Scientists have identified a gene they say is a strong candidate for involvement in premenstrual dysphoric disorder (PMDD) and other maladies associated with the natural flux in hormones during the menstrual cycle. In a paper published Monday in the Proceedings of the National Academy of Sciences, Rockefeller University researchers detail experiments in mice showing that a common human variant of the gene increases anxiety, dampens curiosity and tweaks the effects of estrogen on the brain, impairing memory. If applied in the clinic, the work could help diagnose and treat cognitive and mood disorders related to the menstrual cycle and inform treatments during menopause, such as hormone replacement therapy, researchers say.
The experiments homed in on the gene for a protein that, among other things, works with estrogen to enhance the adaptability of neurons in the hippocampus, a brain region that plays a key role in mood, cognition and memory. A change in one amino acid in this gene, called brain-derived neurotrophic factor (BDNF), creates the variant BDNF Met, which is carried by 20 to 30 percent of Caucasian women. Past research showed that it is a risk factor for psychiatric problems such as depression and bipolar disorder and is generally associated with higher anxiety and impaired memory. The Rockefeller scientists and their colleagues at Weill Cornell Medical College now show that the performance of memory tasks by mice with both the variant and the regular gene depends on where they are in their estrous cycles. It is the first time that a genotype has been shown to interact with a hormone cycle to influence a cognitive behavior, one reviewer of the paper wrote. The researchers also show that mice with the variant gene are more skittish- they spent much less time in the vulnerable center of a well-lit cage before scurrying to a corner. As a result, they spent less time exploring objects placed in their cage.
"Even though the BDNF Met m
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