Sex Hormone-Sensitive Gene Complex Linked to Premenstrual Mood Disorder

Researchers discovered molecular mechanisms that may underlie a woman’s susceptibility to disabling irritability, sadness and anxiety in the days leading up to her menstrual period.

NIH researchers have discovered molecular mechanisms that may underlie a woman’s susceptibility to disabling irritability, sadness and anxiety in the days leading up to her menstrual period. Such premenstrual dysphoric disorder (PMDD) affects 2 to 5 percent of women of reproductive age, whereas less severe premenstrual syndrome (PMS) is much more common.

“We found dysregulated expression in a suspect gene complex which adds to evidence that PMDD is a disorder of cellular response to estrogen and progesterone,” said Dr. Peter Schmidt of NIMH’s Behavioral Endocrinology Branch. “Learning more about the role of this gene complex holds hope for improved treatment of such prevalent reproductive endocrine-related mood disorders.”

Schmidt, Dr. David Goldman of NIAAA and colleagues reported on their findings Jan. 3 in the journal Molecular Psychiatry.

“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 Goldman.

“For the first time, we now have cellular evidence of abnormal signaling in cells derived from women with PMDD and a plausible biological cause for their abnormal behavioral sensitivity to estrogen and progesterone,” said Schmidt.

Using cutting edge “disease in a dish” technologies, the researchers are now following up the leads discovered in blood cell lines in neurons induced from stem cells derived from the blood of PMDD patients. They hope to gain a more direct window into the gene complex’s role in the brain.