Plasma cytokines in minimally treated schizophrenia (original) (raw)
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Meta-Analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects
Biological Psychiatry, 2011
Background-Schizophrenia is associated with immune system dysfunction, including aberrant cytokine levels. We performed a meta-analysis of these associations, considering effects of clinical status and antipsychotic treatment following an acute illness exacerbation. Methods-We identified articles by searching PubMed, PsychInfo, and Institute for Scientific Information and the reference lists of identified studies. Results-Forty studies met the inclusion criteria. Effect sizes were similar for studies of acutely relapsed inpatients (AR) and first-episode psychosis (FEP). Interleukin (IL)-1β, IL-6, and transforming growth factor-β (TGF-β) appeared to be state markers, as they were increased in AR and FEP (p.001 for each) and normalized with antipsychotic treatment (p.001, p.008, and p.005, respectively). In contrast, IL-12, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and soluble IL-2 receptor (sIL-2R) appeared to be trait markers, as levels remained elevated in acute exacerbations and following antipsychotic treatment. There was no difference in IL-6 levels between stable medicated outpatients and control subjects (p.69). In the cerebrospinal fluid, IL-1β was significantly decreased in schizophrenia versus controls (p.01). Conclusions-Similar effect sizes in AR and FEP suggest that the association between cytokine abnormalities and acute exacerbations of schizophrenia is independent of antipsychotic medications. While some cytokines (IL-1β, IL-6, and TGF-β) may be state markers for acute exacerbations, others (IL-12, IFN-γ, TNF-α, and sIL-2R) may be trait markers. Although these results could provide the basis for future hypothesis testing, most studies did not control for potential confounding factors such as body mass index and smoking.
Journal of Neuroinflammation, 2017
Background: Increases in pro-inflammatory cytokines are found in the brain and blood of people with schizophrenia. However, increased cytokines are not evident in all people with schizophrenia, but are found in a subset. The cytokine changes that best define this subset, termed the "elevated inflammatory biotype", are still being identified. Methods: Using quantitative RT-PCR, we measured five cytokine mRNAs (IL-1β, IL-2 IL-6, IL-8 and IL-18) from peripheral blood of healthy controls and of people with schizophrenia or schizoaffective disorder (n = 165). We used a cluster analysis of the transcript levels to define those with low and those with elevated levels of cytokine expression. From the same cohort, eight cytokine proteins (IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12, IFNγ and TNFα) were measured in serum and plasma using a Luminex Magpix-based assay. We compared peripheral mRNA and protein levels across diagnostic groups and between those with low and elevated levels of cytokine expression according to our transcription-based cluster analysis. Results: We found an overall decrease in the anti-inflammatory IL-2 mRNA (p = 0.006) and an increase in three serum cytokines, IL-6 (p = 0.010), IL-8 (p = 0.024) and TNFα (p < 0.001) in people with schizophrenia compared to healthy controls. A greater percentage of people with schizophrenia (48%) were categorised into the elevated inflammatory biotype compared to healthy controls (33%). The magnitude of increase in IL-1β, IL-6, IL-8 and IL-10 mRNAs in people in the elevated inflammation biotype ranged from 100 to 220% of those in the non-elevated inflammatory biotype and was comparable between control and schizophrenia groups. Blood cytokine protein levels did not correlate with cytokine mRNA levels, and plasma levels of only two cytokines distinguished the elevated and low inflammatory biotypes, with IL-1β significantly increased in the elevated cytokine control group and IL-8 significantly increased in the elevated cytokine schizophrenia group. Conclusions: Our results confirm that individuals with schizophrenia are more likely to have elevated levels of inflammation compared to controls. We suggest that efforts to define inflammatory status based on peripheral measures need to consider both mRNA and protein measures as each have distinct advantages and disadvantages and can yield different results.
