycles of her menstrual period. This report adds to prior evidence that PMDD is a disorder of a cell’s response to estrogen and progesterone. It’s the first indication that the cells from women who have PMDD don’t work together properly, and offers a credible explanation for a woman’s abnormal sensitivity to estrogen and progesterone. (1)

This is big news in women’s mental health. It verifies that women who have PMDD have a basic difference in the way their molecules respond to reproductive hormones. It is evidence that PMDD is not just an issue of erratic emotions and behavior that a woman should be able to control on her own, voluntarily. Until now there has not been a lot of scientific evidence linking reproductive hormones and mood disorders, or genes and mood disorders. For years many providers accepted patients’ accounts of symptoms preceding their periods as valid but anecdotal clinical evidence for which there has been limited direct treatment.

In the late 1990’s the NIMH research team showed that women who experience mood symptoms right before their menstrual periods were particularly sensitive to the normal cyclic changes in reproductive hormones. But at the time the cause was not clear. Years later, a research study experimentally “shut off” estrogen and progesterone in these women (with a medication) and found that this eliminated their PMDD symptoms. Re-starting the hormones was found to cause a return of the symptoms. This established that women with PMDD have a biologically based sensitivity to these hormones that might be related to differences in the molecules in their cells.

A related study was done in the laboratory on white blood cells, or wbc’s, from women with PMDD (called a wbc cultured cell line). In this study researchers were able to identify a large set of genes (gene complex) in which the way the genes worked to instruct the body in making proteins (called gene expression) differed greatly in those who have PMDD compared to those in a healthy control group. This gene complex, called ESC/E(Z), regulates the mechanisms that control how genes make proteins, including hormones. The researchers found several instances of altered gene activity where there was abnormal regulation of the cell’s response to these hormones in PMDD.

It’s a first step. It indicates that PMDD has a biologic basis, inherited in our genes. It’s exciting because of the potential for improved treatment options in reproductive hormone-related mood disorders in the future. Research in ongoing to gain a better understanding of the role of this set of genes on the brain.


(1) Dubey N, Hoffman JF, Schuebel K, et al. The ESC/E(Z) complex, an intrinsic cellular molecular pathway differentially responsive to ovarian steroids in Premenstrual Dysphoric Disorder. Molecular Psych. Jan3, 2016, doi:10.1038/mp.2016.229

A modified version of this article was previously posted on Psychology Today.