NEUROTICS SHORTED BY GENE : STUDY FINDS LINK TO PERSONALITIES.

Byline: Natalie Angier The New York Times

They are the type of people who own a one-sided bed: the wrong side. They're often anxious, grumpy and self-pitying, viewing the past with regret, the present with suspicion and the future with dread. The traditional tag for them is neurotic, but a better word is kvetch.

Now it seems that people who are prone to anxiety and pessimism may have drawn a short stick, genetically speaking. Scientists have discovered a modest but measurable link between anxiety-related behavior and the gene that controls the brain's ability to use serotonin, an essential neurochemical.

They have found that individuals who have a slightly abbreviated version of the gene for the so-called serotonin transporter rate higher in negative thoughts and feelings than those with a relatively long rendition of the gene.

The scientists emphasize that the impact of the transporter gene on behavior is quite small, accounting for only about 4 percent of the difference in people's tendency toward neuroticism. They suspect that anywhere from nine to 14 other genes, as well as many environmental factors that have yet to be sorted out, come into play in making one person anxious, another calm.

``You wouldn't know anything about somebody's personality just by looking at this gene in isolation,'' said Dr. Dennis L. Murphy of the National Institute of Mental Health. Nevertheless, he added, ``it does seem to be connected in a small way to anxiety.''

Murphy, Dr. Dean H. Hamer of the National Cancer Institute, Dr. Klaus-Peter Lesch of the University of Wuerzburg in Germany, and their colleagues present their results in today's issue of the journal Science.

Serotonin, famed as the target of Prozac and other antidepressants, acts as a neurotransmitter, relaying signals from one brain cell to the next. It helps orchestrate fundamental tasks such as eating, sleeping and movement, and also affects mood and thought. The serotonin transporter is a separate molecule that allows nerve cells to respond to the serotonin surrounding them.

The new study was designed to look at garden-variety neuroticism, not the extreme sort of anxiety found in panic disorder and other mental illnesses.

Its finding marks the second time that researchers have associated a gene with a normal human personality trait. Earlier this year, scientists announced a link between a taste for novelty and excitement, and a gene involved in the activity of dopamine, another of the brain's neurotransmitters.

The work on novelty-seeking has come under fire lately from some scientists, but the new study on neuroticism and the serotonin transporter is considered more persuasive on a number of counts.

For one thing, the study is quite large. More than 500 people took part in it, the majority of them young, white, male college students.

To determine the degree of the participants' anxiety and neuroticism, the researchers had them fill out personality questionnaires in which they noted the strength with which they agreed or disagreed with statements like ``I am not a worrier,'' or ``Frightening thoughts sometimes come into my head.''

The scientists also took samples of the participants' blood, from which genetic material was extracted. They found that those with the short type of the transporter gene scored higher on the neuroticism scale than those with the long form, while other personality traits, such as extroversion or agreeableness, were not linked to the gene.

But the new study offers more than a statistical association between a gene type and a behavior. Of great importance, that association is buttressed by biochemical evidence. The researchers found that the difference in the two transporter genes occurs in a particular spot, called the promoter, which serves as the gene's on-off switch. In the long version, an extra bit of genetic material is stuck within the promoter. In the short variant, the promoter lacks that DNA insertion.

Often, the presence or absence of a few genetic subunits makes no difference in the performance of a gene. In this case, it does. The scientists determined that the short promoter is relatively weak and that the gene therefore pumps out relatively few copies of the transporter molecule within neurons of the brain.