Neuroinflammation in schizophrenia: meta-analysis of


Journal

Psychological medicine
ISSN: 1469-8978
Titre abrégé: Psychol Med
Pays: England
ID NLM: 1254142

Informations de publication

Date de publication:
10 2019
Historique:
pubmed: 26 10 2018
medline: 29 7 2020
entrez: 26 10 2018
Statut: ppublish

Résumé

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. 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. 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). 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.

Sections du résumé

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.

Identifiants

pubmed: 30355368
pii: S0033291718003057
doi: 10.1017/S0033291718003057
pmc: PMC6366560
mid: EMS78839
doi:

Substances chimiques

Receptors, GABA 0
TSPO protein, human 0

Types de publication

Comparative Study Journal Article Meta-Analysis Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

2186-2196

Subventions

Organisme : Medical Research Council
ID : G0900891
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U120097115
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N026063/1
Pays : United Kingdom
Organisme : MRF
ID : MRF_C0439
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn

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Auteurs

Tiago Reis Marques (TR)

Psychiatric Imaging Group, MRC Clinical Sciences Centre, Du Cane Road, London W12 0NN, UK.
Psychiatric Imaging Group, London Institute of Medical Sciences (LMS), Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.

Abhishekh H Ashok (AH)

Psychiatric Imaging Group, MRC Clinical Sciences Centre, Du Cane Road, London W12 0NN, UK.
Psychiatric Imaging Group, London Institute of Medical Sciences (LMS), Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, UK.

Toby Pillinger (T)

Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, UK.

Mattia Veronese (M)

Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, UK.

Federico E Turkheimer (FE)

Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, UK.

Paola Dazzan (P)

Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, UK.

Iris E C Sommer (IEC)

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.

Oliver D Howes (OD)

Psychiatric Imaging Group, MRC Clinical Sciences Centre, Du Cane Road, London W12 0NN, UK.
Psychiatric Imaging Group, London Institute of Medical Sciences (LMS), Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, UK.

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