Is increased inflammation in schizophrenia associated with increased cardiovascular risk and the etiopathogenesis of this disorder?

Abstract

Objective This study aimed to examine the relationship between increased cardiovascular risk in schizophrenia and immune–inflammatory markers, including toll-like receptor (TLR)-2, TLR-4, and human leukocyte antigen (HLA)-DR expression on monocytes and their subsets, and to investigate the associations between the QRISK3 score and inflammatory markers. Methods Serum cytokines (interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and nuclear factor kappa B (NF-κB)), monocyte subset distribution, and TLR-2/TLR-4/HLA-DR expression were assessed by flow cytometry in 77 individuals with schizophrenia and 50 healthy controls. Cardiovascular risk parameters, including left ventricular ejection fraction (LVEF), QRISK3, carotid intima-media thickness (CIMT), global longitudinal strain (GLS), and diastolic function, were evaluated using standard cardiological methods. Results Compared with controls, the schizophrenia group showed higher IL-6 and IL-10 levels, lower NF-κB and IFN-γ levels, a higher proportion of classical and a lower proportion of non-classical monocytes. TLR-2 and TLR-4 expression differed across monocyte subsets, with higher mean fluorescence intensity (MFI) in classical and intermediate monocytes. They also had higher triglyceride (TG), QRISK3, and CIMT, but lower GLS and mitral E/A values. QRISK3 correlated positively with mean CIMT and negatively with IL-6 and TNF-α, while elevated IL-6 and reduced NF-κB were most strongly associated with schizophrenia in hierarchical regression analysis. In the regression analysis, however, QRISK3 showed no significant association with any inflammatory cytokine. Conclusion Our findings suggest that individuals with schizophrenia may exhibit alterations in immune–inflammatory markers, monocyte subset distribution, TLR-2/TLR-4 and HLA-DR expression, as well as cardiovascular risk indicators. In addition, the identification of IL-6 and NF-κB as the biomarkers most strongly associated with schizophrenia, together with the positive association between IL-6 and CIMT, suggests their potential relevance.