Background: Selective serotonin reuptake inhibitors (SSRIs) show acute effects on the neural processes associated with negative affective bias in healthy people and people with depression. However, whether and how SSRIs also affect reward and punishment processing on a similarly rapid time scale remains unclear. Methods: We investigated the effects of an acute and clinically relevant dose (20 mg) of the SSRI escitalopram on brain response during reward and punishment processing in 19 healthy participants. In a double-blind, placebo-controlled study using functional MRI, participants performed a well-established monetary reward task at 3 time points: at baseline; after receiving placebo or escitalopram; and after receiving placebo or escitalopram following an 8-week washout period. Results: Acute escitalopram administration reduced blood-oxygen-level-dependent (BOLD) response during punishment feedback in the right thalamus (family-wise error corrected [FWE] p = 0.013 at peak level) and the right caudate head (pFWE = 0.011 at peak level) compared to placebo. We did not detect any significant BOLD changes during reward feedback. Limitations: We included only healthy participants, so interpretation of findings are limited to the healthy human brain and require future testing in patient populations. The par-adigm we used was based on monetary stimuli, and results may not be generalizable to other forms of reward. Conclusion: Our findings extend theories of rapid SSRI action on the neural processing of rewarding and aversive stimuli and suggest a specific and acute effect of escitalopram in the punishment neurocircuitry.
Bibliographical noteFunding Information:
Funding: C. Lewis and J. Sacher were supported by the Branco Weiss Fellowship–Society in Science, National Association for Research on Schizophrenia and Depression (NARSAD) Young Investigator Grant 25032 from the Brain and Behavior Research Foundation, and by a Minerva Research Group grant from the Max Planck Society (all awarded to J. Sacher).
Competing interests: E. Forbes declares an honorarium for editorial activities for the Association for Psychological Science; paid consultancy for DSMB, Durham VA (sponsor), Otsuka (funder); an honorarium for mentoring activities as part of Research Centre, Brown University; research funding from the National Institutes of Health; and an honorarium for a grant review from the National Institutes of Health, all outside the published work. No other competing interests declared.
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ASJC Scopus subject areas
- Psychiatry and Mental health
- Biological Psychiatry
- Pharmacology (medical)