ArticleTranslational psychiatry2021
Increased activation product of complement 4 protein in plasma of individuals with schizophrenia.
Article in Translational psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05109065 (Peripheral Immune System in Individuals With Schizophrenia), which is not on this map. Cited by 16 papers.
What it found
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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.
The trial behind it
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.
Peripheral Immune System in Individuals With Schizophrenia
Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Complement component C4 regulates amyloid pathology and glial reactivity in mouse model of Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Loss of SHP1 in Spinal Astrocytes Triggers T-Lymphocyte Infiltration and Nociceptive Hypersensitivity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Peripheral complement C4 protein in schizophrenia: Association with gene copy number and immune cell subtypes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Longitudinal investigation of the T helper (Th)1-Th2 balance and complement system in clinical high risk for psychosis cohort.Translational psychiatry · 2026Article
- Blood-based proteomics for schizophrenia: candidate biomarkers for risk assessment and precision psychiatry.Frontiers in molecular biosciences · 2026Review
- C4d, a high-affinity LilrB2 ligand, is elevated in Alzheimer's disease and mediates synapse pruning.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Lipidomic and proteomic insights from extracellular vesicles in the postmortem dorsolateral prefrontal cortex reveal substance use disorder-induced brain changes.Translational psychiatry · 2025Article
- The role of the microbiota-gut-brain axis in schizophrenia: an immunological perspective.Frontiers in immunology · 2025Review
- New Evidence for the Role of the Blood-Brain Barrier and Inflammation in Stress-Associated Depression: A Gene-Environment Analysis Covering 19,296 Genes in 109,360 Humans.International journal of molecular sciences · 2024Article
- Complement C4, C4A and C4a - What they do and how they differ.Brain, behavior, & immunity - health · 2024Review
- A guide to complement biology, pathology and therapeutic opportunity.Nature reviews. Immunology · 2024Review
- Investigating the dark-side of the genome: a barrier to human disease variant discovery?Biological research · 2023Article
- Deregulation of complement components C4A and CSMD1 peripheral expression in first-episode psychosis and links to cognitive ability.European archives of psychiatry and clinical neuroscience · 2022Article
- Cognitive Dysfunction and Prefrontal Cortical Circuit Alterations in Schizophrenia: Developmental Trajectories.Biological psychiatry · 2022Review
- Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia.CNS drugs · 2022Review
- Toxoplasmosis and Schizophrenia: A Systematic Review and Meta-Analysis of Prevalence and Associations and Future Directions.Psychiatric research and clinical practice · 2022Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Structural variation in the complement 4 gene (C4) confers genetic risk for schizophrenia. The variation includes numbers of the increased C4A copy number, which predicts increased C4A mRNA expression. C4-anaphylatoxin (C4-ana) is a C4 protein fragment released upon C4 protein activation that has the potential to change the blood-brain barrier (BBB). We hypothesized that elevated plasma levels of C4-ana occur in individuals with schizophrenia (iSCZ). Blood was collected from 15 iSCZ with illness duration < 5 years and from 14 healthy controls (HC). Plasma C4-ana was measured by radioimmunoassay. Other complement activation products C3-ana, C5-ana, and terminal complement complex (TCC) were also measured. Digital-droplet PCR was used to determine C4 gene structural variation state. Recombinant C4-ana was added to primary brain endothelial cells (BEC) and permeability was measured in vitro. C4-ana concentration was elevated in plasma from iSCZ compared to HC (mean = 654 ± 16 ng/mL, 557 ± 94 respectively, p = 0.01). The patients also carried more copies of the C4AL gene and demonstrated a positive correlation between plasma C4-ana concentrations and C4A gene copy number. Furthermore, C4-ana increased the permeability of a monolayer of BEC in vitro. Our findings are consistent with a specific role for C4A protein in schizophrenia and raise the possibility that its activation product, C4-ana, increases BBB permeability. Exploratory analyses suggest the novel hypothesis that the relationship between C4-ana levels and C4A gene copy number could also be altered in iSCZ, suggesting an interaction with unknown genetic and/or environmental risk factors.
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Registered trials
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