title: Effects of selective serotonin reuptake inhibition on neural activity related to risky decisions and monetary rewards in healthy males.
abstract: 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.
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Denmark; Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark. Electronic address: julianm@drcmr.dk.
authors.forename: Julian
authors.initials: J
authors.lastname: Macoveanu
authors.affiliation: Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark; Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Fisher
authors.affiliation: Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark; Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Mette E
authors.initials: ME
authors.lastname: Haahr
authors.affiliation: Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark; Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Vibe G
authors.initials: VG
authors.lastname: Frokjaer
authors.affiliation: Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark; Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Denmark; Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark.
authors.forename: Hartwig R
authors.initials: HR
authors.lastname: Siebner
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003657:Decision Making / Q000187:drug effects*; D003863:Depression / Q000523:psychology; D004311:Double-Blind Method; D005473:Fluoxetine / Q000097:blood / Q000494:pharmacology*; D005715:Gambling / Q000523:psychology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012201:Reward; D012309:Risk-Taking; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Decision-making; Orbitofrontal cortex; Raphe; Reward; SSRI; fMRI