Changes in inflammatory balance correlates with conversion to psychosis among individuals at clinical high-risk: A prospective cohort study

Zhang, Tianhong; Zeng, Jiahui; Wei, Yanyan; Ye, JiaYi; Tang, Xiaochen; Xu, Li-Hua; Hu, YeGang; Cui, Huiru; Xie, YuOu; Tang, Yingying; Liu, Xiaohua; Liu, HaiChun; Chen, Tao; Li, Chunbo; Wang, Jijun

doi:10.1016/j.psychres.2022.114938

Cited by 18 publications

(19 citation statements)

References 44 publications

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“…As reported in a recent meta-analysis, the levels of IL-6, TNF-α, IFN-γ, IL-17, and transforming growth factor-beta (TGF-β) elevate in FEP compared with healthy controls (HCs) (28). In addition, several studies have demonstrated the systemic alterations of cytokine levels in UHR group, while the results remain controversial (29). A meta-analysis of studies on inflammatory biomarkers reports that IL-6 level increases in UHR group compared with control group, while interleukin-1β (IL-1β) level decreases in UHR group compared with control group (30).…”

Section: Introductionmentioning

confidence: 99%

IL-17 and TNF-β: Predictive biomarkers for transition to psychosis in ultra-high risk individuals

Ouyang

et al. 2022

Front. Psychiatry

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BackgroundDysregulation of immunity, such as levels of inflammatory factors, has been regarded as a sign of schizophrenia. Changes in cytokine levels are not only described in the early onset of disease, but also observed in ultra-high risk (UHR) individuals. This study aimed to investigate the potential of cytokines as biomarkers for psychotic disorders and in individuals at UHR of developing a psychotic disorder in the future.MethodsThe Luminex liquid chip technology was used to detect the concentrations of Interferon-gamma (INF-γ), Interleukin (IL)-2, Interleukin (IL)-4, Interleukin (IL)-6, Interleukin (IL)-17, Interleukin-1beta (IL-1β), and Tumor Necrosis Factor-beta (TNF-β) in the plasma of all subjects. Meanwhile, the plasma level of Tumor Necrosis Factor-Alpha (TNF-α) was measured with the enzyme-linked immunosorbent assay (ELISA) kits. Then, the levels of these cytokines were compared among patients with Drug-naïve first-episode schizophrenia (FES; n = 40), UHR population (UHR; n = 49), and healthy controls (HCs; n = 30). Baseline cytokine levels were compared among UHR individuals who later transitioned (UHR-T; n = 14), those who did not transition (UHR-NT; n = 35), and HCs (n = 30).ResultsOur analysis results showed that IL-1β levels were significantly higher in UHR group than HC group (p = 0.015). Meanwhile, TNF-α concentration was significantly increased in FES group compared with HC group (p = 0.027). IL-17 (p = 0.04) and TNF-β (p = 0.008) levels were significantly higher in UHR-T group compared with UHR-NT group.ConclusionIn conclusion, our findings suggest that the immuno-inflammatory activation level is increased in the early stage of psychosis before psychotic conversion and the Drug-naïve FES. IL-1β and TNF-α are the representatives of the specific biomarkers for UHR and FES, respectively. IL-17 and TNF-β may be the potential selective predictive biomarkers for future transition in UHR individuals.

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Section: Introductionmentioning

confidence: 99%

IL-17 and TNF-β: Predictive biomarkers for transition to psychosis in ultra-high risk individuals

Ouyang

et al. 2022

Front. Psychiatry

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“…Consistently, Hayes et al [36] investigated molecular changes in cerebrospinal fluid from antipsychotic naïve patients with schizophrenia and CHR, in comparison with HC, and found that IL-6 levels were substantially increased in patients with schizophrenia and slightly decreased in CHR individuals. Our previous study [37] with an independent CHR sample tested the hypothesis of the imbalance between Th1 cytokines (IL-1β) and Th2 cytokines (IL-6) in 84 CHR individuals. This study also found that serum IL-1β level was significantly lower in the CHR-converter group compared to those of the CHR-non-converter and HC groups.…”

