Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers.
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.


METHODS
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.
Breier
A
A
Experimental Therapeutics Branch, NIMH, Bethesda, MD 20892, USA.
Malhotra
A K
AK
Pinals
D A
DA
Weisenfeld
N I
NI
Pickar
D
D
D000328:Adult; D003847:Deoxyglucose / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D007839:Functional Laterality; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D011569:Psychiatric Status Rating Scales; D011605:Psychoses, Substance-Induced / Q000209:etiology* / Q000378:metabolism / Q000523:psychology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; D016194:Receptors, N-Methyl-D-Aspartate; D019788:Fluorodeoxyglucose F18; D007649:Ketamine; D003847:Deoxyglucose; D005947:Glucose