title: Dopamine transporter (SLC6A3) genotype impacts neurophysiological correlates of cognitive response control in an adult sample of patients with ADHD.
abstract: Studies provide ample evidence for a dysfunction in dopaminergic neurotransmission in Attention-Deficit/Hyperactivity Disorder (ADHD). In that respect, a common variable number of tandem repeats (VNTR) polymorphism in the 3' untranslated region (UTR) of the dopamine transporter gene (SLC6A3) has been repeatedly associated with the disorder. Here, we examined the influence of the common 9- and 10-repeat alleles of SLC6A3 on prefrontal brain functioning and cognitive response control in a large sample of adult ADHD patients (n=161) and healthy controls (n=109). To this end, we inspected a neurophysiological marker of cognitive response control (NoGo anteriorization, NGA) elicited by means of a Go-NoGo task (continuous performance test, CPT). Within the group of ADHD patients, nine-repeat allele carriers showed significantly reduced NGA, whereas no influence of SLC6A3 genotype was observed in the control group. In contrast to previous association studies of children, the nine-repeat-not the 10-repeat-allele was associated with functional impairments in our sample of adult ADHD patients. Our findings confirm a significant effect of the SLC6A3 genotype on the neurophysiological correlates of cognitive response control in ADHD, and indicate that still to-be-identified age-related factors are important variables modulating the effect of genetic factors on endophenotypes.
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, Wuerzburg, Germany. Dresler_T@klinik.uni-wuerzburg.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Dresler
authors.forename: Ann-Christine
authors.initials: AC
authors.lastname: Ehlis
authors.forename: Sebastian
authors.initials: S
authors.lastname: Heinzel
authors.forename: Tobias J
authors.initials: TJ
authors.lastname: Renner
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.forename: Christina G
authors.initials: CG
authors.lastname: Baehne
authors.forename: Monika
authors.initials: M
authors.lastname: Heine
authors.forename: Andrea
authors.initials: A
authors.lastname: Boreatti-Hümmer
authors.forename: Christian P
authors.initials: CP
authors.lastname: Jacob
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Fallgatter
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000503:physiopathology; D003071:Cognition / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D005260:Female; D005787:Gene Frequency / Q000235:genetics / Q000502:physiology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011930:Reaction Time / Q000502:physiology*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human