Study: Why Women Are More Sensitive to Stress

Women are more likely to suffer from depression and stress out than their cool male counterparts. New research suggests there might be a biological reason for the gender difference.

The new study, done on rats, finds females are more sensitive to low levels of an important stress hormone and less able to adapt to high levels of it than males. Since rats do have some of the same neural systems we do, the rat research could have implications for humans, though stress in humans is more complicated than in rodents, the researchers say.

It has long been recognized that women have a higher incidence of depression, post-traumatic stress disorder, and other anxiety disorders, said study researcher Rita Valentino, a behavioral neuroscientist at The Children’s Hospital of Philadelphia. But the underlying biological mechanisms for that difference have been unknown.

Valentino's research focuses on corticotropin-releasing factor (CRF), a hormone released in the brain in responses to stress, in both humans and rats. CRF is a neurotransmitter, meaning it helps communicate signals between brain cells. Some neurons "send out" the CRF signal while others contain receptors to receive it.

Valentino and her colleagues analyzed the brains of rats as they responded to a swim stress test, aimed to trigger the release of the CRF hormone.

In female rats, neurons had receptors for CRF that bound more tightly to the hormone than in male rats, and so were more responsive to CRF.

Also, after exposure to stress, male rats had an adaptive response, called internalization, in their brain cells. Their cells reduced the number of CRF receptors, and became less responsive to the hormone. In female rats this adaptation did not occur.

"This is an animal study, and we cannot say that the biological mechanism is the same in people," Valentino said, adding that other mechanisms play a role in human stress responses, including the actions of other hormones. However, "researchers already know that CRF regulation is disrupted in stress-related psychiatric disorders, so this research may be relevant to the underlying human biology," she said.

In addition much of the previous research on stress disorders in animal models used only male rodents, so important sex differences may have gone undetected, Valentino said. "Pharmacology researchers investigating CRF antagonists as drug treatments for depression may need to take into account gender differences at the molecular level," she said.

The results of the study are published online June 17 in the journal Molecular Psychiatry.