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Is There a Gene for Shyness?
  
By Melissa Hendricks


Featured Article.

That causes shyness? To Lilly Polk, a retired bookkeeper in northern California, shyness seems like a family trait. Polk, who enjoys crunching numbers but fears calling customers, has been shy her whole life. Her mother was shy and so is her adult daughter.

Yet other shy people attribute their timidness to an external cause, such as having been raised by an overprotective parent or having been constantly teased by classmates. Many decades of research into the roots of shyness find truth in each of these homespun theories: nature and nurture are part of the recipe for shyness. What's new is that geneticists are finding the first leads to genes that seem to predispose people toward being shy.

While the research is still in its early stages, it represents a huge shift in how geneticists study shyness. Until recently, research on the genetics of shyness (and other behaviors such as aggression and risk-taking) did not involve hunting for genes per se. Rather, investigators made inferences about heredity by examining behavior patterns in families, especially in twins and adopted children—a field called quantitative genetics. In these studies, researchers attempt to tease apart the influences of heredity and the environment by comparing behavior in identical and fraternal twins, for example. Twins generally share the same environment—they are raised by the same parents and attend the same schools. Identical twins share the same genes; fraternal twins share, on average, half their genes. Thus, if shyness is inherited, it should be seen more often in both identical twins than in pairs of fraternal twins.


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In one of the major twin studies to date, researchers at the University of Colorado and Pennsylvania State University observed fraternal and identical twins in their homes and in the laboratory when they were 14 and 20 months old. Data showed that genetics contributes substantially to the babies' tendency to cling to their mothers, cry or exhibit other shy behavior when encountering a stranger, new toys and other novelties. These researchers and others indicate that genetics constitutes roughly half of the foundation of shyness.

But which genes are involved? One line of evidence leads to serotonin, which has numerous functions in the nervous system including an influence on mood, memory and learning. Irregularities in the expression or control of serotonin have been linked to depression, anxiety and a variety of other disorders. Drugs such as Prozac™ which affect serotonin are are now widely used in medicine.

In 1996, geneticist Dean Hamer of the National Institutes of Health and his colleagues reported that they had found an association between the serotonin transporter gene and neuroticism, a complex of behaviors that includes depression, low self-confidence, and shyness around strangers. Hamer reported in Science that adult volunteers who rated high on the scale of neuroticism tend to have a short version of the serotonin transporter promoter, a stretch of DNA that controls how much of the serotonin transporter gets made. Adults who ranked low in neuroticism tended to have a long version of the promoter.

Both the long and short copies of the gene are functioning, says Hamer. However, the short version appears to result in less of the serotonin transporter, and thus less serotonin activity. Hamer called it the "anxiety gene." Meanwhile, other studies suggest that another gene, DRD4, may also play a role in traits such as shyness and anxiety. The DRD4 gene codes for a protein that binds dopamine, another chemical messenger that has powerful effects in the brain. Again, the DRD4 gene comes in two forms: a long and a short version.

In a study reported in a recent issue of Molecular Psychiatry, behavioral scientist Judith Auerbach, of Ben-Gurion University, Beer Sheva, Israel, said that infants with short copies of the DRD4 gene and serotonin transporter promoter are less responsive to stimulation and show more distress during daily routines, compared to infants with different versions of these genes. Auerbach cautions that her findings do not define a gene or genes that predispose infants to future shyness. "That will only be clearer when the infants are older," says Auerbach, who is continuing to study the behavior of these infants as they grow. It is also interesting that a number of studies have linked the longer DRD4 gene to novelty-seeking behavior, just the opposite of being shy.

Feeling Shy

Still to be determined is how having these or other genes associated with shyness might cause a person to feel shy. Some clues may come from the extensive literature on the biological basis of shyness. Studies by Jerome Kagan, of Harvard University, and others by Nathan Fox, of the University of Maryland, reveal key physiological differences between shy and non-shy children. When shy children meet a stranger or encounter other unfamiliar situations, their hearts beat faster and stronger, their muscles tense, and they secrete higher levels of stress hormones than children who are not shy. Brain wave patterns also show differences: shy children have stronger activity on the right side of the frontal lobe. Other children show just the opposite.

But correlating a gene with any behavior has many limitations. Indeed, while several teams of investigators have replicated Hamer's results on the "anxiety gene," other groups have tried, but failed, to confirm them. The contradictory findings are not surprising, say Hamer and others who study the genetics of behavior, given the challenges of pinpointing genes for behavior.

"It's not like you have a gene for 'X'—like you have a gene for eye color," says Louis Schmidt, an assistant professor of psychology at McMaster University, in Ontario, Canada, "There are probably many genes and many interactions of genes that contribute to shyness." Any one gene may account for only a small portion of shyness, perhaps only one or two percent. Furthermore, each of those genes probably corresponds to a predisposition to shyness, but does not guarantee that shyness will occur. The gene's final impact is probably influenced by interactions with other genes as well as the environment.

Further research may help clarify the genetics underlying shyness. Hamer and Schmidt, along with Maryland's Nathan Fox, are now screening DNA collected from several hundred children who have been identified as shy through intensive behavioral and physiological measures. The researchers are looking at differences between these children and other children in the genes that regulate serotonin and dopamine. "We're very excited about the prospects," says Hamer. "These [studies] are a matter of fundamental curiosity about what makes people unique." Even aside from the influence of a person's mom or dad or first grade teacher, there are aspects of personality that appear to be rooted in the genes that remain throughout life.

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Auerbach, J.G. et al. Dopamine D4 receptor (D4DR) and serotonin transporter promoter (5-HTTLPR) polymorphisms in the determination of temperament in 2-month-old infants. Mol Psychiatry 4, 369-373 (July 1999).
 
Lesch, K., et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527-1531 (November 29, 1996).
 
Cherny, S.S. et al. Continuity and change in infant shyness from 14 to 20 months. Behav Genet 24, 365-379 (1994).
 

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