Abstract
Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [11C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87±8.65) and 18 healthy male controls (age: 25.44±6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [11C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [11C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.
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Acknowledgements
We thank P Lajeix for ascertaining diagnosis on an ADHD subject; Y Goto for critical discussion and reading of the findings; A Perna for contribution to participant evaluation; K Auclair and F Durand for nursing support; R Fukasawa, G Sauchuck, and S Mattei for technical assistance at the PET unit; D Jolly and M Kovacevic for preparation of radiotracers; G Rauw for technical assistance in plasma amphetamine determinations; and K Larcher, SM Cox, and K Welfeld for assistance in PET image analysis. This study was funded by Canadian Institutes of Health Research grant number 77728 to CB and ML.
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These data were presented in part at the 47th and 49th (2010) Annual Meetings of the American College of Neuropsychopharmacology at Scottsdale AZ (December 2008) and Miami FL (December 2010), respectively.
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Cherkasova, M., Faridi, N., Casey, K. et al. Amphetamine-Induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults with ADHD. Neuropsychopharmacol 39, 1498–1507 (2014). https://doi.org/10.1038/npp.2013.349
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DOI: https://doi.org/10.1038/npp.2013.349
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