Dopamine Transporter (SLC6A3) genotype impacts neurophysiological correlates of cognitive response control in an adult sample of patients with ADHD

Thomas Dresler (1) , Ann-Christine Ehlis (1) , Sebastian Heinzel (1) , Tobias J. Renner (1) , Andreas Reif (1) , Christina G. Baehne (1) , Monika Heine (1) , Andrea Boreatti-Hümmer (1) , Christian Jacob (1) , Klaus-Peter Lesch (1) , Andreas J. Fallgatter (1)

1 Department of Psychiatry and Psychotherapy

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, 9-repeat allele carriers showed a significantly reduced NGA, whereas no influence of SLC6A3 genotype was observed in the control group. In contrast to previous association studies in children, the 9-repeat - not the 10-repeat - allele was associated with functional impairments in our sample of adult ADHD patients. Our findings confirm a significant impact of SLC6A3 genotype on neurophysiological correlates of cognitive response control in ADHD, and indicate that still to-be-identified age-related factors are important variables modulating the impact of genetic factors on endophenotypes.

Mots clés: Biological Psychiatry; Dopamine; Imaging; Clinical or Preclinical; Psychiatry & Behavioral Sciences; ADHD; Continuous Performance Test; NoGo-Anteriorization; Cognitive Response Control; Imaging Genetics

Thomas Dresler, Ann-Christine Ehlis, Sebastian Heinzel, Tobias J. Renner, Andreas Reif, et al.. Dopamine Transporter (SLC6A3) genotype impacts neurophysiological correlates of cognitive response control in an adult sample of patients with ADHD. Neuropsychopharmacology, 2010, ⟨10.1038/npp.2010.91⟩. ⟨hal-00555621⟩