title: The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Neuropsychopharmacology and Brain Imaging, University Hospital of Psychiatry, University of Zurich, Zurich, Switzerland. andre.schmidt@bli.uzh.ch
authors: André
authors: A
authors: Schmidt
authors: Michael
authors: M
authors: Kometer
authors: Rosilla
authors: R
authors: Bachmann
authors: Erich
authors: E
authors: Seifritz
authors: Franz
authors: F
authors: Vollenweider
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D004644:Emotions; D005074:Evoked Potentials, Visual / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005149:Facial Expression; D005260:Female; D006213:Hallucinogens / Q000494:pharmacology; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D011562:Psilocybin / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D055815:Young Adult
chemical_list: D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D011562:Psilocybin; D007649:Ketamine