J Psychiatry Neurosci 2021;46(3):E319-E327 | PDF
Carolin A. Lewis, MSc; Karsten Mueller, PhD; Rachel G. Zsido, BA; Janis Reinelt, MD; Ralf Regenthal, MD, PhD; Hadas Okon-Singer, PhD; Erika E. Forbes, PhD; Arno Villringer, MD, PhD; Julia Sacher, MD, PhD
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 doubleblind, 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 paradigm 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.
Submitted Jul. 6, 2020; Oct. 12, 2020; Revised Nov. 20, 2020; Accepted Dec. 12, 2020
Affiliations: From the Emotion Neuroimaging Lab, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (Lewis, Zsido, Sacher); the International Max Planck Research School on Neuroscience of Communication: Function, Structure, and Plasticity, Leipzig, Germany (Lewis, Zsido); the Department of Psychiatry and Psychotherapy, Medical School, University of Tuebingen, Germany (Lewis); the Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany (Mueller, Reinelt, Villringer); the Max Planck School of Cognition, Leipzig, Germany (Zsido); the Division of Clinical Pharmacology, Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany (Regenthal); the Department of Psychology, School of Psychological Sciences, University of Haifa, Haifa, Israel (Okon-Singer); the Integrated Brain and Behavior Research Center (IBBR), University of Haifa, Haifa, Israel (Okon-Singer); the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA (Forbes); and the Clinic for Cognitive Neurology, University of Leipzig, Leipzig, Germany (Villringer, Sacher).
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.
Contributors: E. Forbes, A. Villringer and J. Sacher designed the study. R. Regenthal and J. Sacher acquired the data, which C. Lewis, K. Mueller, R. Zsido, J. Reinelt, H. Okon-Singer and J. Sacher analyzed. C. Lewis, R. Zsido, R. Regenthal and J. Sacher wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.
Content licence: This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BYNC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is non-commercial (i.e. research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/
Correspondence to: J. Sacher, Max Planck Institute for Human Cognitive and Brain Sciences, P.O. Box 500355, 04303 Leipzig Germany; firstname.lastname@example.org