Menopausal brain changes support estrogen’s protective role in schizophrenia

Researchers have found morphological differences between pre- and postmenopausal women with schizophrenia that support a protective role for estrogen in the psychiatric disorder.

The results of their cerebral magnetic resonance imaging study showed that postmenopausal women had more gray matter volume reduction than premenopausal women at the left middle frontal gyrus.

This suggests that "the effect of menopause on brain structural changes in schizophrenia patients could be attributable to the loss of the protective effect of estrogen against the pathophysiology of schizophrenia," Yoshiro Okubo (Nippon Medical School, Tokyo, Japan) and colleagues explain.

The theory of a protective role for estrogen may also partly explain why women with schizophrenia have fewer morphological brain changes than men with the condition, and why women have a second peak of onset, often around 45-54 years of age during the premenopausal phase.

As reported in Psychiatry and Clinical Neurosciences, the researchers compared the volume of regional gray matter in 40 women with schizophrenia (20 premenopausal and 20 postmenopausal) and 50 mentally healthy women.

Women with schizophrenia had significantly greater gray matter reductions than mentally healthy women in the insula, superior temporal gyrus, anterior cingulate, parahippocampal gyrus, and thalamus. The differences were found predominantly on the left side.

The same comparisons between the pre-and postmenopausal women showed that postmenopausal women had significantly smaller regional gray matter volume at the left middle frontal gyrus than premenopausal women.

There was also a significant correlation between brain morphology in the right superior frontal gyrus and interval after menopause, with the longer the interval, the larger the volume deficit.

"These regions are not identical, but both are located in the prefrontal area," the researchers comment. They add that previous studies have linked morphological changes in the prefrontal area to negative symptoms and cognitive impairment, and showed that the right middle frontal cortex is especially vulnerable to the long-term effects of schizophrenia.

"According to these reports, the present results may indicate that postmenopausal patients are at a more advanced stage of progression," says the team.

They conclude: "These results support the hypothesis of the protective role of estrogen against schizophrenia."

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