| Objectives:（1）To study the association between atmospheric particulate matter exposure and the risk of recurrence of schizophrenia prospectively based on a cohort,（2）To use the Early Sign Scales（ESS）for Schizophrenia to explore which symptom dimensions of schizophrenia are more vulnerable to particulate pollution,（3）To investigate whether and to what extent immune cytokines mediate the exposure of particulate matter to an increased risk of schizophrenia recurrence.Methods:From August 2018 to June 2019,volunteers with chronic stable schizophrenia were recruited in communities in Hefei,Anhui Province according to predetermined inclusion and exclusion criteria.Each study subject was required to complete at least 3follow-up surveys,with each survey spaced two weeks apart.Collect the general demographic indicators,disease history,living habits,physical health of the study subjects,assess the risk of recurrence of schizophrenia,and collect the fasting venous blood of the study subjects for Luminex multiplex cytokine testing.The hourly concentrations of six air pollutants(PM10,PM2.5,SO2,NO2,CO,and O3)at 10 state-controlled monitoring stations in Hefei and the precise address of each research object were collected.The inverse distance weighted（IDW）method was used to estimate individual pollutant exposure levels.A linear mixed-effects model（LMEM）was used to investigate whether and to what extent 9 cytokines play a mediating role in rising particulate exposure to increase the risk of schizophrenia recurrence.Results:（1）A total of 58 patients with stable schizophrenia were recruited in the community.48.28%of the subjects participated in all follow-up surveys（6 times）,and a total of 266 effective follow-up surveys were completed.（2）For PM2.5,the increase in PM2.5concentration at lag0 had the greatest impact on the relapse of schizophrenia(for each 10μg/m3 increase in PM2.5,the relapse risk score increased by 1.504,that is to say,odds ratio（OR）=4.500（95%confidence interval（CI）:2.849-7.106,P<0.001）),and cumulative effects lasted for four days with the cumulative effects reaching the maximum for two days(for each 10μg/m3 increase in PM2.5,the relapse risk score increased by1.301,OR=3.673（95%CI:1.962-6.876,P<0.001）).For PM10,the increase in concentration at lag1 had the greatest effect on the relapse of schizophrenia(for each 10μg/m3 increase in PM10,the relapse risk score increased by 1.545,OR=4.688（95%CI:2.689-8.953,P<0.001）).The cumulative exposure to particulate matter within 0-71hours（lag03）had the greatest impact on the risk of relapse of schizophrenia(for each 10μg/m3 increase in PM10,the relapse risk score increased by 2.167,OR=8.732（95%CI:2.930-26.034,P<0.001）).（3）Environmental particulate matter exposure was statistically related to the four symptom dimensions of early signs of schizophrenia relapse.According to the lag effect value of PM2.5and the risk of relapse,the symptoms most affected by the increased atmospheric PM2.5were depression/withdrawal（N）（OR=1.990,95%CI:1.701-2.328）,and anxiety/agitation（A）（OR=1.537,95%CI:1.340-1.763）,initial psychosis（IP）（OR=1.398,95%CI:1.151-1.697）,disinhibition（D）（OR=1.235,95%CI:1.133-1.347）.（4）We found three pathways in the intermediary analysis of PM2.5and relapse risk:“PM2.5→IL-17→ESS”,“PM2.5→IL-17→ESSA”,“PM2.5→IL-17→ESSN”,the intermediary ratio was between 11.66%and 22.55%.In the intermediary analysis of PM10 and relapse risk,two pathways were also found:“PM10→IL-17→ESSA”,“PM10→IL-17→ESSN”,and the intermediary ratio was 14.13%-14.61%.Conclusions:（1）Increased environmental particulate matter increases the risk of schizophrenia recurrence,and there is a short-term lag effect;（2）Environmental particulate matter exposure increases the risk of overall relapse by firstly aggravating the non-psychiatric symptoms of schizophrenia;（3）Inflammatory cytokines IL-17 may play a mediating role in the process of particulate matter exposure to increase the risk of schizophrenia relapse,and the mediation ratio is 11.66%-22.55%. |
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