4.8 Article

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

Journal

MOLECULAR PSYCHIATRY
Volume 16, Issue 11, Pages 1147-1154

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2010.97

Keywords

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

Funding

  1. Eli Lilly
  2. Ortho-McNeil Janssen
  3. Addrenex Pharmaceuticals
  4. Otsuka Pharmaceuticals
  5. Shire Pharmaceuticals
  6. McNeil
  7. Novartis
  8. Shire
  9. Alza
  10. Richwood
  11. Celgene
  12. Celltech
  13. Gliatech
  14. Cephalon
  15. Watson
  16. CIBA
  17. Janssen
  18. National Institutes of Health (NIH)
  19. National Institute of Mental Health [MH66961-02]

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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 [(11)C]raclopride and [(11)C]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. Molecular Psychiatry (2011) 16, 1147-1154; doi:10.1038/mp.2010.97; published online 21 September 2010

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