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Provoking panic
Anxiety, psychology, and genetics
Edward R. Winstead

Provoking panic in people is one way to figure out why we are the way we are. Testing DNA is another. When scientists used both approaches in a recent study of anxiety, they learned a little about anxiety and a lot about how to conduct research.

As reported in the Journal of Abnormal Psychology, the study found that individuals with a certain form of the serotonin transporter gene tended to express more fear during a psychological test. Since the brain chemical serotonin has been linked to anxiety, the researchers expected as much. More interesting than the finding is the uncommon marriage of genetics and psychology that produced the result.

"The novel aspect of this study was to show that you can look at a specific psychological risk factor and a specific genetic risk factor and their interactions," says Norman Schmidt, of the Department of Psychology at Ohio State University. The psychological risk factor is what psychologists call anxiety sensitivity. People with this disposition tend to be hypersensitive to their bodies and notice every little ache and pain, according to Schmidt. The genetic risk factor is serotonin, which plays a role in eating disorders and addiction, as well as nervousness.

taking the CO2 challenge

Apparently very few researchers have tried to investigate the two factors together using this sort of integrated approach. "Everyone researching complex psychological disorders pays lip service to the role of complex gene-environmental interactions, but almost no one studies it," says Schmidt. As the researchers note in their paper, however, several recent studies have looked at smoking behavior and genes.

Schmidt's team analyzed DNA from 72 subjects to determine which versions of the serotonin transporter gene they had. Then, the subjects underwent a laboratory test used in psychological evaluations known as the "CO2 challenge." Each person received two breaths about ten seconds apart of pressurized air from a mouthpiece. The first breath was oxygen, but the second was a combination of oxygen and carbon dioxide, intended to make subjects feel momentarily breathless. In people with anxiety disorders, the CO2 challenge usually triggers a panic attack.

None of the subjects experienced anything close to a panic attack, and that was by design. The researchers recruited a sample of "pure" subjects—individuals who did not have a history of psychiatric or medical disorders that might influence their behavior. "We didn't want our results to be confounded by a subject's prior diagnosis," explains Schmidt.

next question: what is normal?

The ultimate goal of the research is to be able to predict how cognitive disposition and genetics will interact in an individual before symptoms appear. Plans are underway for a long-term study that could track changes in a larger population. Most anxiety disorders begin in young adulthood, says Schmidt, so the sample would be weighted toward the young and have a high percentage of women, who are disproportionately affected by these disorders for reasons that are not known.

One of Schmidt's collaborators is Dennis L. Murphy, who runs the Laboratory of Clinical Science at the National Institute of Mental Health. In the mid-1990s Murphy's team of researchers helped characterize the role of the serotonin transporter gene. While the current study does not add a great deal in terms of data, Murphy says, the novel approach might encourage future collaborations between researchers of different stripes, such as gene hunters and psychologists.

Murphy signed on to Schmidt's study in part because the goal was to try to understand the normal dimensions of a behavior that clearly is shaped by genes and environment. Although most genetics research targets disorders, such as schizophrenia or colon cancer, Murphy predicts that researchers increasingly will use new technologies and approaches to study normal variation in humans. "All of us," he says, "are different in slightly small ways that make for interesting people who marry each other, associate as friends, or dislike each other."

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Schmidt, N.B. et al. Evaluating gene psychological risk factor effects in the pathogenesis of anxiety: A new model approach J Abnormal Psychol 109, 308-320 (May 2000).

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