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Peripheral levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and interleukin-1β across the mood spectrum in bipolar disorder: A meta-analysis of mean differences and variability

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dc.contributor.author신재일-
dc.date.accessioned2022-02-23T00:59:11Z-
dc.date.available2022-02-23T00:59:11Z-
dc.date.issued2021-10-
dc.identifier.issn0889-1591-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/187479-
dc.description.abstractImportance: It is unclear whether differences exist in the magnitude and variability of pro-inflammatory mediators in the different phases of bipolar disorder (BD) and among subjects with BD, as compared to healthy controls. Objective: To run a comparative meta-analysis of C-Reactive Protein (CRP), IL-1, IL-6, TNF-α in BD vs healthy controls, measuring mean and variability effects on all subjects. Sensitivity analyses include disease activity. Data sources: Systematic review of observational studies in PubMed and PsycInfo up to February 2nd, 2020. Study selection: Case-control studies reporting inflammatory mediators' levels in BD and controls. Data extraction and synthesis: Summary distribution measures of circulating CRP, IL-1β, IL-6, TNF-α in participants with BD and control groups were extracted. Random-effects multivariate meta-analyses were conducted based on individual study/mediator effect sizes (Hedge's g). Main outcomes and measures: Co-primary outcomes were inflammatory mediators' levels (Hedge's g) and variability (coefficient of variance ratio (CVR)) differences between participants with BD across the mood spectrum and controls. Results: Out of the initial 729 papers, 72 were assessed and then excluded after full-text review, and ultimately 53 studies were included in the systematic review, while 49 were included in the meta-analysis. The mean age was 36.96 (SD: 9.29) years, and the mean female percentage was 56.31 (SD: 16.61). CRP (g = 0.70, 95% CI 0.31-1.09, k = 37, BD = 2,215 vs HC = 3,750), IL-6 (g = 0.81, 95% CI 0.46-1.16, k = 45, BD = 1,956 vs HC = 4,106), TNF-α (g = 0.49, 95% CI 0.19-0.78, k = 49, BD = 2,231 vs HC = 3,017) were elevated in subjects with BD vs HC, but not IL-1β (g = -0.28, 95% CI -0.68-0.12, k = 4, BD = 87 vs HC = 66). When considering euthymic, depressive, and manic episodes separately, CRP and TNF-α were elevated in both depressive and manic episodes, but not in euthymia, while IL-6 remained elevated regardless of the disease state. No difference in CVR emerged for CRP, IL-1β, and TNF-α, while a lower CVR was observed for IL-6. When considering disease phases, CVR was higher in BD than in HCs for CRP during depressive episodes, lower for IL-6 during euthymia, and higher during manic episodes for CRP, IL-6, and TNF-α. Sensitivity analyses after excluding outliers identified with funnel plot visual inspection, low-quality studies, and considering only studies matched per body mass index confirmed the main results. Meta-regression showed that age (IL-6, TNF-α), gender (CRP), duration of illness (CRP) moderated elevated individual inflammatory levels. Conclusions and relevance: Peripheral pro-inflammatory marker elevations were confirmed in BD. CRP and TNF-α could represent state markers, as they were only elevated during mood episodes, while IL-6 appeared to be a trait marker for BD. Increased variability of specific inflammatory mediators in specific disease active states suggests that a subset of subjects with BD may exhibit elevated inflammation as part of a manic or depressive episode.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherElsevier-
dc.relation.isPartOfBRAIN BEHAVIOR AND IMMUNITY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAdult-
dc.subject.MESHBipolar Disorder*-
dc.subject.MESHC-Reactive Protein-
dc.subject.MESHFemale-
dc.subject.MESHHumans-
dc.subject.MESHInterleukin-1beta-
dc.subject.MESHInterleukin-6*-
dc.subject.MESHTumor Necrosis Factor-alpha-
dc.titlePeripheral levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and interleukin-1β across the mood spectrum in bipolar disorder: A meta-analysis of mean differences and variability-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pediatrics (소아과학교실)-
dc.contributor.googleauthorMarco Solmi-
dc.contributor.googleauthorManu Suresh Sharma-
dc.contributor.googleauthorEmanuele F Osimo-
dc.contributor.googleauthorMichele Fornaro-
dc.contributor.googleauthorBeatrice Bortolato-
dc.contributor.googleauthorGiovanni Croatto-
dc.contributor.googleauthorAlessandro Miola-
dc.contributor.googleauthorEduard Vieta-
dc.contributor.googleauthorCarmine M Pariante-
dc.contributor.googleauthorLee Smith-
dc.contributor.googleauthorPaolo Fusar-Poli-
dc.contributor.googleauthorJae Il Shin-
dc.contributor.googleauthorMichael Berk-
dc.contributor.googleauthorAndre F Carvalho-
dc.identifier.doi10.1016/j.bbi.2021.07.014-
dc.contributor.localIdA02142-
dc.relation.journalcodeJ00389-
dc.identifier.eissn1090-2139-
dc.identifier.pmid34332041-
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0889159121002786-
dc.subject.keywordBipolar disorder-
dc.subject.keywordC-reactive protein-
dc.subject.keywordCytokine-
dc.subject.keywordDepression-
dc.subject.keywordIL-1β-
dc.subject.keywordIL-6-
dc.subject.keywordInflammation-
dc.subject.keywordInterleukin-
dc.subject.keywordMania-
dc.subject.keywordMental disorders-
dc.subject.keywordMeta-analysis-
dc.subject.keywordNeuroscience-
dc.subject.keywordPsychiatry-
dc.subject.keywordTNF-α-
dc.contributor.alternativeNameShin, Jae Il-
dc.contributor.affiliatedAuthor신재일-
dc.citation.volume97-
dc.citation.startPage193-
dc.citation.endPage203-
dc.identifier.bibliographicCitationBRAIN BEHAVIOR AND IMMUNITY, Vol.97 : 193-203, 2021-10-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers

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