Inflammation-related biomarkers in major psychiatric disorders: a cross-disorder assessment of reproducibility and specificity in 43 meta-analyses

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Inflammation is a natural defence response of the immune system against environmental insult, stress and injury, but hyper- and hypo-inflammatory responses can trigger diseases. Accumulating evidence suggests that inflammation is involved in multiple psychiatric disorders. Using inflammation-related factors as biomarkers of psychiatric disorders requires the proof of reproducibility and specificity of the changes in different disorders, which remains to be established. We performed a cross-disorder study by systematically evaluating the meta-analysis results of inflammation-related factors in eight major psychiatric disorders, including schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), major depression disorder (MDD), post-trauma stress disorder (PTSD), sleeping disorder (SD), obsessive–compulsive disorder (OCD) and suicide. A total of 43 meta-analyses involving 704 publications on 44 inflammation-related factors were included in the study. We calculated the effect size and statistical power for every inflammation-related factor in each disorder. Our analyses showed that well-powered case–control studies provided more consistent results than underpowered studies when one factor was meta-analysed by different researchers. After removing underpowered studies, 30 of the 44 inflammation-related factors showed significant alterations in at least one disorder based on well-powered meta-analyses. Eleven of them changed in patients of more than two disorders when compared with the controls. A few inflammation-related factors showed unique changes in specific disorders (e.g., IL-4 increased in BD, decreased in suicide, but had no change in MDD, ASD, PTSD and SCZ). MDD had the largest number of changes while SD has the least. Clustering analysis showed that closely related disorders share similar patterns of inflammatory changes, as genome-wide genetic studies have found. According to the effect size obtained from the meta-analyses, 13 inflammation-related factors would need <50 cases and 50 controls to achieve 80% power to show significant differences ( p < 0.0016) between patients and controls. Changes in different states of MDD, SCZ or BD were also observed in various comparisons. Studies comparing first-episode SCZ to controls may have more reproducible findings than those comparing pre- and post-treatment results. Longitudinal, system-wide studies of inflammation regulation that can differentiate trait- and state-specific changes will be needed to establish valuable biomarkers.

Related collections

Most cited references 51

Record: found
Abstract: found
Article: not found

Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects.

Brian Miller, Peter Buckley, Wesley Seabolt … (2011)

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. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

0 comments Cited 553 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis.

Jonas Hannestad, Nicole DellaGioia, Michael Howard Bloch (2011)

Serum levels of inflammatory cytokines, for example, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1 beta (IL-1β), are elevated in subjects with major depressive disorder (MDD). The reason why this occurs is unclear. Elevated levels of inflammatory cytokines could be a result of brain dysfunction in MDD. It is also possible that inflammatory cytokines contribute to depressive symptoms in MDD. If the first assumption is correct, one would expect levels to normalize with resolution of the depressive episode after treatment. Several studies have measured changes in cytokine levels during antidepressant treatment; however, the results vary. The purpose of this study was to pool all available data on changes in serum levels of TNFα, IL-6, and IL-1β during antidepressant treatment to determine whether these levels change. Studies were included if they used an approved pharmacological treatment for depression, patients had a diagnosis of MDD, and serum levels of TNFα, IL-6, and/or IL-1β were measured before and after treatment. Twenty-two studies fulfilled these criteria. Meta-analysis of these studies showed that, overall, while pharmacological antidepressant treatment reduced depressive symptoms, it did not reduce serum levels of TNFα. On the other hand, antidepressant treatment did reduce levels of IL-1β and possibly those of IL-6. Stratified subgroup analysis by class of antidepressant indicated that serotonin reuptake inhibitors may reduce levels of IL-6 and TNFα. Other antidepressants, while efficacious for depressive symptoms, did not appear to reduce cytokine levels. These results argue against the notion that resolution of a depressive episode is associated with normalization of levels of circulating inflammatory cytokines; however, the results are consistent with the possibility that inflammatory cytokines contribute to depressive symptoms and that antidepressants block the effects of inflammatory cytokines on the brain.

0 comments Cited 295 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis.

