September 08, 2009
ADHD Driven By Dopamine Receptor Concentrations?

PET scans show brain receptor differences in people with attention deficit hyperactivity disorder (ADHD).

UPTON, NY A brain-imaging study conducted at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory provides the first definitive evidence that patients suffering from attention deficit hyperactivity disorder (ADHD) have lower-than-normal levels of certain proteins essential for experiencing reward and motivation.

"These deficits in the brain's reward system may help explain clinical symptoms of ADHD, including inattention and reduced motivation, as well as the propensity for complications such as drug abuse and obesity among ADHD patients," said lead author Nora Volkow, Director of the National Institute on Drug Abuse and a long-time collaborator on neuroimaging research at Brookhaven Lab.

The study, published in the September 9, 2009, issue of the Journal of the American Medical Association, also has important implications for treatment. "Finding ways to address the underlying reward-system deficit could improve the direct clinical outcome of ADHD, and potentially reduce the likelihood of other negative consequences of this condition," said study co-author Gene-Jack Wang, chair of Brookhaven's medical department.

Can't pay attention? It is all down to your dopamine receptors. You don't have enough of them to get rewarded for paying attention.

The scientists used positron emission tomography (PET) to measure two markers of the dopamine system dopamine receptors, to which the chemical messenger binds to propagate the "reward" signal, and dopamine transporters, which take up and recycle excess dopamine after the signal is sent.

Lying in a PET scanner, each patient was injected with a minute amount of a "radiotracer" compound a chemical labeled with a radioactive form of carbon and designed to bind specifically to one of the targets. Different tracers were used for each target, and patients were scanned for each at separate times. By detecting the signal from the radiotracers, the PET machine can measure the receptor and transporter locations and concentrations in various parts of the brain.

The results clearly showed that, relative to the healthy control subjects, the ADHD patients had lower levels of dopamine receptors and transporters in the accumbens and midbrain two key regions of the brain directly involved in processing motivation and reward. In addition, the measurements of dopamine markers correlated with measures of behavior and clinical observations of ADHD symptoms, such as reduced levels of attention as measured by standard psychological tests.

A drug that would stimulate neurons to increase the synthesis of dopamine receptors would probably improve the ability of people to pay attention for longer periods of time. Do any existing drugs increase dopamine receptor synthesis?

Think about the continuing stream of discoveries about how neurotransmitter receptor concentrations alter behavior and mood. These discoveries are building up a foundation of knowledge needed to develop drugs that will alter mood, motivation, and intellectual performance. We will become more pharmacologically malleable as a result of drug development guided by these discoveries. Those new drugs might be 10 or 20 years off. But they'll come eventually.

Share |      Randall Parker, 2009 September 08 11:25 PM  Brain Performance

Kyle Webb said at September 9, 2009 8:46 AM:

There have been a number of studies for some time that have linked disregulation in the dopamine system to ADHD. Low dopamine levels seem to be involved but where the actual problem is has been unclear. This study does a better job of eliminating some of the confounding factors by using untreated ADHD sufferers in larger numbers.

There are a whole series of dopamine receptors and they're through the body rather than just in the central nervous system. This is one of the problems in treating Parkinson's disease (another dopamine related disorder), for example, as the meds can cause side effects in the rest of the body, and also be degraded outside the brain.

Certain variants of dopamine receptor genes have been linked to ADHD, but again it's not a clear cut story. Rather like depression (which it's linked to, in that both involve problems in the catecholamine system) it's not likely it has just one cause. Given the low concentration of both transport and receptors for dopamine, which is effect and which (if either) is cause? Also, if the problem is based on lack of receptors, which receptor type is it? Some are excitatory, some are inhibitory.

There are certainly quite a number of pharmaceutical ways try to to treat it. You can increase the release of dopamine (amphetamines), you can alter the re-uptake of dopamine (Ritalin) rather like the SSRI antidepressants do with serotonin, or you can use a dopamine agonist (don't think this is widely done at the moment). You can also treat it with other types of medications like Strattera, which is a norepinephrine re-uptake inhibitor but indirectly helps with ADHD. Also, some other types of anti-depressants seem to help.

This is interesting news as it makes a clearer picture that the dopamine system isn't working right in untreated patients and with better numbers of subjects, but there's still a long way to go for understanding what's really happening.

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