OBJECTIVE: Agents that antagonize the N-methyl-D-aspartic acid (NMDA)
receptor, such as phencyclidine and ketamine, produce an acute psychotic
state in normal individuals that resembles some symptoms of schizophrenia.
The aim of this study was to determine which brain regions are involved in
NMDA receptor-mediated psychosis. METHOD: Positron emission tomography with
[18F]fluorodeoxyglucose was used to determine cerebral metabolic activity
in 17 healthy volunteers while an acute psychotic state was induced
simultaneously by the administration of subanesthetic doses of ketamine.
RESULTS: Ketamine produced focal increases in metabolic activity in the
prefrontal cortex and an acute psychotic state. A change in one psychotic
symptom, conceptual disorganization, was significantly related to
prefrontal activation. CONCLUSIONS: These data suggest that the prefrontal
cortex may be involved in mediating NMDA receptor-induced psychosis.