Investigation of systemic immune-inflammation index, neutrophil/high-density lipoprotein ratio, lymphocyte/high-density lipoprotein ratio, and monocyte/high-density lipoprotein ratio as indicators of inflammation in patients with schizophrenia and bipolar disorder

Abstract

Background: The systemic immune-inflammation index (SII), system inflammation response index (SIRI), neutrophil/high-density lipoprotein (HDL) ratio (NHR), lymphocyte/HDL ratio (LHR), monocyte/HDL ratio (MHR), and platelet/HDL ratio (PHR) have been recently investigated as new markers for inflammation. The purpose of this research is to use large-scale clinical data to discuss and compare the predictive ability of the SII, SIRI, NHR, LHR, MHR, and PHR in patients with schizophrenia (SCZ) and bipolar disorder (BD), to investigate potential biomarkers.

Materials and methods: In this retrospective, naturalistic, cross-sectional study, we collected the hematological parameter data of 13,329 patients with SCZ, 4,061 patients with BD manic episodes (BD-M), and 1,944 patients with BD depressive episodes (BD-D), and 5,810 healthy subjects served as the healthy control (HC) group. The differences in the SII, SIRI, NHR, LHR, MHR, and PHR were analyzed, and a receiver operating characteristic (ROC) curve was used to analyze the diagnostic potential of these parameters.

Results: Compared with the HC group, the values of the SII, SIRI, NHR, LHR, MHR, and PHR and the levels of neutrophils, monocytes, and triglycerides (TG) were higher in SCZ and BD groups, and levels of platelets, cholesterol (CHO), HDL, low-density lipoprotein (LDL), and apoprotein B (Apo B) were lower in SCZ and BD groups. Compared to the BD group, the values of the SIRI, lymphocytes, monocytes, and HDL were lower and the values of the SII, NHR, PHR, and platelet were higher in the SCZ group. In contrast to the BD-D group, the values of the SII; SIRI; NHR; and MHR; and levels of neutrophils, monocytes, and platelets were higher in the BD-M group, and the levels of CHO, TG, LDL, and Apo B were lower in the BD-M group. The MHR and NHR were predictors for differentiating the SCZ group from the HC group; the SIRI, NHR, and MHR were predictors for differentiating the BD-M group from the HC group; and the MHR was a predictor for differentiating the BD-D group from the HC group. The combination model of the indicators improved diagnostic effectiveness.

Conclusion: Our study highlights the role of systemic inflammation in the pathophysiology of SCZ, BD-M, and BD-D, the association between inflammation and lipid metabolism, and these inflammation and lipid metabolism indicators showed different variation patterns in SCZ, BD-D, and BD-M.

Keywords: MHR; bipolar disorder; inflammation; lipid metabolism; schizophrenia.

FIGURE 1

Comparison of inflammation ratios among SCZ, BD-M, BD-D, and HCs. (A) Comparison of SII; (B) comparison of SIRI; (C) comparison of NHR; (D) comparison of LHR; (E) comparison of MHR; (F) comparison of PHR. Data are represented as the mean ± SEM; * vs. HC group, P < 0.05; # vs. BD-D group, P < 0.05; & vs. BD-M group, P < 0.05. SCZ, schizophrenia; BD-M, bipolar disorder manic episodes; BD-D, bipolar disorder depressive episodes; HC, healthy control; SII, systemic immune-inflammation index; SIRI, system inflammation response index; NHR, neutrophil/HDL ratio; LHR, lymphocyte/HDL ratio; MHR, monocyte/HDLratio; PHR, platelet/HDLratio.

FIGURE 2

(A) ROC curves for the diagnostic ability of the parameters for SCZ (SCZ vs. HCs). NHR: AUC 0.611 (95% CI = 0.604 to 0.618), P < 0.001; MHR: AUC 0.632 (95% CI = 0.625 to 0.639), P < 0.001; combined model: AUC 0.647 (95% CI = 0.639 to 0.655), P < 0.001. (B) ROC curves for the diagnostic ability of the parameters for BD-M (BD-M vs. HCs). SIRI: AUC 0.608 (95% CI = 0.598 to 0.618), P < 0.001; NHR: AUC 0.603 (95% CI = 0.593 to 0.612), P < 0.001; MHR: AUC 0.661 (95% CI = 0.651 to 0.670), P < 0.001; combined model: AUC 0.677 (95% CI = 0.668 to 0.686), P < 0.001. (C) ROC curves for the diagnostic ability of the parameters for BD-D (BD-D vs. HCs). MHR: AUC 0.615 (95% CI = 0.606 to 0.626), P < 0.001; combined model: AUC 0.623 (95% CI = 0.612 to 0.634), P < 0.001. SCZ, schizophrenia; BD-M, bipolar disorder manic episodes; BD-D, bipolar disorder depressive episodes; HCs: healthy controls.