Anxiety is in the Gene

Clipped version of 1 gene linked to brain changes in emotion center

Written by Adam Marcus

Updated on July 19, 2002

FRIDAY, July 19, 2002 (HealthDayNews) -- The thought of a tax audit is enough to make anyone's palms sweat, but those of us whose anxiety runs even stronger may have our parents to blame.

People with a clipped version of a gene that controls a key emotion molecule have overactive brain reactions to stressful stimuli, a new study has found.

The gene is called SLC6A4, and the protein it encodes helps brain cells transport a messenger molecule known as serotonin after they've released the chemical. A region of this gene, called the promoter, controls how much of the transporter is produced.

One-third of people in this country have two long versions, or alleles, of the SLC6A4 promoter region. As a result, their brains produce more of the protein, which keeps their serotonin from lingering before it's absorbed. The rest have one or two short forms that lead to less efficient transport of the messenger chemical.

Serotonin is an important actor in depression and anxiety, and studies have shown that people with one or two copies of the short allele lean slightly toward the anxious and fearful on personality tests. This effect is modest -- 3 percent to 4 percent, on average -- and it's not clear how much it might influence behavior. However, studies in twins have determined that between 40 percent to 60 percent of the variation in anxiety levels between people are genetic in origin.

The new research, reported in today's issue of Science, sought to learn if the impact of the short allele might show up in brain activity, specifically in the amygdala. This almond-shaped site acts as the organ's emotion conductor, signaling the heart to pump faster, boosting breathing.

Dr. David Goldman, a neurogeneticist at the National Institute on Alcohol Abuse and Alcoholism, and his colleagues administered face recognition and memory tests to 28 men and women. Half had one or two copies of the short allele, and the rest had two of the long version.

The researchers were interested in performance on the tests, but they really wanted to see if the two groups had different electrical activity in their amygdalas. They monitored the impulses with a kind of magnetic resonance imaging (MRI) machine that can tolerate movement.

The subjects performed equally on the two tests. However, when those with the short anxiety gene alleles were shown images of angry or fearful faces, their amygdalas became hyperactive, an effect not seen in the other volunteers.

"The groups are performing well, but their brains are doing something different, which we think reflects the higher anxiety levels in the people who have the" short gene type, Goldman says.

Although subjects in the two groups scored similarly on personality tests for general anxiety and fearfulness, Goldman says that's predictable in such a small study. "I wouldn't expect that it would be detectable in a data set of this size," he says.

The discovery that SLC6A4 has a hand in anxiety is something of a paradox. Modern antidepressants, like Pfizer's Zoloft and Eli Lilly's Prozac, are serotonin reuptake inhibitors. In other words, these drugs, which also help treat anxiety, work much like the shortened allele does naturally.

Why, then, do people with the shortened gene worry more rather than less?

"We don't really know the answer to that," Goldman says. Scientists are now trying to resolve the question, including by engineering mice missing the gene, he says.

What To Do

To find out more about anxiety disorders, try the National Institute of Mental Health, or the Anxiety Disorders Association of America.

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