Evaluating dopamine reward pathway in ADHD: clinical implications.

Autor: Volkow ND, Wang GJ, Kollins SH, Wigal TL, Newcorn JH, Telang F, Fowler JS, Zhu W, Logan J, Ma Y, Pradhan K, Wong C, Swanson JM, Volkow, Nora D, Wang, Gene-Jack, Kollins, Scott H, Wigal, Tim L, Newcorn, Jeffrey H, Telang, Frank, Fowler, Joanna S
Zdroj: JAMA: Journal of the American Medical Association; 2009 Sep 9, Vol. 302 Issue 10, p1084-1091, 8p
Abstrakt: 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 D(2)/D(3) 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 [(11)C]cocaine and for D(2)/D(3) receptors using [(11)C]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 < or = .001); for D(2)/D(3) 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 D(2)/D(3) for controls was 2.80 vs 2.47 for those with ADHD (95% CI, 0.10-0.56; P = .005) and differences in D(2)/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 D(2)/D(3) 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 < or = .001).Conclusion: A reduction in dopamine synaptic markers associated with symptoms of inattention was shown in the dopamine reward pathway of participants with ADHD. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index