Effects of PM2.5 pollution and single nucleotide polymorphisms of neurotrophin signaling pathway genes acting together on schizophrenia relapse

Abstract

Purpose: The objective of this study was to investigate the co-effect of long-term exposure to atmospheric particulate matter PM_2.5 and single nucleotide polymorphisms on schizophrenia relapse.

Methods: A total of 332 patients with schizophrenia were recruited. Genotyping of eight SNPs for five genes along the neurotrophin signaling pathway was performed by the Sequenom Massarray technology platform. Based on the data from the monitoring stations, the PM_2.5 level of each patient's residence was assessed by the inverse distance weighting method using Arc GIS software. Cox regression analysis was used to determine independent risk factors. The relationship between PM_2.5 levels and the risk of schizophrenia relapse was evaluated using the restricted cubic spline (RCS) method.

Results: In this study, a total of 191 of 332 patients with schizophrenia relapsed with hospitalization. The risk of schizophrenia relapse was 13.62 (95% CI 8.29 to 22.37) in areas with PM_2.5 concentrations of 48.43 to 75.35 µg/m³. The risk of schizophrenia relapse was 5.81 (95% CI 3.58-9.42, p < 0.001) and 13.62 (95% CI 8.29-22.37, p < 0.001) in the exposure categories Q3 and Q4, respectively, compared with Q1, and non-linear relationship between cumulative PM_2.5 exposure and risk of schizophrenia relapse. A greater association was observed in the YWHAB gene polymorphic locus rs6031849 genotype TG (Hazard ratio 16.62, 95% CI 5.73 to 48.24).

Conclusions: PM_2.5 levels, YWHAB gene polymorphism locus rs6031849, and gender jointly influenced schizophrenia relapse, with long-term exposure to high levels of PM_2.5 having the greatest effect on schizophrenia relapse.

Keywords: Air pollution; PM2.5; Relapse; Schizophrenia; Single nucleotide polymorphism.