Gene Identified That May Play Role In Psychological Disorders

A new study found that people with a particular variation in the serotonin transporter gene (5-HTT) showed a greater fear response during a laboratory experiment.

"While a single gene cannot be held accountable for complex emotional states - such as anxiety disorders - we're beginning to pinpoint which genetic traits may make a person susceptible to developing psychological disorders," said Norman Schmidt, a study co-author and an associate professor of psychology at Ohio State University.

The study appears in the new issue of the Journal of Abnormal Psychology, published June 14.

The 5-HTT gene is responsible for regulating the chemical serotonin, which helps transmit messages in the brain. The people who showed a greater fear response during an experiment had a variation in the gene. This variation is linked to increasing the regulation of serotonin levels in the brain.

Increased regulation means that the neurons in the brain take up serotonin faster, leaving less available. "A decreased availability of serotonin may play a role in a variety of psychological disorders," Schmidt said.

In the study, 72 participants were separated into two groups based on each individual's expression of the 5-HTT gene. The researchers analyzed blood samples to determine how each subject expressed the gene. These subjects were considered "super-normal," because none had a history of psychiatric or medical disorders.

"When studying a risk factor for anxiety or other psychological disorders, it's best to use subjects in whom the factor hasn't yet manifested," Schmidt said.

In order to determine each subject's fear response, the participants took two breaths of pressurized air through a mouthpiece. The breaths were spaced 10 minutes apart. One breath consisted of pressurized room air, and the other was a carbon dioxide-oxygen mix (35 percent CO2 and 65 percent O2). The carbon dioxide mix is designed to make subjects feel they are momentarily short of breath, Schmidt said, which can aggravate anxiety-related symptoms for some people.

Subjects with the "long" form of the 5-HTT gene - the one implicated in the increased regulation of serotonin - reported feeling more anxiety when they took the CO2 breath than did people with the "short" form of the gene. "People with the long variation of this gene seem to be at greater risk for responding with high levels of anxiety or panic when in fearful situations," Schmidt said. "People in this category may have a greater chance of developing anxiety disorders."

The researchers also found a relationship between the 5-HTT gene, a psychological trait called anxiety sensitivity, and how the subjects' heart rates responded during the experiment.

Anxiety sensitivity - which was tested in the subjects before the experiment began - involves the perception that certain bodily sensations may produce harmful consequences. For example, people high in anxiety sensitivity may perceive that shortness of breath indicates suffocation, or that heart palpitations indicate a heart attack. People low in anxiety sensitivity experience these sensations as unpleasant but non-threatening.

The results showed that the long form of the 5-HTT gene and high anxiety sensitivity may be a particularly bad combination. People with that combination showed less heart rate variability during the experiment than those with the long form and low anxiety sensitivity, or those with the short form of the gene and high anxiety sensitivity.

People in the former group had an increase in their heart rate when they took the carbon dioxide test, and their heart rate remained high afterwards. For other people, the heart rate increased as a result of the carbon dioxide test, but then dropped after it was clear to them they were in no danger.

"People with both the genetic risk factor and the psychological risk factor for anxiety showed the worst response to the fear-inducing experiment," he said. "These people seemed to be at risk for responding with more fear when faced with unpleasant bodily symptoms such as they had in this experiment."

Researchers are just beginning to look at a host of candidate genes - such as 5-HTT - that may be linked to anxiety and panic disorders. "More candidate genes will be examined," Schmidt said. "It's clear that a single gene is rarely the culprit - there are multiple genes that are involved in most types of psychological disorders.

"But I think that the combination of genetic traits and psychological traits may ultimately be the best way to predict psychological disorders."

Schmidt co-wrote the study with Benjamin Greenberg, Qian Li and Dennis Murphy, all with the National Institutes of Mental Health; and Julie Storey and Helen Santiago, both with the Uniformed Services University of the Health Sciences (USUHS). The research was supported by a grant from the USUHS.