Schizophrenia Research, 2002
Cytokines have been one of the recent focal points of immunological research in schizophrenia. The present study was to assess the serum levels of some of interleukins in schizophrenia and their relationships with the psychopathological parameters. Seventy physically healthy Chinese patients, who met DSM-III-R criteria for schizophrenia and who were drug-free for at least 2 weeks, were compared with 30 age-and sex-matched Chinese normal controls. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Serum levels of IL-6 and IL-8 were measured by sandwich enzyme-linked immunosorbent assay (ELISA), and serum IL-2 level was assayed by radioimmunometric assay (RIA). Serum levels of IL-2, IL-6 and IL-8 were significantly elevated in patients with a chronic form of schizophrenia (all p < 0.05). There was a significant inverse relationship between IL-2 level and the PANSS positive subscale P (r = À 0.31, p = 0.006) and a significant positive correlation between IL-8 level and PANSS negative subscale N (r = 0.25, p = 0.036) in schizophrenic patients. In control subjects, a significant and positive relationship between serum IL-2 and IL-6 (r = 0.513, p = 0.004) was noted, whereas, there was a significant and negative relationship between IL-2 and IL-8 in schizophrenic patients (r = À 0.28, p = 0.02). Our data confirms and supports the view that immune disturbance is involved in schizophrenia, which is compatible with the possibility that Chinese schizophrenic patients have an ongoing autoimmune process. This immune disturbance is related to the subgroup of schizophrenic patients with characteristic clinical variables. The dysfunction of interaction or interadjustment between different cytokines may exist in schizophrenic patients. D
Psychiatry and Clinical Psychopharmacology
OBJECTIVES: Inflammation and the cytokine hypotheses have been proposed for schizophrenia. Several proinflammatory and anti-inflammatory cytokines have been studied in drug-naive, first-episode, and/or chronic schizophrenia patients. However, there were limited data on clinical stable outpatients reflecting daily routine. The aim of this study was to compare the serum levels of cytokines, including transforming growth factor-beta (TGF-β), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-α), between clinically stable patients with schizophrenia and healthy controls, as well as to examine the relationship between these inflammation parameters and clinical variables (positive and negative symptom severity and cognitive functions). METHODS: Thirty clinically stable outpatients with schizophrenia and 30 healthy controls with similar sex and age were included in this study. Serum IL-6, TGF-β, and TNF-α levels were assessed by enzyme-linked immunosorbent assay (ELISA) and immunoenzyme microplate measurement, respectively. Illness severity was evaluated using the Positive and Negative Syndrome Scale (PANSS), and the cognitive functions of the participants were assessed using a broad neuropsychological test battery. RESULTS: The serum levels of IL-6 and TGF-β were significantly higher in patients with schizophrenia compared to healthy controls (p = .048, p = .012). There was no significant difference between groups in terms of TNF-α levels (p = .726). Global impairment of cognitive functions was observed in the patient group compared to healthy controls, and PANSS scores and cognitive functions showed no correlation with cytokine levels (IL-6, TNF-α, and TGF-β). CONCLUSIONS: The present study demonstrated an increased inflammatory response in clinically stable patients with schizophrenia compared to healthy controls. However, symptom severity and cognitive functions showed no correlation with cytokine levels. Further research studies are needed to clarify the effects of cytokine levels on schizophrenia symptomatology and etiopathogenesis.
Inflammatory Cytokine Alterations in Schizophrenia: A Systematic Quantitative Review
Biological Psychiatry, 2008
Background: Cytokines play an important role in infection and inflammation and are crucial mediators of the cross-talk between the brain and the immune system. Schizophrenia would be associated with an imbalance in inflammatory cytokines, leading to a decrease in Th1 and an increase in Th2 cytokine secretion. However, data published so far have been inconsistent. The primary objective of the present meta-analysis was to verify whether the cytokine imbalance hypothesis of schizophrenia is substantiated by evidence.
A differential role for interleukin-6 and tumor necrosis factor-α in schizophrenia?
