Metabolic hyperfrontality and psychopathology in the ketamine model of psychosis using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG).
To date, the ketamine/PCP model of psychosis has been proposed to be one of the best pharmacological models to mimic schizophrenic psychosis in healthy volunteers, since ketamine can induce both positive and negative 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 schizophrenia. Positron emission tomography was used to study ketamine-induced psychotic symptom formation in relation to cerebral metabolic alterations in healthy volunteers. Our study shows that NMDA receptor blockade results in a hyperfrontal metabolic pattern. Increased metabolic activity in the frontomedial and anterior cingulate cortex correlated positively with psychotic symptom formation, in particular with ego pathology. Analysis of correlations between syndrome scores and metabolic rate of glucose (CMRglu) or metabolic gradients (ratios) revealed that each psychopathological syndrome was associated with a number of metabolic alterations in cortical and subcortical brain regions, suggesting that not a single brain region, but distributed neuronal networks are involved in acute psychotic symptom formation.
Vollenweider
F X
FX
Research Department, Psychiatric University Hospital of Zürich, Switzerland. vollen@bli.unizh.ch
Leenders
K L
KL
Scharfetter
C
C
Antonini
A
A
Maguire
P
P
Missimer
J
J
Angst
J
J
D000328:Adult; D001923:Brain Chemistry / Q000187:drug effects; D003847:Deoxyglucose / Q000031:analogs & derivatives; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005625:Frontal Lobe / Q000378:metabolism*; D007839:Functional Laterality / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007649:Ketamine / Q000493:pharmacokinetics; D008297:Male; D011594:Psychometrics; D011605:Psychoses, Substance-Induced / Q000378:metabolism* / Q000523:psychology*; D011795:Surveys and Questionnaires; D014055:Tomography, Emission-Computed
D018691:Excitatory Amino Acid Antagonists; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D007649:Ketamine; D003847:Deoxyglucose; D005947:Glucose