Vol. 12, No. 1, 2006 Page 1&7

Gene variant linked to higher risk for early antisocial behavior

A specific gene variant greatly elevates the risk for antisocial behavior in at-risk children, according to a new study.

Anita Thapar and colleagues recruited 240 children diagnosed with attention deficit hyperactivity disorder (ADHD), and evaluated them for symptoms of conduct disorder. Thapar and colleagues then performed genetic testing to determine which variants of a particular gene—the catechol O-methyltransferase (COMT) gene—each child possessed. Because early-onset antisocial behavior is also linked to an adverse prenatal environment, the researchers obtained data on the children's birth weights as well.

In one variant of the COMT gene, methionine (met) is substituted for valine (val) in one section. Research indicates that individuals possessing two "val" variants of the gene perform more poorly on tasks measuring prefrontal cortical function than do individuals with two "met" variants or a "met/val" combination. Poor prefrontal cortical function is also associated with antisocial behavior.

"Given the links between prefrontal cortical deficits and antisocial behavior and between COMT and prefrontal cortical functioning, we hypothesized that the [val/val] variant would be associated with antisocial behavior," the researchers say. "We specifically set out to examine the subtype of antisocial behavior purported to have the strongest neurobiological and heritable origins, that is, childhood-onset conduct disorder symptoms accompanied by ADHD."

As predicted, both the "val/val" genotype and low birth weight were independent risk factors for conduct disorder in the ADHD children. Moreover, the researchers found significant evidence for an interaction between val/val status and prenatal environment.

"These results are of considerable interest," Thapar and her colleagues say, "because they suggest not only that COMT genotype and birth weight influence antisocial behavior in this high-risk group but also that those with the val/val genotype are particularly susceptible to the effects of lower birth weight."


"Catechol O-methyltransferase gene variant and birth weight predict early-onset antisocial behavior in children with attention- deficit/hyperactivity disorder," Anita Thapar, Kate Langley, Tom Fowler, Frances Rice, Darko Turic, Naureen Whittinger, John Aggleton, Marianne Van den Bree, Michael Owen, and Michael O'Donovan, Archives of General Psychiatry, Vol. 62, No. 11, November 2005, 1275-8. Address: Anita Thapar, Department of Psychological Medicine, Cardiff University, Heath Park, Cardiff, Wales, thapar@cardiff.ac.uk.

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