title: Immune involvement in the pathogenesis of schizophrenia: a meta-analysis on postmortem brain studies.
abstract: Although the precise pathogenesis of schizophrenia is unknown, genetic, biomarker and imaging studies suggest involvement of the immune system. In this study, we performed a systematic review and meta-analysis of studies investigating factors related to the immune system in postmortem brains of schizophrenia patients and healthy controls. Forty-one studies were included, reporting on 783 patients and 762 controls. We divided these studies into those investigating histological alterations of cellular composition and those assessing molecular parameters; meta-analyses were performed on both categories. Our pooled estimate on cellular level showed a significant increase in the density of microglia (P=0.0028) in the brains of schizophrenia patients compared with controls, albeit with substantial heterogeneity between studies. Meta-regression on brain regions demonstrated this increase was most consistently observed in the temporal cortex. Densities of macroglia (astrocytes and oligodendrocytes) did not differ significantly between schizophrenia patients and healthy controls. The results of postmortem histology are paralleled on the molecular level, where we observed an overall increase in expression of proinflammatory genes on transcript and protein level (P=0.0052) in patients, while anti-inflammatory gene expression levels were not different between schizophrenia and controls. The results of this meta-analysis strengthen the hypothesis that components of the immune system are involved in the pathogenesis of schizophrenia.
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: C F M G
authors.initials: CF
authors.lastname: van Kesteren
authors.affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Gremmels
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: L D
authors.initials: LD
authors.lastname: de Witte
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Neuroscience, Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.|Faculty of Science, Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: Hol
authors.affiliation: Department of Psychiatry, Yulius Mental Health Organization, Barendrecht, The Netherlands.
authors.forename: A R
authors.initials: AR
authors.lastname: Van Gool
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany.
authors.forename: P G
authors.initials: PG
authors.lastname: Falkai
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: R S
authors.initials: RS
authors.lastname: Kahn
authors.affiliation: Department of Psychiatry, Brain Center Rudolf Magnus Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: I E C
authors.initials: IE
authors.lastname: Sommer
mesh_terms: D001253:Astrocytes / Q000473:pathology; D001344:Autopsy; D001921:Brain / Q000276:immunology / Q000473:pathology*; D016022:Case-Control Studies; D002452:Cell Count; D006801:Humans; D007249:Inflammation; D017628:Microglia / Q000276:immunology / Q000473:pathology*; D009836:Oligodendroglia / Q000473:pathology; D012559:Schizophrenia / Q000276:immunology / Q000473:pathology*; D013702:Temporal Lobe / Q000276:immunology / Q000473:pathology; D059467:Transcriptome