The Role of Cytokines in the Pathogenesis of Schizophrenia
Open accessAbstract
Schizophrenia is a chronic mental illness of unknown etiology. A growing and compelling body of evidence implicates immunologic dysfunction as the key element in its pathomechanism. Cytokines, whose altered levels have been increasingly reported in various patient populations, are the major mediators involved in the coordination of the immune system. The available literature reports both elevated levels of proinflammatory as well as reduced levels of anti-inflammatory cytokines, and their effects on clinical status and neuroimaging changes. There is evidence of at least a partial genetic basis for the association between cytokine alterations and schizophrenia. Two other factors implicated in its development include early childhood trauma and disturbances in the gut microbiome. Moreover, its various subtypes, characterized by individual symptom severity and course, such as deficit schizophrenia, seem to differ in terms of changes in peripheral cytokine levels. While the use of a systematic review methodology could be difficult due to the breadth and diversity of the issues covered in this review, the applied narrative approach allows for a more holistic presentation. The aim of this narrative review was to present up-to-date evidence on cytokine dysregulation in schizophrenia, its effect on the psychopathological presentation, and links with antipsychotic medication. We also attempted to summarize its postulated underpinnings, including early childhood trauma and gut microbiome disturbances, and propose trait and state markers of schizophrenia.
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Cytokines present in the gut are important immune system mediators that impact the central system and the pathogenesis of schizophrenia.
“Cytokines present in the gut are important immune system mediators, through the regulation of immune cells, exerting an impact on the central system as well as on the pathogenesis of SZ [13].”
From Effect of Supplementation with Probiotics in Patients with Schizophrenia: Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials (2025) · cites this paper as [13]
The Introduction says cytokines regulate immune-cell activity and may affect neurodevelopment and behavior; the Conclusions link cytokines to schizophrenia pathogenesis. The Introduction and section 6 discuss a possible link between gut microbiome disturbance and peripheral or cerebrospinal-fluid cytokines, but do not establish that the cytokines described are present in the gut or that gut cytokines exert the stated effects. (LLM, conf=0.84)
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Research works printed but not linked: 1
- [96]Galderisi S. Delisi L.E. Borgwardt S. Neuroimaging of Schizophrenia and Other Primary Psychotic Disorders Springer International Publishing Cham, Switzerland 2019 9783319973067
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Li, L., Du, F., Liu, X., Song, M., Grosso, G., Battino, M., Boesch, C., Li, H., & Liu, X. (2025) · Foods · doi:10.3390/foods14101773 · Cited by 6 · see citing works
“Cytokines present in the gut are important immune system mediators, through the regulation of immune cells, exerting an impact on the central system as well as on the pathogenesis of SZ [13].”
- Authors
- Dawidowski, B., Górniak, A., Podwalski, P., Lebiecka, Z., Misiak, B., & Samochowiec, J.
- Affiliations
- Pomeranian Medical University (PL)
- Wroclaw Medical University (PL)
- Corresponding author
- Podwalski, Piotr
- Venue
- Journal of Clinical Medicine
- Publisher
- MDPI AG
- Published
- 2021-08-27
- Volume
- 10
- Issue
- 17
- Pages
- 3849
- ISSN
- 2077-0383 (ISSN-L)
- PMC
- PMC8432006
- OpenAlex
- W3197710304
- Cited by
- 102
- References
- 151
- Citations by year
- 2026: 14 · 2025: 18 · 2024: 26 · 2023: 22 · 2022: 19 · 2021: 3
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Polish Minister of Science and Higher Education (002/RID/2018/19)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- schizophrenia, cytokines, cytokine imbalance, inflammatory cytokines, anti-inflammatory cytokines, immune dysfunction, genetic susceptibility, early childhood trauma, gut microbiota, deficit schizophrenia, antipsychotic drugs, neuroimaging
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