Researchers have identified molecular mechanisms in the brain that may explain why some people are less vulnerable to the stress caused by difficult situations.

While the research was done with mice, the findings could eventually lead to better treatments for chronic stress, depression and the post-traumatic stress disorder suffered by troops in Iraq and other battlefields, said study coauthor Eric Nestler, MD, chairman of psychiatry at the University of Texas Southwestern Medical Center at Dallas.


"One important lesson we have shown even in previous papers is that a series of genetically identical animals respond differently to chronic stress," Dr. Nestler said. "Thirty to 40% seemed to be resilient and did not develop bad symptoms. The clinical implications are that the ability to identify mechanisms of resistance can help provide new and novel approaches to stress."

New Study

The key lies in a pair of molecules used by some brain cells to communicate with one another, said Vaishnav Krishnan, lead author of the report and a student in a University of Texas Southwestern Medical Center program that leads to simultaneous MD and PhD degrees.

"Under stress, vulnerable mice increase the frequency of nerve activity using the neurotransmitter dopamine," Krishnan said. "That subsequently causes release of a nerve growth factor called brain-derived neurotrophic factor (BDNF). Resilient mice overcome these changes by increasing the expression of molecules that prevent the release of dopamine."

A neurotransmitter is a molecule that sends signals from one nerve cell to another.

Mice in the experiments were so inbred that they were genetically identical. Then they were put under stress by being placed in the territory of larger, more aggressive mice. Some of the test mice adjusted well to the stress of the situation, while others avoided contact and showed submissive behavior.

The researchers then made detailed studies of two brain regions-the ventral tegmental area (VTA) and the nucleus accumbens (NACC), which are part of the brain's reward area that promotes acts that aid in survival. They found that the excess BDNF production in vulnerable mice occurred in the VTA but not the NAcc region. Chemical signals sent by the protein from the VTA to the NAcc made the mice vulnerable to stress. Experimental compounds that blocked those signals turned vulnerable mice into resistant mice.


According to Dr. Nestler, the findings raise the possibility of tools to develop things in the brain that encourage resilience, to help people with stress"

"We have always tried to understand the changes in the brain that lead to such things as the symptoms of post-traumatic stress disorder," Krishnan added. This study shows we can increase our understanding and development of new therapeutic measures to overcome those changes."

But new therapies might not be easy to develop, Dr. Nestler said, since a decrease of dopamine or BDNF activity might be helpful in one part of the brain but harmful in another area.

Thomas R. Insel, MD, director of the US National Institute of Mental Health, which funded the research, said "What's exciting here is that it is important for resilience, being able to recover from a traumatic event," Dr. Insel added. "One of the great values of this work is to help us understand how mammals, including humans, might be able to recover from the traumas inherent in daily existence."

In a recent study of 716 men (average age 65), I those who dealt well with stress (such as by directly addressing problems) had higher HDL "good" cholesterol levels than men who reacted to stress in negative ways (such as by blaming and/or isolating themselves).

Theory: Good coping mechanisms may decrease stress hormones, such as cortisol, thereby promoting healthful HDL levels.

Stress Promotes Gum Disease

High levels of stress, as well as anxiety, II depression and loneliness, increase levels of the hormone cortisol. Cortisol inhibits the immune response, which can provoke periodontal tissue breakdown. Also, people under stress tend to neglect oral hygiene and increase nicotine and alcohol use.

Self-defense: Seek healthy ways to relieve stress-exercise, maintain a balanced diet and get plenty of sleep.

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