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Motivation deficit in ADHD is associated with dysfunction of the dopamine reward pathway

Abstract

Attention-deficit hyperactivity disorder (ADHD) is typically characterized as a disorder of inattention and hyperactivity/impulsivity but there is increasing evidence of deficits in motivation. Using positron emission tomography (PET), we showed decreased function in the brain dopamine reward pathway in adults with ADHD, which, we hypothesized, could underlie the motivation deficits in this disorder. To evaluate this hypothesis, we performed secondary analyses to assess the correlation between the PET measures of dopamine D2/D3 receptor and dopamine transporter availability (obtained with [11C]raclopride and [11C]cocaine, respectively) in the dopamine reward pathway (midbrain and nucleus accumbens) and a surrogate measure of trait motivation (assessed using the Achievement scale on the Multidimensional Personality Questionnaire or MPQ) in 45 ADHD participants and 41 controls. The Achievement scale was lower in ADHD participants than in controls (11±5 vs 14±3, P<0.001) and was significantly correlated with D2/D3 receptors (accumbens: r=0.39, P<0.008; midbrain: r=0.41, P<0.005) and transporters (accumbens: r=0.35, P<0.02) in ADHD participants, but not in controls. ADHD participants also had lower values in the Constraint factor and higher values in the Negative Emotionality factor of the MPQ but did not differ in the Positive Emotionality factor—and none of these were correlated with the dopamine measures. In ADHD participants, scores in the Achievement scale were also negatively correlated with symptoms of inattention (CAARS A, E and SWAN I). These findings provide evidence that disruption of the dopamine reward pathway is associated with motivation deficits in ADHD adults, which may contribute to attention deficits and supports the use of therapeutic interventions to enhance motivation in ADHD.

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Acknowledgements

This research was carried out at Brookhaven National Laboratory (BNL) and was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), the National Institute of Mental Health (MH66961-02) and infrastructure support from the Department of Energy. We thank the following BNL employees: Donald Warner for PET operations; David Schlyer and Michael Schueller for cyclotron operations; Pauline Carter, Millard Jayne and Barbara Hubbard for nursing care; Payton King for plasma analysis and Lisa Muench, Youwen Xu and Colleen Shea for radiotracer preparation; Karen Appelskog for protocol coordination; to the following Duke employees: Joseph English and Allan Chrisman, for subject recruitment and evaluation; to the following NIH employee: Linda Thomas for editorial assistance. We also thank the individuals who volunteered for these studies.

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Correspondence to N D Volkow.

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Competing interests

Dr Newcorn reported being a recipient of research support from Eli Lilly and Ortho-McNeil Janssen, and serves as a consultant, advisor or both for Astra Zeneca, BioBehavioral Diagnostics, Eli Lilly, Novartis, Ortho-McNeil Janssen and Shire, and as a speaker for Ortho-McNeil Janssen. Dr Kollins reported receiving research support, consulting fees or both from Addrenex Pharmaceuticals, Otsuka Pharmaceuticals and Shire Pharmaceuticals. Dr Wigal reported receiving support from Eli Lilly, McNeil, Novartis and Shire. Dr Swanson reported receiving support from Alza, Richwood, Shire, Celgene, Novartis, Celltech, Gliatech, Cephalon, Watson, CIBA, Janssen and McNeil; has been on the advisory boards of Alza, Richwood, Shire, Celgene, Novartis, Celltech, UCB, Gliatech, Cephalon, McNeil and Eli Lilly; has been on the speaker's bureaus of Alza, Shire, Novartis, Cellthech, UCB, Cephalon, CIBA, Janssen and McNeil; and has consulted to Alza, Richwood, Shire, Clegene, Novarits, Celltech, UCB, Gliatech, Cephalon, Watson, CIBA, Jansen, McNeil and Eli Lilly. The other authors declare no conflict of interest.

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Volkow, N., Wang, GJ., Newcorn, J. et al. Motivation deficit in ADHD is associated with dysfunction of the dopamine reward pathway. Mol Psychiatry 16, 1147–1154 (2011). https://doi.org/10.1038/mp.2010.97

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Keywords

  • attention
  • brain imaging
  • catecholamines
  • personality
  • psychiatric disorder
  • PET

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