ArticleJournal of psychiatry & neuroscience : JPN2015
Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia--significance for activation of the kynurenine pathway.
Article in Journal of psychiatry & neuroscience : JPN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04159207 (A Longitudinal Study of Inflammatory Pathways in Depression), which is not on this map. Cited by 123 papers, 12 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.
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.
A Longitudinal Study of Inflammatory Pathways in Depression
Who cites it
123 citing papers in PubMed, 12 syntheses or guidelines pooled it, 223 citations in OpenAlex.
- Biomarkers in the cerebrospinal fluid of patients with psychotic disorders compared to healthy controls: a systematic review and meta-analysis.Molecular psychiatry · 2023Pooled it
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- The tryptophan catabolite or kynurenine pathway in schizophrenia: meta-analysis reveals dissociations between central, serum, and plasma compartments.Molecular psychiatry · 2022Pooled it
- Effect of immune activation on the kynurenine pathway and depression symptoms - A systematic review and meta-analysis.Neuroscience and biobehavioral reviews · 2020Pooled it
- Effects of inflammation on the kynurenine pathway in schizophrenia - a systematic review.Journal of neuroinflammation · 2020Pooled it
- Neuroinflammation in schizophrenia: meta-analysis ofPsychological medicine · 2019Pooled it
- Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis.Molecular psychiatry · 2019Pooled it
- Cytokines in cerebrospinal fluid of patients with schizophrenia spectrum disorders: New data and an updated meta-analysis.Schizophrenia research · 2018Pooled it
- Meta-analysis of Cerebrospinal Fluid Cytokine and Tryptophan Catabolite Alterations in Psychiatric Patients: Comparisons Between Schizophrenia, Bipolar Disorder, and Depression.Schizophrenia bulletin · 2018Pooled it
- Kynurenic Acid in Schizophrenia: A Systematic Review and Meta-analysis.Schizophrenia bulletin · 2017Pooled it
- Effects of psychotropic drugs on inflammation: consequence or mediator of therapeutic effects in psychiatric treatment?Psychopharmacology · 2016Pooled it
- C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications.Molecular psychiatry · 2016Pooled it
- Effects of Heat Exposure on Kynurenine Pathway Metabolism-Comparison Between Exertional and Exogenous Heating of the Human Body.Acta physiologica (Oxford, England) · 2025Trial
- Associations between expression of indoleamine 2, 3-dioxygenase enzyme and inflammatory cytokines in patients with first-episode drug-naive Schizophrenia.Translational psychiatry · 2021Trial
- The role of proinflammatory response and the kynurenine pathway in the association between childhood maltreatment and lifetime substance use disorder.Neurobiology of stress · 2026Article
- Metabolic Mechanisms in Electroconvulsive Therapy for Schizophrenia: Role, Potential and Future Directions.International journal of molecular sciences · 2026Review
- UntargetedTranslational psychiatry · 2026Article
- A dual-marker peripheral signature of IL-6 elevation andActa neuropsychiatrica · 2026Article
- Immunometabolic reprogramming of central and peripheral immune cells in mental disorders: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Markers of neuroinflammation in the CSF of patients with difficult to treat psychiatric disease.Frontiers in psychiatry · 2026Article
63 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAccumulating evidence indicates that schizophrenia is associated with brain immune activation. While a number of reports suggest increased cytokine levels in patients with schizophrenia, many of these studies have been limited by their focus on peripheral cytokines or confounded by various antipsychotic treatments. Here, well-characterized patients with schizophrenia, all receiving olanzapine treatment, and healthy volunteers were analyzed with regard to cerebrospinal fluid (CSF) levels of cytokines. We correlated the CSF cytokine levels to previously analyzed metabolites of the kynurenine (KYN) pathway.
methodsWe analyzed the CSF from patients and controls using electrochemiluminescence detection with regard to cytokines. Cell culture media from human cortical astrocytes were analyzed for KYN and kynurenic acid (KYNA) using high-pressure liquid chromatography or liquid chromatography/mass spectrometry.
resultsWe included 23 patients and 37 controls in our study. Patients with schizophrenia had increased CSF levels of interleukin (IL)-6 compared with healthy volunteers. In patients, we also observed a positive correlation between IL-6 and the tryptophan:KYNA ratio, indicating that IL-6 activates the KYN pathway. In line with this, application of IL-6 to cultured human astrocytes increased cell medium concentration of KYNA. LIMITATIONS: The CSF samples had been frozen and thawed twice before analysis of cytokines. Median age differed between patients and controls. When appropriate, all present analyses were adjusted for age.
conclusionWe have shown that IL-6, KYN and KYNA are elevated in patients with chronic schizophrenia, strengthening the idea of brain immune activation in patients with this disease. Our concurrent cell culture and clinical findings suggest that IL-6 induces the KYN pathway, leading to increased production of the N-methyl-D-aspartate receptor antagonist KYNA in patients with schizophrenia.
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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.