Abstract

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.

Highlights

  • Schizophrenia is a chronic mental disorder with a complex etiopathogenesis, which involves both congenital and environmental factors [1]

  • IL-6 is one of the most extensively investigated cytokines in schizophrenia research, and with the exception of the meta-analysis by Miller et al, which reported its unaltered levels in stable chronic (SCh) patients [12], there are consistent reports of elevated peripheral and cerebrospinal fluid (CSF) levels compared to healthy controls (HC) in all patient populations [13,14,41,42,43], including chronic early onset psychosis (EOP), clinical high risk (CHR) and ultra-high risk (UHR) patients [38,39,40]

  • This study suggests that elevated peripheral levels of Transforming growth factor β (TGF-β), but not IL-6, IL-1β, tumor necrosis factor-α (TNF-α), interferon γ (IFN-γ) or interleukin 10 (IL-10), may predispose one to the development of schizophrenia, but may be a consequence of childhood trauma [83]

Read more

Summary

Introduction

Schizophrenia is a chronic mental disorder with a complex etiopathogenesis, which involves both congenital and environmental factors [1]. Produced by a wide variety of cell populations, they play a critical role in the coordination of the inflammatory response [9] Another factor considered important in studies on the etiopathogenesis of schizophrenia are chemokines, i.e., a subgroup of cytokines whose main role is to attract immune cells to the site of inflammation [10]. Far less studied patient populations include those with early onset psychosis (EOP) and patients at clinical high risk (CHR) or ultra-high risk (UHR) of psychosis The aim of this narrative review is to present the most valuable evidence on cytokine dysregulation in schizophrenia, the links between cytokine levels and psychopathological presentation, as well as their alterations in response to antipsychotics. We will investigate the possible underpinnings of changes in the cytokine system

Materials and Methods
Cytokines and Schizophrenia
Interleukin-1β
Interleukin-2
Interleukin-4
Interleukin-6
Interleukin-8
Interleukin-10
Interleukin-12
Interleukin-17
Interleukin-18
3.10. Tumor Necrosis Factor α
3.11. Interferon γ
3.12. Transforming Growth Factor β
3.13. Chemokines
Immunogenetics of Cytokine Alternations in Schizophrenia
The Role of Early Childhood Trauma
Gut Microbiome Dysbiosis in Schizophrenia
Association of Alterations in the Cytokine Network with Neuroimaging
Glial Dysfunction
The Role of Nuclear Factor-κB and Human Endogenous Retroviruses
10. Patient Stratification
Findings
11. Conclusions
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call