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The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions

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Abstract

Rationale

Both glutamate and serotonin (5-HT) play a key role in the pathophysiology of emotional biases. Recent studies indicate that the glutamate N-methyl-d-aspartate (NMDA) receptor antagonist ketamine and the 5-HT receptor agonist psilocybin are implicated in emotion processing. However, as yet, no study has systematically compared their contribution to emotional biases.

Objectives

This study used event-related potentials (ERPs) and signal detection theory to compare the effects of the NMDA (via S-ketamine) and 5-HT (via psilocybin) receptor system on non-conscious or conscious emotional face processing biases.

Methods

S-ketamine or psilocybin was administrated to two groups of healthy subjects in a double-blind within-subject placebo-controlled design. We behaviorally assessed objective thresholds for non-conscious discrimination in all drug conditions. Electrophysiological responses to fearful, happy, and neutral faces were subsequently recorded with the face-specific P100 and N170 ERP.

Results

Both S-ketamine and psilocybin impaired the encoding of fearful faces as expressed by a reduced N170 over parieto-occipital brain regions. In contrast, while S-ketamine also impaired the encoding of happy facial expressions, psilocybin had no effect on the N170 in response to happy faces.

Conclusion

This study demonstrates that the NMDA and 5-HT receptor systems differentially contribute to the structural encoding of emotional face expressions as expressed by the N170. These findings suggest that the assessment of early visual evoked responses might allow detecting pharmacologically induced changes in emotional processing biases and thus provides a framework to study the pathophysiology of dysfunctional emotional biases.

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Acknowledgments

The present study was supported by the Swiss Neuromatrix Foundation (AS, MK, RB, FXV) and the Heffter Research Center Zurich (FXV).

Conflict of interest

None of the authors have any financial, personal, or organizational conflicts of interest to report in relation to this manuscript.

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Authors and Affiliations

  1. Neuropsychopharmacology and Brain Imaging, University Hospital of Psychiatry, University of Zurich, Zurich, Switzerland

    André Schmidt, Michael Kometer, Rosilla Bachmann & Franz Vollenweider

  2. Clinic of Affective Disorders and General Psychiatry, University Hospital of Psychiatry, University of Zurich, Zurich, Switzerland

    Erich Seifritz

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  1. André Schmidt
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  2. Michael Kometer
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  3. Rosilla Bachmann
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  4. Erich Seifritz
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Correspondence to André Schmidt.

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Schmidt, A., Kometer, M., Bachmann, R. et al. The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions. Psychopharmacology 225, 227–239 (2013). https://doi.org/10.1007/s00213-012-2811-0

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