Elevated levels of IL‐18 associated with schizophrenia and first episode psychosis: A systematic review and meta‐analysis

Abstract Aim To determine whether interleukin 18 (IL‐18) is elevated in the blood of schizophrenia (SCZ) and first episode psychosis patients, as well as investigate whether this potential relationship is causal. Method We conducted a systematic review and meta‐analysis of IL‐18 levels in the blood of SCZ patients, comprising of both chronic and first episode psychosis (FEP) cohorts. To investigate causality, we undertook the two‐sample Mendelian randomization (MR) study. Results A total of eight studies were included in our meta‐analysis, our results did indeed show an association between elevated levels of IL‐18 and SCZ compared to healthy controls ( Z = 3.50, P = .0005). This association remained significant in subsequent subgroup analyses for chronic ( Z = 3.15, P = .002) and achieved borderline significance in FEP ( Z = 1.93, P = .05) SCZ. Our MR analysis failed to detect any causal relationship between IL‐18 levels and SCZ. Conclusion The results of our study demonstrate that even though IL‐18 levels are elevated in SCZ patients, IL‐18 levels do not seem to cause of the disorder itself. Our findings suggest that IL‐18 may have utility as a biomarker of SCZ and aid in research into the early intervention of the disease.