Neuroinflammation in schizophrenia-related psychosis: a PET study.
Schizophrenia is a chronic and disabling brain disease characterized by psychotic episodes with unknown etiology. It is suggested that neuroinflammation plays a role in the pathophysiology of schizophrenia. Neuroinflammation is characterized by the activation of microglia cells, which show an increase in the expression of the peripheral benzodiazepine receptor. The isoquinoline (R)-N-(11)C-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide ((11)C-(R)-PK11195) is a peripheral benzodiazepine receptor ligand that can be used for the imaging of activated microglia cells, and thus neuroinflammation, with PET. We hypothesized that neuroinflammation would be more profound in schizophrenic patients during psychosis, and it was therefore investigated whether neuroinflammation was present in patients within the schizophrenia spectrum who were in a psychotic phase.


METHODS
Seven patients within the schizophrenia spectrum who were recovering from psychosis were included. Recovering psychosis was defined by a score of 5 or more on 1 item of the positive scale of the positive and negative symptoms scale (PANSS) or a score of 4 on 2 items. The patients were compared with 8 age-matched healthy volunteers. Dynamic 60-min PET scans were acquired after the injection of (11)C-(R)-PK11195. All subjects underwent T1- and T2-weighted MRI, and the scans were visually examined for abnormalities and used for anatomic coregistration in data analysis. The PET data were analyzed with a 2-tissue-compartment model to calculate the binding potential, using the metabolite-corrected plasma curve as input.


RESULTS
A significantly higher binding potential of (11)C-(R)-PK11195, indicative of neuroinflammation, was found in the hippocampus of schizophrenic patients than in healthy volunteers (2.07 +/- 0.42 vs. 1.37 +/- 0.30; P = 0.004). A nonsignificant 30% higher (11)C-(R)-PK11195 binding potential was found in the whole-brain gray matter of schizophrenic patients. The MR images did not reveal any visual abnormalities.


CONCLUSIONS
The present study suggests that focal neuroinflammation may play an important role in schizophrenia during psychosis.
Doorduin
Janine
J
Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. j.doorduin@ngmb.umcg.nl
de Vries
Erik F J
EF
Willemsen
Antoon T M
AT
de Groot
Jan Cees
JC
Dierckx
Rudi A
RA
Klein
Hans C
HC
D000328:Adult; D000577:Amides; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000000981:diagnostic imaging*; D007546:Isoquinolines; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D012559:Schizophrenia / Q000150:complications* / Q000000981:diagnostic imaging*; D055815:Young Adult
C504060:(R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide; D000577:Amides; D007546:Isoquinolines