Meta-analysis of cytokine and C-reactive protein levels in high-risk psychosis

Objective: Schizophrenia is associated with aberrant blood cytokine and C-reactive protein (CRP) levels. However, less is known about alterations in these markers prior to the onset of psychosis. We performed a meta-analysis of blood cytokines and CRP in subjects at high-risk for psychosis. Method: We identified articles by systematic searches of PubMed, PsycINFO, and Web of Science databases, and the reference lists of identified studies. Eight studies met the inclusion criteria, including seven studies of high-risk psychosis versus controls, and four studies of high-risk subjects who converted to a psychotic disorder versus non-converters. Results: Blood IL-6 levels were significantly higher (SMD = 0.31, 95% CI 0.02–0.59, p = 0.04) and blood IL-1β levels were significantly lower (SMD = −0.66, 95% CI −1.27 to −0.05, p = 0.05) in subjects at high-risk for psychosis versus controls. Between-study heterogeneity was not significant for either IL-1β or IL-6, and there was no evidence of publication bias. There was a non-significant trend for higher blood IL-12 levels in converters versus non-converters (SMD = 0.86, 95% CI −0.06–1.79, p = 0.07). Conclusion: We found limited evidence for blood cytokine and CRP alterations in subjects at high-risk for psychosis. Our findings should be interpreted with caution in light of a small number of studies, cumulative sample size, and heterogeneity of high-risk criteria, but warrant investigation in larger samples. This includes studies of subjects at high-risk of developing psychosis and controls, as well as the potential of inflammation as a predictor of conversion to psychosis. These findings have important potential implications for our understanding of the pathophysiology of schizophrenia.