Evaluating dopamine reward pathway in ADHD: Clinical Implications

Nora 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

Research output: Contribution to journalArticlepeer-review

497 Scopus citations

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/D 3 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 D 2/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/D 3 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.

Original languageEnglish
Pages (from-to)1084-1091
Number of pages8
JournalJAMA - Journal of the American Medical Association
Volume302
Issue number10
DOIs
StatePublished - 9 Sep 2009

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