Meta-analyses of cross-sectional studies suggest that patients with psychosis have higher circulating levels of C-reactive protein (CRP) compared with healthy controls; however, cause and effect is unclear. We examined the prospective association between CRP levels and subsequent risk of developing a psychotic disorder by conducting a systematic review and meta-analysis of population-based cohort studies. Databases were searched for prospective studies of CRP and psychosis. We obtained unpublished results, including adjustment for age, sex, body mass index, smoking, alcohol use, and socioeconomic status and suspected infection (CRP > 10 mg/L). Based on random effect meta-analysis of 89,792 participants (494 incident cases of psychosis at follow-up), the pooled odds ratio (OR) for psychosis for participants with high (>3 mg/L), as compared to low (≤3 mg/L) CRP levels at baseline was 1.50 (95% confidence interval [CI], 1.09-2.07). Evidence for this association remained after adjusting for potential confounders (adjusted OR [aOR] = 1.31; 95% CI, 1.03-1.66). After excluding participants with suspected infection, the OR for psychosis was 1.36 (95% CI, 1.06-1.74), but the association attenuated after controlling for confounders (aOR = 1.23; 95% CI, 0.95-1.60). Using CRP as a continuous variable, the pooled OR for psychosis per standard deviation increase in log(CRP) was 1.11 (95% CI, 0.93-1.34), and this association further attenuated after controlling for confounders (aOR = 1.07; 95% CI, 0.90-1.27) and excluding participants with suspected infection (aOR = 1.07; 95% CI, 0.92-1.24). There was no association using CRP as a categorical variable (low, medium or high). While we provide some evidence of a longitudinal association between high CRP (>3 mg/L) and psychosis, larger studies are required to enable definitive conclusions.

Applied Research Collaboration East of England National Institute for Health Research England UK

Barking Havering and Redbridge University Hospitals NHS Trust Romford UK

Cambridgeshire and Peterborough NHS Foundation Trust Cambridge UK

Center for Clinical Research and Prevention Bispebjerg and Frederiksberg Hospital Frederiksberg Denmark

Central Finland Health Care District Department of Medicine Jyväskylä Finland

Centre for Academic Mental Health Population Health Sciences Bristol Medical School University of Bristol Bristol UK

Department of Clinical Biochemistry Herlev and Gentofte Hospitals Herlev Denmark

Department of Kinanthropology and Humanities Charles University Prague Czech Republic

Department of Psychiatry University of Cambridge Cambridge UK

Department of Public Health and Primary Care University of Cambridge Cambridge UK

Institute of Clinical Medicine Department of Medicine University of Eastern Finland Kuopio Finland

Institute of Public Health and Clinical Nutrition University of Eastern Finland Kuopio Finland

MRC Integrative Epidemiology Unit Population Health Sciences Bristol Medical School University of Bristol Bristol UK

MRC London Institute of Medical Sciences Institute of Clinical Sciences Imperial College London London UK

National Institute for Health Research Bristol Biomedical Research Centre University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol Bristol UK

Psychiatric Center Ballerup Ballerup Denmark

Translational Health Sciences Bristol Medical School University of Bristol Learning and Research Building Southmead Hospital Bristol UK

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