Peripheral Biomarkers for First-Episode Psychosis—Opportunities from the Neuroinflammatory Hypothesis of Schizophrenia

Trovão, Nuno; Prata, Joana; Doellinger, Orlando von; Santos, Susana G.; Barbosa, Mário A.; Coelho, Rui

doi:10.30773/pi.2018.12.19.1

Cited by 42 publications

(25 citation statements)

References 124 publications

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“…We found that IFNy level showed a significant correlation with PANSS-total, PANSS-positive, PANSS-general subscores, and CGI score, thus IFNy level could be an indicative marker of disease severity in schizophrenia. IL-8 is an inflammatory chemokine significantly upregulated in the dorsolateral prefrontal cortex of individuals with schizophrenia (24) and a peripheral inflammatory biomarker found in FEP patients (25) and in multiple-episode schizophrenia (MES) patients (24). A significant positive correlation was shown between serum concentration of IL-8 The serum concentration of OPN was significantly decreased (p = 0.021) in patients on long-term antipsychotic therapy (8.8 ± 5.9 years) compared to patients on short-term therapy (3.5 ± 1.9 weeks).…”

Section: Discussionmentioning

confidence: 99%

Elevated Osteopontin and Interferon Gamma Serum Levels and Increased Neutrophil-to-Lymphocyte Ratio Are Associated With the Severity of Symptoms in Schizophrenia

et al. 2020

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Inflammation and immune dysregulation could contribute to the pathogenesis of schizophrenia. Osteopontin (OPN) is a cytokine-like glycoprotein involved in inflammation and in modulating immune responses, and it can also directly modify the cytokine expression and survival of microglia. Furthermore, elevated gene expression of OPN in first episode psychosis has recently been described, but to date OPN level has not been investigated in schizophrenia. Imbalance of T-helper subtypes could also represent a vulnerability factor for schizophrenia. In this study, we analyzed the concentration of OPN, levels of cytokines associated with T-helper subtypes: interferon gamma (IFNy) for Th1, interleukin (IL)-10 for Th2, IL-8 for Th17, and neutrophil-to-lymphocyte ratio (NLR) in 22 patients with schizophrenia assessed for the intensity of their symptoms by the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression scale (CGI) scores. Serum OPN, IFNy, IL-10, and IL-8 concentrations were measured by ELISA kits and NLR was calculated from blood count. We found significant correlation between the level of OPN and PANSS-total and PANSS-general scores. IFNy level and NLR showed significant correlation with PANSS-total, PANSS-positive, PANSS-general, and CGI score. Among the measured markers antipsychotic therapy only had significant effects on NLR and OPN level, both of which were significantly reduced after long-term antipsychotic treatment. Our results indicate that elevated OPN and IFNy concentrations, and increased NLR are associated with severe symptoms in schizophrenia and suggest the importance of Th1 subtype in patients with high PANSS-positive and PANSS-general subscore. Significant correlation between NLR and PANSS scores strengthens the inflammation hypothesis of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Elevated Osteopontin and Interferon Gamma Serum Levels and Increased Neutrophil-to-Lymphocyte Ratio Are Associated With the Severity of Symptoms in Schizophrenia

et al. 2020

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“…Table 3 presents CSF cytokine levels in patients with schizophrenia. Based on the available meta-analytical data, it is hypothesized that there is a certain disturbance in the balance between pro-inflammatory cytokines, such as interleukin-6 (IL-6) or IL-1β, and anti-inflammatory cytokines such as interleukin 10 (IL-10) [6,29]. This hypothesis is supported by the protective effect of Th2 cytokines and anti-inflammatory cytokines, whose elevated prenatal levels in the maternal blood may reduce the risk of schizophrenia in the offspring [30,31].…”

Section: Cytokines and Schizophreniamentioning

confidence: 99%

The Role of Cytokines in the Pathogenesis of Schizophrenia

Dawidowski

Górniak

Podwalski

et al. 2021

JCM

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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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“…In ASD, immune disturbances have been detected from childhood [31,32] through to adulthood [33] (reviewed in [34]). Similarly, in schizophrenia, cytokine changes are being considered as potential biological markers, as differential profiles have been detected across disease states (reviewed in [35]).…”

Section: Introductionmentioning

confidence: 99%

Immune network dysregulation associated with child neurodevelopmental delay: modulatory role of prenatal alcohol exposure

Bodnar

Wertelecki

Yevtushok

et al. 2020

J Neuroinflammation

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Background: Evidence suggests that cytokine imbalances may be at the root of deficits that occur in numerous neurodevelopmental disorders, including schizophrenia and autism spectrum disorder. Notably, while clinical studies have demonstrated maternal cytokine imbalances with alcohol consumption during pregnancy-and data from animal models have identified immune disturbances in alcohol-exposed offspring-to date, immune alterations in alcohol-exposed children have not been explored. Thus, here we hypothesized that perturbations in the immune environment as a result of prenatal alcohol exposure will program the developing immune system, and result in immune dysfunction into childhood. Due to the important role of cytokines in brain development/function, we further hypothesized that child immune profiles might be associated with their neurodevelopmental status. Methods: As part of a longitudinal study in Ukraine, children of mothers reporting low/no alcohol consumption or moderate-to-heavy alcohol consumption during pregnancy were enrolled in the study and received neurodevelopmental assessments. Group stratification was based on maternal alcohol consumption and child neurodevelopmental status resulting in the following groups: A/TD, alcohol-consuming mother, typically developing child; A/ND, alcohol-consuming mother, neurodevelopmental delay in the child; C/TD, control mother (low/no alcohol consumption), typically development child; and C/ND, control mother, neurodevelopmental delay in the child. Forty cytokines/chemokines were measured in plasma and data were analyzed using regression and constrained principle component analysis. Results: Analyses revealed differential cytokine network activity associated with both prenatal alcohol exposure and neurodevelopmental status. Specifically, alcohol-exposed children showed activation of a cytokine network including eotaxin-3, eotaxin, and bFGF, irrespective of neurodevelopmental status. However, another cytokine network was differentially activated based on neurodevelopmental outcome: A/TD showed activation of MIP-1β, MDC, and MCP-4, and inhibition of CRP and PlGF, with opposing pattern of activation/inhibition detected in the A/ND group. By contrast, in the absence of alcohol-exposure, activation of a network including IL-2, TNF-β, IL-10, and IL-15 was associated with neurodevelopmental delay.

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Peripheral Biomarkers for First-Episode Psychosis—Opportunities from the Neuroinflammatory Hypothesis of Schizophrenia

Cited by 42 publications

References 124 publications

Elevated Osteopontin and Interferon Gamma Serum Levels and Increased Neutrophil-to-Lymphocyte Ratio Are Associated With the Severity of Symptoms in Schizophrenia

Elevated Osteopontin and Interferon Gamma Serum Levels and Increased Neutrophil-to-Lymphocyte Ratio Are Associated With the Severity of Symptoms in Schizophrenia

The Role of Cytokines in the Pathogenesis of Schizophrenia

Immune network dysregulation associated with child neurodevelopmental delay: modulatory role of prenatal alcohol exposure

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