| Background: Schizophrenia pose the severe disease burden caused by its frequent relapses and the hazards of environmental risk factors have attracted global attention,but limited studies have assessed the effects of co-exposures to air pollution on the risk of schizophrenia relapse,and the underlying mechanism has not been well characterized.This repeated-measurement study based on communities aims to investigate(1)the relationship between short-term exposure to air pollutants and the risk of relapse and blood cortisol levels in patients with schizophrenia.(2)the effect of co-exposure to air pollutants on the risk of relapse in schizophrenia and to identify the major risk pollutants.(3)whether blood cortisol plays a mediating role in the association between air pollution exposure and increased risk of schizophrenia relapse.Methods: We conducted a prospective panel study involving three repeated measurements of 66 patients with stable schizophrenia followed up three times in Hefei,China.Inverse distance weighted(IDW)was used to evaluate the individual exposure level of six air pollutants,PM2.5,PM10,SO2,CO,NO2,and O3,which were monitored by the national monitoring stations.Linear mixed-effects models were used to estimate the associations between six air pollutants and the relapse risk of schizophrenia,which was evaluated by the early signs scale(ESS)and blood cortisol levels.The Bayesian kernel machine regression(BKMR)model was conducted to explore the joint effects of co-exposure to four pollutants(PM2.5,SO2,NO2,and CO)that had significant hazard effects in univariate analysis.And the mediation analysis was performed to explore the potential mediation effect of log-cortisol.Results:(1)General: A total of 66 patients with stable schizophrenia were recruited,all of whom completed two or more repeated measures,for a total of 144 visits.(2)Effect of air pollutants on the risk of schizophrenia relapse: Higher concentrations of PM2.5,NO2,SO2,and CO were associated with an increased risk of relapse of schizophrenia.Per 10 μg/m3 increase of PM2.5 concentration had the greatest effect on the ESS score(β = 1.477;95% CI: 0.850,2.044)in lag0,with a cumulative effect lasting four days(lag03).The increase by 0.179(95% CI: 0.064,0.294)and 1.076(95% CI: 0.085,2.067)of the ESS score per 1μg/m3 increase in NO2 and SO2.The maximum effect of CO on ESS appeared at the lag0(β = 1.624;95% CI: 0.899,2.349).(3)Combined effects of co-exposure to pollutants: BKMR results showed a joint effect of co-exposure on ESS,where PM2.5 and SO2 were the main risk pollutants.(4)Effects of air pollutants on cortisol: Log-cortisol increased by 0.0175(95% CI: 0.0023,0.0328)and 0.0195(95% CI: 0.0016,0.0374)per 10 μg/m3 increase in PM2.5 concentration and per 0.1 mg/m3 increase in CO concentration at lag0.Each 1 μg/m3 increase in SO2 was associated with 0.0309(95% CI: 0.0044,0.0573)increase of log-cortisol.(5)Mediating effects of cortisol: We found significant mediated effects in the four pathways:“PM2.5→cortisol→ESS”,“PM2.5→cortisol→ESS-A”,“PM2.5→cortisol→ESS-N”,and “SO2→cortisol→ESS”,and the proportions were 37.13%,35.53%,30.69%,and 46.29%,respectively.Conclusion: The results of this study suggest that single and co-exposure to PM2.5,SO2,NO2 and CO increase the risk of relapse in schizophrenia.Cortisol mediated37.13% and 46.29% of the association between PM2.5 and SO2 and the risk of relapse,respectively.The results of this study may provide scientific basis for early prevention of schizophrenia in order to reduce the disease burden. |
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