JAN 04, 2017 3:45 PM PST

Premenstrual Mood Disorder Gene Network Discovered

WRITTEN BY: Jennifer Ellis

Premenstrual dysphoric disorder (PMDD) affects 2 to 5 percent of women and causes disabling irritability, sadness, and anxiety. And while premenstrual syndrome (PMS) is much more common, it is also less severe than PMDD. It is not clear what causes either PMS or PMDD, except that they are directly associated with the onset of hormonal changes that occur during the menstrual cycle. However, clinicians have not found any difference in hormone levels in those with PMDD and those without.

National Institutes of Health (NIH) researchers have recently discovered that although hormone levels between PMDD patients and those who do not have severe symptoms remain similar, their cells’ reaction to the normal hormonal changes is quite different.

Expression of this ESC/E(Z) gene network was found to be systematically disturbed in PMDD. (Peter Schmidt, M.D., NIMH., David Goldman, M.D., NIAAA)

Scientists have known that these women have some sort of biologically-based behavioral sensitivity to normal hormone changes. Previous research shows that turning off estrogen and progesterone production halts PMDD symptoms, and adding the hormones back into the system causes a re-emergence of symptoms. So while the hormone levels are not an issue, a sensitive response to the hormones seems to be a problem.

Peter Schmidt, M.D., of the NIH's National Institute of Mental Health, Behavioral Endocrinology Branch and David Goldman, M.D., of the NIH's National Institute on Alcohol Abuse and Alcoholism, worked with colleagues to study gene expression in cultured white blood cell lines from women with PMDD and from asymptomatic controls. Interestingly, these cells express many of the same genes expressed in brain cells, hinting that there is a neural relationship between the symptoms and potential gene expression differences in patients.

“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.

After in-depth transcriptome analysis, the group found a link between PMDD affected cells and differential expression levels in a large gene network, called the ESC/E(Z) (Extra Sex Combs/Enhancer of Zeste) gene complex, that regulates epigenetic mechanisms controlling gene transcription in response to environmental changes, including sex hormones and stressors.

RNA and protein expression of the genes in the ESC/E(Z) gene complex were individually quantitated, revealing increased expression in more than half of the genes in comparison to the controls. These findings confirm that women with PMDD have a different cellular response in their gene function within this gene complex.

“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,” explained Schmidt.

The study, published in Molecular Psychiatry, holds promise for increased understanding of endocrine-related mood disorders and potential approaches to new treatments. The group is also investigating the connection of the gene complex to gene expression in the brain.

Sources: NIH, NCBI, Nature

About the Author
  • I love all things science and am passionate about bringing science to the public through writing. With an M.S. in Genetics and experience in cancer research, marketing and technical writing, it is a pleasure to share the latest trends and findings in science on LabRoots.
You May Also Like
MAY 13, 2021
Immunology
Tumors Hide From the Immune System by Masquerading as Baby Cells
MAY 13, 2021
Tumors Hide From the Immune System by Masquerading as Baby Cells
The immune system is programmed to recognize foreign bodies as potentially dangerous, promptly removing them before the ...
MAY 20, 2021
Genetics & Genomics
Mitochondrial DNA May be Affecting More Traits Than we Knew
MAY 20, 2021
Mitochondrial DNA May be Affecting More Traits Than we Knew
While the vast majority of our genes are in the genome that's held in the nuclei of cells, mitochondria are also known t ...
MAY 31, 2021
Genetics & Genomics
Gene Expression is Different in Two Parts of the Hippocampus
MAY 31, 2021
Gene Expression is Different in Two Parts of the Hippocampus
The hippocampus is a region of the brain thought to play a role in many different neurological and psychiatric disorders ...
JUL 01, 2021
Microbiology
Plague Bacteria Found In the Remains of a 5,000 Year Old Man
JUL 01, 2021
Plague Bacteria Found In the Remains of a 5,000 Year Old Man
This image by Dominik Göldner, BGAEU, shows the skull of a hunter gatherer that was recovered from a site in present-day ...
AUG 01, 2021
Genetics & Genomics
Rethinking the Cause of Mutations That Lead to Melanoma
AUG 01, 2021
Rethinking the Cause of Mutations That Lead to Melanoma
Throughout our lives, new cells often replace the ones that become damaged or worn out. As cells divide, they have to re ...
AUG 02, 2021
Microbiology
The Unique Microbiomes of Long-Lived People
AUG 02, 2021
The Unique Microbiomes of Long-Lived People
What's the secret of people that live a long life? The answer may be complex but for some, it could include the microbio ...
Loading Comments...