Meta-Analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects

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. We identified articles by searching PubMed,...

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Published inBiological psychiatry (1969) Vol. 70; no. 7; pp. 663 - 671
Main Authors Miller, Brian J., Buckley, Peter, Seabolt, Wesley, Mellor, Andrew, Kirkpatrick, Brian
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.10.2011
Subjects
Online AccessGet full text
ISSN0006-3223
1873-2402
1873-2402
DOI10.1016/j.biopsych.2011.04.013

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Abstract 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. We identified articles by searching PubMed, PsychInfo, and Institute for Scientific Information and the reference lists of identified studies. 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). 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.
AbstractList 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.
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. We identified articles by searching PubMed, PsychInfo, and Institute for Scientific Information and the reference lists of identified studies. 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). 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.
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.BACKGROUNDSchizophrenia 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.We identified articles by searching PubMed, PsychInfo, and Institute for Scientific Information and the reference lists of identified studies.METHODSWe identified articles by searching PubMed, PsychInfo, and Institute for Scientific Information and the reference lists of identified studies.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).RESULTSForty 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).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.CONCLUSIONSSimilar 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.
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. We identified articles by searching PubMed, PsychInfo, and Institute for Scientific Information and the reference lists of identified studies. 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). 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.
Author Miller, Brian J.
Seabolt, Wesley
Buckley, Peter
Mellor, Andrew
Kirkpatrick, Brian
Author_xml – sequence: 1
  givenname: Brian J.
  surname: Miller
  fullname: Miller, Brian J.
  email: brmiller@georgiahealth.edu
  organization: Department of Psychiatry and Health Behavior, Georgia Health Sciences University, Augusta, Georgia
– sequence: 2
  givenname: Peter
  surname: Buckley
  fullname: Buckley, Peter
  organization: School of Medicine, Georgia Health Sciences University, Augusta, Georgia
– sequence: 3
  givenname: Wesley
  surname: Seabolt
  fullname: Seabolt, Wesley
  organization: Department of Psychiatry and Health Behavior, Georgia Health Sciences University, Augusta, Georgia
– sequence: 4
  givenname: Andrew
  surname: Mellor
  fullname: Mellor, Andrew
  organization: Immunotherapy Center, Georgia Health Sciences University, Augusta, Georgia
– sequence: 5
  givenname: Brian
  surname: Kirkpatrick
  fullname: Kirkpatrick, Brian
  organization: Department of Psychiatry and Behavioral Science, Texas A&M University and Scott and White Hospital, Temple, Texas
BackLink https://www.ncbi.nlm.nih.gov/pubmed/21641581$$D View this record in MEDLINE/PubMed
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Issue 7
Keywords meta-analysis
schizophrenia
Cytokines
relapse
first-episode psychosis
Language English
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Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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SecondaryResourceType review_article
Snippet Schizophrenia is associated with immune system dysfunction, including aberrant cytokine levels. We performed a meta-analysis of these associations, considering...
Background Schizophrenia is associated with immune system dysfunction, including aberrant cytokine levels. We performed a meta-analysis of these associations,...
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elsevier
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SubjectTerms Antipsychotic Agents - pharmacology
Antipsychotic Agents - therapeutic use
Biomarkers - blood
Biomarkers - cerebrospinal fluid
Cytokines
Cytokines - blood
Cytokines - cerebrospinal fluid
Cytokines - drug effects
first-episode psychosis
Humans
Interleukin 1 Receptor Antagonist Protein - blood
Interleukin 1 Receptor Antagonist Protein - cerebrospinal fluid
Interleukin 1 Receptor Antagonist Protein - drug effects
meta-analysis
Psychiatry
Receptors, Cytokine - blood
Receptors, Cytokine - drug effects
Recurrence
relapse
schizophrenia
Schizophrenia - blood
Schizophrenia - cerebrospinal fluid
Schizophrenia - diagnosis
Schizophrenia - drug therapy
Title Meta-Analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects
URI https://www.clinicalkey.com/#!/content/1-s2.0-S0006322311004045
https://www.clinicalkey.es/playcontent/1-s2.0-S0006322311004045
https://dx.doi.org/10.1016/j.biopsych.2011.04.013
https://www.ncbi.nlm.nih.gov/pubmed/21641581
https://www.proquest.com/docview/892947188
https://pubmed.ncbi.nlm.nih.gov/PMC4071300
Volume 70
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