Hyperactivity Linked to Mutation

There's no mistaking kids with Attention Deficit Hyperactivity Disorder (ADHD)--they are easily distracted, impulsive, and hyperactive. So, it's hardly a stretch to suspect problems with a chemical messenger in the brain, norepinephrine, that helps control attention. Yet scientists have failed to nail down a link. Now, a new study has for the first time connected the dots by identifying a mutation that indirectly boosts norepinephrine levels. The findings, if replicated, could improve understanding of the disorder and better drugs.

Norepinephrine is one of the most important chemical messengers neurons use. The cells have tiny pumps called transporters that maintain a balanced level of the messenger in the brain. Both the messenger and the transporter play significant roles in disorders such as anxiety and depression. But the only solid evidence to for a role with ADHD has come from the drug Strattera, which targets the transporter and is used to treat some ADHD cases. Other studies have failed to conclusively link the transporter with ADHD.

Taking an approach previously used by studies that linked the dopamine transporter gene with ADHD, psychiatrist Kwang-Soo Kim of Harvard Medical School looked for genetic changes that would influence expression of the norepinephrine transporter gene. They found a single mutation in the promoter region of the gene that significantly lowers the levels of gene expression. The 68 kids with ADHD in the study were more likely to have the mutation than the 60 children without, the team reports online this week in the Proceedings of the National Academy of Sciences. A deficit of transporters can affect attention span and impulsiveness by leading to increased levels of norepinephrine. The results suggest that this mutation might increase the risk of developing ADHD.

The molecular analysis of the mutation is convincing, says neurologist Daniel Weinberger of the National Institute of Mental Health. But he says he won't believe the connection with ADHD until it is reproduced in a larger group of patients. Study author Kim is also cautious, although he contends the finding is a valuable clue to the role of the transporter gene in ADHD and other disorders.

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Posted in Brain & Behavior