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Published on: June 14, 2018
Neuroinflammation in schizophrenia-related psychosis: a PET study
Janine Doorduin1, Erik F J de Vries, Antoon T M Willemsen
1Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. j.doorduin@ngmb.umcg.nl
Unlabelled:
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.
Conclusion:
The present study suggests that focal neuroinflammation may play an important role in schizophrenia during psychosis.
Insights
Neuroinflammation, indicated by increased peripheral benzodiazepine receptor binding, is present in the hippocampus of schizophrenia patients during psychosis. This suggests a role for neuroinflammation in the pathophysiology of schizophrenia.
Area of Science:
- Neuroscience
- Psychiatry
- Medical Imaging
Background:
- Schizophrenia is a chronic brain disease with unknown causes, but neuroinflammation is a suspected factor.
- Neuroinflammation involves activated microglia, identified by increased peripheral benzodiazepine receptor (PBR) expression.
- The PBR ligand (11)C-(R)-PK11195 enables PET imaging of activated microglia and neuroinflammation.
Purpose of the Study:
- To investigate the presence and extent of neuroinflammation in schizophrenia patients experiencing psychosis.
- To test the hypothesis that neuroinflammation is more pronounced during psychotic phases of schizophrenia.
Main Methods:
- Seven schizophrenia spectrum patients recovering from psychosis and eight healthy volunteers underwent PET scans with (11)C-(R)-PK11195.
- Dynamic 60-minute PET scans were analyzed using a 2-tissue-compartment model to calculate binding potential.
- All subjects also had MRI scans for anatomical reference and to rule out gross abnormalities.
Main Results:
- Schizophrenia patients showed significantly higher (11)C-(R)-PK11195 binding potential in the hippocampus compared to healthy controls (P = 0.004).
- A trend towards higher binding potential was observed in the whole-brain gray matter of patients, though not statistically significant.
- MRI scans did not reveal any visible abnormalities in the subjects.
Conclusions:
- The findings suggest that focal neuroinflammation, particularly in the hippocampus, is associated with schizophrenia during psychosis.
- This supports the role of neuroinflammation in the pathophysiology of schizophrenia.
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