Mismatch negativity generation in the human 5HT2A agonist and NMDA antagonist model of psychosis
Karsten Heekeren, Jörg Daumann, Anna Neukirch, Carsten Stock, Wolfram Kawohl, Christine Norra, Till D. Waberski, Euphrosyne Gouzoulis-Mayfrank
Psychopharmacology May 16, 2008 DOI: 10.1007/s00213-008-1129-4 via OpenAlex
Summary
AI-generated from the abstractBoth S-ketamine (an NMDA antagonist) and DMT (a 5HT2A agonist) reduced mismatch negativity (MMN) and impaired performance on a continuous performance test in healthy volunteers, but the effects differed. S-ketamine produced a more pronounced overall reduction in MMN and specifically affected the frontal source of MMN, while DMT did not. These distinct neurocognitive profiles suggest that the two classes of hallucinogens model different aspects of psychosis.
Study at a glance
| Characteristics | Randomized, double-blind, crossover study Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Healthy subjects |
| Interventions | S-ketamine DMT |
| Citations | 158 |
| Key finding | Both S-ketamine and DMT blunted MMN and impaired performance, but S-ketamine had a stronger overall effect and uniquely reduced frontal MMN activity. |
Abstract
RATIONALE: 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). OBJECTIVES: 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. RESULTS: 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. CONCLUSIONS: 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.