Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis

Infections and inflammatory processes have been associated with the development of schizophrenia and affective disorders; however, no study has yet systematically reviewed all available studies on cerebrospinal fluid (CSF) immune alterations. We aimed to systematically review the CSF immunological f...

Descripción completa

Detalles Bibliográficos
Autores principales: Orlovska-Waast, Sonja, Köhler-Forsberg, Ole, Brix, Sophie Wiben, Nordentoft, Merete, Kondziella, Daniel, Krogh, Jesper, Benros, Michael Eriksen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756288/
https://www.ncbi.nlm.nih.gov/pubmed/30116031
http://dx.doi.org/10.1038/s41380-018-0220-4
_version_ 1783453371910324224
author Orlovska-Waast, Sonja
Köhler-Forsberg, Ole
Brix, Sophie Wiben
Nordentoft, Merete
Kondziella, Daniel
Krogh, Jesper
Benros, Michael Eriksen
author_facet Orlovska-Waast, Sonja
Köhler-Forsberg, Ole
Brix, Sophie Wiben
Nordentoft, Merete
Kondziella, Daniel
Krogh, Jesper
Benros, Michael Eriksen
author_sort Orlovska-Waast, Sonja
collection PubMed
description Infections and inflammatory processes have been associated with the development of schizophrenia and affective disorders; however, no study has yet systematically reviewed all available studies on cerebrospinal fluid (CSF) immune alterations. We aimed to systematically review the CSF immunological findings in schizophrenia spectrum and affective disorders. We identified all studies investigating CSF inflammatory markers in persons with schizophrenia or affective disorders published prior to March 23, 2017 searching PubMed, CENTRAL, EMBASE, Psychinfo, and LILACS. Literature search, data extraction and bias assessment were performed by two independent reviewers. Meta-analyses with standardized mean difference (SMD) including 95% confidence intervals (CI) were performed on case-healthy control studies. We identified 112 CSF studies published between 1942–2016, and 32 case-healthy control studies could be included in meta-analyses. Studies varied regarding gender distribution, age, disease duration, treatment, investigated biomarkers, and whether recruitment happened consecutively or based on clinical indication. The CSF/serum albumin ratio was increased in schizophrenia (1 study [54 patients]; SMD = 0.71; 95% CI 0.33–1.09) and affective disorders (4 studies [298 patients]; SMD = 0.41; 95% CI 0.23–0.60, I(2) = 0%), compared to healthy controls. Total CSF protein was elevated in both schizophrenia (3 studies [97 patients]; SMD = 0.41; 95% CI 0.15–0.67, I(2) = 0%) and affective disorders (2 studies [53 patients]; SMD = 0.80; 95% CI 0.39–1.21, I(2) = 0%). The IgG ratio was increased in schizophrenia (1 study [54 patients]; SMD = 0.68; 95% CI 0.30–1.06), whereas the IgG Albumin ratio was decreased (1 study [32 patients]; SMD = −0.62; 95% CI −1.13 to −0.12). Interleukin-6 (IL-6) levels (7 studies [230 patients]; SMD = 0.55; 95% CI 0.35–0.76; I(2) = 1%) and IL-8 levels (3 studies [95 patients]; SMD = 0.46; 95% CI 0.17–0.75, I(2) = 0%) were increased in schizophrenia but not significantly increased in affective disorders. Most of the remaining inflammatory markers were not significantly different compared to healthy controls in the meta-analyses. However, in the studies which did not include healthy controls, CSF abnormalities were more common, and two studies found CSF dependent re-diagnosis in 3.2–6%. Current findings suggest that schizophrenia and affective disorders may have CSF abnormalities including signs of blood-brain barrier impairment and inflammation. However, the available evidence does not allow any firm conclusion since all studies showed at least some degree of bias and vastly lacked inclusion of confounding factors. Moreover, only few studies investigated the same parameters with healthy controls and high-quality longitudinal CSF studies are lacking, including impact of psychotropic medications, lifestyle factors and potential benefits of anti-inflammatory treatment in subgroups with CSF inflammation.
format Online
Article
Text
id pubmed-6756288
