December 12, 2007

The Chemistry of Calm

Why do some people seem to weather life's catastrophes better than others? We all know people who handle horrific experiences — violence, war or natural disaster — and move on, while others become emotionally bogged down.

This is equally true at the lower end of the stress scale, where some of us take everyday hassles such as traffic jams or a canceled flight in stride and others become overwrought or paralyzed by stress.

Emotionally, it was as if they were driving a car with an accelerator but no brakes.

Now, new research suggests that genetics and biological processes in the brain play a big role in how we handle stress, and that someday there may be a way to "fix" an extreme response.

An article published in the online journal, Cell, argues that stress resilience — our resistance to stress and ability to recover from it — is determined by an active biological process. In other words, it is not that people who recover more easily from stress are superior in their abilities to handle it, but that they are lucky enough to have brains that process it more effectively biochemically.

In a series of studies, researchers found that stress resilient mice have an adaptation in their brain's response to stress that enables them to recover more quickly. Because these same biological mechanisms operate in people, further research may eventually explain why some people are more vulnerable to stress than others, as well as point the way toward new treatments.

As NIMH (National Institute of Mental Health) Director Dr. Thomas R. Insel put it, "We now know that the mammalian brain can launch molecular machinery that promotes resilience to stress, and we know what several major components are. This is an excellent indicator that there are similar mechanisms in the human brain."

First, the mice in the studies were stressed by being put in cages with bigger, more aggressive mice. Scientists then studied the part of the mice's brains that emits, or "fires," triggering the release of the neurotransmitter dopamine, which is part of the normal stress response.

Less stress resilient mice had higher rates of firing. They then remained afraid of all social interaction for as long as a month after meeting the aggressive mice. More stress resilient mice had lower rates of firing, recovered quickly and continued to interact with other mice. Researchers found resilient mice had a biochemical braking process involving potassium that slowed the rate of firing. Less stress resilient mice lacked this mechanism. Emotionally, it was as if they were driving a car with an accelerator but no brakes.

Further work by the same team of researchers, Vaishnav Krishnan, Ming-Hu Han, PhD, Eric J. Nestler, MD, PhD, and colleagues from the University of Texas, Harvard and Cornell, identified genetic variations behind the differences in the brains of the mice. Using the information, they were able to block the excessive, runaway signals with experimental compounds and turn stress-vulnerable mice into resilient mice.

Keep in mind that stress is not all bad. A proper response to stress is key to our ability to learn and to survive. Animals — whether two-legged or four-legged — do not live long without learning how to deal with a threatening situation. Once a stressful situation has passed, however, it is equally important to be able to recover and move on.

The less stress resilient among us, as well as combat veterans, crime victims and others who have undergone extreme stress, show how important it is to be able to recover from our own response to stress. The connection these researchers have found between the stress response, stress resilience and the chemistry of the brain will hopefully lead to better treatments for the anxiety, obsessive thoughts and trauma suffered by those with PTSD and other stress disorders.

Source: Cell,131, 2. Oct. 18, 2007: Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions.
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