| Objective The study aimed to describe the epidemiology of anxiety and depression disorders in high-risk regions of esophageal cancer,to investigate the association between anxiety,depression and esophageal cancer,to evaluate the short-term and long-term psychological impact of esophageal cancer screening on anxiety and depression,and to identify psychological distress-associated gut microbiota among screeners.The objective of this study was to add new evidence for optimizing the screening strategy and comprehensively evaluating the effectiveness of esophageal cancer screening in China.Materials and Methods 1.Based on the screening program in high-risk regions of esophageal cancer,a population-based multicenter cross-sectional study was carried out between 2017 to 2019.Information on risk factor exposures,anxiety and depression was collected using inform e-questionnaire among screeners.The anxiety and depression were evaluated by the Generalized Anxiety Disorder Scale-7(GAD-7)and Patient Health Questionnaire-9(PHQ-9)instruments.The levels of anxiety and depression were evaluated by continuous variable(mean score)and binary variable(positive rate).Screeners underwent endoscopy examination and biopsy,and they were diagnosed with normal,esophagitis,Low-grade intraepithelial neoplasia(LGIN),High-grade intraepithelial neoplasia(HGIN)and esophageal cancer.Multiple logistic regression was used to evaluate the association between anxiety,depression and esophageal cancer.2.The population-based multicenter study was carried out in five high-risk regions in 2020.We refer to those who underwent endoscopic screening of esophageal cancer as the screening participants.We dynamically evaluated the anxiety and depression in the screening process,including baseline,after endoscopy,informing pathological results.Variance trend tests and x2 trend tests were used to compare the difference among those points in the screening process.Analysis of Variance was performed to compare the difference among different esophageal pathological grades.Besides,we selected screeners in Cixian from 2020 to 2021 and wore an intelligent bracelet on them for tracking emotion in the screening process.The Sympathetic Activity Index(SAI)and Parasympathetic Activity Index(PAI)were obtained to reflect the sympathetic and parasympathetic activity.3.This multicenter population-based prospective study was conducted to follow up on anxiety and depression among screeners in five high-risk regions of esophageal cancer from 2019 to 2020.We selected those who had participated in the screening of esophageal cancer in 2017-2019 and had a definite diagnosis(baseline).Patients screened and diagnosed with normal,esophagitis and LGIN at baseline were followed up by random sampling.HGIN and esophageal cancer were all followed up.McNemar’s test was performed to compare anxiety and depression of screeners at baseline and follow-up.χ2 test was used to compare the difference in anxiety and depression among pathological grades at follow-up.Besides,we selected 61 subjects who had participated in twice screening of esophageal cancer in Linzhou and Cixian from 2017 to 2019.Cortisol,IgA,IgM and IgG were tested in two blood samples(baseline and follow-up)in the laboratory.Two-way repeated-measures ANOVA was used to evaluate hormone cortisol and immunoglobulin levels,reflecting their stress,immune function,and biological correlations at baseline and follow-up.4.We characterized the microbial communities of fecal samples collected through the FOBT card among screeners with anxiety and depression and paired controls in Henan in 2019(1:2,N=69).The 16S rRNA gene was sequenced using MiniSeq and processed using QIIME1.We described and compared the microbial characteristics including a diversity,β diversity,and relative abundance at phylum,family,genus and species levels between the two groups.LEfSe was used to identify psychological distress-associated gut microbiota.Results 1.A total of 25650 participants in high-risk regions of esophageal cancer were included in 2017-2019(mean age:55.5 ± 7.7 years),9586(37.4%)of whom were suspicious in endoscopy and confirmed by esophageal pathology(1055 normal,6780 esophagitis,1377 LGIN,272 HGIN and 102 esophageal cancer cases).The mean score(95%CI)of anxiety and depression of screeners in high-risk regions were 2.0(1.9-2.0)and 2.2(2.2-2.3),and the corresponding prevalence(cut-off:5)was 16.9%and 25.7%,respectively.The prevalence of anxiety at baseline for normal,esophagitis,LGIN,HGIN and esophageal cancer were 5.2%,18.5%,17.7%,43.5%and 36.3%,respectively(P<0.001).The corresponding prevalence of depression for each grade were 16.1%,26.4%,25.7%,38.0%and 40.2%,respectively(P<0.001).Women,participants who were unmarried/living alone/divorced/widowed,highly educated individuals,with low-income and poor self-rated health may be more likely to suffer anxiety and depression symptoms.Anxiety and depression may be positively correlated with HGIN and esophageal cancer.Taking normal as reference,the adjusted OR(95%CI)of anxiety and esophageal pathological grades were 1.08(1.05-1.12),1.03(0.99-1.07),1.35(1.29-1.42)and 1.19(1.10-1.29)(P<0.001).The adjusted OR(95%CI)of depression and esophageal pathological grades were 1.08(1.05-1.11),1.04(1.01-1.08),1.20(1.15-1.26)and 