title: Serotonin reuptake inhibitors and serotonin transporter genotype modulate performance monitoring functions but not their electrophysiological correlates.
abstract: Serotonin (5-HT) has been hypothesized to be implicated in performance monitoring by promoting behavioral inhibition in the face of aversive events. However, it is unclear whether this is restricted to external (punishment) or includes internal (response errors) events. The aim of the current study was to test whether higher 5-HT levels instigate inhibition specifically in the face of errors, measured as post-error slowing (PES), and whether this is represented in electrophysiological correlates of error processing, namely error-related negativity (ERN) and positivity. Therefore, from a large sample of human subjects (n = 878), two extreme groups were formed regarding hypothesized high and low 5-HT transporter (5-HTT) expression based on 5-HTTLPR and two additional single nucleotide polymorphisms (rs25531, rs25532). Seventeen higher (LL) and 15 lower (SS) expressing Caucasian subjects were administered the selective serotonin reuptake inhibitor (SSRI) citalopram (10 mg) intravenously in a double-blind crossover design. We found pharmacogenetic evidence for a role of 5-HT in mediating PES: SSRI administration increased PES in both genetic groups, and SS subjects displayed higher PES. These effects were absent on post-conflict slowing. However, ERN and error positivity were unaffected by pharmacogenetic factors, but ERN was decoupled from behavioral adaptation by SSRI administration in the LL group. Thus, pharmacogenetic evidence suggests that increased 5-HT levels lead to behavioral inhibition in the context of internal aversive events, but electrophysiological correlates of performance monitoring appear unrelated to the 5-HT system. Therefore, our findings are consistent with theories suggesting that 5-HT mediates the link between aversive processing and inhibition.
authors.affiliation: Otto-von-Guericke University, Institute of Psychology, D-39106 Magdeburg, Germany, Max Planck Institute for Neurological Research, D-50866 Cologne, Germany, adrian.fischer@ovgu.de.
authors.forename: Adrian G
authors.identifier: http://orcid.org/0000-0001-8779-9051
authors.initials: AG
authors.lastname: Fischer
authors.affiliation: Otto-von-Guericke University, Institute of Psychology, D-39106 Magdeburg, Germany.
authors.forename: Tanja
authors.identifier: http://orcid.org/0000-0002-8845-8803
authors.initials: T
authors.lastname: Endrass
authors.affiliation: Department of Psychology, University of Bonn, D-53111 Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reuter
authors.affiliation: Institute of Human Genetics, University of Ulm, D-89081 Ulm, Germany, University Medical Center Hamburg-Eppendorf, Institute of Human Genetics, D-20246 Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kubisch
authors.affiliation: Otto-von-Guericke University, Institute of Psychology, D-39106 Magdeburg, Germany, Max Planck Institute for Neurological Research, D-50866 Cologne, Germany, Radboud University, Donders Institute for Brain, Cognition and Behaviour, 6525 Nijmegen, The Netherlands, and Center for Behavioral Brain Sciences, D-39106 Magdeburg, Germany.
authors.forename: Markus
authors.identifier: http://orcid.org/0000-0003-3970-1982
authors.initials: M
authors.lastname: Ullsperger
mesh_terms: D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects* / Q000379:methods; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010775:Photic Stimulation / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human
keywords: 5-HTTLPR; EEG; citalopram; performance monitoring; serotonin