Attention-Deficit Hyperactivity Disorder Related To Advantageous Gene

The human gene study, which appears in the Jan. 8 issue of Proceedings of the National Academy of Science, suggests that behavior now considered inappropriate in a classroom may be related to behavior that once helped humans overcome their environment.

Robert Moyzis, professor of biological chemistry, and his colleagues studied genes from 600 individuals worldwide. Among numerous new genetic variations of the receptor for the dopamine neurotransmitter, they found one linked strongly to both ADHD and a behavior trait called "novelty seeking," a condition often underlying addiction. Their analysis of the genetic variations also suggests that this variation occurred recently in human evolution between 10,000 and 40,000 years ago.

"We found a significant positive selection for the genetic variation associated with ADHD and novelty-seeking behavior in the human genome," Moyzis said. "This study strengthens significantly the connection between genetic variations and ADHD. It also provides a clue as to why ADHD is so pervasive and may show us a way to provide more effective treatments."

The researchers found 56 variations, or alleles (al-LEELEs) of a gene called DRD4, which produces the receptor for dopamine, a neurotransmitter. One allele, known as 7R, was strongly associated with ADHD. By analyzing the variations in DRD4, they also found that the 7R allele was created recently and may have provided an evolutionary advantage at some time in human history. The study could not determine, however, if that evolutionary selection is still occurring.

Brain cells signal each other with a number of neurotransmitters, including dopamine. The dopamine system, among other things, controls movement behavior and may be involved in learning and responding to psychological rewards. It also has been implicated in addictive behavior.

ADHD is the most common disorder in early childhood, affecting about 3 percent of all elementary school children in the United States. The disorder is marked by developmentally inappropriate conduct, lack of attention, impulsive and hyperactive behavior, all occurring before a child becomes 7 years old. Approximately half of children with ADHD have the 7R allele.

Between 10,000 and 40,000 years ago, anthropologists concur that humans were developing the first signs of complex societies, replete with agriculture, rudimentary governments and the creation of cities for the first time. Humans also were rapidly expanding and exploring the planet. These revolutionary changes in human societies may have changed the forces that selected for certain genetic traits.

"Our data show that the creation of the 7R allele was an unusual, spontaneous mutation, which became an advantage for humans," Moyzis said. "Because it was an advantage, the gene became increasingly prevalent. This is very different from other genes that predispose to genetic disorders, where the mutations are detrimental. We believe this helps explain why a disorder with such a strong genetic association is so common today."

The researchers are now working on determining how the genetic variations in DRD4 may actually predispose individuals to ADHD and other behaviors, and on examining the relationship between other complex genetic variations and ADHD.

Moyzis's colleagues include Yuan-Chun Ding, Han-Chang Chi, Deborah Grady, Pam Flodman, M. Anne Spence, Sabrina Schuck and James Swanson of UCI; Ya-Ping Zhang of the Chinese Academy of Sciences, Kunming, China; and Atsuyuki Morishima, Judith Kidd and Kenneth Kidd of Yale University.

The study was supported by grants from the U.S. Department of Energy and the National Institute of Mental Health.