title: DAT1 and COMT effects on delay discounting and trait impulsivity in male adolescents with attention deficit/hyperactivity disorder and healthy controls.
abstract: Choice impulsivity has been linked to dopamine function and is consistently observed in attention deficit/hyperactivity disorder (ADHD) as a preference for smaller-immediate over larger-delayed rewards using choice-delay paradigms. More sophisticated delay discounting paradigms have yielded inconsistent results. Context and sample characteristics may have contributed to these variations. In this study we examine the effect of type (real vs hypothetical) and magnitude of reward as well as of variation in dopamine genes on choice impulsivity. We selected 36 male adolescents with ADHD-combined subtype (ADHD-CT) and 32 controls (mean age=15.42, SD=2.05) to form four roughly equally sized subgroups on the basis of DAT1(10/6) haplotype dosage (2 copies and <2 copies). Participants, who were also genotyped for the COMT(val158met) and DRD4(48bp-VNTR) polymorphisms, performed a hypothetical and a real-time discounting task and provided self-ratings of trait impulsivity. The ADHD-CT group discounted rewards more steeply than controls only in the hypothetical task, with delay, but not reward magnitude, influencing choices. They also rated themselves as more impulsive compared with controls. DAT1(10/6) dosage and the COMT(Val158Met) genotype predicted trait impulsivity and discounting rates in the hypothetical task, but not in the real-time task. Our results directly link variation in genes putatively influencing dopamine signaling in the prefrontal cortex (COMT(Val158Met)) and the striatum (DAT1(10/6)) with discounting rates in a hypothetical task (but not a real-time task) and self-ratings of trait impulsivity in ADHD-CT and healthy controls. The lack of magnitude effects in the hypothetical task suggests that discounting in this task may be influenced by different processes in ADHD-CT than in healthy controls.
authors.affiliation: MRC SDGP Centre, Institute of Psychiatry, King's College London, London, UK. yannis.paloyelis@kcl.ac.uk
authors.forename: Yannis
authors.initials: Y
authors.lastname: Paloyelis
authors.forename: Philip
authors.initials: P
authors.lastname: Asherson
authors.forename: Mitul A
authors.initials: MA
authors.lastname: Mehta
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Jonna
authors.initials: J
authors.lastname: Kuntsi
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D002755:Choice Behavior; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007175:Impulsive Behavior / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D050638:Receptors, Dopamine D4 / Q000235:genetics; D012201:Reward; D057566:Self Report; D055815:Young Adult
chemical_list: C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; D002394:Catechol O-Methyltransferase