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Gene May Contribute to Anxiety, Study Finds

Behavior: One version may instill confidence, another a bent toward worrying. Findings are tentative in a field fraught with controversy.


WASHINGTON — Scientists for the first time have identified a personality gene that seems to influence whether a person will be a hand-wringing worrier or a self-assured warrior.

The gene can act like natural Prozac in the brain, enhancing self-confidence and contributing to a cheerful temperament, according to a report in today's issue of the journal Science. But the researchers found that most people inherit a different version of the gene that apparently has the opposite effect, predisposing them to mild but chronic anxiety.

But the researchers cautioned that the gene accounts for only about 4% of the difference between chronically anxious people and those who stride through life with cheerful aplomb.

The rest of the difference, scientists believe, is due to a dozen or more still-unidentified genes and a host of environmental factors, including parenting practices, that are as important as all those genes combined.

If confirmed and extended in follow-up studies, the finding could shed light on the genetics of personality and facilitate development of better mood-altering medications. Already it has ignited a burst of speculation about why evolution might have favored individuals with an anxious bent.

The work is the latest in a string of recent efforts to find the genetic basis of complex behaviors--a new scientific specialty that has stirred controversy over its tentative findings of genes for homosexuality, alcoholism, manic-depression and "novelty-seeking."

Virtually all those findings have crumbled upon further analysis. And experts cautioned that the new gene, which in its most common form is linked to what psychologists call "neuroticism," could easily succumb to the same fate.

The new study, led by Klaus-Peter Lesch of the University of Wuerzburg in Germany, with scientists from the U.S. National Institutes of Health, focuses on a gene that regulates a kind of molecular pump that in turn affects brain levels of serotonin, a chemical messenger known to affect mood and personality.

Dean H. Hamer, a National Cancer Institute researcher who helped conduct the study, emphasized that many other factors contribute to personality and that the gene findings are only true on average. "There are people who score high for anxiety with long forms of the gene and vice versa. This gene is not their fate."

Moreover, Hamer said, the correlation relates only to "garden-variety anxiety and depression," not serious disorders such as clinical depression. And he noted that the study was conducted almost entirely on men--about half of them gay men who had already been recruited for another study. Although results did not differ between homosexual and heterosexual participants, it is uncertain for now whether the study's conclusions apply to women.


If the findings hold up, however, scientists will have to answer a difficult question: Why has a genetic variant that predisposes to anxiety persisted through evolution in a majority of the population?

"There may be some useful things about being somewhat more anxious . . . as long as it's within a normal range," said Dennis L. Murphy, chief of the National Institute of Mental Health's laboratory of clinical science and a collaborator on the new research. For example, Murphy said, "many people who are afraid to speak publicly say they get sharpened by the fear, and end up performing better."

Perhaps the most alluring explanation for anxiety's persistence comes from Hamer at the NCI. Evolutionary theory says that genes tend to be preserved if they increase the number of offspring, Hamer said, but one of Prozac's more common side effects is loss of libido. If serotonin's salutary effects on mood are linked to a dampening of eroticism, he speculates, then the reverse may also be true, and people who are anxious may tend to have more sex than their happier counterparts.

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