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.
Highlights
Schizophrenia is a severe psychiatric disorder with a worldwide prevalence just below 1%, that often leads to dysfunction and suffering for patients and their families and places a significant burden on global health.[1]
Genetic studies consistently observe the strongest association with schizophrenia in the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1,6,7 which was recently linked to the complement system, in particular to complement factor 4.8 Additional suggestion of immune involvement comes from nation-wide cohort studies reporting an increased risk of schizophrenia patients and their relatives for autoimmune diseases and vice versa.[9]
The following keywords were used in the search, both alone and in combinations: ‘Schizophrenia’, ‘psychosis’, ‘autopsy’, ‘postmortem’, immune system’, ‘inflammation’, ‘cytokines’, ‘interleukins’, ‘chemokines’, ‘complement’, ‘microglia’, ‘gliosis’, ‘astrocytes’, ‘macrophages’, ‘lymphocytes’, ‘leukocytes’, ‘MHC I’, ‘MHC II’ and ‘HLA’
Summary
Schizophrenia is a severe psychiatric disorder with a worldwide prevalence just below 1%, that often leads to dysfunction and suffering for patients and their families and places a significant burden on global health.[1]. PET studies have limiting factors such as small sample size, non-specific tracer binding and variability in binding affinity patterns between humans These findings can be of relevance, as they may point out signs of altered activity of the immune system both prodromal and throughout disease. Several postmortem studies assessed alterations of immune processes in brain tissue of patients with schizophrenia, yet with inconsistent results. In this manuscript, we Subtyping of assessments in included studies Study characteristics were grouped into larger umbrella categories,[22] for example, those assessing cells and those assessing molecular targets.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
