Evaluating dopamine reward pathway in ADHD: Clinical Implications

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.