ADHD Gene Doesn't Predict Response to Drugs

But variant is linked to disease severity, researchers report

By Jeffrey Perkel
HealthDay Reporter

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WEDNESDAY, June 25 (HealthDay News) -- Canadian researchers report that a gene variant that seems to affect the severity of attention-deficit hyperactivity disorder did not help them predict which patients are likely to respond to a class of drugs widely used to treat the disorder.

The lack of a connection between the variant and response to methylphenidates was a blow for researchers, who have hoped to use genetic data to better predict who might be the best candidates for this treatment. Ritalin is one example of a methylphenidate.

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"It is a negative study," said Dr. Andrew Adesman, chief of developmental and behavioral pediatrics at Schneider Children's Hospital in New Hyde Park, N.Y. "The goal is to try and better identify patients who are best going to respond to which medicine, and they didn't get the findings they were hoping to find. Their theory wasn't supported by the data."

The research was published Wednesday online in Neuropsychopharmacology.

Attention deficit-hyperactivity disorder (ADHD) is a complex syndrome affecting between 8 percent and 12 percent of school-aged children worldwide. Likely the result of a combination of genes and environmental factors, the biology of the disease has proven difficult to nail down.

Ridha Joober and his team from the Douglas Mental Health University Institute in Montreal focused on the gene encoding catechol-O-methyltransferase (COMT). COMT regulates levels of the brain chemical dopamine in the prefrontal cortex, and dopamine appears to regulate precisely the behaviors that tend to be disrupted in children with ADHD.

The COMT gene is marked by a particular genetic variant that changes an amino acid in the gene from a valine (Val) to methionine (Met).

"We know that the Met isoform is less active than the Val isoenzyme," he said. "Therefore, the hypothesis is that children who are carrying Met isoform would have more dopamine in their prefrontal cortex, because the enzyme is less active. And if they have more dopamine available in the prefrontal cortex, then they will be able to better orient their behavior towards their goals."

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