ReviewMolecular psychiatry2017
The complement system: a gateway to gene-environment interactions in schizophrenia pathogenesis.
Review in Molecular psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 4 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
58 citing papers in PubMed, 4 syntheses or guidelines pooled it, 115 citations in OpenAlex.
- Pitfalls in complement analysis: A systematic literature review of assessing complement activation.Frontiers in immunology · 2022Pooled it
- Peripheral complement proteins in schizophrenia: A systematic review and meta-analysis of serological studies.Schizophrenia research · 2020Pooled it
- Regionally Distinct Alterations in Membrane Phospholipid Metabolism in Schizophrenia: A Meta-analysis of Phosphorus Magnetic Resonance Spectroscopy Studies.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2020Pooled it
- An update on the efficacy of anti-inflammatory agents for patients with schizophrenia: a meta-analysis.Psychological medicine · 2019Pooled it
- Immunological predictors in first-episode psychosis: findings from one-year prospective follow-up study.Acta neuropsychiatrica · 2026Article
- Blood-based proteomics for schizophrenia: candidate biomarkers for risk assessment and precision psychiatry.Frontiers in molecular biosciences · 2026Review
- Article
- Effect of olanzapine on changes in serum complement factors levels in patients with first-episode schizophrenia.BMC psychiatry · 2025Article
- Emerging role of complement system in the induction of neuroinflammation in adenylosuccinate lyase deficiency disorder.Brain, behavior, & immunity - health · 2025Review
- Neurological Complications in Inborn Errors of Immunity: A Scoping Review of Clinical Spectrum, Pathophysiological Mechanisms, and Therapeutic Strategies.Clinical reviews in allergy & immunology · 2025Article
- Age-Dependent Correlation between Immune Parameters and Symptoms in Young Adults with Schizophrenia.Current neuropharmacology · 2025Article
- Onset age moderates the associations between neutrophil-to-lymphocyte ratio and clinical symptoms in first-episode patients with schizophrenia.Schizophrenia (Heidelberg, Germany) · 2024Article
- Gene expression changes in Brodmann's Area 46 differentiate epidermal growth factor and immune system interactions in schizophrenia and mood disorders.Schizophrenia (Heidelberg, Germany) · 2024Article
- PolyI:C Maternal Immune Activation on E9.5 Causes the Deregulation of Microglia and the Complement System in Mice, Leading to Decreased Synaptic Spine Density.International journal of molecular sciences · 2024Article
- Recent anti-infective exposure as a risk factor for first episode of suicidal thoughts and/or behaviors in pediatric patients.Brain, behavior, & immunity - health · 2024Article
- Review
- Microglial contribution to the pathology of neurodevelopmental disorders in humans.Acta neuropathologica · 2023Review
- The Gut-Brain Axis in Schizophrenia: The Implications of the Gut Microbiome and SCFA Production.Nutrients · 2023Review
- Lipid-correlated alterations in the transcriptome are enriched in several specific pathways in the postmortem prefrontal cortex of Japanese patients with schizophrenia.Neuropsychopharmacology reports · 2023Article
- Evaluation of Serum Complement Levels and Factors Affecting Treatment Resistance in Patients with Schizophrenia.Psychiatry and clinical psychopharmacology · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The pathogenesis of schizophrenia is considered to be multi-factorial, with likely gene-environment interactions (GEI). Genetic and environmental risk factors are being identified with increasing frequency, yet their very number vastly increases the scope of possible GEI, making it difficult to identify them with certainty. Accumulating evidence suggests a dysregulated complement pathway among the pathogenic processes of schizophrenia. The complement pathway mediates innate and acquired immunity, and its activation drives the removal of damaged cells, autoantigens and environmentally derived antigens. Abnormalities in complement functions occur in many infectious and autoimmune disorders that have been linked to schizophrenia. Many older reports indicate altered serum complement activity in schizophrenia, though the data are inconclusive. Compellingly, recent genome-wide association studies suggest repeat polymorphisms incorporating the complement 4A (C4A) and 4B (C4B) genes as risk factors for schizophrenia. The C4A/C4B genetic associations have re-ignited interest not only in inflammation-related models for schizophrenia pathogenesis, but also in neurodevelopmental theories, because rodent models indicate a role for complement proteins in synaptic pruning and neurodevelopment. Thus, the complement system could be used as one of the 'staging posts' for a variety of focused studies of schizophrenia pathogenesis. They include GEI studies of the C4A/C4B repeat polymorphisms in relation to inflammation-related or infectious processes, animal model studies and tests of hypotheses linked to autoimmune diseases that can co-segregate with schizophrenia. If they can be replicated, such studies would vastly improve our understanding of pathogenic processes in schizophrenia through GEI analyses and open new avenues for therapy.
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