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Brain scans 'could reveal mental strength'

By Roger Highfield, Science Editor
Last Updated: 6:01pm BST 18/10/2007

Brain scans to reveal who is most likely to crumple under the stress of bereavement, divorce, disaster and redundancy, along with new treatments for a wide range of mental disorders, could result from a study published today.

Researchers have found important clues in the brain about why some succumb in the face of adversity while others prevail by remaining upbeat and optimistic.

Brain scanners could, in theory, be used to examine mental toughness, which depends on how parts of the brain "talk" to each other. "We may be getting close, perhaps within the next five years," commented one of the team, Prof Eric Nestler, from the University of Texas Southwestern Medical Centre.


In the long term, this research will help scientists learn how to enhance a naturally occurring mechanism in the brain that promotes the ability to tolerate psychological stress, after the successful use of an experimental drug to increase the mental resilience of rodents.

"The fact that we could increase these animals' ability to adapt to stress means that it may be possible to develop compounds that improve resilience. This is a great opportunity to explore potential ways of increasing stress-resistance in people faced with situations that might otherwise result in post-traumatic stress disorder", said Prof Nestler.

This could have wide ranging implications because in people stress can play a major role in the development of several mental illnesses. "This means that chronic stress, depression, post-traumatic stress disorder and similar disorders might be treated by promoting the mechanisms that underlie resilience," said Prof Nestler.

A key question in mental health research is: Why are some people resilient to stress, while others are not? The answer is published today in the journal Cell, by Prof Nestler and colleagues from the University of Texas Southwestern Medical Centre, Harvard University, and Cornell University, who studied the social withdrawal in mice after putting them in cages with bigger, more aggressive mice.

Even a month after the encounter, some mice were timid and avoided the bigger mice, even sugar and sex - an indication that stress had overwhelmed them - but most adapted and continued to interact, giving researchers the opportunity to examine the biological underpinnings of the protective adaptations.

Looking at the reward and pleasure areas of the brain, which promote acts that ensure survival, the researchers found differences in the activity of cells that make the chemical messenger dopamine, with vulnerable mice showing excessive activity during stressful situations and more activity of a molecule called BDNF.

But adaptive mice maintained normal rates of firing, and lower BDNF activity, because of a protective mechanism in the VTA (ventral tegmental area) and the NAc (nucleus accumbens) of the brain. Chemical signals carried by BDNF from the VTA to the NAc played an essential role in making the mice vulnerable.

Blocking the signals with experimental drugs turned vulnerable mice into resistant mice, suggesting that drugs could be developed to make people tougher and more resilient. "Preventing BDNF signalling to the nucleus accumbens may be a key mechanism of resistance to stress and depression," Prof Nestler said.

Another component of the study revealed that mice with a naturally occurring variation in part of the gene that produces the BDNF protein are resistant to stress. The variation results in lower production of BDNF, consistent with the finding that low BDNF activity promotes resilience.

The scientists also examined brain tissue of deceased people with a history of depression, and compared it with brain tissue of mice that showed vulnerability to stress. In both cases, the researchers found higher-than-average BDNF in the brain's reward areas, offering a potential biological explanation of the link between stress and depression.

However, Prof Nesler said that much more work must be done to ensure that a drug to enhance mental resilience does not have side effects. "It doesn't happen in a vacuum. Blocking BDNF at certain stages in the process could perturb other systems in negative ways."

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