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Biologic Link Between Genes and PMDD (premenstrual dysphoric disorder)

Source: ZF foto at

Source: ZF foto at

The NIMH, National Institute of Mental Health, released exciting news this week.  It’s about a study on genes and PMDD, and I will try to explain it to you as clearly as possible.  Dated January 3, 2017, the press release 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 characterized by sadness, irritability, and anxiety that occurs 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.  Reproductive hormones in women include estrogen and progesterone; these hormones rise and fall during 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 because 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 the woman should be able to control on her own, voluntarily.  Up until now there has not been a lot of scientific evidence linking reproductive hormones and mood disorders; many providers accepted patients’ accounts as valid anecdotal evidence for which there has been limited direct treatment.

Historically, 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.  In later years an attempt to experimentally “shut off” estrogen and progesterone in these women (with a medication) 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 follow-up study was done in the laboratory on white blood cells, or wbc’s, from women with PMDD (a wbc cultured cell line).  Researchers were able to identify a large gene complex (set of genes) 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 a healthy control group.  This gene complex, called ESC/E(Z), regulates the mechanisms that control how genes make proteins such as 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.  What does it mean?  It indicates that PMDD has a biologic basis to it that is linked to the genes we inherit.  It’s exciting because of the future potential for improved treatment options in reproductive hormone-related mood disorders.  Research in ongoing to gain a better understanding of the role of this set of genes on the brain.


A modified version of this article was previously posted in View From the Mist on Psychology Today.



(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

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