Response to ADHD drugs may depend on gene

Variations in a gene linked to attention-deficit hyperactivity disorder (ADHD) may help determine how well a child responds to the stimulant medications used to treat the condition, according to US researchers.

If confirmed in further studies, the findings could provide a way for doctors to predict which children are likely to do well with the medications, and which may need to try a different tack.

The study, of 47 children with ADHD, found that those with a particular, less-common gene variant responded poorly to methylphenidate, a stimulant medication sold in several forms, including the brands Ritalin and Concerta.

The gene in question is called the dopamine transporter gene. Research has suggested that the gene, which helps regulates levels of the brain chemical dopamine, plays a role in a person's susceptibility to ADHD. The gene is also integral to the action of stimulant medications, which bind to the dopamine transporter protein and affect the amounts of dopamine available to the body.

In the new study, researchers led by Dr. Mark A. Stein of the University of Chicago focused on how the two most common variants of the dopamine transporter gene affect children's response to methylphenidate.

The most common form of the gene is known as the 10-repeat variant. As with other genes, individuals inherit two copies of the dopamine transporter gene, one from each parent, and most people carry at least one copy of the 10-repeat variant.

The second-most common variation of the gene is the 9-repeat form, but relatively few people carry two copies of it.

Stein and his colleagues found that of the 47 children in their study, six carried two copies of the 9-repeat gene. And these children tended to do poorly after 4 weeks of treatment with methylphenidate - Concerta, in this case.

At the highest dose of the medication, 57 percent of children with at least one copy of the 10-repeat gene saw their symptoms improve significantly, according to findings published in the journal Neuropsychopharmacology.

In contrast, none of the children with two 9-repeat genes fared so well.

Given the small number of children in the study with this genetic characteristic, more research is needed to solidify the findings, Stein told Reuters Health.

If they're confirmed, he said, the results could end up taking some of the "guesswork" out of prescribing treatment for ADHD - allowing doctors to identify, through a blood test, which patients may not respond to stimulant medication.

It's likely, according to Stein, that carriers of two 9-repeat genes may respond poorly to stimulants other than methylphenidate as well. He pointed to one study of healthy college students that found that those with two 9-repeat variants reported less of a subjective "feeling" from taking amphetamine, which is the basis of other stimulant medications.