Neuroinflammation in schizophrenia: meta-analysis of in-vivo microglial imaging studies
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Supplementary information
Author(s)
Type
Journal Article
Abstract
Background
Converging lines of evidence implicate an important role for the immune system in schizophrenia. Microglia are the resident immune cells of the central nervous system and have many functions including neuroinflammation, axonal guidance and neurotrophic support. We aimed to provide a quantitative review of in vivo PET imaging studies of microglia activation in patients with schizophrenia compared with healthy controls.
Methods
Demographic, clinical and imaging measures were extracted from each study and meta-analysis was conducted using a random-effects model (Hedge's g). The difference in 18-kDa translocator protein (TSPO) binding between patients with schizophrenia and healthy controls, as quantified by either binding potential (BP) or volume of distribution (VT), was used as the main outcome. Sub-analysis and sensitivity analysis were carried out to investigate the effects of genotype, ligand and illness stage.
Results
In total, 12 studies comprising 190 patients with schizophrenia and 200 healthy controls met inclusion criteria. There was a significant elevation in tracer binding in schizophrenia patients relative to controls when BP was used as an outcome measure, (Hedge's g = 0.31; p = 0.03) but no significant differences when VT was used (Hedge's g = −0.22; p = 0.29).
Conclusions
In conclusion, there is evidence for moderate elevations in TSPO tracer binding in grey matter relative to other brain tissue in schizophrenia when using BP as an outcome measure, but no difference when VT is the outcome measure. We discuss the relevance of these findings as well as the methodological issues that may underlie the contrasting difference between these outcomes.
Converging lines of evidence implicate an important role for the immune system in schizophrenia. Microglia are the resident immune cells of the central nervous system and have many functions including neuroinflammation, axonal guidance and neurotrophic support. We aimed to provide a quantitative review of in vivo PET imaging studies of microglia activation in patients with schizophrenia compared with healthy controls.
Methods
Demographic, clinical and imaging measures were extracted from each study and meta-analysis was conducted using a random-effects model (Hedge's g). The difference in 18-kDa translocator protein (TSPO) binding between patients with schizophrenia and healthy controls, as quantified by either binding potential (BP) or volume of distribution (VT), was used as the main outcome. Sub-analysis and sensitivity analysis were carried out to investigate the effects of genotype, ligand and illness stage.
Results
In total, 12 studies comprising 190 patients with schizophrenia and 200 healthy controls met inclusion criteria. There was a significant elevation in tracer binding in schizophrenia patients relative to controls when BP was used as an outcome measure, (Hedge's g = 0.31; p = 0.03) but no significant differences when VT was used (Hedge's g = −0.22; p = 0.29).
Conclusions
In conclusion, there is evidence for moderate elevations in TSPO tracer binding in grey matter relative to other brain tissue in schizophrenia when using BP as an outcome measure, but no difference when VT is the outcome measure. We discuss the relevance of these findings as well as the methodological issues that may underlie the contrasting difference between these outcomes.
Date Issued
2018-10-25
Date Acceptance
2018-09-25
Citation
Psychological Medicine, 2018, 49 (13), pp.2186-2196
ISSN
0033-2917
Publisher
Cambridge University Press (CUP)
Start Page
2186
End Page
2196
Journal / Book Title
Psychological Medicine
Volume
49
Issue
13
Copyright Statement
© Cambridge University Press 2018 This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Identifier
https://www.cambridge.org/core/journals/psychological-medicine/article/neuroinflammation-in-schizophrenia-metaanalysis-of-in-vivo-microglial-imaging-studies/991843292F0212960314A007D052003F
Subjects
Social Sciences
Science & Technology
Life Sciences & Biomedicine
Psychology, Clinical
Psychiatry
Psychology
Microglia
neuroinflammation
schizophrenia
TSPO
PERIPHERAL BENZODIAZEPINE-RECEPTOR
ULTRA-HIGH RISK
BINDING-SITES
TRANSLOCATOR PROTEIN
ANTIPSYCHOTIC TREATMENT
1ST-EPISODE PSYCHOSIS
ADULT SCHIZOPHRENIA
AUTOIMMUNE-DISEASES
CEREBROSPINAL-FLUID
18 KDA
Microglia
TSPO
neuroinflammation
schizophrenia
Psychiatry
1701 Psychology
1117 Public Health and Health Services
1109 Neurosciences
Publication Status
Published
Date Publish Online
2018-10-25