| ObjectiveThe physical and mental health development of children and adolescents is affected by various factors in their growing process and their interaction.Adverse childhood experiences(ACEs),the most common adverse stressors in human life,has been gradually demonstrated to be harmful for the physical and mental health of adolescents.As the opposite of ACEs,the protective effect of positive childhood experiences(PCEs)on human physical and mental health has also been gradually reported.However,it is unclear that positive and negative experiences in childhood interact with each other to jointly affect the development of adolescent anxiety and depression,and the underlying biological mechanism has not been completely explored.Therefore,based on the data of cross-sectional and longitudinal follow-up study of primary and secondary school students in Anhui Province,this study was conducted to explore the association between ACEs,PCEs,inflammatory burden,and anxiety and depression in adolescents.MethodsStudy I was a cross-sectional study that between October and December 2020,students on grade 4thto 9thin some primary and secondary schools located in northern,central,and southern of Anhui province,China were enrolled to participate in a questionnaire survey.Information about demographic characteristics,ACEs,PCEs,youth resilience,anxiety and depression were collected.Finally,a total of 6494 primary and middle school students participated in the survey.Logistic regression analysis was performed to explore the association between ACEs,PCEs and the risk of anxiety,depression and comorbidity of depression with anxiety.Relative Excess Risk due to Interaction(RERIOR)and ratio of odds ratios(ORs)were used to evaluate the addition and multiplication interactions of ACEs and PCEs.Study?was a cohort study which was conducted based on a cross-sectional study sample of 1409 students on grade 4thand 7thwho were followed every 6 months.The first follow-up was conducted from May to June 2021,and a total of 1161 patients were followed up.The second follow-up was conducted between October and November 2021,and a total of 1150 patients were followed up with a total follow-up rate of 81.6%.The Generalized Estimation equation(GEE)was used to analyze the effects of different types of ACEs or PCEs and their combined exposure on the risk of anxiety,depression,comorbidity of depression with anxiety and scores development of anxiety and depression.Latent Profile analysis(LPA)and Logistic regression analysis were performed to investigate the independent and cumulative effects of ACEs and PCEs on the developmental trajectory patterns of anxiety and depression.Study?was a nested case control study.The case group was primarily selected from primary and secondary school students in study?who had no anxiety and depression at baseline but were observed to have anxiety and/or depression during the first and second follow-up or only during the second follow-up.The control group was primarily selected from primary and secondary school students who had no anxiety and depression at both baseline and follow-up periods.In addition,students with recent illness,trauma,chronic disease,or menstrual period in the survey,or no urine specimens collected at baseline and follow-up were excluded from the case and control groups.Finally,248 students were included,including 35 students in the case group and213 students in the control group.Collected information by questionnaire on the baseline and follow up was used for data analysis.The levels of three inflammatory biomarkers(soluble urokinase plasminogen activator receptor(su PAR),C-reactive protein(CRP),and interleukin-6(IL-6))in urine collected on three surveys were measured by Enzyme Linked Immunosorbent Assay(ELISA).Logistic regression models and KHB methods were used to explore the mediating effect of inflammatory biomarker levels on the association between positive,negative childhood experiences and anxiety,depression.ResultsResults of study IIn terms of the prevalence of ACEs,51.2%students reported at least one ACEs,26.1%students reported two or more ACEs,and 5.2%students reported four or more ACEs.Among different types of ACEs,physical abuse had the highest prevalence(24.6%).As for the prevalence of PCEs,46.4%students reported 3-5 terms of PCEs and26.4%students reported terms of 6-7 PCEs.The prevalence of feel security was the highest among different types of PCEs(82.0%).Results of logistic regression analyses showed that all types of ACEs were significantly positively associated with anxiety,depression and comorbidity of depression with anxiety.The strength of the association varied between different types of ACEs and risk of anxiety,depression and comorbidity of depression with anxiety,and emotional abuse was the most harmful(for depression:adjusted OR:6.52,95%CI:4.55-9.35;for anxiety:adjusted OR:3.76,95%CI:2.77-5.11;for comorbidity:adjusted OR:7.80,95%CI:5.24-11.59).The risk of anxiety,depression and the