Association between C-reactive protein and risk of schizophrenia: An updated meta-analysis.

Zhichao Wang,Ping Li,Guangcheng Cui,Dianyuan Chi,Tong Wu,Zubing Mei

doi:10.18632/oncotarget.17995

Abstract

C-reactive protein (CRP) has been indicated to be associated with the pathogenesis of schizophrenia (SZ) and other psychiatric disorders. The aim of this study is to investigate whether peripheral blood CRP levels are associated with the risk of SZ. We searched literature from databases of Pubmed, Embase and the Cochrane Library from inception to November 1, 2016 for studies that reported serum or plasma CRP levels in patients with SZ and non-SZ controls. At least two reviewers decided on eligibility and extracted data from included studies. Random effects meta-analyses were performed using standardized mean difference (SMD) as the effect estimate of the differences in CRP levels between subjects with SZ and healthy controls. We identified 18 studies representing 1963 patients with SZ and 3683 non-SZ controls. Compared with non-schizophrenics, blood CRP levels were moderately increased in people with SZ (SMD 0.53, 95% CI 0.30 to 0.76) irrespective of study region, sample size of included studies, patient mean age, age of SZ onset and patient body mass index. Publication bias was not detected through Egger's linear regression test (P = 0.292). We noticed that patients in Asia or Africa (n = 6, SMD 0.73, 95% CI 0.26 to 1.21) and whose age less than 30 years (n = 5, SMD 0.76, 95% CI 0.07 to 1.58) had substantially higher CRP levels. Our study provides evidence that higher CRP levels are associated with increased risk of SZ, especially for young adult patients less than 30 years. Further large-scale studies are strongly warranted to further confirm this association.

Highlights

Immune system dysfunctions and inflammatory processes have been implicated in the pathogenesis of schizophrenia (SZ) [1,2,3,4,5]
We noticed that patients in Asia or Africa (n = 6, standardized mean difference (SMD) 0.73, 95% confidence interval (CI) 0.26 to 1.21) and whose age less than 30 years (n = 5, SMD 0.76, 95% CI 0.07 to 1.58) had substantially higher C-reactive protein (CRP) levels
Duval and Tweedie’s trim and fill method indicated that no missing study was inputed and the adjusted SMD was the same as the primary one, confirming the robustness of the analysis. In this meta-analysis based on 18 case-control studies, we found that serum and plasma CRP levels were moderately increased in patients with SZ, irrespective of study region, sample size of included studies, patient mean age, age of SZ onset and patient body mass index

Summary

Introduction

Immune system dysfunctions and inflammatory processes have been implicated in the pathogenesis of schizophrenia (SZ) [1,2,3,4,5]. A vast observational studies, mainly case-control studies provide increasing evidence that patients with SZ have elevated levels of some inflammatory biomarkers, such as cytokines in plasma or serum [1, 4]. C-reactive protein (CRP) is produced by some inflammatory stimula and is mainly induced by some pro-inflammatory cytokines [8]. Increased CRP levels have been reported in numerous observational studies in psychosis including SZ and in bipolar disorder [9]. Metcalf et al reported that individuals with high (> 3 mg/L) compared with low (< 1 mg/L) CRP levels at baseline were more likely to develop SZ (adjusted odd ratio 4.25, 95% CI, 1.30 to 13.93) [55]. Zhang et al found that high sensitivity CRP/ interleukin-10 was a potential peripheral biomarker of SZ [56]

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