title: Genetic variability in the dopamine system (dopamine receptor D4, catechol-O-methyltransferase) modulates neurophysiological responses to gains and losses.
abstract: BACKGROUND
  Interindividual variability in the processing of reward might be partially explained by genetic differences in the dopamine system. Here, we study whether brain responses (event-related potentials [ERPs], oscillatory activity) to monetary gains and losses in normal human subjects are modulated as a function of two dopaminergic polymorphisms (catechol-O-methyltransferase [COMT] valine [Val]158methionine [Met], dopamine receptor D4 [DRD4] single nucleotide polymorphism [SNP] -521).
  
  
  METHODS
  Forty participants homozygous for the different alleles of both polymorphisms were selected from a larger population to assess the main effects and interactions. Based on the phasic/tonic dopamine hypothesis, we expected increased brain responses to losses and gains in participants homozygous for the Val/Val variant of the COMT polymorphism (related to higher enzyme activity).
  
  
  RESULTS
  The medial frontal negativity (MFN) of the ERP and the increase in beta power for gains were enhanced for participants homozygous for the COMT ValVal allele when compared with homozygous MetMet participants. In contrast, no modulations in gain- and loss-related brain activity were found to be a function of the DRD4 SNP -521 polymorphism.
  
  
  CONCLUSIONS
  The results demonstrate the role of the COMT Val/Met polymorphism in the processing of reward, consistent with theoretical explanations that suggest the possible role of dopamine in the MFN and beta power increase generation. In addition, the present results might agree with the phasic/tonic dopamine theory that predicts higher phasic dopamine responses in ValVal participants.
authors.affiliation: Department of Neuropsychology, Otto von Guericke University, Magdeburg, Germany.
authors.forename: Josep
authors.initials: J
authors.lastname: Marco-Pallarés
authors.forename: David
authors.initials: D
authors.lastname: Cucurell
authors.forename: Toni
authors.initials: T
authors.lastname: Cunillera
authors.forename: Ulrike M
authors.initials: UM
authors.lastname: Krämer
authors.forename: Estela
authors.initials: E
authors.lastname: Càmara
authors.forename: Wido
authors.initials: W
authors.lastname: Nager
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
authors.forename: Rebecca
authors.initials: R
authors.lastname: Schüle
authors.forename: Ludger
authors.initials: L
authors.lastname: Schöls
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Münte
authors.forename: Antoni
authors.initials: A
authors.lastname: Rodriguez-Fornells
mesh_terms: D000293:Adolescent; D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003627:Data Interpretation, Statistical; D004569:Electroencephalography; D005071:Evoked Potentials / Q000502:physiology; D030141:Feedback, Psychological / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000502:physiology; D005715:Gambling / Q000523:psychology*; D014644:Genetic Variation; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012201:Reward; D055815:Young Adult
chemical_list: D050638:Receptors, Dopamine D4; D002394:Catechol O-Methyltransferase