Research article summary (published 7 Sep 2009):

Evaluating dopamine reward pathway in ADHD: clinical implications.

Full 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 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.

Author information

Author/s: Volkow, Nora D (ND); Wang, Gene-Jack (GJ); Kollins, Scott H (SH); Wigal, Tim L (TL); Newcorn, Jeffrey H (JH); Telang, Frank (F); Fowler, Joanna S (JS); Zhu, Wei (W); Logan, Jean (J); Ma, Yeming (Y); Pradhan, Kith (K); Wong, Christopher (C); Swanson, James M (JM);

Affiliation: National Institute on Drug Abuse, 6001 Executive Blvd, Room 5274, MSC 9581, Bethesda, MD 20892, USA. nvolkow(-atsign-)nida.nih.gov

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Intramural

Journal: JAMA : the journal of the American Medical Association (JAMA), published in United States. (Language: eng)

Reference: 2009-Sep; vol 302 (issue 10) : pp 1084-91

Dates: Created 2009/09/09; Completed 2009/09/14; Revised 2009/10/07;

PMID: 19738093, status: MEDLINE (last retrieval date: 10/7/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

ErratumIn: JAMA. 2009 Oct 7;302(13):1420.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adult Attention Deficit Disorder with Hyperactivity - physiopathology; psychology; radionuclide imaging Brain - metabolism; radionuclide imaging Brain Mapping Carbon Radioisotopes - diagnostic use Cocaine - diagnostic use Dopamine - physiology Dopamine Agents - diagnostic use Dopamine Plasma Membrane Transport Proteins - metabolism

Female Humans Male Mesencephalon - metabolism; radionuclide imaging Positron-Emission Tomography Raclopride - diagnostic use Receptors, Dopamine D2 - metabolism Reward Synaptic Transmission

Associated Chemicals: Carbon Radioisotopes (0) ; Dopamine Agents (0) ; Dopamine Plasma Membrane Transport Proteins (0) ; Receptors, Dopamine D2 (0) ; Cocaine (50-36-2) ; Raclopride (84225-95-6)

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