Mismatch negativity generation in the human 5HT2A agonist and NMDA antagonist model of psychosis
Many studies have reported deficits of mismatch negativity (MMN) in schizophrenic patients. Pharmacological challenges with hallucinogens in healthy humans are used as models for psychotic states. Previous studies reported a significant reduction of MMN after ketamine (N-methyl-d-aspartate acid [NMDA] antagonist model) but not after psilocybin (5HT2A agonist model).
The aim of the present study was to directly compare the two models of psychosis using an intraindividual crossover design.
Materials and methods
Fifteen healthy subjects participated in a randomized, double-blind, crossover study with a low and a high dose of the 5HT2A agonist dimethyltryptamine (DMT) and the NMDA antagonist S-ketamine. During electroencephalographic recording, the subjects were performing the AX-version of a continuous performance test (AX-CPT). A source analysis of MMN was performed on the basis of a four-source model of MMN generation.
Nine subjects completed both experimental days with the two doses of both drugs. Overall, we found blunted MMN and performance deficits in the AX-CPT after both drugs. However, the reduction in MMN activity was overall more pronounced after S-ketamine intake, and only S-ketamine had a significant impact on the frontal source of MMN.
The NDMA antagonist model and the 5HT2A agonist model of psychosis display distinct neurocognitive profiles. These findings are in line with the view of the two classes of hallucinogens modeling different aspects of psychosis.
- Mismatch negativity generation in the human 5HT2A agonist and NMDA antagonist model of psychosis
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Volume 199, Issue 1 , pp 77-88
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Mismatch negativity
- Model psychosis
- Industry Sectors
- Author Affiliations
- 1. Department of Psychiatry and Psychotherapy, University of Cologne, Kerpener Strasse 62, 50924, Cologne, Germany
- 3. Psychiatric University Hospital, Lenggstrasse 31, 8032, Zurich, Switzerland
- 2. Department of Psychiatry and Psychotherapy, University of Technology Aachen (RWTH), Pauwelsstrasse 30, 52074, Aachen, Germany
- 4. Max-Planck-lnstitute for Experimental Medicine, Göttingen, Germany
- 5. Department of Neurology, University of Technology Aachen (RWTH), Pauwelsstrasse 30, 52074, Aachen, Germany