Association Of Organophosphorus Pesticide Exposure With Risk Of Depression In Adults

Background Organophosphorus pesticides(OPPs)are widely used worldwide,and because of their neurotoxicity,research scholars have begun to focus on their effects on central nervous system disorders in recent years.However,studies on their effects on depression are limited,with no studies exploring the combined effects of multiple OPPs on depression,in addition to the lack of evidence from studies in the general population.To this end,the main objectives of this study were(1)to explore the association between organophosphorus pesticide exposure and the risk of depression in adults based on population-based studies;(2)to investigate the effects of organophosphorus pesticide exposure alone and in combination on the risk of depression in the general population using multiple statistical models;and(3)to analyze the differences in the risk of depression caused by organophosphorus pesticides in different subgroups of the population and thus identify susceptible populations.Methods Based on data from 4 cycles of the National Health and Nutrition Examination Survey(NHANES),we included 5206 participants aged 20 years and older.Exposure to human OPPs was estimated by measuring the concentrations of six urinary OPPs metabolites by gas chromatography-tandem mass spectrometry(GC-MS/MS).The Patient Health Questionnaire-9(PHQ-9)was used to assess the depression status of the population.Survey-weighted generalized linear regression models(SWGLM)were used to explore the risk of increased depression by a single metabolite of OPPs.Subgroup analyses were performed stratified by age(≦60years,>60 years)and gender.A weighted quantile sum regression model(WQS)was used to explore the overall association between combined exposure to six OPPs metabolites and the risk of depression and to identify the relative contribution of each OPPs metabolite to the effect of depression.In addition,Bayesian kernel machine regression(BKMR)models were used to explore the interaction and joint exposure effects between multiple metabolites of OPPs and depression risk.Results A total of 5206 study subjects were eventually included in this study,with essentially the same number of males and females and a mean age of 47.06 ± 0.45 years,of which a total of 445 were identified as depressed population,accounting for8.5%.SWGLM results showed that two metabolites,dimethyl phosphate(DMP)and dimethyl thiophosphate(DMTP),both as continuous or categorical variables,showed a positive association with depression.Diethyl phosphate(DEP)and dimethyl dithiophosphate(DMDTP)in the highest quartile were positively associated with depression compared to study subjects with the lowest quartile of OPPs metabolites in their urine.In the subgroup analysis,we found that the effects of the above-mentioned chemicals on depression were mainly present in male and middle-aged subjects,while women were mainly affected by DMP.In the WQS,we found a significant overall effect between six OPPs metabolites and depression [OR = 1.23,95% CI:(1.01,1.50)],with a large relative effect of: diethyl phosphate(DEP)and diethyl dithiophosphate(DMDTP),accounting for up to 30.7% and 26.4%,respectively.In addition,the BKMR model also showed a positive trend of association between the overall effects of the six OPPs metabolites on depression.Conclusions Our findings suggest that exposure to OPPs may increase the risk of depression in U.S.adults,with the relatively important effects of two substances,DEP and DMDTP.In comparison,men and young middle-aged populations were more susceptible to the effects of OPPs.Also,combined exposure to OPPs metabolites may predispose to the development of depression.Our findings strengthen the evidence for an association between long-term low-dose exposure and organophosphorus pesticides and depression in the general population and provide a scientific basis for practical guidance on preventing and controlling depressive effects due to organophosphorus pesticides in the general population.