Serotonin reuptake inhibitors and serotonin transporter genotype modulate performance monitoring functions but not their electrophysiological correlates.

J Neurosci

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.

Published: May 2015

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605345PMC
http://dx.doi.org/10.1523/JNEUROSCI.5124-14.2015DOI Listing

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