Brain Scans Reveal Changes Linked to PMDD

Premenstrual dysphoric disorder (PMDD) is characterized by severe irritability, tension, and mood swings during the last week of the premenstrual cycle. The cause or causes have been unclear.

For example, even though PMDD symptoms correspond with a menstrual cycle phase, no differences in female hormone levels in the blood have been detected between PMDD subjects and healthy comparison subjects.

Now a new study offers up a possible explanation—it supports the clinical relevance of the proposal that dorsolateral prefrontal cortex dysfunction represents a substrate of risk for PMDD. This hypothesis was reported by Karen Berman, M.D., of the National Institute of Mental Health Intramural Research Program and colleagues online January 30 in AJP in Advance.

Berman and her colleagues asked 15 subjects with PMDD to engage in a cognitive task under three artificially contrived hormone conditions—when the subjects were producing estrogen only, when they were producing progesterone only, and when they were producing neither.

The subjects’ brain activity was measured during each of the three paradigms with two types of neuroimaging—PET and fMRI.

The researchers also had 15 control subjects engage in the same cognitive task, during which their brain activity was likewise measured with PET and fMRI.

The PMDD group showed greater activation of the dorsolateral prefrontal cortex during the cognitive task than the control group did, and under all three hormone conditions. Moreover, in the PMDD group, the degree to which the dorsolateral prefrontal cortex was activated correlated with the severity of the subjects’ PMDD symptoms and the age of onset of PMDD. That is, the greater the activation, the greater the symptoms and the earlier the onset of the illness.

Berman and colleagues thus believe that the prefrontal cortex, specifically the dorsolateral prefrontal cortex, “plays an important role in PMDD” and irrespective of a woman’s current female hormone situation. However, they do not rule out that progesterone and estrogen contribute to PMDD to some degree, since these two hormones are known to interact with the dorsolateral prefrontal cortex.

“PMDD is not a diagnosis without controversy in women’s mental health circles,” Claudia Reardon, M.D., an assistant professor of psychiatry at the University of Wisconsin and an expert on women’s mental health issues, told Psychiatric News. “Studies like this that start to look at objective data will hopefully help us move toward a more informed understanding of the nature of the underlying dysfunction. This study found a correlation, which doesn’t imply causality, but the data are thought-provoking and hypothesis-generating nonetheless.”

The research was supported by the Intramural Research Program of the National Institute of Mental Health. ■