1.17(1.10-1.25)(P<0.001).Sensitivity analysis showed that the positive association persisted.2.1 A total of 2337 subjects completed all surveys in the screening process(normal:355,esophagitis:1713,LGIN:213,HGIN:43,esophageal cancer:13).The fluctuation of anxiety and depression showed a "V" pattern in the screening process.The levels of anxiety and depression among screeners were high at baseline and after knowing the pathological diagnosis.The prevalence of anxiety symptoms at baseline,after endoscopy,after knowing the pathological results were 5.6%,0.3%and 3.2%,respectively(P<0.001),and the corresponding prevalence of depression were 3.6%,0.2%and 2.1%,respectively(P<0.001).With the aggravation of pathological grade,the levels of anxiety and depression increased significantly(P<0.001),especially in patients diagnosed with HGIN(16.3%and 9.3%)and esophageal cancer(23.1%and 30.8%).2.2 Based on bracelet emotion tracking,we included 43 subjects(6 normal,28 esophagitis,7 LGIN,2 esophageal cancer),with a mean age of 63.9 years.There was no significant change in bracelet indicators from before screening to in endoscopy(SAI,P=0.161).The sympathetic nerve was excited after knowing the pathological results(SAI,P<0.001).Similar patterns of SAI and PAI in the screening process were shown in each pathological grade.3.1 A total of 1973 screeners were followed up finally(593 normal,527 esophagitis,649 LGIN,147 HGIN,57 esophageal cancer),with an average follow-up of 22.2 months.Compared with the baseline,the prevalence of anxiety and depression symptoms among screeners at follow-up decreased(14.3%vs.5.3%,18.4%vs.5.4%,all P<0.001).The negative psychological impact of screening on anxiety and depression weakened at followup and gradually normalized for normal,esophagitis and LGIN,but the adverse influence was continuous and high at follow-up for HGIN and esophageal cancer.Patients with HGIN and esophageal cancer were more likely to change from the non-anxiety and nondepression group to the anxiety and/or depression group,or maintain existing anxiety and/or depression symptoms at follow-up.3.2 61 participants undertook twice endoscopic screening of esophageal cancer from 2017 to 2019(normal and esophagitis:31,LGIN:30),with an average follow-up of 14.0 months.After normality transformation,no significant differences were found in cortisol,IgG,and IgM at baseline and follow-up(P=0.778,P=0.064,P=0.1 10).IgA level slightly decreased at follow-up(P=0.015).There was no significant difference in cortisol,IgA,IgG and IgM levels between the two groups,no matter at baseline or follow-up.4.A total of 69 screeners were included(anxiety and depression group:23;control group:46).The intestinal microbial environments of screeners by phylum were all composed primarily of Firmicutes,Bacteroidetes,and Proteobacteria,and the corresponding top genera were Faecalibacterium,Roseburia,and Prevotella.Compared with controls,the ranking of the top five genera in the anxiety and depression group changed.The dominant genus was Prevotella in the anxiety and depression group and Faecalibacterium in the control group.There was a lower relative abundance of Gemmiger(1.4%vs.2.3%,P=0.025),Ruminococcus(0.6%vs.0.8%,P=0.037)and Veillonella(0.6%vs.1.3%,P=0.020)in the anxiety and depression group.This may be linked to the lower alpha diversity in participants with anxiety and depression,although no significant differences were observed.Conclusions1.The anxiety and depression levels in high-risk regions cannot be ignored.There may be a positive correlation between anxiety,depression and esophageal lesions(HGIN and esophageal cancer).The results indicated that anxiety and depression may be potential and promising for concentrating on high-risk groups of esophageal cancer.And the findings provided informative clues for comprehensive prevention and control of esophageal cancer in China.2.Participation in endoscopic screening may bring adverse psychological effects.The anxiety and depression were obvious at baseline and when knowing the pathological results,especially for those who were told they had HGIN or esophageal cancer.The findings provided useful suggestions for optimizing the screening process.More attention should be paid to participants at baseline.And the way of informing the screening results of HGIN and esophageal cancer should be improved.The negative psychological impact of screening should be considered when comprehensively evaluating the effectiveness of cancer screening.The results suggested that it was necessary to further explore methods of concentrating high-risk groups,reducing the number of endoscopic screening participants,and improving the detection rate of esophageal cancer screening to reduce the psychological impact of screening.3.The adverse psychological influence of screening weakened over time and gradually normalized,except for HGIN and EC(remain lasting and high).The findings provided new evidence and for comprehensively evaluating the effectiveness of endoscopic screening.4.Our study showed differing microbial characterization among screeners with anxiety and depression.Gemmiger,Ruminococcus and Veillonella were characteristic intestinal microbiota,which was informative and had potential clinical implications for the treatment of psychological diseases. |
