Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment.
BACKGROUND
Selective serotonin reuptake inhibitors (SSRIs) are popular medications for anxiety and depression, but their effectiveness, particularly in patients with prominent symptoms of loss of motivation and pleasure, has been questioned. There are few studies of the effect of SSRIs on neural reward mechanisms in humans.


METHODS
We studied 45 healthy participants who were randomly allocated to receive the SSRI citalopram, the noradrenaline reuptake inhibitor reboxetine, or placebo for 7 days in a double-blind, parallel group design. We used functional magnetic resonance imaging to measure the neural response to rewarding (sight and/or flavor of chocolate) and aversive stimuli (sight of moldy strawberries and/or an unpleasant strawberry taste) on the final day of drug treatment.


RESULTS
Citalopram reduced activation to the chocolate stimuli in the ventral striatum and the ventral medial/orbitofrontal cortex. In contrast, reboxetine did not suppress ventral striatal activity and in fact increased neural responses within medial orbitofrontal cortex to reward. Citalopram also decreased neural responses to the aversive stimuli conditions in key "punishment" areas such as the lateral orbitofrontal cortex. Reboxetine produced a similar, although weaker effect.


CONCLUSIONS
Our findings are the first to show that treatment with SSRIs can diminish the neural processing of both rewarding and aversive stimuli. The ability of SSRIs to decrease neural responses to reward might underlie the questioned efficacy of SSRIs in depressive conditions characterized by decreased motivation and anhedonia and could also account for the experience of emotional blunting described by some patients during SSRI treatment.
McCabe
Ciara
C
Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford OX3 7JX, United Kingdom. ciara.mccabe@psych.ox.ac.uk
Mishor
Zevic
Z
Cowen
Philip J
PJ
Harmer
Catherine J
CJ
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000339:Affect / Q000187:drug effects*; D001008:Anxiety Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D015283:Citalopram / Q000494:pharmacology* / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use; D009415:Nerve Net / Q000187:drug effects* / Q000503:physiopathology*; D000077593:Reboxetine; D012201:Reward; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D055815:Young Adult
D018759:Adrenergic Uptake Inhibitors; D015283:Citalopram; D009025:Morpholines; D000077593:Reboxetine; D017367:Selective Serotonin Reuptake Inhibitors