comorbidity increased with the higher level of ACEs,and there was a significant dose-response relationship.All types of PCEs were significantly negatively associated with depression,and family security had the greatest protective effect which can reduce the risk of depression by 60%(adjusted OR:0.40,95%CI:0.35-0.46).Except that the positive experience of being cared by other adults than family members and emotional communication with family members was not significantly associated with anxiety,other types of PCEs significantly reduced the risk of anxiety.In terms of the association between PCEs and comorbidity of anxiety and depression,all types of positive experiences,except those cared about by other adults than family members,were significantly negatively correlated with the comorbidity of anxiety with depression,which could reduce the risk of comorbidity by 9%?54%.In addition,with the increase of the level of PCEs,the risk of depression gradually decreased,presenting a significant inverse dose-response relationship.However,only with medium or high level of PCEs,the protective effect on anxiety and comorbidity of anxiety and depression would be significant.The results of interaction analysis showed that there was a significant negative additive interaction between medium and high level of PCEs and?1 ACEs on depression and comorbidity of anxiety and depression.Moreover,the interactions of medium and high levels of PCEs and other levels of ACEs(?2 ACEs or?4 ACEs)on anxiety,depression and its comorbidity were not significant on the additive interaction scale,but were significant on the multiplicative interaction scale.Results of study?In general,students with ACEs exposure at baseline showed higher scores and prevalence of anxiety and depression in the three surveys than those without ACEs.However,the scores of anxiety and depression and the prevalence of anxiety and depression in the students with ACEs declined during the survey.The generalized estimation equation(GEE)was used to analyze the association between ACEs and risks of anxiety,depression and the comorbidity of anxiety with depression..The results showed that emotional abuse(OR=5.13,95%CI:1.77-14.89),physical abuse(OR=2.79,95%CI:1.50-5.19),physical neglect(OR=1.62,95%CI:1.16-2.27),parental separation or divorce(OR=1.55,95%CI:1.06-2.26)and domestic violence(OR=1.70,95%CI:1.20-2.69)were risk factors for depression;emotional abuse(OR=3.25,95%CI:1.34-7.85),physical abuse(OR=2.07,95%CI:1.20-3.56),physical neglect(OR=1.44,95%CI:1.03-2.00),and domestic violence(OR=1.85,95%CI:1.23-2.79)were risk factors for anxiety;emotional abuse(OR=6.93,95%CI:1.96-24.42),physical abuse(OR=3.51,95%CI:1.76-7.01),and domestic violence(OR=2.44,95%CI:1.49-3.99)were risk factors for the comorbidity of anxiety with depression.Cumulative levels of ACEs significantly increased the risk of depression,anxiety,and the comorbidity of depression with anxiety.For each additional ACEs,the risk of depression increased by41%(OR=1.41,95%CI:1.23-1.61),the risk of anxiety increased by 26%(OR=1.26,95%CI:1.11-1.42),and the risk of comorbidity of anxiety with depression increased by48%(OR=1.48,95%CI:1.25-1.74).Results of GEE analyses on association between ACEs and anxiety and depression scores showed that emotional abuse,physical abuse,emotional neglect,physical neglect,parental separation or divorce,and domestic violence significantly increased depression scores;emotional abuse,physical abuse and domestic violence can significantly increase anxiety scores.The scores of anxiety and depression increased along with the level of ACEs.For each additional ACEs,depression scores increased by 1.59(?=1.59,95%CI:1.00-2.17)points and anxiety scores increased by 1.59(?=1.59,95%CI:0.77-2.41)points.Results of GEE analyses on association between PCEs and the risk of anxiety,depression and the comorbidity of depression with anxiety showed that family support(OR=0.67,95%CI:0.48-0.93),sense of security(OR=0.61,95%CI:0.41-0.90),and school belonging(OR=0.56,95%CI:0.40-0.77)were protective factors for depression;friend support(OR=0.71,95%CI:0.52-0.96)and school belonging(OR=0.71,95%CI:0.51-0.97)were protective factors for anxiety;family support(OR=0.63,95%CI:0.42-0.95)and school belonging(OR=0.54,95%CI:0.37-0.80)were protective factors for the comorbidity of anxiety with depression.In addition,for each additional PCEs,the risk of depression decreased by 13%(OR=0.87,95%CI:0.79-0.95),the risk of anxiety decreased by 8%(OR=0.92,95%CI:0.84-1.00),and the risk of anxiety and depression comorbidity decreased by13%(OR=0.87,95%CI:0.79-0.95).With anxiety and depression scores as dependent variables,results of GEE models showed that emotional communication with family,family support,security,friend support,school belonging can significantly reduce depression scores;emotional communication with family members and school belonging significantly reduced anxiety scores.Analysis of the combined effects of ACEs and PCEs showed that