Effects of selective serotonin reuptake inhibition on neural activity related to risky decisions and monetary rewards in healthy males

TY - JOUR

T1 - Effects of selective serotonin reuptake inhibition on neural activity related to risky decisions and monetary rewards in healthy males

AU - Macoveanu, Julian

AU - Fisher, Patrick M

AU - Haahr, Mette E

AU - Frokjaer, Vibe G

AU - Knudsen, Gitte M

AU - Siebner, Hartwig R

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are commonly prescribed antidepressant drugs targeting the dysfunctional serotonin (5-HT) system, yet little is known about the functional effects of prolonged serotonin reuptake inhibition in healthy individuals. Here we used functional MRI (fMRI) to investigate how a three-week fluoxetine intervention influences neural activity related to risk taking and reward processing. Employing a double-blinded parallel-group design, 29 healthy young males were randomly assigned to receive 3 weeks of a daily dose of 40 mg fluoxetine or placebo. Participants underwent task-related fMRI prior to and after the three-week intervention while performing a card gambling task. The task required participants to choose between two decks of cards. Choices were associated with different risk levels and potential reward magnitudes. Relative to placebo, the SSRI intervention did not alter individual risk-choice preferences, but modified neural activity during decision-making and reward processing: During the choice phase, SSRI reduced the neural response to increasing risk in lateral orbitofrontal cortex, a key structure for value-based decision-making. During the outcome phase, a midbrain region showed an independent decrease in the responsiveness to rewarding outcomes. This midbrain cluster included the raphe nuclei from which serotonergic modulatory projections originate to both cortical and subcortical regions. The findings corroborate the involvement of the normally functioning 5HT-system in decision-making under risk and processing of monetary rewards. The data suggest that prolonged SSRI treatment might reduce emotional engagement by reducing the impact of risk during decision-making or the impact of reward during outcome evaluation.

AB - Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are commonly prescribed antidepressant drugs targeting the dysfunctional serotonin (5-HT) system, yet little is known about the functional effects of prolonged serotonin reuptake inhibition in healthy individuals. Here we used functional MRI (fMRI) to investigate how a three-week fluoxetine intervention influences neural activity related to risk taking and reward processing. Employing a double-blinded parallel-group design, 29 healthy young males were randomly assigned to receive 3 weeks of a daily dose of 40 mg fluoxetine or placebo. Participants underwent task-related fMRI prior to and after the three-week intervention while performing a card gambling task. The task required participants to choose between two decks of cards. Choices were associated with different risk levels and potential reward magnitudes. Relative to placebo, the SSRI intervention did not alter individual risk-choice preferences, but modified neural activity during decision-making and reward processing: During the choice phase, SSRI reduced the neural response to increasing risk in lateral orbitofrontal cortex, a key structure for value-based decision-making. During the outcome phase, a midbrain region showed an independent decrease in the responsiveness to rewarding outcomes. This midbrain cluster included the raphe nuclei from which serotonergic modulatory projections originate to both cortical and subcortical regions. The findings corroborate the involvement of the normally functioning 5HT-system in decision-making under risk and processing of monetary rewards. The data suggest that prolonged SSRI treatment might reduce emotional engagement by reducing the impact of risk during decision-making or the impact of reward during outcome evaluation.

KW - Adult

KW - Brain

KW - Decision Making

KW - Depression

KW - Double-Blind Method

KW - Fluoxetine

KW - Gambling

KW - Humans

KW - Magnetic Resonance Imaging

KW - Male

KW - Reward

KW - Risk-Taking

KW - Serotonin Uptake Inhibitors

KW - Young Adult

U2 - 10.1016/j.neuroimage.2014.05.040

DO - 10.1016/j.neuroimage.2014.05.040

M3 - Journal article

C2 - 24857827

SN - 1053-8119

VL - 99

SP - 434

EP - 442

JO - NeuroImage

JF - NeuroImage

ER -