Finding the 'worrier-warrior' gene It determines whether you're fretful or forceful. Each has advantages.

Posted: June 02, 2003

Whether life's little snags make you fret like Woody Allen or spring into action like Arnold Schwarzenegger is influenced by a single gene.

"I call it the worrier-warrior gene," said David Goldman, chief of neurogenetics at the National Institutes of Health.

A multitude of genetic and environmental factors go into shaping a person's personality and temperament, but as scientists unravel the genetic code, they are finding dozens of genes that seem to come in several forms and influence physical traits, as well as mental health or cognitive abilities.

These findings go beyond genetic causes of disease, such as cystic fibrosis and Huntington's disease. Those are inherited through genetic variants, or mutations, that occur only rarely. More common genetic variants almost always carry a mixed blessing.

The "worrier" gene, for instance, has been implicated in making people more prone to alcoholism and other psychological problems. But it has advantages, as well.

The recent findings discredit the old notion that some types of genes are superior to others - an idea that has lingered from the eugenics movement of the early 20th century, when people thought they could breed better people by culling "desirable" traits.

Just as there's nothing inherently better about gene variant for blue eyes, there's also no clear superiority to having the warrior gene over the worrier version.

"Eugenics is based on the mistaken belief that anyone is a perfect genetic specimen," said Harvard psychologist Steven Hyman, former director of the National Institute of Mental Health. Hyman and Goldman were speakers at a recent Washington conference organized by the American Association for the Advancement of Science.

The worrier-warrior gene is properly known as the COMT gene (for Catechol-O-Methyl-Transferase). It carries a recipe for making a protein that's important in the functioning of the brain. But the two versions, or alleles, make slightly different forms of this. At one particular site on the protein, the worrier version has a building block called methionine, or Met, where the warrior version has valine, or Val. The scientists use Met and Val to distinguish the genes.

Goldman said he and other researchers first got interested in this gene because people with the Met form rarely developed schizophrenia. Met people also performed better on cognitive tasks that involved recategorizing items in different ways. The test captured a kind of mental flexibility known as meta executive function, said Goldman.

Despite the apparent advantages of the Met form, it's less common in the United States population than the Val variety.

About 16 percent carry two Met versions, 36 percent have two Vals, and 48 percent have one of each (humans inherit two copies of most genes, one from their mother and one from their father).

"The thing that had bothered me is why this valine allele should be so common since it seemed it wasn't such a good thing," Goldman said.

A study from Finland held a clue - people with one or two copies of the valine type were less likely to suffer from alcoholism. But why?

Through a series of tests, Goldman and colleagues found that women with two copies of the Met version of the gene were more prone to anxiety. In testing both women and men he found that people with one or two copies of the Met version experienced more stress when confronted with pain - those with two Mets faring the worst.

To reach this conclusion he and colleagues administered something called a pain stress test. Volunteers had to endure one of the scientists' sticking a needle filled with saline solution into their jaw muscle. "It hurts a lot," said Goldman, who tried the experiment on himself.

He then monitored how much people winced, and with a brain scanning device called functional MRI he examined how well their brains could produce natural painkillers called opioids.

People with the worry-prone Met version of the COMT gene already had lots of these opioids floating around in their systems so they were not as well-equipped to summon an additional burst to deal with the pain and stress of the needle. People with the Val (Arnold Schwarzenegger) gene fared much better, as their brains naturally filled with opioids.

The COMT gene is one of many that appear to come in two forms, each with advantages and disadvantages, sometimes seemingly unrelated to each other. Scientists have identified one gene that in one form makes people less likely to suffer heart disease but more likely to get colon cancer, for example. There's also a "novelty-seeking" gene that seems to influence whether people seek adventure or cling to the familiar.

Any seemingly deleterious gene that spreads widely through the population is likely to carry some survival advantage, as well - otherwise people who carried it would not have survived and proliferated.

Mental illnesses such as depression, schizophrenia and obsessive-compulsive disorder have been connected to many different genes.

Alone, most of these genes are common in the healthy population. Only in certain combinations do they cause harm.

That's why Goldman - who has two Met genes - doesn't worry about being a worrier. It comes with certain health advantages and, on average, seems to improve the capacity of the brain's intellectual center - the frontal lobe.

"Worriers have a very well-functioning frontal lobe," he said, "but that well-functioning frontal lobe makes it difficult to let go of worrisome thoughts."

Contact staff writer Faye Flam at 215-854-4977 or fflam@phillynews.com.

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