C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis

Fernandes, Brisa S; Steiner, Johann; Molendijk, Marc L; Dodd, Seetal; Nardin, Patricia; Gonçalves, Carlos-Alberto; Jacka, Felice; Köhler, Cristiano A; Karmakar, Chandan; Carvalho, André F; Berk, Michael

doi:10.1016/s2215-0366(16)30370-4

Cited by 247Bipolar Disorder and TreatmentTryptophan and brain disordersTreatment of Major Depression

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C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis

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Fernandes, Brisa S, Steiner, Johann, Molendijk, Marc L, Dodd, Seetal, Nardin, Patricia, Gonçalves, Carlos-Alberto, Jacka, Felice, Köhler, Cristiano A, Karmakar, Chandan, Carvalho, André F, Berk, Michael·2016·The Lancet Psychiatry

DOI 10.1016/s2215-0366(16)30370-4

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Abstract

Background Inflammatory processes and neural-immune interactions have been implicated in the pathogenesis of psychiatric conditions, but studies in bipolar disorder are inconclusive so far. We aimed to investigate whether peripheral concentrations of C-reactive protein (CRP), an acute-phase response protein of inflammatory activity, are increased in bipolar disorder across the mood spectrum.Methods In this systematic review and meta-analysis, we searched MEDLINE, the Cochrane Library, Scopus, and Web of Knowledge from database inception to Aug 14, 2016, for studies that measured serum and plasma CRP concentrations in adult patients with bipolar disorder (as defined by DSM-IV-TR) and healthy controls. We extracted data from published reports. We did three between-group meta-analyses comparing CRP concentrations in patients in mania, depression, or euthymia, with those in healthy controls (cross-sectional studies), and two within-group meta-analyses comparing changes in CRP concentrations before and after treatment of an index manic or depressive episode (longitudinal studies). We used Hedges' adjusted g to calculate effect sizes and pooled results using random-effect models. We also did meta-regression analyses by mood state to investigate possible moderators of CRP concentrations.Findings We identified 27 studies representing 2161 patients with bipolar disorder and 81 932 healthy controls. Compared with healthy individuals, CRP concentrations were moderately increased in people with bipolar disorder during depression (g 0·67, 95% CI 0·23 to 1·11; p=0·003) and euthymia (0·65, 0·40 to 0·90; p<0·0001) and more substantially increased during mania (0·87, 0·58 to 1·15; p<0·0001). The extent of the increases in CRP concentrations in mania and depression was not related to symptom severity (p=0·256 for mania and p=0·626 for depression). CRP concentrations were moderately decreased after resolution of an index manic episode (-0·36, -0·66 to -0·05; p=0·022) and slightly decreased after resolution of an index depressive episode (-0·18, -0·30 to -0·07; p=0·002).Interpretation CRP concentrations are increased in bipolar disorder regardless of mood state, but are higher during mania than in depression and euthymia, suggesting an increased inflammatory burden in mania.Funding None.

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The depression state has conflicting results for CRP.
“But the depression state has conflicting results43,44.”
From Inflammation-related biomarkers in major psychiatric disorders: a cross-disorder assessment of reproducibility and specificity in 43 meta-analyses (2019) · cites this paper as [43]

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Authors: Fernandes, B. S., Steiner, J., Molendijk, M. L., Dodd, S., Nardin, P., Gonçalves, C.-A., Jacka, F., Köhler, C. A., Karmakar, C., Carvalho, A. F., & Berk, M.
Affiliations: Universidade Federal do Rio Grande do Sul (BR)
Leiden University (NL)
Barwon Health (AU)
Universidade Federal do Ceará (BR)
Deakin University (AU)
Corresponding author: Fernandes, Brisa S
ORCID: Fernandes, Brisa S
Molendijk, Marc L
Dodd, Seetal
Gonçalves, Carlos-Alberto
Jacka, Felice
Köhler, Cristiano A
Karmakar, Chandan
Venue: The Lancet Psychiatry
Publisher: Elsevier BV
Published: 2016-12
Volume: 3
Issue: 12
Pages: 1147-1156
ISSN: 2215-0366 (ISSN-L)
DOI: 10.1016/s2215-0366(16)30370-4
OpenAlex: W2556709183
Cited by: 247
References: 72
Citations by year: 2026: 22 · 2025: 20 · 2024: 29 · 2023: 30 · 2022: 35 · 2021: 28 · 2020: 23 · 2019: 19 · 2018: 20 · 2017: 18 · 2016: 2
FWCI: 2.82
Type: journal article
Language: en
Open access: green
figshare.com
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Lancet Psychiatry (publishedVersion)
PubMed (publishedVersion)
Figshare (submittedVersion, cc-by)
Funders: postdoctoral scholarship and a research grant (14/2014461833/2014-0)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords: C-reactive protein, bipolar disorder, inflammation, mood states, mania, depression, euthymia, acute phase response, serum biomarkers, treatment response, symptom severity, neuroimmune interactions, mood stabilizers, antipsychotic drugs, antidepressants, valproic acid, aripiprazole, olanzapine, lamotrigine
MeSH terms: Bipolar Disorder, C-Reactive Protein, Humans, Randomized Controlled Trials as Topic

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C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis

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