Meta-analysis of soluble tumour necrosis factor receptors in severe mental illnesses

Tumour necrosis factor (TNF), as an innate immune defense molecule, functions through binding to TNF receptor 1 (TNFR1) or TNF receptor 2 (TNFR2). Peripheral levels of soluble TNFR1 (sTNFR1) and soluble TNFR2 (sTNFR2) were widely measured in severe mental illnesses (SMIs) including schizophrenia (SCZ), bipolar disorder (BD) and major depressive disorder (MDD) but inconsistencies existed. Hence, the present meta-analysis was conducted to identify the overall association between plasma/serum sTNFR1 and sTNFR2 levels and SMIs. Published studies were searched using Pubmed and Scopus. Data were analysed using Comprehensive Meta-Analysis version 2. Hedges's g effect sizes and 95% confidence intervals were pooled using fixed-effect or random-effects models. Heterogeneity, publication bias and study quality were assessed. Sensitivity analysis and subgroup analysis were performed. Our findings revealed that sTNFR1 level was significantly higher in SMI, particularly in BD. The sTNFR2 level significantly elevated in SMI but with smaller effect size. These findings further support the association between altered immune system and inflammatory abnormalities in SMI, especially in patients with BD. Subgroup analysis showed that younger age of onset, longer illness duration and psychotropic medication raised both sTNFR levels, especially sTNFR1, as these factors may contribute to the activation of inflammation. Future studies were suggested to identify the causality between TNFR pathway and SCZ, BD and MDD respectively using homogenous group of each SMI, and to determine the longitudinal effect of each psychotropic medication on TNFR pathway.