New dopamine transporter gene findings may be relevant for substance abuse, tobacco smoking, and ADHD

Confirming findings in a previous study, Yale researchers observed an altered availability of the dopamine transporter in healthy persons with a genetic variation linked to substance abuse and attention deficit hyperactivity disorder (ADHD).

"Healthy people who carry a particular variant of the dopamine transporter gene, the nine repeat allele, have significantly higher levels of dopamine transporter in the brain," said the lead author, Christopher van Dyck, M.D., associate professor of psychiatry and neurobiology and director of the Alzheimer's Disease Research Unit and the Cognitive Disorders Clinic in the Department of Psychiatry.

The new study included 96 healthy European Americans--54 men and 42 women--who underwent a clinical examination to exclude any neurological or psychiatric disease, alcohol abuse or substance abuse. The levels of dopamine transporter availability were measured using SPECT imaging, and the dopamine transporter genotypes were determined by co-author Joel Gelernter, M.D.

"We are not yet sure if the effects of the variant on transporter levels in our healthy subjects can be generalized to neuropsychiatric disorders," van Dyck said. "If they can be, our results may be relevant for substance abuse, tobacco smoking, and ADHD. "The results suggest that the mechanism of association of this gene with several disorders could be altered levels of central dopamine transporter protein, influencing concentrations of extracellular dopamine."

This study replicated and expanded on a preliminary report by Leslie Jacobsen, M.D., and colleagues at Yale, although other studies of the effects of this variation on the availability of the dopamine transporter have yielded contradictory results.

In addition to Jacobsen and Gelernter, co-authors included Robert Malison, M.D., John Seibyl, M.D., Julie Staley, Marc Laruelle, M.D., Ronald Baldwin, and Robert Innis, M.D. The study was supported by grants and funds from the American Federation for Aging Research; Rose and Philip Hoffer; the Department of Veterans Affairs; the National Institute of Mental Health, and the National Institute on Drug Abuse.