May 15, 2012

New clue to ADHD

A rare genetic change adds support to the idea that altered dopamine signaling is a key risk factor for ADHD.

(Wellcome Images)

Attention deficit hyperactivity disorder (ADHD) has been linked to alterations in the production, release and signaling of the neurotransmitter dopamine. Genetic changes that support these alterations, however, have been difficult to associate with specific molecular insults.

Now, Randy Blakely, Allan D. Bass Chair in Pharmacology, and colleagues have identified a novel coding variant in a 13-year-old boy with ADHD that prevents the dopamine transporter, a protein involved in inactivating dopamine at synapses, from carrying out its normal function. In essence, the transporter doesn’t go to the correct location on the nerve cell surface, and therefore doesn’t respond to normal regulatory signals, the researchers reported in the April 18 issue of the Journal of Neuroscience. Although the genetic change is rare, it points to a regulatory network where changes may individually or collectively make a much larger contribution to ADHD risk.

This is the second functional dopamine transporter alteration identified by the Blakely group in subjects with ADHD, adding support to the idea that altered dopamine signaling is a key risk factor for the disorder.

The research was supported by National Institutes of Health grants from the National Institute of Mental Health, the National Heart, Lung and Blood Institute, and the National Institute on Drug Abuse, and by the National Science Foundation.