Evaluating Dopamine Reward Pathway in ADHD

By Nora D. Volkow, Gene-Jack Wang, Scott H. Kollins, T. Wigal, Jeffrey H. Newcorn, Frank Telang, J. S. Fowler, Wei Zhu, Jean Logan, Yeming Ma and 3 more. Journal of the American Medical Association (JAMA), 2009

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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.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/73303180da9a733fdf01dc78501b5769db289660

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Citations in the corpus

The roles of dopamine and noradrenaline in the pathophysiology and treatment of attention-deficit/hyperactivity disorder. (2011, methodology): “2009 (11) [(11)C]cocaine A 53-44 Naïve None Whole brain analysis and template ROIs from the Talairach Daemon database SWAN Decreased DAT in L accumbens, midbrain, CAU and in hypothalamic region.”
The ESSENCE in child psychiatry: Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations. (2010, background): “There is also growing evidence that the brain’s dopaminedependent reward system is dysfunctional in ADHD (Volkow et al., 2009).”
Prospective Association of Childhood Attention-deficit/hyperactivity Disorder (ADHD) and Substance Use and Abuse/Dependence: A Meta-Analytic Review (2011, background): “…neurotransmission is central to currentmodels of ADHD and SUD (Bédard et al., 2010; Ray et al., 2010; Volkow, Fowler, Wang, Baler, & Telang, 2009; Volkow et al., 2009) and methylphenidate (MPH) is a highly efficacious treatment for the core symptoms of ADHD, although recent evidence suggests…”
European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD (2010, background): “gests that the main underlying pathophysiological process may involve deficits or imbalances in catecholaminergic, dopaminergic, and nicotinergic functioning [109-111].”