Interleukin-6 Blockade, Low C-reactive Protein Levels May Increase Schizophrenia Risk

HealthDay News — Specific inflammatory biomarkers may impact the risk of developing schizophrenia, with a protective effect noted for C-reactive protein (CRP) and a risk-increasing effect for soluble interleukin-6 receptor (sIL-6R), according to a study published in JAMA Psychiatry.

Fernando Pires Hartwig, from the University of Pelotas in Brazil, and colleagues performed a 2-sample mendelian randomization study to examine whether inflammatory biomarkers impact the risk of developing schizophrenia. The authors used summary association results from large consortia of candidate gene or genome-wide association studies. Gene-inflammatory biomarker associations were estimated in pooled samples that ranged from 1645 to more than 80,000 individuals, and gene-schizophrenia links were estimated in more than 30,000 cases and more than 45,000 ancestry-matched controls.

The researchers found that using 18 CRP genetic instruments, the pooled odds ratio [OR] estimate was 0.9 (random effects 95% CI, 0.84-0.97) per two-fold increment in CRP levels; the results were consistent using different methods of mendelian randomization and with a more conservative set of instruments. Per twofold increment in sIL-6R, the OR was 1.06 (95% CI, 1.01-1.12). Inconsistent estimates were seen for interleukin-1 receptor antagonist among instruments, with imprecise pooled estimates centered on the null.

“Our findings suggest a protective effect of CRP and a risk-increasing effect of sIL-6R (potentially mediated at least in part by CRP) on schizophrenia risk,” the authors wrote. “It is possible that such effects are a result of increased susceptibility to early life infection.”

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Hartwig FP, Borges MC, Horta BL, Bowden J, Davey Smith G. Imflammatory biomarkers and risk of schizophrenia: a 2-sample mendelian randomization study [published online November 1, 20217]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.3191