The fact that women are the more stressed sex may not be a surprise. The numbers alone tell a compelling story -- women are two times more likely to suffer from depression, post-traumatic stress disorder and other stress-related disorders.

Now, neuroscientists have discovered women may be wired to be more sensitive to stress.

The study, performed on rats, involved a hormone secreted in the brain, called corticotropin-releasing factor, which orchestrates the body's response to stress. For those with stress-related disorders, such as depression and anxiety, the evidence suggests that the hormone malfunctions in some way, causing a person to feel overly emotional, anxious or fearful.

In the study lead investigators Rita Valentino and Debra Bangasser showed that female rats were vulnerable to levels of CRF that were too low to affect male rats.

They compared how female and male rat brains responded to a 15-minute swim stress test. As expected, the swim test triggered the rats to release CRF. However, the female and male rats responded differently to the hormone. CRF bound more tightly to the CRF receptors in female rats than in male rats.

"The translation from rats to humans is that females may have a lower threshold for stress," said Valentino, a behavioral neuroscientist at the Children's Hospital of Philadelphia. "In other words, females may respond to a small stimulus that would not elicit a response in males."

The male rats were also better at handling and adapting to stress in the long term. After the swim test, male rats had lowered the number of CRF receptors in their brains. This indicates that the male rats had adapted to the previous stressful experience and were now less responsive to the hormone. This adaptation did not occur in the female rats.

The study, however, only measured the activity of these CRF neurons, not the actual behavioral changes in the rats, said Tracy Bale, from the University of Pennsylvania's School of Veterinary Medicine, who was not involved with the study. The interpretation of the results is based on the ability of these neurons to recover from the stress of swimming, she noted.

Although rats have similar neural systems to humans, humans react to stress in much more complex ways and the researchers acknowledge they cannot say for certain that the biological mechanism is the same in rats and people.

Bale said, however, that any sex differences in how stress receptors react to or recover from stress may have important implications for drug development. Drugs that manipulate the CRF receptor are now being developed to treat stress-related disorders.

It's also possible that men and women react differently to other neurotransmitters besides CRF. "This is something to look into, particularly for diseases that occur more frequently in females," said Bangasser.