Schizophrenia Research, 1997
Pro-inflammatory cytokines are dysregulated in schizophrenia. To determine the nature of the so-called inflammatory syndrome in schizophrenia, we investigated the circulating levels of various cytokines (interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)alpha), their natural antagonist (IL1-ra, TNF-RI, TNF-RII) and leukocyte activation markers (the soluble receptor of interleukin-2, soluble CD14 and soluble CD23) in subjects with chronic schizophrenia (n = 18) and in normal controls (n = 21). The levels of IL-1 beta and its antagonist and the levels of leukocyte activation markers were not significantly differents between patients and controls. Circulating levels of TNF alpha were significantly (p < 0.05) higher in patients than in controls and did not result from variations of its antagonist levels. The significant (p < 0.05) increase in patient IL-6 was related specifically to clinical status, i.e. illness duration. These data suggest a specific cytokine-mediated syndrome in schizophrenia. We hypothesize that TNF alpha and IL-6 reflect the genetic background of disease suceptibility.
Cytokines dysregulation in schizophrenia: A systematic review of psychoneuroimmune relationship
Introduction: Schizophrenia is a multifactorial psychiatric disease with complex interactions among the brain and the immune system. A psycho-immune relationship underling schizophrenia is supported by several studies and integrates a specific area of knowledge-psychoneuroimmunology. Methods: A systematic review was performed by 2009 Preferred Reporting Items (PRISMA) recommendations. Based on the inclusion/exclusion criteria, publications with relevant information (evaluated by the Joanna Briggs Institute Critical Appraisals tools to quality assessment) were included. Results: In this review, we considered the inflammatory activity promoted by cytokine alterations in schizophre-nia aetiology, which reflects the systemic comprehension of this disease in opposition to the traditional approach focused solely on the brain. We focus on the analysis of several specific outcomes, such as proinflammatory cy-tokines, sample sort, laboratory techniques, diagnosis scales and results of each publication. Conclusion: This systematic review confirms the existence of cytokines abnormalities in schizophrenia disease. Immune imbalances such as increased levels of some cytokines (either at protein level or at mRNA expression), cytokine mRNAs, as well as cytokine gene polymorphisms have been reported with a large support in schizo-phrenia. These findings provide a strong evidence of a concomitant process of inflammatory activity in schizo-phrenia illness course.
Cytokines in schizophrenia: Hope or hype?
Indian Journal of Psychological Medicine, 2016
Although there is a cumulative evidence for the inflammation pathophysiology in schizophrenia, it has not been conclusively proven yet. One reason for this is the lack of studies that have controlled for major confounding factors such as obesity, smoking, antipsychotic use, and stress. The studies in which the major confounding factors were controlled were done in subjects in acute relapse and in treatment-resistant schizophrenia. To date, no studies have been done in stable outpatients with schizophrenia controlling for major confounding factors. Data on cerebrospinal fluid cytokines in large sample independent of confounding factors are also lacking. The efficacy signal from anti-inflammatory medications in schizophrenia has been modest. In this study, the inconsistent and nonvalidated cytokine findings independent of the confounding factors are discussed.
Molecular psychiatry, 2000
A pattern of aberrations in the T-cell cytokine system that is typical for autoimmune disorders has also been reported in patients with schizophrenia, namely a decreased interleukin-2 (IL-2) production and increased levels of the soluble IL-2 receptor (sIL-2R). It has also been reported that the production of interferon-gamma (IFN-gamma) may be lowered. In a longitudinal design, we studied the production of both IFN-gamma and IL-2 and their correlation in patients with schizophrenia during treatment and investigated whether associations exist between cytokine production and clinical variables. The production of IFN-gamma and IL-2 was measured in equal numbers (n = 29) of patients with schizophrenia (DSM-IV) and controls who were matched for age and gender. Patients were measured 1 day after admission (T1), after 14 (T2) and 28 (T2) days of treatment. Psychopathology was assessed after these times. The production of both IFN-gamma and IL-2 was significantly lower in patients than in ...