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

TY - JOUR

T1 - Serotonin reuptake inhibitors and serotonin transporter genotype modulate performance monitoring functions but not their electrophysiological correlates

AU - Fischer, Adrian G

AU - Endrass, Tanja

AU - Reuter, Martin

AU - Kubisch, Christian

AU - Ullsperger, Markus

N1 - Copyright © 2015 the authors 0270-6474/15/358181-10$15.00/0.

PY - 2015/5/27

Y1 - 2015/5/27

N2 - 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.

AB - 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.

KW - Double-Blind Method

KW - Electroencephalography

KW - Female

KW - Genotype

KW - Humans

KW - Male

KW - Photic Stimulation

KW - Polymorphism, Single Nucleotide

KW - Psychomotor Performance

KW - Reaction Time

KW - Serotonin Plasma Membrane Transport Proteins

KW - Serotonin Uptake Inhibitors

KW - Young Adult

U2 - 10.1523/JNEUROSCI.5124-14.2015

DO - 10.1523/JNEUROSCI.5124-14.2015

M3 - SCORING: Journal article

C2 - 26019334

VL - 35

SP - 8181

EP - 8190

JO - J NEUROSCI

JF - J NEUROSCI

SN - 0270-6474

IS - 21

ER -