ArticleNature communications2022
Cerebrospinal fluid concentration of complement component 4A is increased in first episode schizophrenia.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Quantitative analysis of literature on diagnostic biomarkers of Schizophrenia: revealing research hotspots and future prospects.BMC psychiatry · 2025Pooled it
- Biomarkers in the cerebrospinal fluid of patients with psychotic disorders compared to healthy controls: a systematic review and meta-analysis.Molecular psychiatry · 2023Pooled it
- Schizophrenia Spectrum Biomarkers Consortium: Establishment of a Biorepository for the Discovery of Quantitative Fluid Biomarkers.Schizophrenia bulletin · 2026Article
- Cerebrospinal fluid biomarkers reveal transdiagnostic synaptic dysfunction across major psychiatric disorders.Nature communications · 2026Article
- Neuroinflammation: an unfortunate term to describe schizophrenia.Molecular psychiatry · 2026Review
- 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
- Divergence of C4A and C4B in first-episode psychosis: Insights from CSF and plasma immune profiling.Translational psychiatry · 2026Article
- Primary Amoebic Meningoencephalitis caused by Complement C2 Deficiency.medRxiv : the preprint server for health sciences · 2026Article
- Risk genes in progressive supranuclear palsy (PSP) affect integrity and function of microtubules.Frontiers in aging · 2026Review
- Cognition before and after psychosis onset: A naturalistic study of change, heterogeneity, and prognosis.Schizophrenia research. Cognition · 2025Review
- Tracking inflammation status for improving patient prognosis: A review of current methods, unmet clinical needs and opportunities.Biotechnology advances · 2025Review
- Three cases with chronic obsessive compulsive disorder report gains in wellbeing and function following rituximab treatment.Molecular psychiatry · 2025Article
- Dynamic astrocytic complement C3 activation in the epileptic hippocampus.Frontiers in neurology · 2025Article
- The role of the microbiota-gut-brain axis in schizophrenia: an immunological perspective.Frontiers in immunology · 2025Review
- Antenatal steroids elicited neurodegenerative-associated transcriptional changes in the hippocampus of preterm fetal sheep independent of lung maturation.BMC medicine · 2024Article
- Complement C4, C4A and C4a - What they do and how they differ.Brain, behavior, & immunity - health · 2024Review
- Synaptic pruning in schizophrenia is not classical.Brain, behavior, and immunity · 2024Article
- A genetic-epigenetic interplay at 1q21.1 locus underlies CHD1L-mediated vulnerability to primary progressive multiple sclerosis.Nature communications · 2024Article
- Elevated serum kynurenic acid in individuals with first-episode psychosis and insufficient response to antipsychotics.Schizophrenia (Heidelberg, Germany) · 2024Article
- Plastics in the environment in the context of UV radiation, climate change and the Montreal Protocol: UNEP Environmental Effects Assessment Panel, Update 2023.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
32 authors.
Funding
Abstract
Postsynaptic density is reduced in schizophrenia, and risk variants increasing complement component 4A (C4A) gene expression are linked to excessive synapse elimination. In two independent cohorts, we show that cerebrospinal fluid (CSF) C4A concentration is elevated in patients with first-episode psychosis (FEP) who develop schizophrenia (FEP-SCZ: median 0.41 fmol/ul [CI = 0.34-0.45], FEP-non-SCZ: median 0.29 fmol/ul [CI = 0.22-0.35], healthy controls: median 0.28 [CI = 0.24-0.33]). We show that the CSF elevation of C4A in FEP-SCZ exceeds what can be expected from genetic risk variance in the C4 locus, and in patient-derived cellular models we identify a mechanism dependent on the disease-associated cytokines interleukin (IL)-1beta and IL-6 to selectively increase neuronal C4A mRNA expression. In patient-derived CSF, we confirm that IL-1beta correlates with C4A controlled for genetically predicted C4A RNA expression (r = 0.39; CI: 0.01-0.68). These results suggest a role of C4A in early schizophrenia pathophysiology.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.