METABOLIC HYPERFRONTALITY AND PSYCHOPATHOLOGY IN THE KETAMINE MODEL OF PSYCHOSIS USING POSITRON EMISSION TOMOGRAPHY (PET) AND [F-18] FLUORODEOXYGLUCOSE (FDG)

To date, the ketamine/PCP model of psychosis has been proposed to be o ne of the best pharmacological models to mimic schizophrenic psychosis in healthy volunteers, since ketamine can induce both positive and ne gative symptoms of schizophrenia. At subanesthetic doses, ketamine has been reported to primarily block N-methyl-D-aspartate (NMDA) receptor complex giving support to a glutamate deficiency hypothesis in schizo phrenia. Positron emission tomography was used to study ketamine-induc ed psychotic symptom formation in relation to cerebral metabolic alter ations in healthy volunteers. Our study shows that NMDA receptor block ade results in a hyperfrontal metabolic pattern. Increased metabolic a ctivity in the frontomedial and anterior cingulate cortex correlated p ositively with psychotic symptom formation, in particular with ego pat hology. Analysis of correlations between syndrome scores and metabolic rate of glucose (CMRglu) or metabolic gradients (ratios) revealed tha t each psychopathological syndrome was associated with a number of met abolic alterations in cortical and subcortical brain regions, suggesti ng that not a single brain region, but distributed neuronal networks a re involved in acute psychotic symptom formation. (C) 1997 Elsevier Sc ience B.V.