Section: Baseline Differencesmentioning

confidence: 99%

Changes in Inflammatory Markers in Clinical High Risk of Developing Psychosis

et al. 2023

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Introduction: Immune alterations are associated with the progression of psychosis. However, there are few studies designed to longitudinally measure inflammatory biomarkers during psychotic episodes. We aimed to assess changes in biomarkers from the prodromal phase to psychotic episodes in individuals with clinical high risk (CHR) of psychosis and compare converters and non-converters to psychosis as well as healthy controls (HCs). Methods: We enrolled 394 individuals with CHR and 100 HCs. A total of 263 individuals with CHR completed the 1-year follow-up, and 47 had converted to psychosis. Interleukin (IL)-1β, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor levels were measured at baseline and 1 year after completion of the clinical assessment. Results: The baseline serum levels of IL-10, IL-2, and IL-6 were significantly lower in the conversion group than in the non-conversion group (IL-10, p = 0.010; IL-2, p = 0.023; IL-6, p = 0.012) and HC (IL-6: p = 0.034). Self-controlled comparisons showed that IL-2 changed significantly (p = 0.028), and IL-6 levels tended toward significance (p = 0.088) in the conversion group. In the non-conversion group, serum levels of TNF-α (p = 0.017) and VEGF (p = 0.037) changed significantly. Repeated measures analysis of variance revealed a significant time effect related to TNF-α (F = 4.502, p = 0.037, effect size (η2) = 0.051), a group effect related to IL-1β (F = 4.590, p = 0.036, η2 = 0.062), and IL-2 (F = 7.521, p = 0.011, η2 = 0.212), but no time × group effect. Discussion: Alterations in the serum levels of inflammatory cytokines were found to precede the first episode of psychosis in the CHR population, particularly for those who later converted to psychosis. Longitudinal analysis supports the varied roles of cytokines in individuals with CHR with later psychotic conversion or non-conversion outcomes.

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“…The occurrence and development of psychosis is not only a change in behavioral appearance or brain function but also a characteristic change in the characteristics of immunoinflammatory markers in the early stage. The SHARP team 29,34,35 found that the imbalance of The results suggest that antipsychotic drugs should not be used prematurely in the at-risk population 27,28,40 as they are only valuable for <15% of the CHR population of a certain subtype [41][42][43] ; it is necessary to carry out individualized new intervention technologies for CHR subtypes of different biological dimensions. 3 Approximately 30% of the CHR population may recover naturally without intervention, and a large proportion of CHR are teenagers.…”

Section: Immune Dimension Of Inflammatory Cytokines and Complement Pr...mentioning

confidence: 99%

Comprehensive review of multidimensional biomarkers in the ShangHai At Risk for Psychosis (SHARP) program for early psychosis identification

Zhang,

Xu,

Tang

et al. 2023

PCN Reports

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Psychosis is recognized as one of the largest contributors to nonfatal health loss, and early identification can largely improve routine clinical activity by predicting the psychotic course and guiding treatment. Clinicians have used the clinical high‐risk for psychosis (CHR) paradigm to better understand the risk factors that contribute to the onset of psychotic disorders. Clinical factors have been widely applied to calculate the individualized risks for conversion to psychosis 1–2 years later. However, there is still a dearth of valid biomarkers to predict psychosis. Biomarkers, in the context of this paper, refer to measurable biological indicators that can provide valuable information about the early identification of individuals at risk for psychosis. The aim of this paper is to critically review studies assessing CHR and suggest possible biomarkers for application of prediction. We summarized the studies on biomarkers derived from the findings of the ShangHai at Risk for Psychosis (SHARP) program, including those that are considered to have the most potential. This comprehensive review was conducted based on expert opinions within the SHARP research team, and the selection of studies and results presented in this paper reflects the collective expertise of the team in the field of early psychosis identification. The three dimensions with potential candidates include neuroimaging dimension of brain structure and function, electrophysiological dimension of event‐related potentials (ERPs), and immune dimension of inflammatory cytokines and complement proteins, which proved to be useful in supporting the prediction of psychosis from the CHR state. We suggest that these three dimensions could be useful as risk biomarkers for treatment optimization. In the future, when available for the integration of multiple dimensions, clinicians may be able to obtain a comprehensive report with detailed information of psychosis risk and specific indications about preferred prevention.

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Changes in inflammatory balance correlates with conversion to psychosis among individuals at clinical high-risk: A prospective cohort study

Cited by 18 publications

References 44 publications

IL-17 and TNF-β: Predictive biomarkers for transition to psychosis in ultra-high risk individuals

IL-17 and TNF-β: Predictive biomarkers for transition to psychosis in ultra-high risk individuals

Changes in Inflammatory Markers in Clinical High Risk of Developing Psychosis

Comprehensive review of multidimensional biomarkers in the ShangHai At Risk for Psychosis (SHARP) program for early psychosis identification

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