IL1B基因多态性与儿童期创伤交互作用对抗抑郁剂疗效的影响

发布时间：2018-03-23 04:35

本文选题：抑郁症　切入点：白介素1B基因　出处：《东南大学》2015年硕士论文　论文类型：学位论文

【摘要】：背景抑郁症是人类最为常见的精神障碍,然而目前抗抑郁剂临床应用仍存在治愈率较低、起效延迟、个体差异显著等缺憾,因此探寻抗抑郁剂疗效的影响因素,实现抗抑郁药物个体化治疗是目前亟待解决的重要科学问题。近十年的研究指出,抑郁相关基因启动子区域的功能多态性,及其与环境因素的相互作用,可以预测抑郁症表型。有研究表明,促炎性细胞因子白介素1-β可通过降低5-HT系统功能,激活HPA轴,影响神经元再生等途径,参与抑郁症及抗抑郁剂治疗的病理生理过程。另有报道儿童期创伤可能增加体内细胞因子水平,并影响抑郁发作的病程和药物治疗效果。因此,本研究将聚焦细胞因子ILlB基因多态性和儿童期创伤,着重探讨其对抗抑郁剂疗效的影响。目的探讨白介素1B基因启动子区域单核苷酸多态性、儿童期创伤及其交互作用对抗抑郁剂临床疗效的影响。方法纳入统计的204例抑郁症患者使用单种抗抑郁药物治疗并随访8周,采用汉密尔顿抑郁17项量表(17-item hamilton depression rating scale, HAMD-17)评定疾病严重程度和治疗疗效,儿童创伤经历问卷简化版(childhood trauma questionnaire-short form, CTQ-SF)评定儿童期创伤经历刺激量及各分量表刺激量。选定白介素1B基因启动子区域rs16944单核苷酸多态性(single nucleotide polymorphism, SNP),采用多重单碱基延伸SNP分型技术(Multiplex SNaPshot)进行基因分型。运用SPSS 20.0软件包对8周治愈组和未治愈组间的一般资料及CTQ量表值进行t检验或Pearson's x2检验。Unphased 3.0.13软件包用于分析选取位点与抗抑郁疗效关联性。运用SPSS 20.0软件包x2检验分析儿童期创伤经历高低组间抑郁症首发年龄、发作次数、性别的差异；使用Pearson相关分析儿童期虐待总项及各分项对抑郁症状严重性及抗抑郁剂疗效的影响。采用logistic回归统计方法分析基因与环境因素的相互作用对抗抑郁药物疗效的影响。结果8周治愈组和未治愈组间各临床资料均无显著性差异。药物基因关联分析发现整体组中,IL1B基因rs16944位点AA基因型携带者相对AG、GG基因型携带者抗抑郁即治疗疗效较差(x2=3.931,P=0.047)。同样在SSRI亚组也发现此相关性(x2=6.235,P=0.0125)。儿童期情感虐待及性虐待可使抑郁症首发年龄提前,以儿童期情感虐待尤为显著。儿童期创伤经历及各分项不同严重程度组间在发作次数、性别上均无显著性差异。儿童期创伤经历及各分项对抑郁症状严重性及抗抑郁剂疗效无显著影响。基因和环境交互分析发现IL1B基因rs16944位点AA基因型与重度儿童期创伤经历/情感虐待的相互作用与较差的抗抑郁剂疗效相关(r=0.189, P=0.043; r=0.158, P=0.026)。结论在本研究中儿童期创伤经历可能不是影响抗抑郁剂疗效的独立因素,但儿童期创伤尤其是情感虐待可能是抑郁症首发年龄提前的关键因素；IL1B基因rs16944位点多态性及其与儿童期创伤经历相互作用可能影响抑郁患者临床疗效。
[Abstract]:Background depression is one of the most common mental disorder for human. However, clinical application of antidepressant has low cure rate, delayed onset of action, individual differences and other defects, so explore the factors influencing the efficacy of antidepressants, achieve antidepressant drug individualized treatment is an important problem to be solved at present. In recent ten years pointed out that the related gene polymorphism depression start function sub area, and its interaction with environmental factors, can predict depression phenotype. Studies have shown that proinflammatory cytokine interleukin 1- beta can reduce the 5-HT system function, HPA axis activation, affecting neuronal regeneration and other ways to participate in depression and antidepressant treatment the physiological and pathological processes. Other reports of childhood trauma may increase the level of cytokines in vivo, and influence the course and effect of drug treatment on depression. Therefore, this research will focus on the fine Cell factor ILlB gene polymorphism and childhood trauma, focusing on the effects of antidepressant treatment. Objective to investigate interleukin 1B gene promoter region single nucleotide polymorphism, effects of childhood trauma and their interaction on antidepressant treatment. Methods included in the statistics of 204 patients using single antidepressant treatment and follow up of 8 weeks, the Hamilton Depression Scale (17 17-item Hamilton Depression Rating Scale, HAMD-17) to assess the curative effect of disease severity and treatment of childhood trauma questionnaire, simplified version (childhood trauma Questionnaire-Short Form, CTQ-SF) for childhood traumatic experiences of stimulation and each subscale stimulus. Selected the interleukin 1B gene promoter region rs16944 single nucleotide polymorphism (single nucleotide polymorphism, SNP), using multiple single nucleotide extension SNP typing technique (Multiplex SNa Pshot). Genotyping was performed using the SPSS 20 software package for 8 weeks the cure group and no cure general information and CTQ scale between group values were analyzed by t test or Pearson's x2 test.Unphased 3.0.13 software package for the analysis of selected sites and the antidepressant effect of relevance. Using the SPSS 20 software package x2 test analysis of childhood trauma the level of experience among groups depressive episodes, age, gender differences; use Pearson correlation analysis of childhood abuse total items and each item of the severity of depressive symptoms and antidepressant effect. Using logistic regression statistical analysis base affect the efficacy of antidepressants for interaction with environmental factors. The results of 8 weeks cure group and cure group among the clinical data showed no significant difference. Correlation analysis shows that the overall drug gene group, IL1B gene rs16944 site AA genotype AG GG genotype relative. The carriers of antidepressant treatment less (x2=3.931, P=0.047). The correlation was also found in the SSRI subgroup (x2=6.235, P=0.0125). Emotional abuse and sexual abuse in childhood depression can make the age of onset in advance to childhood emotional abuse is particularly significant. Childhood trauma experience and sub groups in different severity the number of attacks, the gender difference was not significant. Childhood trauma experience and each item has no significant effect on the severity of depressive symptoms and antidepressant effect. Genetic and environmental interaction analysis showed that IL1B gene rs16944 genotype AA and severe childhood trauma / interaction and poor emotional abuse of antidepressants effect of correlation (r=0.189, P=0.043; r=0.158, P=0.026). Conclusion in this study, the independent factors of childhood trauma may not affect the efficacy of antidepressants, but childhood trauma especially emotional abuse It may be a key factor for the onset age of depression. IL1B gene rs16944 polymorphism and its interaction with childhood trauma experience may affect the clinical efficacy of depression.

【学位授予单位】：东南大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R749.4

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