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Depression Health Center

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Estrogen Is Involved in Stress Response

Findings Could Explain Why Depression Is More Common in Women
WebMD Health News

Dec. 3, 2003 -- New research from Yale University may help explain why women are twice as likely as men to suffer from stress-related mental illnesses such as depression. Animal studies show that high levels of the female sex hormone estrogen affect the brain's ability to deal with stress.

Estrogen was found to amplify the stress response in areas of the brain most closely identified with depression and other stress-related mental illnesses. Researchers say the findings may one day lead to the development of treatments for depression that specifically target women.

"These findings suggest that there is a difference between men and women in how the prefrontal cortex responds to stress," says graduate student Rebecca M. Shansky, who was the study's lead researcher.

Estrogen Increases Stress Sensitivity

The Yale team exposed male and female rats to different levels of stress and then had the rats perform a short-term memory task designed to assess prefrontal cortex function. This region of the brain has been shown in previous brain imaging studies to be abnormal in depressed people. In the absence of stress, both the males and females performed the task equally well, and both sexes performed poorly when exposed to relatively high levels of stress.

Yet when levels of estrogen were high, female rats were impaired by lower levels of stress than male rats. During periods when this hormone was low, they responded similarly to male rats to stress.

"High estrogen levels made these animals more sensitive to the effects of stress," Shansky tells WebMD.

To further investigate estrogen's role in stress response, the investigators removed the ovaries from another group of female rats, and then implanted a time-released capsule containing either estrogen or placebo. When these rats performed a memory task, increased stress sensitivity was seen after estrogen replacement. The findings are reported in the December issue of the journal Molecular Psychiatry.

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