title: Influence of DAT1 and COMT variants on neural activation during response inhibition in adolescents with attention-deficit/hyperactivity disorder and healthy controls.
abstract: BACKGROUND
  Impairment of response inhibition has been implicated in attention-deficit/hyperactivity disorder (ADHD). Dopamine neurotransmission has been linked to the behavioural and neural correlates of response inhibition. The current study aimed to investigate the relationship of polymorphisms in two dopamine-related genes, the catechol-O-methyltransferase gene (COMT) and the dopamine transporter gene (SLC6A3 or DAT1), with the neural and behavioural correlates of response inhibition.
  
  
  METHODS
  Behavioural and neural measures of response inhibition were obtained in 185 adolescents with ADHD, 111 of their unaffected siblings and 124 healthy controls (mean age 16.9 years). We investigated the association of DAT1 and COMT variants on task performance and whole-brain neural activation during response inhibition in a hypothesis-free manner. Additionally, we attempted to explain variance in previously found ADHD effects on neural activation during response inhibition using these DAT1 and COMT polymorphisms.
  
  
  RESULTS
  The whole-brain analyses demonstrated large-scale neural activation changes in the medial and lateral prefrontal, subcortical and parietal regions of the response inhibition network in relation to DAT1 and COMT polymorphisms. Although these neural activation changes were associated with different task performance measures, no relationship was found between DAT1 or COMT variants and ADHD, nor did variants in these genes explain variance in the effects of ADHD on neural activation.
  
  
  CONCLUSIONS
  These results suggest that dopamine-related genes play a role in the neurobiology of response inhibition. The limited associations between gene polymorphisms and task performance further indicate the added value of neural measures in linking genetic factors and behavioural measures.
authors.affiliation: Department of Psychiatry,University of Groningen,University Medical Center Groningen,Groningen,The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: van Rooij
authors.affiliation: Department of Psychiatry,University of Groningen,University Medical Center Groningen,Groningen,The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Hoekstra
authors.affiliation: Department of Cognitive Neuroscience,Radboud University Medical Center,Donders Institute for Brain,Cognition and Behaviour,Nijmegen,The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Bralten
authors.affiliation: Department of Human Genetics,Radboud University Medical Center,Donders Institute for Brain,Cognition and Behaviour,Nijmegen,The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Hakobjan
authors.affiliation: Department of Neuropsychology,VU University Amsterdam,Amsterdam,The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Oosterlaan
authors.affiliation: Department of Human Genetics,Radboud University Medical Center,Donders Institute for Brain,Cognition and Behaviour,Nijmegen,The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Franke
authors.affiliation: Department of Psychiatry,Radboud University Medical Center,Donders Institute for Brain,Cognition and Behaviour,Nijmegen,The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Rommelse
authors.affiliation: Department of Cognitive Neuroscience,Radboud University Medical Center,Donders Institute for Brain,Cognition and Behaviour,Nijmegen,The Netherlands.
authors.forename: J K
authors.initials: JK
authors.lastname: Buitelaar
authors.affiliation: Department of Psychiatry,University of Groningen,University Medical Center Groningen,Groningen,The Netherlands.
authors.forename: C A
authors.initials: CA
authors.lastname: Hartman
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D011597:Psychomotor Performance / Q000502:physiology*; D035781:Siblings
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: Attention-deficit/hyperactivity disorder; COMT; DAT1; dopamine; response inhibition