title: Reward modulation of cognitive function in adult attention-deficit/hyperactivity disorder: a pilot study on the role of striatal dopamine.
abstract: Attention-deficit/hyperactivity disorder (ADHD) is accompanied by impairments in cognitive control, such as task-switching deficits. We investigated whether such problems, and their remediation by medication, reflect abnormal reward motivation and associated striatal dopamine transmission in ADHD. We used functional genetic neuroimaging to assess the effects of dopaminergic medication and reward motivation on task-switching and striatal BOLD signal in 23 adults with ADHD, ON and OFF methylphenidate, and 26 healthy controls. Critically, we took into account interindividual variability in striatal dopamine by exploiting a common genetic polymorphism (3'-UTR VNTR) in the DAT1 gene coding for the dopamine transporter. The results showed a highly significant group by genotype interaction in the striatum. This was because a subgroup of patients with ADHD showed markedly exaggerated effects of reward on the striatal BOLD signal during task-switching when they were OFF their dopaminergic medication. Specifically, patients carrying the 9R allele showed a greater striatal signal than healthy controls carrying this allele, whereas no effect of diagnosis was observed in 10R homozygotes. Aberrant striatal responses were normalized when 9R-carrying patients with ADHD were ON medication. These pilot data indicate an important role for aberrant reward motivation, striatal dopamine and interindividual genetic differences in cognitive processes in adult ADHD.
authors.affiliation: aCentre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen bDepartment of Psychiatry cDepartment of Human Genetics dDepartment of Cognitive Neuroscience, Centre for Neuroscience, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour eKarakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Aarts
authors.forename: Mieke
authors.initials: M
authors.lastname: van Holstein
authors.forename: Martine
authors.initials: M
authors.lastname: Hoogman
authors.forename: Marten
authors.initials: M
authors.lastname: Onnink
authors.forename: Cornelis
authors.initials: C
authors.lastname: Kan
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Jan
authors.initials: J
authors.lastname: Buitelaar
authors.forename: Roshan
authors.initials: R
authors.lastname: Cools
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D016022:Case-Control Studies; D003071:Cognition / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D009042:Motivation; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D012201:Reward
chemical_list: D020413:3' Untranslated Regions; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D004298:Dopamine