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Preliminary Communication
September 9, 2009

Evaluating Dopamine Reward Pathway in ADHD: Clinical Implications

Author Affiliations

Author Affiliations: National Institute on Drug Abuse (Dr Volkow) and Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism (Drs Volkow, Telang, and Ma), Bethesda, Maryland; Medical and Chemistry Departments, Brookhaven National Laboratory, Upton, New York (Drs Wang, Fowler, and Logan, Messrs Pradhan and Wong); Department of Psychiatry, Mount Sinai Medical Center, New York, New York (Drs Wang, Newcorn, and Fowler); Department of Psychiatry, Duke University Medical Center, Durham, North Carolina (Dr Kollins); Child Development Center, University of California, Irvine (Drs Wigal and Swanson); Department of Applied Mathematics and Statistics, State University of New York at Stony Brook, Stony Brook (Dr Zhu).

JAMA. 2009;302(10):1084-1091. doi:10.1001/jama.2009.1308

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.