by A new study i Biological Psychiatry, published by Elsevier, explored the interaction between the serotonin system and estradiol in the brain, showing that the central nervous system in patients with premenstrual dysphoric disorder (PMDD) appears to increase serotonin transporter density from the periovulatory phase (when when estradiol levels are high) to the premenstrual cycle phase (when both estradiol and progesterone are decreasing). The results may advance the clinical treatment of PMDD.
Premenstrual syndrome (PMS), which can include physical symptoms as well as depression and anxiety, affects about half of all menstruating individuals a few days before the start of their period. About 3 to 8% of people who menstruate experience PMDD, a much less recognized diagnosis. PMDD is also associated with mood swings, depression, and anxiety, but the symptoms are more severe and can last for up to two weeks at a time. The lifetime toll of PMDD is comparable to that of people with major depressive disorder.
Previous studies comparing ovarian hormone fluctuations between women with PMDD and healthy women have found no significant differences, suggesting that peripherally dysregulated hormones are not the root cause of the disorder. Another idea is that the brain’s response to normal endogenous hormonal changes differs in patients with PMDD, although it is not yet clear how this occurs. Treating PMDD with selective serotonin reuptake inhibitors, or SSRIs, relieves symptoms very quickly — on the order of hours or days, rather than weeks as in the treatment of depression.
In the current study, led by Julia Sacher, MD, PhD, from the Max Planck Institute for Cognitive and Human Brain Sciences, Leipzig, Germany, 30 patients with PMDD and 29 unaffected control women were examined over two menstrual cycles. The researchers used positron emission tomography (PET) imaging to look at the availability of the serotonin transporter protein in the brain throughout the cycle, showing short-term changes in its expression.
“​​​​We found a significant increase in serotonin transporter from periovulatory to premenstrual phase in patients with PMDD — an 18% change in the midbrain, the brain region with the richest expression of serotonin transporter. This increase was associated with mood intensity pre-existing depression,” said Dr. Sacher.
Unexpectedly, Dr. Sacher and his colleagues also found a decrease in midbrain serotonin transporter density in healthy women, which may indicate a protective mechanism of the healthy brain of women amid a changing hormonal environment.
“Typically, serotonin transporter density is assumed to be an individual trait, with only about 10% change over a ten-year period as the human brain ages, rather than a state that changes within shorter periods of time. However, studies in patients with seasonal affective disorder (SAD) show seasonal changes in the serotonin transporter,” explained Dr. Sacher. “Although the reports regarding the availability of the serotonin transporter in depression are mixed, this may be due to the heterogeneity of that disease. In more homogeneous types of affective disorders, such as PMDD or SAD, there seems to be a relatively fast dynamics of availability important serotonin transporter. role.”
John Krystal, MD, editor of Biological Psychiatrysaid of the work, “This technically demanding study identifies a potential new mechanism contributing to negative premenstrual mood states in some women. It also supports the use of SSRIs to treat premenstrual dysphoric mood.”
The results provide evidence that individuals with PMDD experience short-term changes in serotonin transporter density during the menstrual cycle, suggesting that patients may benefit from taking SSRIs at specific times during the cycle to focus on these changes the best.
