A Gene for the Uptight and Edgy

Ever wonder why some people are more nervous than others? At least part of the answer, says a Report in the 29 November issue of Science, may lie in a swatch of DNA that helps regulate levels of serotonin, a chemical that transmits nerve signals in the brain and elsewhere in the body.

Previous work had shown that the DNA region in question, a promoter located on chromosome 17, switches on a nearby gene coding for a protein that shuttles serotonin back into nerve cells so they can reuse it as a neurotransmitter. Two versions of this promoter have been found in people; one is 44 base pairs longer than the other. Individuals with the shorter version have lower levels of the serotonin transport protein, allowing serotonin to persist longer in brain cells. And because altered levels of this neurotransmitter have been linked to anxiety-related disorders and to depression, Klaus-Peter Lesch of the University of Würzburg in Germany, Dennis Murphy of the National Institute of Mental Health in Bethesda, Maryland, and their colleagues wanted to find out whether the short promoter variant is linked to personality traits like high anxiety.

The researchers tested 505 people, about half of whom turned out to have the short promoter form and half the long form, and then had them complete an extensive personality questionnaire. The team found that people with the shorter version were more likely to admit to worrying a lot and said they were often tense and jittery. The short promoter accounted for about 4% of the variation in the personality scores in the group tested and about 8% of the variation in anxiety-related traits, such as fretting about the future.

Although more studies are needed to confirm a genetic link between anxiety and the promoter and its associated serotonin transporter gene, this DNA "is one of the best prospects for a gene in anxiety-related behaviors that we have," says David Goldman, a geneticist at the National Institute on Alcohol Abuse and Alcoholism in Rockville, Maryland. "It won't be long before we know whether it's related to ... psychiatric diseases like phobia or panic disorders," he says.

Posted in Biology