Researchers find gene link to anxiety

Sunday, July 21, 2002

Prone to anxiety? It may be in the genes.

Federal scientists have discovered that inheriting a certain form of a gene called the serotonin transporter leads to an exaggerated response in the area of the brain that regulates fear and other negative emotions.

Dr. Daniel Weinberger and his colleagues at the National Institute of Mental Health took brain scans of 28 volunteers as they looked at images of frightening faces. The scan was measuring activity in the amygdala, the brain's fear center, as the person looked at the images.

Then the investigators analyzed the volunteers' DNA to see which form of the serotonin transporter gene they inherited. There are two varieties of the gene, one short and the other long.

Weinberger and his colleague, Ahmad Hariri, were interested in this particular gene because it's been linked to many behavioral disorders, including depression and anxiety. Animals whose serotonin systems are disrupted early in life have altered fear reponses that last until they die.

In the study, published Friday in the journal Science, people with the short version of the gene had a lot more activity in the amygdala when looking at the scary faces than did those with the long version. This is the first time scientists have directly shown how a genetic mechanism can predispose how the brain perceives emotional stimuli. This bias, says Weinberger, can contribute to temperament and a person's vulnerability to anxiety.

"The technique to image a genetic difference is unique," said Dr. Jack Gorman, the Lieber professor of psychiatry at Columbia University College of Physicians and Surgeons. "It's a spectacular finding."

The amygdala alerts humans and animals to danger so that their bodies can mount the appropriate biological response to protect themselves.

50-50 split

The gene under review makes a protein that shuttles serotonin around the brain.

About half the population has the short form of the gene, Harari said. The study was not large enough to reach conclusions about how the brain's exaggerated response affects behavior. Such studies are now being designed but will be extraordinarily complex.

"Behavior represents a complex interaction between biology, genes and the environment," Weinberger said. "To manifest anxiety you need a brain response to something in the environment that signals danger. Then, there are other genetic factors and learned behavior that interact to alter the expression of emotion."

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