Could CRP be a differential biomarker of illness stages in schizophrenia? A systematic review and meta-analysis.

BACKGROUND: Patients with schizophrenia display peripheral inflammation but the impact of illness phase is not clear. Our meta-analysis investigated the difference in CRP levels between patients with schizophrenia and controls according to their illness phase. METHODS: After a systematic search, all studies measuring CRP in patients with schizophrenia and controls were included. Standardized mean differences were calculated between patients and controls according to illness phase. The influence of sociodemographic and clinical variables on our results was investigated using a meta-regression analysis. RESULTS: Fifty studies were included in this meta-analysis. Patients with schizophrenia had higher CRP levels than controls in the acute (p < 0.00001) and stable (p < 0.00001) stage of their disease. Patients with acute exacerbation of schizophrenia had higher CRP levels than stable patients (p = 0.02) but this difference did not persist when considering antipsychotic-medicated patients in both phases. Meta-regressions found that the increase of CRP in acutely ill patients as compared to controls was influenced by age (p < 0.01), BMI (p = 0.01) and first episode (p = 0.02), whereas the increase in CRP levels of stable patients as compared to controls was moderated by BMI (p = 0.004). CONCLUSIONS: In conclusion, this meta-analysis provides strong evidence that patients with schizophrenia have higher CRP levels than controls, but also show an increase in inflammatory response in the acute stage of the disease as compared to the stable stage. CRP could thus be considered as a state marker and a trait marker of the disease.