 |
|
Evaluating Dopamine Reward Pathway in ADHDClinical Implications
Nora D. Volkow, MD;
Gene-Jack Wang, MD;
Scott H. Kollins, PhD;
Tim L. Wigal, PhD;
Jeffrey H. Newcorn, MD;
Frank Telang, MD;
Joanna S. Fowler, PhD;
Wei Zhu, PhD;
Jean Logan, PhD;
Yeming Ma, PhD;
Kith Pradhan, MS;
Christopher Wong, MS;
James M. Swanson, PhD
JAMA. 2009;302(10):1084-1091.
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.
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).
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Unraveling ADHD Pathogenesis
JWatch Psychiatry 2009;2009:2-2.
FULL TEXT
|
