Interleukin 1 receptor antagonist and soluble tumor necrosis factor receptor 1 are associated with general severity and psychotic symptoms in schizophrenia and bipolar disorder
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BACKGROUND: Previous studies suggest elevated inflammation in schizophrenia and bipolar disorder, with increased activity of the Interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor (TNF)-alpha, von Willebrand factor (vWf) and osteoprotegerin (OPG). It is unclear how immune activation is involved in the psychopathology. We investigated if elevated inflammation was associated with disease severity (trait) or current symptom level (state), comparing psychotic with general characteristics. METHODS: Plasma levels of sTNF receptor 1 (sTNF-R1), IL-1 receptor antagonist (IL-1Ra), IL-6, vWf and OPG were measured with ELISA techniques in 322 patients with schizophrenia spectrum and bipolar disorder. Current symptom level (state) was measured with Global Assessment of Functioning (GAF) and Positive and Negative Syndrome Scale (PANSS). Disease severity (trait) was measured with premorbid adjustment scale (PAS), age at onset, number of psychotic episodes and number and length of hospitalizations. RESULTS: After controlling for confounders, IL-1Ra and TNF-R1 were independently associated with GAF, and significantly correlated with PANSS negative and positive, respectively. In addition, Il-1Ra was associated with PAS, and sTNF-R1 with number of hospitalizations and psychotic episodes. VWf was significantly correlated with psychotic episodes, OPG with hospitalizations and IL-6 with history of psychosis. Linear regression analysis showed that GAF remained associated with sTNF-R1 and IL-1Ra with PANSS, after controlling for the other clinical measures. CONCLUSIONS: This supports that inflammatory markers, particularly IL-1Ra and sTNF-R1 are associated with both general disease severity and psychotic features. This supports a role of immune activation in the core pathological mechanisms of severe mental disorders.
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Pro-inflammatory markers such as interleukin 1 (IL-1) and CRP have been linked to the severity of bipolar disorder and psychotic symptoms.
“Pro-inflammatory markers such as interleukin 1 (IL-1) and CRP have been linked to the severity of bipolar disorder and psychotic symptoms.11”
From Association Between Mood Disorder Severity, Treatment Response and Systemic Inflammatory Markers: Exploring the Role of NLR, PLR, MLR, and SII (2024) · cites this paper as [11]
The Discussion reports associations between IL-1 receptor antagonist (a marker of the IL-1 pathway) and clinical severity and psychotic symptoms in patients with schizophrenia and bipolar disorder. But Results §3.1.1 says hsCRP was not significantly correlated with any disease characteristics. The paper therefore does not support the claim’s inclusion of CRP as a marker linked to severity or psychotic symptoms. (LLM, conf=0.90)
Experimental — accuracy not yet measuredSoluble TNF-R1 and IL-1 receptor antagonist levels were found to be associated with the psychotic state of total bipolar disorder and schizophrenia patients in a study on the subject, but when only bipolar disorder patients were included, this relationship was not significant.
“Soluble TNF-R1 and IL-1 receptor antogonist levels were found to be associated with the psychotic state of total bipolar disorder and schizophrenia patients in a study on the subject. However, when only bipolar disorder patients were included, this relationship was not significant.11”
From Association Between Mood Disorder Severity, Treatment Response and Systemic Inflammatory Markers: Exploring the Role of NLR, PLR, MLR, and SII (2024) · cites this paper as [11]
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- Authors
- Hope, S., Ueland, T., Steen, N. E., Dieset, I., Lorentzen, S., Berg, A. O., Agartz, I., Aukrust, P., & Andreassen, O. A.
- Affiliations
- Oslo University Hospital (NO)
- University of Oslo (NO)
- Corresponding author
- Hope, Sigrun
- ORCID
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 145
- Issue
- 1-3
- Pages
- 36-42
- ISSN
- 0920-9964 (ISSN-L)
- OpenAlex
- W2079187454
- Cited by
- 131
- References
- 66
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 10 · 2021: 7 · 2020: 12 · 2019: 15 · 2018: 16 · 2017: 13 · 2016: 16 · 2015: 11 · 2014: 11 · 2013: 3
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Schizophrenia Research (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor 1
- MeSH terms
- Adolescent, Adult, Aged, Bipolar Disorder, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Psychotic Disorders, Regression Analysis, Schizophrenia, Severity of Illness Index, von Willebrand Factor, Interleukin-6, Receptors, Tumor Necrosis Factor, Osteoprotegerin, Interleukin 1 Receptor Antagonist Protein, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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