title: Amphetamine-induced dopamine release and neurocognitive function in treatment-naive adults with ADHD.
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 [(11)C]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 [(11)C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [(11)C]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.
authors.affiliation: Department of Psychology, McGill University, Montreal, QC, Canada.
authors.forename: Mariya V
authors.initials: MV
authors.lastname: Cherkasova
authors.affiliation: Department of Psychiatry, McGill University, Montreal, QC, Canada.
authors.forename: Nazlie
authors.initials: N
authors.lastname: Faridi
authors.affiliation: 1] Department of Psychiatry, McGill University, Montreal, QC, Canada [2] Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Casey
authors.affiliation: 1] Department of Psychology, McGill University, Montreal, QC, Canada [2] Department of Psychiatry, McGill University, Montreal, QC, Canada.
authors.forename: Gillian A
authors.initials: GA
authors.lastname: O'Driscoll
authors.affiliation: Department of Psychiatry, McGill University, Montreal, QC, Canada.
authors.forename: Lily
authors.initials: L
authors.lastname: Hechtman
authors.affiliation: Douglas Institute, Montreal, QC, Canada.
authors.forename: Ridha
authors.initials: R
authors.lastname: Joober
authors.affiliation: Department of Psychiatry, University of Alberta, Edmonton, AB, Canada.
authors.forename: Glen B
authors.initials: GB
authors.lastname: Baker
authors.affiliation: McGill University School of Medicine, Montreal, QC, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Palmer
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Dagher
authors.affiliation: 1] Department of Psychology, McGill University, Montreal, QC, Canada [2] Department of Psychiatry, McGill University, Montreal, QC, Canada [3] Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada [4] Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, QC, Canada.
authors.forename: Marco
authors.initials: M
authors.lastname: Leyton
authors.affiliation: 1] Department of Psychiatry, McGill University, Montreal, QC, Canada [2] Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
authors.forename: Chawki
authors.initials: C
authors.lastname: Benkelfat
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D001931:Brain Mapping; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D003913:Dextroamphetamine / Q000097:blood / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D018765:Dopamine Uptake Inhibitors / Q000097:blood / Q000494:pharmacology*; D056344:Executive Function / Q000502:physiology; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D020891:Raclopride / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D013647:Task Performance and Analysis
chemical_list: D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D020891:Raclopride; D003913:Dextroamphetamine; D004298:Dopamine