Effects of the 5-HT2A agonist psilocybin on mismatch negativity generation and AX-continuous performance task: implications for the neuropharmacology of cognitive deficits in schizophrenia.
Previously the NMDA (N-methyl-D-aspartate) receptor (NMDAR) antagonist ketamine was shown to disrupt generation of the auditory event-related potential (ERP) mismatch negativity (MMN) and the performance of an 'AX'-type continuous performance test (AX-CPT)--measures of auditory and visual context-dependent information processing--in a similar manner as observed in schizophrenia. This placebo-controlled study investigated effects of the 5-HT(2A) receptor agonist psilocybin on the same measures in 18 healthy volunteers. Psilocybin administration induced significant performance deficits in the AX-CPT, but failed to reduce MMN generation significantly. These results indirectly support evidence that deficient MMN generation in schizophrenia may be a relatively distinct manifestation of deficient NMDAR functioning. In contrast, secondary pharmacological effects shared by NMDAR antagonists and the 5-HT(2A) agonist (ie disruption of glutamatergic neurotransmission) may be the mechanism underlying impairments in AX-CPT performance observed during both psilocybin and ketamine administration. Comparable deficits in schizophrenia may result from independent dysfunctions of 5-HT(2A) and NMDAR-related neurotransmission.
Umbricht
Daniel
D
Psychiatric University Hospital of Zurich Department of Research, Switzerland. umbricht@bli.unizh.ch
Vollenweider
Franz X
FX
Schmid
Liselotte
L
Grübel
Claudia
C
Skrabo
Anja
A
Huber
Theo
T
Koller
Rene
R
D000328:Adult; D003072:Cognition Disorders / Q000523:psychology*; D004192:Discrimination, Psychological / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D009949:Orientation / Q000187:drug effects; D011562:Psilocybin / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects*; D044402:Receptor, Serotonin, 5-HT2A; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D012565:Schizophrenic Psychology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D044402:Receptor, Serotonin, 5-HT2A; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D011562:Psilocybin