title: Effects of transcranial direct current stimulation (tDCS) on executive functions: influence of COMT Val/Met polymorphism.
abstract: BACKGROUND
  Transcranial direct current stimulation (tDCS) is a frequently used technique to investigate healthy and impaired neuronal functions. Its modulatory effect on executive functions is of particular interest for understanding the mechanisms underlying integration of cognition and behavior. The key role of prefrontal dopamine function for executive functions suggest that differences of the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene would interact with tDCS interventions in this domain. In this study, we hypothesized that the COMT Met allele homozygosity, associated with higher levels of prefrontal dopamine, would influence the effect of tDCS on higher-level executive functions.
  
  
  METHODS
  Forty-six healthy subjects participated in a double-blind sham-controlled crossover study and underwent COMT genotyping. Anodal tDCS (20 min, 1 mA) to the left dorsolateral prefrontal cortex (dlPFC) or sham stimulation was applied during the performance of a parametric Go/No-Go (PGNG) test measuring sustained attention, response inhibition and cognitive flexibility as measured by set-shifting.
  
  
  RESULTS
  In COMT Met/Met allele carrier anodal tDCS of the dlPFC was associated with a deterioration of set-shifting ability, which is assessed by the most challenging level of the PGNG. Without regard to the carrier status of the COMT Val158Met polymorphism no effects of anodal tDCS on executive functions could be determined.
  
  
  CONCLUSIONS
  In line with the model of non-linear effects of l-dopa on cortical plasticity high dopaminergic prefrontal activity mediated by COMT Val158Met polymorphism predicts a detrimental effect of anodal tDCS on cognitive flexibility. Therefore, we suggest that the individual genetic profile may modulate behavioral effect of tDCS. More precise application of brain stimulation techniques according to the individual genetic patterns may support the development of personalized treatment approaches.
authors.affiliation: Department of Psychiatry and Psychotherapy, Neurophysiology & Interventional Neuropsychiatry, University of Tübingen, Germany. christian.plewnia@uni-tuebingen.de
authors.forename: Christian
authors.initials: C
authors.lastname: Plewnia
authors.forename: Bastian
authors.initials: B
authors.lastname: Zwissler
authors.forename: Isabella
authors.initials: I
authors.lastname: Längst
authors.forename: Brigitte
authors.initials: B
authors.lastname: Maurer
authors.forename: Katrin
authors.initials: K
authors.lastname: Giel
authors.forename: Rejko
authors.initials: R
authors.lastname: Krüger
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D001288:Attention / Q000502:physiology; D001921:Brain / Q000502:physiology*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D018592:Cross-Over Studies; D004247:DNA / Q000235:genetics; D004298:Dopamine / Q000502:physiology; D004311:Double-Blind Method; D004558:Electric Stimulation; D056344:Executive Function / Q000502:physiology*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D017397:Prefrontal Cortex / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D012718:Set, Psychology; D055815:Young Adult
chemical_list: D004247:DNA; D002394:Catechol O-Methyltransferase; D004298:Dopamine