C-Reactive Protein as a Peripheral Biomarker in Schizophrenia. An Updated Systematic Review.

Objectives: The objective of this systematic review was to synthetize the published data on the relationships between elevated blood C-reactive protein (CRP) levels and schizophrenia (SZ) onset risk, illness characteristics and treatments, cognition and physical health. Method: The systematic bibliographic searches have been carried out according to the Cochrane methodology. Medline, web of science, Google Scholar with each database being searched from inception to November 2017. Results: 53 studies were included in the present review. While meta-analyses including case-control studies suggest a clear association between CRP and SZ, one other study has suggested that CRP-associated genes were associated with a lower risk of SZ onset. Increased CRP has been significantly associated with positive symptoms in acute phase psychosis, while studies including community-dwelling stabilized subjects did not find such an association. Abnormal CRP has been associated with a wide range of cognitive impairment in SZ stabilized individuals. Body Mass index has been extensively associated with increased CRP in SZ subjects; and increased CRP has been identified as a risk factor for metabolic syndrome and cardiovascular risk in SZ subjects. Increased CRP has also been associated with high nicotine dependence in SZ smokers and one study has suggested that increased CRP was associated with sedentary behavior. Conclusion: In the light of the above-mentioned studies, increased hs-CRP may be reasonably suggested as a marker for SZ onset risk, as well as a risk factor for increased positive symptoms, cognitive impairment, hypovitaminosis D, microbiota disturbances, cardiovascular and metabolic syndrome risk in SZ subjects, and increased nicotine dependence in SZ smokers. In case of increased CRP levels, anti-inflammatory strategies (add-on anti-inflammatory drugs including aspirin and omega 3 fatty acids, vitamin D supplementation, physical activity, probiotics) should be also further evaluated. Limits: Most of the studies were cross-sectional and cohort studies are needed to determine the temporal relationship between increased CRP and the psychiatric outcomes.