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-67562882019-09-27 Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis Orlovska-Waast, Sonja Köhler-Forsberg, Ole Brix, Sophie Wiben Nordentoft, Merete Kondziella, Daniel Krogh, Jesper Benros, Michael Eriksen Mol Psychiatry Review Article Infections and inflammatory processes have been associated with the development of schizophrenia and affective disorders; however, no study has yet systematically reviewed all available studies on cerebrospinal fluid (CSF) immune alterations. We aimed to systematically review the CSF immunological findings in schizophrenia spectrum and affective disorders. We identified all studies investigating CSF inflammatory markers in persons with schizophrenia or affective disorders published prior to March 23, 2017 searching PubMed, CENTRAL, EMBASE, Psychinfo, and LILACS. Literature search, data extraction and bias assessment were performed by two independent reviewers. Meta-analyses with standardized mean difference (SMD) including 95% confidence intervals (CI) were performed on case-healthy control studies. We identified 112 CSF studies published between 1942–2016, and 32 case-healthy control studies could be included in meta-analyses. Studies varied regarding gender distribution, age, disease duration, treatment, investigated biomarkers, and whether recruitment happened consecutively or based on clinical indication. The CSF/serum albumin ratio was increased in schizophrenia (1 study [54 patients]; SMD = 0.71; 95% CI 0.33–1.09) and affective disorders (4 studies [298 patients]; SMD = 0.41; 95% CI 0.23–0.60, I(2) = 0%), compared to healthy controls. Total CSF protein was elevated in both schizophrenia (3 studies [97 patients]; SMD = 0.41; 95% CI 0.15–0.67, I(2) = 0%) and affective disorders (2 studies [53 patients]; SMD = 0.80; 95% CI 0.39–1.21, I(2) = 0%). The IgG ratio was increased in schizophrenia (1 study [54 patients]; SMD = 0.68; 95% CI 0.30–1.06), whereas the IgG Albumin ratio was decreased (1 study [32 patients]; SMD = −0.62; 95% CI −1.13 to −0.12). Interleukin-6 (IL-6) levels (7 studies [230 patients]; SMD = 0.55; 95% CI 0.35–0.76; I(2) = 1%) and IL-8 levels (3 studies [95 patients]; SMD = 0.46; 95% CI 0.17–0.75, I(2) = 0%) were increased in schizophrenia but not significantly increased in affective disorders. Most of the remaining inflammatory markers were not significantly different compared to healthy controls in the meta-analyses. However, in the studies which did not include healthy controls, CSF abnormalities were more common, and two studies found CSF dependent re-diagnosis in 3.2–6%. Current findings suggest that schizophrenia and affective disorders may have CSF abnormalities including signs of blood-brain barrier impairment and inflammation. However, the available evidence does not allow any firm conclusion since all studies showed at least some degree of bias and vastly lacked inclusion of confounding factors. Moreover, only few studies investigated the same parameters with healthy controls and high-quality longitudinal CSF studies are lacking, including impact of psychotropic medications, lifestyle factors and potential benefits of anti-inflammatory treatment in subgroups with CSF inflammation. Nature Publishing Group UK 2018-08-16 2019 /pmc/articles/PMC6756288/ /pubmed/30116031 http://dx.doi.org/10.1038/s41380-018-0220-4 Text en © The Author(s) 2018 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/.
spellingShingle Review Article
Orlovska-Waast, Sonja
Köhler-Forsberg, Ole
Brix, Sophie Wiben
Nordentoft, Merete
Kondziella, Daniel
Krogh, Jesper
Benros, Michael Eriksen
Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis
title Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis
title_full Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis
title_fullStr Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis
title_full_unstemmed Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis
title_short Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis
title_sort cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756288/
https://www.ncbi.nlm.nih.gov/pubmed/30116031
http://dx.doi.org/10.1038/s41380-018-0220-4
work_keys_str_mv AT orlovskawaastsonja cerebrospinalfluidmarkersofinflammationandinfectionsinschizophreniaandaffectivedisordersasystematicreviewandmetaanalysis
AT kohlerforsbergole cerebrospinalfluidmarkersofinflammationandinfectionsinschizophreniaandaffectivedisordersasystematicreviewandmetaanalysis
AT brixsophiewiben cerebrospinalfluidmarkersofinflammationandinfectionsinschizophreniaandaffectivedisordersasystematicreviewandmetaanalysis
AT nordentoftmerete cerebrospinalfluidmarkersofinflammationandinfectionsinschizophreniaandaffectivedisordersasystematicreviewandmetaanalysis
AT kondzielladaniel cerebrospinalfluidmarkersofinflammationandinfectionsinschizophreniaandaffectivedisordersasystematicreviewandmetaanalysis
AT kroghjesper cerebrospinalfluidmarkersofinflammationandinfectionsinschizophreniaandaffectivedisordersasystematicreviewandmetaanalysis
AT benrosmichaeleriksen cerebrospinalfluidmarkersofinflammationandinfectionsinschizophreniaandaffectivedisordersasystematicreviewandmetaanalysis