C-Reactive Protein Alterations in Bipolar Disorder: A Meta-Analysis

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.