N Powell, Daniel G. Miller, Steve Cole … (2013)

Across a variety of adverse life circumstances, such as social isolation and low socioeconomic status, mammalian immune cells have been found to show a conserved transcriptional response to adversity (CTRA) involving increased expression of proinflammatory genes. The present study examines whether such effects might stem in part from the selective up-regulation of a subpopulation of immature proinflammatory monocytes (Ly-6c(high) in mice, CD16(-) in humans) within the circulating leukocyte pool. Transcriptome representation analyses showed relative expansion of the immature proinflammatory monocyte transcriptome in peripheral blood mononuclear cells from people subject to chronic social stress (low socioeconomic status) and mice subject to repeated social defeat. Cellular dissection of the mouse peripheral blood mononuclear cell transcriptome confirmed these results, and promoter-based bioinformatic analyses indicated increased activity of transcription factors involved in early myeloid lineage differentiation and proinflammatory effector function (PU.1, NF-κB, EGR1, MZF1, NRF2). Analysis of bone marrow hematopoiesis confirmed increased myelopoietic output of Ly-6c(high) monocytes and Ly-6c(intermediate) granulocytes in mice subject to repeated social defeat, and these effects were blocked by pharmacologic antagonists of β-adrenoreceptors and the myelopoietic growth factor GM-CSF. These results suggest that sympathetic nervous system-induced up-regulation of myelopoiesis mediates the proinflammatory component of the leukocyte CTRA dynamic and may contribute to the increased risk of inflammation-related disease associated with adverse social conditions.

0 comments Cited 222 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Chunyu Liu:

ORCID: http://orcid.org/0000-0002-5986-4415

+1 (315) 464-3448 , liuch@upstate.edu

Journal

Journal ID (nlm-ta): Transl Psychiatry

Journal ID (iso-abbrev): Transl Psychiatry

Title: Translational Psychiatry

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2158-3188

Publication date (Electronic): 18 September 2019

Publication date PMC-release: 18 September 2019

Publication date Collection: 2019

Volume: 9

Electronic Location Identifier: 233

Affiliations

[1 ]ISNI 0000 0001 0379 7164, GRID grid.216417.7, Department of Psychiatry, The Second Xiangya Hospital; Mental health Institute of the Second Xiangya Hospital; National Clinical Research Center on Mental Disorders; National Technology Institute on Mental Disorders, , Central South University, ; Changsha, Hunan China

[2 ]ISNI 0000 0004 1765 5169, GRID grid.488482.a, Department of Psychiatry, Hunan Provincial Brain Hospital; Clinical Research Center for Mental Behavioral Disorder in Hunan Province, , Clinical Medical School of Hunan University of Chinese Medicine, ; Changsha, Hunan China

[3 ]ISNI 0000 0001 0379 7164, GRID grid.216417.7, Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, , Central South University, ; Changsha, Hunan China

[4 ]ISNI 0000 0000 9159 4457, GRID grid.411023.5, Department of Psychiatry, , SUNY Upstate Medical University, ; Syracuse, NY USA

[5 ]ISNI 0000 0004 1759 8395, GRID grid.412498.2, School of Psychology, , Shaanxi Normal University, ; Xi’an, Shaanxi China

Author information

Yan Xia http://orcid.org/0000-0001-6432-9911

Chunyu Liu http://orcid.org/0000-0002-5986-4415

Article

Publisher ID: 570

DOI: 10.1038/s41398-019-0570-y

PMC ID: 6751188

PubMed ID: 31534116

SO-VID: 33542d20-5090-4de0-9dcf-9b4f49780236

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 9 May 2019

Date accepted : 24 May 2019

Funding

Funded by: FundRef https://doi.org/10.13039/100000025, U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH);

Award ID: 1U01MH116489

Award ID: 1R01MH110920

Award ID: 1U01MH103340

Award Recipient : Chunyu Liu

Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);

Award ID: 31871276

Award Recipient : Chunyu Liu

Funded by: Hunan Provincial Health Commission Research Fund (B20180114); Hunan Provincial Natural Science Fund (2019JJ50312); Research Fund of People's Hospital Affiliated to Hunan University of Chinese Medicine (2017A01); and Diagnosis and Treatment Enhancement Project Fund of Hunan Provincial Severe Mental Illness.