New research suggests the levels of a brain protein traditionally used as a marker for development of attention-deficit hyperactivity disorder (ADHD), is not a reliable indicator. The finding challenges the notion that ADHD is caused by a dysfunction in brain circuits that depend on the neurotransmitter dopamine to modulate attention, motivation, and interest.
ADHD is the most frequently recognized psychiatric disorder in children, with some 3 million children younger than 18 currently receiving treatment in the U.S. Yet the mechanism underlying this disorder and its treatment are still poorly understood.
Investigators using a brain-imaging study found lower levels of “dopamine transporter” proteins in certain brain regions of ADHD patients compared with controls. In fact, they found that for any given level of dopamine in the brain, ADHD patients experienced greater levels of inattention compared to controls.
This discovery refutes the prior opinion that ADHD subjects have elevated levels of dopamine transporters (proteins on dopamine-producing cells that take up excess dopamine) that take up too much dopamine, ending up with depleted dopamine levels and reduced motivation/attention.
Four independent studies have reported that ADHD subjects have higher than normal levels of dopamine transporters in a brain region called the striatum. But the magnitude of the increase has varied widely, ranging from 70 percent to 5 percent elevations in transporter levels. Two other studies found no elevation of transporter levels, though one found a decrease in dopamine transporter levels in a different brain region.
“Because these discrepancies could reflect differences in medication or drug-abuse histories among subjects, we designed the current study to investigate dopamine transporter levels in ADHD subjects and control subjects while excluding these potentially confounding factors,” Wang said.
The researchers measured dopamine transporter levels in 20 adult ADHD subjects who had never received medication, never abused drugs (except nicotine), and had no past or present history of mental or neurological disease or other medical conditions that could affect cerebral function. They also asked subjects to respond to a questionnaire to gauge levels of inattention. The scientists ran the same tests in 25 healthy control subjects with the same exclusion criteria.
Jeffrey Newcorn, a child and adolescent psychiatrist and lead collaborator from Mount Sinai, emphasized that ADHD is not a simple, one-type-fits-all disorder. There are very likely variations in dopamine transporter levels among and even within ADHD subgroups.
“The significant differences across studies and investigators clearly highlight the need to look for factors affecting these inconsistencies to improve our ability to diagnose and treat ADHD,” he said. “Although levels of dopamine transporters alone do not determine whether an individual has ADHD, the association of inattention ratings and transporter levels in both ADHD and normal subjects is consistent with the use of treatments such as stimulant medications, which block activity of the transporter, in ADHD.”
Ongoing research in adults with ADHD, currently being conducted at Brookhaven National Laboratory and Mount Sinai, is investigating the potential long-term impact of treatment with stimulants on the dopamine system.
The study was conducted at the U.S. Department of Energy’s Brookhaven National Laboratory in collaboration with Mount Sinai School of Medicine in New York and will be published in an upcoming issue of the journal Neuroimage.