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C-Reactive Protein Alterations in Bipolar Disorder: A Meta-Analysis
Abstract
OBJECTIVE: There is growing evidence that bipolar disorder (BD) is associated with inflammation, including abnormal levels of acute-phase C-reactive protein (CRP). Our meta-analysis was conducted to estimate the size of the association between CRP levels and BD, accounting also for subgroup differences (mood phases and treatment). DATA SOURCES: MEDLINE, EMBASE, PsycINFO, and ISI Web of Science and references of identified articles were searched up to June 2013 using the keywords (bipolar disorder) AND (C-reactive protein OR CRP). STUDY SELECTION: English language studies measuring blood levels of CRP in patients with BD and control subjects were selected, 136 abstracts were reviewed, 20 articles retrieved, and 11 studies included. DATA EXTRACTION: Two independent reviewers extracted data. All studies were included in the primary analyses, and between-group differences for subanalyses were also reported. This meta-analysis was performed using random-effects models. RESULTS: Eleven studies comprising 1,618 subjects were eligible for inclusion. Overall, CRP levels were significantly elevated in patients with BD versus controls (standardized mean difference [SMD] = 0.39; 95% CI, 0.24 to 0.55; P < .0001). CRP levels were significantly higher in manic (SMD = 0.73; 95% CI, 0.44 to 1.02; P < .001) and euthymic (SMD = 0.26; 95% CI, 0.01 to 0.51; P = .04), but not in depressed (SMD = 0.28; 95% CI, -0.17 to 0.73; P = .22) patients with BD compared to controls. CRP levels were unrelated to use of lithium or antipsychotic medication. CONCLUSIONS: This meta-analysis supports an association between increased CRP levels and BD. Given that an elevated level of CRP is a marker of low-grade inflammation and a risk factor for cardiovascular and malignant diseases, measurement of CRP level might be relevant to the clinical care of bipolar patients.
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“In addition to a host of physical health consequences, these inflammatory processes have been linked to psychopathology as shown in meta-analyses of depression (Howren et al. 2009), BPD (Dargél et al. 2015), psychosis (Miller et al. 2011), and PTSD (Passos et al. 2015).”
From Child Sexual Abuse as a Unique Risk Factor for the Development of Psychopathology: The Compounded Convergence of Mechanisms (2021) · cites this paper as Dargél et al. 2015
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“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 [44]
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McIntyre, R. S., Berk, M., Brietzke, E., Goldstein, B. I., López-Jaramillo, C., Kessing, L. V., Malhi, G. S., Nierenberg, A. A., Rosenblat, J. D., Majeed, A., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)31544-0 · Cited by 1,047
Inflammation in psychiatric disorders: what comes first?
Bauer, M. E., & Teixeira, A. L. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13712 · Cited by 500
Yuan, N., Chen, Y., Xia, Y., Dai, J., & Liu, C. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0570-y · Cited by 428
Psychoneuroimmunology of early-life stress: the hidden wounds of childhood trauma?
Danese, A., & J Lewis, S. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.198 · Cited by 393
“Meta-analyses of clinical studies showed that, compared to controls, bipolar patients have small-to-moderate elevation in levels of proinflammatory cytokines (Modabbernia et al, 2013) and of CRP (Dargél et al, 2015).”
BackgroundResultInfluentialThe role of childhood trauma in bipolar disorders
Aas, M., Henry, C., Andreassen, O. A., Bellivier, F., Melle, I. S., & Étain, B. (2016) · International Journal of Bipolar Disorders · doi:10.1186/s40345-015-0042-0 · Cited by 373
Metadata
- Authors
- Dargél, A. A., Godin, O., Kapczinski, F., Kupfer, D. J., & Leboyer, M.
- Affiliations
- Hôpital Albert-Chenevier (FR)
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2015-02-25
- Volume
- 76
- Issue
- 02
- Pages
- 142-150
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W1974846472
- Cited by
- 155
- References
- 0
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 6 · 2023: 14 · 2022: 13 · 2021: 18 · 2020: 14 · 2019: 13 · 2018: 14 · 2017: 17 · 2016: 29 · 2015: 6
- FWCI
- 17.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-11-IDEX-0004)
- 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
- bipolar disorder, C-reactive protein, inflammation, acute phase proteins, manic episodes, euthymic state, depressive episodes, lithium, antipsychotic drugs, cardiovascular risk
- MeSH terms
- Affect, Bipolar Disorder, C-Reactive Protein, Humans, Predictive Value of Tests, Biomarkers
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