HEALTH NEWS

Study Title:

ADHD Invovles Significant Dopamine Problems

Study Abstract

Context Attention-deficit/hyperactivity disorder (ADHD)—characterized by symptoms of inattention and hyperactivity-impulsivity—is the most prevalent childhood psychiatric disorder that frequently persists into adulthood, and there is increasing evidence of reward-motivation deficits in this disorder.

Objective To evaluate biological bases that might underlie a reward/motivation deficit by imaging key components of the brain dopamine reward pathway (mesoaccumbens).

Design, Setting, and Participants We used positron emission tomography to measure dopamine synaptic markers (transporters and D2/D3 receptors) in 53 nonmedicated adults with ADHD and 44 healthy controls between 2001-2009 at Brookhaven National Laboratory.

Main Outcome Measures We measured specific binding of positron emission tomographic radioligands for dopamine transporters (DAT) using [11C]cocaine and for D2/D3 receptors using [11C]raclopride, quantified as binding potential (distribution volume ratio –1).

Results For both ligands, statistical parametric mapping showed that specific binding was lower in ADHD than in controls (threshold for significance set at P < .005) in regions of the dopamine reward pathway in the left side of the brain. Region-of-interest analyses corroborated these findings. The mean (95% confidence interval [CI] of mean difference) for DAT in the nucleus accumbens for controls was 0.71 vs 0.63 for those with ADHD (95% CI, 0.03-0.13, P = .004) and in the midbrain for controls was 0.16 vs 0.09 for those with ADHD (95% CI, 0.03-0.12; P .001), for D2/D3 receptors, the mean accumbens for controls was 2.85 vs 2.68 for those with ADHD (95% CI, 0.06-0.30, P = .004), and in the midbrain, it was for controls 0.28 vs 0.18 for those with ADHD (95% CI, 0.02-0.17, P = .01). The analysis also corroborated differences in the left caudate: the mean DAT for controls was 0.66 vs 0.53 for those with ADHD (95% CI, 0.04-0.22; P = .003) and the mean D2/D3 for controls was 2.80 vs 2.47 for those with ADHD (95% CI, 0.10-0.56; P = .005) and differences in D2/D3 in the hypothalamic region, with controls having a mean of 0.12 vs 0.05 for those with ADHD (95% CI, 0.02-0.12; P = .004). Ratings of attention correlated with D2/D3 in the accumbens (r = 0.35; 95% CI, 0.15-0.52; P = .001), midbrain (r = 0.35; 95% CI, 0.14-0.52; P = .001), caudate (r = 0.32; 95% CI, 0.11-0.50; P = .003), and hypothalamic (r = 0.31; CI, 0.10-0.49; P = .003) regions and with DAT in the midbrain (r = 0.37; 95% CI, 0.16-0.53; P .001).

Conclusion A reduction in dopamine synaptic markers associated with symptoms of inattention was shown in the dopamine reward pathway of participants with ADHD.

From press release via BBC news:

US researchers have pinned down new differences in the brain chemistry of people with attention deficit hyperactivity disorder (ADHD).

They found ADHD patients lack key proteins which allow them to experience a sense of reward and motivation.

The Brookhaven National Laboratory study appears in the Journal of the American Medical Association.

It is hoped it could help in the design of new ways to combat the condition.

Previous research looking at the brains of people with ADHD had uncovered differences in areas controlling attention and hyperactivity.

But this study suggests ADHD has a profound impact elsewhere in the brain too.

Researcher Dr Nora Volkow said: "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."

The researchers compared brain scans of 53 adult ADHD patients who had never received treatment with those from 44 people who did not have the condition.

All of the participants had been carefully screened to eliminate factors which could potentially skew the results.

Dopamine pathway

Using a sophisticated form of scan called positron emission tomography (PET), the researchers focused on how the participants' brains handled the chemical dopamine, a key regulator of mood.

In particular they measured levels of two proteins - dopamine receptors and transporters - without which dopamine cannot function effectively to influence mood.

ADHD patients had lower levels of both proteins in two areas of the brain known as the nucleus accumbens and midbrain.

Both form part of the limbic system, responsible for the emotions, and sensations such as motivation and reward.

Patients with more pronounced ADHD symptoms had the lowest levels of the proteins in these areas.

Study Information

a D. Volkow; Gene-Jack Wang; Scott H. Kollins; Tim L. Wigal; Jeffrey H. Newcorn; Frank Telang; Joanna S. Fowler; Wei Zhu; Jean Logan; Yeming Ma; Kith Pradhan; Christopher Wong; James M. Swanson.
Evaluating Dopamine Reward Pathway in ADHD: Clinical Implications.
JAMA
2009 September
National Institute on Drug Abuse and Laboratory of Neuroimaging.