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Study: Biology Might Explain Higher Rates of Anxiety, Depression in Women

A new study offers the first clues as to why anxiety disorders and depression are more common among women than men. Researchers say it might have to do with how women's brains respond to stress.

Researchers have long known that women are more prone to depression, anxiety and other stress-related disorders than men. But the underlying reasons for the gender difference have been elusive. A new study suggests it has to do with the way women process stress hormones at the molecular level.

One hormone in particular, corticotropin-releasing factor or CRF, initiates a cascade of biochemical events in the brain to produce a stress response.

Research led by behavioral neuroscientist Rita Valentino at The Children's Hospital of Philadelphia says that female brains are more receptive to CRF and produce stronger stress signals than male brains. "Those cells are going to respond to levels that wouldn't do anything in males. So they would respond perhaps to lower magnitudes of stressors," she said.

Valentino and her colleagues analyzed the stress response of rats in a swim test. Compared to male rat brains, researchers found that neurons in female rat brains had receptors to CRF that formed a tighter bond to cell-signaling proteins, heightening the stress response.

Investigators discovered that the brains of female rats did not have the same adaptive mechanism, called internalization, as the brains in male rats. Internalization keeps neurons previously exposed to stress hormones from becoming repeatedly over-excited.

Valentino says this process does not occur in female rats because a key protein involved in internalization fails to bind to cell receptors already stimulated by CRF.

Valentino says this difference could help explain chronic depression and anxiety in some women. "Here you are dealing with disorders that are more prevalent in females and with targets that are different in females. I think one of the things our paper brings to light is the importance of considering that not everything works the same in males and females," she said.

Although animal studies do not always translate well to humans, co-author Debra Bangasser, who is also a neuroscientist at The Children's Hospital of Philadelphia, says the research with rats might explain why people respond differently to anti-depressants designed to quell anxiety.

"A lot of people have been thinking there may be different genetic factors and I think something that our research points to is that sex may also be one of those factors that may, for certain treatments, help women or men respond better to a particular drug," she said.

Valentino notes that previous studies of stress disorders used only male rats. She says that might be the reason why gender differences in stress response have not been noticed.

An article investigating biochemical differences in male and female stress response is published in the journal Molecular Biology.