exposure to non ACEs and high PCEs level(6-7 items)reduced the risk of depression by 65%(OR=0.35,95%CI:0.16-0.73),and anxiety by69%(OR=0.31,95%CI:0.15-0.64),and the risk of anxiety and depression comorbidity by 75%(OR=0.25,95%CI:0.10-0.62);exposure to?4 ACEs and low PCEs level(0-2items)increased the risk of depression by 259%(OR=3.59,95%CI:1.22-10.58);exposure to?4 ACEs and moderate level of PCEs(3-5 items)significantly increased the risk of depression(OR=11.97,95%CI:2.93-48.92)and anxiety and depression comorbidity(OR=9.30,95%CI:2.11-40.94).The development of anxiety and depression scores were divided into"alleviation group"(Category 1)and"high score fluctuation group"(Category 2)by LPA(Latent Profile Analysis).Taking wheteher the anxiety or depression show high score fluctuation as outcome variables,results of logistic regression analyses showed that gambling or alcoholism of family members,parental separation or divorce,domestic violence,mental disorder of family members,and family economic difficulties were the risk factors of the high score fluctuation of depression;mental disorder of family members was the risk factor of the high score fluctuation of anxiety.With the increase of cumulative ACEs level,the risk of high score fluctuation of anxiety and depression gradually increased.However,only the dimension of feeling security had a significant protective effect on the high score fluctuation of depression among all types of PCEs,while the other types of PCEs and accumulated levels of PCEs had no significant effect on anxiety and depression development.The results of association between combined exposure of ACEs and PCEs and risk of development of anxiety and depression scores showed that high level of ACEs and medium/low level of PCEs exposure significantly increased the risk of high score fluctuation of depression score.Results of study?Taking the outcome of anxiety and/or depression as a dependent variable,ACEs was significantly associated with anxiety and/or depression(OR:2.89,95%CI:1.07-7.77,P=0.035),while the direct effect was not significant for the association between ACEs and anxiety and/or depression(OR:1.57,95%CI:0.58-4.26,P=0.373),and su PAR level had a significant mediating effect on the impact of ACEs on anxiety and/or depression(OR:1.84,1.12-3.03,P=0.018),accounting for 57.5%of the total effect.Taking the presence of anxiety as a dependent variable,the overall effect of ACEs on anxiety was significant(OR:4.35,95%CI:1.12-16.95,P=0.035),while the direct effect of ACEs on anxiety was not significant(OR:2.27,95%CI:0.61-9.12,P=0.216).su PAR level had a significant mediating effect on the impact of ACEs on anxiety(P=0.029),and the mediating effect accounted for 42.2%of the total effect.Taking the presence of depression as the outcome variable,the overall effect of ACEs on depression was significant(OR:5.87,95%CI:1.90-17.99,P=0.002),the direct effect of negative childhood experience on depression was significant(P=0.033),and su PAR level had a significant mediating effect on the impact of ACEs on depression,accounting for 31.6%of the total effect.However,the mediating effects of IL-6 and CRP levels on the effect of ACEs on anxiety,depression and anxiety and/or depression were not significant.The mediating effects of su PAR,IL-6 and CRP levels on the effect of PCEs on anxiety,depression and anxiety and/or depression were not significant.Conclusion(1)All types of ACEs can increase the risk of anxiety and depression,among which emotional abuse is the most harmful.Some types of PCEs have protective effects on anxiety and depression.(2)The risks of anxiety,depression and comorbidity of anxiety with depression in adolescents increase along with cumulative ACEs level,and there is a significant dose-response relationship.Cumulative PCEs reduce the risk of depression and comorbidity of anxiety and depression in adolescents,and there is a significant inverse dose response relationship.(3)The effect of cumulative PCEs on anxiety was significant only at high levels.Medium or high level of PCEs can moderate the impact of low level of ACEs on adolescent depression,but cannot eliminate the harm of high level of ACEs.(4)ACEs are risk factors for the development of anxiety and depression in primary and secondary school students,and emotional abuse has the most harmful effect.PCEs are protective factors for the development of anxiety and depression in primary and secondary school students,and school belonging has the strongest protective effect on anxiety and depression.(5)Medium and high level of PCEs can alleviate the harm of low level of ACEs on the development of anxiety and depression,but it seems not enough to offset the harm of high level of exposure to ACEs.(6)The inflammation biomarker of su PAR can mediate the impact of ACEs on anxiety and depressive symptoms.Inflammatory burden maybe can not mediate the association between PCEs and anxiety or depression. |
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