Association Between Defense Mechanism And Anxiety:Coping Style As A Mediator And Polymorphisms Of GPx-1,GST Gene As A Moderator

Objective: Defense mechanisms are an unconscious function of the ego,and they are used to protect the individual from anxiety.In the previous research,we found that individual defense mechanisms and anxiety have gene polymorphisms,which proved that they may have biological tendency.Coping is defined as thoughts and behaviors that are mobilized to manage internal and external stressful situations.Researches showed that mature defense mechanisms are positively correlated with positive coping styles,while immature defense mechanisms are correlated with negative coping styles.However,the relationship between coping and defense mechanisms is controversial.Coping styles and defense mechanisms were classified as two independent key resources that did not interfere with each other for stress-adaptation processes,and some scholars tend to put coping styles in place before defense mechanisms,while others believed that defense mechanisms take precedence over coping styles.On the other hand,a body of clinical evidence indicates that oxidative stress is implicated in the many neuropsychiatric disorders.Glutathione Peroxidase(GPx)and Glutathione S-transferase(GST)protected biofilm and cellular components from oxidative stress.It is unclear whether changes in GPX and GST cause anxiety or vice versa.However,research on the involvement of GPx and GST in anxiety is lacking.Whether GPx-1 and GST gene polymorphisms affect individual’s defense mechanisms,coping styles and anxiety or not is worthy of investigating.Therefore,the purposes of this study were coping styles mediated the association between the defense mechanisms and anxiety,and the GPx-1 and GST gene polymorphisms moderated the relationship between defense mechanisms and anxiety.Method: Participants: All subjects included medical staff and students of China Medical University,Shenyang,Liaoning Province,China.All subjects were healthy Han Chinese volunteers(n = 402,198 males,204 females)with no psychiatric,neurological,or chronic physical illnesses.The age range was 19-58 years.Methods: The defense mechanisms,anxiety levels,and coping styles were assessed using the Defense Style Questionnaire,State-Trait Anxiety Inventory,and Simplified Coping Style Questionnaire,respectively.2m L of EDTA treated blood was taken from each volunteer for DNA isolation using aDNA extraction kit.GPx-1 and GST gene polymorphisms were assessed by a PCR-based amplification strategy.Statistical Analysis: Statistical analyses were conducted using SPSS version 26.0 software(SPSS Inc.,Chicago,Ill.,USA)with the PROCESS 4.0plug-in.The chi-square test was used to analyze Hardy-Weinberg equilibrium(HWE),gene frequencies,and allele frequencies.Pearson correlation analysis was used to analyze the correlation among the studied variables.The mediation analysis of coping styles was performed by Model 4 and the moderating effect analysis of the genotypes was performed by Model in the PROCESS 4.0 plug-in.The 95% Bootstrap confidence intervals(Boot CIs)that did not include zero were considered statistically significant in the mediation model.Data are presented as the mean ± SD,frequency,or percentage.P-values of less than 0.05 were considered statistically significant in the other statistical analyses.Result:Part 1.Effects of coping styles on the relationship between defense mechanisms and anxiety: Coping Style as a Mediator1.Immature defense had a significant negative correlation with positive coping,and significant positive correlations with passive coping,state and trait anxiety(all P<0.001).Mature defense was positively correlated with positive coping(P<0.001),but negatively correlated with state and trait anxiety(P<0.001,P<0.01).Moreover,Intermediate defense was only significantly positively correlated with positive coping(P < 0.001).Finally,the analyses showed that positive coping had a significant negative relationship with state and trait anxiety(all P<0.001).3.Positive coping mediated the association between the immature defense and anxiety(both state and trait anxiety),and the ratio of mediating effect to total effect was 9.9885% for state anxiety and 8.4112% for trait anxiety.Meanwhile,positive coping mediated the association between the mature defense and anxiety(both state and trait anxiety),and the ratio of mediating effect to total effect was50.1448% for state anxiety and 55.5485% for trait anxiety.Finally,positive coping mediated the association between projection,passive aggression,help-rejecting complaining,regression and somatization and anxiety,and the ratio of mediating effect to total effect was 13.3845%,12.9630%,15.8015%,9.9817% and 41.3212% for state anxiety and 11.4836%,12.4053%,13.5905%,9.9130% and 28.5132% for trait anxiety.Part 2.Effects of coping styles on the relationship between defense mechanisms and anxiety: GPx-1 and GST gene Polymorphisms as a Moderator1.The genotype distributions of rs1800668,rs1050450 and rs1695 polymorphisms did not deviate from the Hardy-Weinberg equilibrium.The genotype deletion frequencies of GSTM1 and GSTT1 were 33.3333% and 22.1393%,respectively,which were consistent with the genotype deletion frequencies of Asian populations.2.There were no statistical associations of the rs1800668C/T and rs1050450C/T genotypes with positive and passive coping,immature defense,intermediate defense and mature defense scores,state and trait anxiety levels(all P>0.05).3.There were no statistical associations of the GSTM1-null genotype,GSTM1-present genotype,and the combined genotypes of GSTM1 and GSTT1 with positive and passive coping,immature defense,intermediate defense and mature defense scores,state and trait anxiety levels(all P>0.05).There were significant differences in the intermediate defense mechanisms and mature defense mechanisms between healthy subjects with GSTT1-null genotype and those with GSTT1-present genotype(P<0.05).There was statistical association of the rs1695 A/G genotype with state anxiety(P<0.05).There were statistical associations of the dominant model of the GSTP1 gene rs1695(carrier G genotype vs AA genotype)with positive coping,intermediate defense scores,state and trait anxiety levels(all P<0.05).4.The GPx-1 gene rs1800668(carrier T genotype vs CC genotype)moderated the relationship between mature defense and state and trait anxiety(all P<0.05).The GPx-1 gene rs1050450(carrier T genotype vs CC genotype)moderated the relationship between mature defense and state(P<0.05)and trait anxiety(P<0.01).5.The GSTM1(null vs present)moderated the relationship between mature defense and state and trait anxiety(P<0.05).The GSTT1(null vs present)moderated the relationship between mature defense and state and trait anxiety(P<0.05).The combined genotypes of GSTM1 and GSTT1 moderated the relationship between mature defense and state and trait anxiety(P<0.05).Conclusion: 1.Defense mechanisms affects anxiety.2.The effect of defense mechanisms on anxiety is mediated by positive coping style.3.GPx-1 gene rs1800668 and rs1050450 were not directly related to anxiety.4.GSTM1,GSTT1 gene deletion polymorphisms and the combined genotypes of GSTM1 and GSTT1 polymorphisms were not directly associated with anxiety.5.GSTP1 rs1695A/G polymorphism is associated with state and trait anxiety.6.The effect of mature defense on anxiety was mediated by GPx-1,GSTM1,GSTT1 gene and the combined genotypes of GSTM1 and GSTT1 polymorphisms.