本文選題：抑郁癥　切入點(diǎn)：白介素1B基因　出處：《東南大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：背景抑郁癥是人類最為常見的精神障礙,然而目前抗抑郁劑臨床應(yīng)用仍存在治愈率較低、起效延遲、個(gè)體差異顯著等缺憾,因此探尋抗抑郁劑療效的影響因素,實(shí)現(xiàn)抗抑郁藥物個(gè)體化治療是目前亟待解決的重要科學(xué)問題。近十年的研究指出,抑郁相關(guān)基因啟動(dòng)子區(qū)域的功能多態(tài)性,及其與環(huán)境因素的相互作用,可以預(yù)測抑郁癥表型。有研究表明,促炎性細(xì)胞因子白介素1-β可通過降低5-HT系統(tǒng)功能,激活HPA軸,影響神經(jīng)元再生等途徑,參與抑郁癥及抗抑郁劑治療的病理生理過程。另有報(bào)道兒童期創(chuàng)傷可能增加體內(nèi)細(xì)胞因子水平,并影響抑郁發(fā)作的病程和藥物治療效果。因此,本研究將聚焦細(xì)胞因子ILlB基因多態(tài)性和兒童期創(chuàng)傷,著重探討其對(duì)抗抑郁劑療效的影響。目的探討白介素1B基因啟動(dòng)子區(qū)域單核苷酸多態(tài)性、兒童期創(chuàng)傷及其交互作用對(duì)抗抑郁劑臨床療效的影響。方法納入統(tǒng)計(jì)的204例抑郁癥患者使用單種抗抑郁藥物治療并隨訪8周,采用漢密爾頓抑郁17項(xiàng)量表(17-item hamilton depression rating scale, HAMD-17)評(píng)定疾病嚴(yán)重程度和治療療效,兒童創(chuàng)傷經(jīng)歷問卷簡化版(childhood trauma questionnaire-short form, CTQ-SF)評(píng)定兒童期創(chuàng)傷經(jīng)歷刺激量及各分量表刺激量。選定白介素1B基因啟動(dòng)子區(qū)域rs16944單核苷酸多態(tài)性(single nucleotide polymorphism, SNP),采用多重單堿基延伸SNP分型技術(shù)(Multiplex SNaPshot)進(jìn)行基因分型。運(yùn)用SPSS 20.0軟件包對(duì)8周治愈組和未治愈組間的一般資料及CTQ量表值進(jìn)行t檢驗(yàn)或Pearson's x2檢驗(yàn)。Unphased 3.0.13軟件包用于分析選取位點(diǎn)與抗抑郁療效關(guān)聯(lián)性。運(yùn)用SPSS 20.0軟件包x2檢驗(yàn)分析兒童期創(chuàng)傷經(jīng)歷高低組間抑郁癥首發(fā)年齡、發(fā)作次數(shù)、性別的差異；使用Pearson相關(guān)分析兒童期虐待總項(xiàng)及各分項(xiàng)對(duì)抑郁癥狀嚴(yán)重性及抗抑郁劑療效的影響。采用logistic回歸統(tǒng)計(jì)方法分析基因與環(huán)境因素的相互作用對(duì)抗抑郁藥物療效的影響。結(jié)果8周治愈組和未治愈組間各臨床資料均無顯著性差異。藥物基因關(guān)聯(lián)分析發(fā)現(xiàn)整體組中,IL1B基因rs16944位點(diǎn)AA基因型攜帶者相對(duì)AG、GG基因型攜帶者抗抑郁即治療療效較差(x2=3.931,P=0.047)。同樣在SSRI亞組也發(fā)現(xiàn)此相關(guān)性(x2=6.235,P=0.0125)。兒童期情感虐待及性虐待可使抑郁癥首發(fā)年齡提前,以兒童期情感虐待尤為顯著。兒童期創(chuàng)傷經(jīng)歷及各分項(xiàng)不同嚴(yán)重程度組間在發(fā)作次數(shù)、性別上均無顯著性差異。兒童期創(chuàng)傷經(jīng)歷及各分項(xiàng)對(duì)抑郁癥狀嚴(yán)重性及抗抑郁劑療效無顯著影響�；蚝铜h(huán)境交互分析發(fā)現(xiàn)IL1B基因rs16944位點(diǎn)AA基因型與重度兒童期創(chuàng)傷經(jīng)歷/情感虐待的相互作用與較差的抗抑郁劑療效相關(guān)(r=0.189, P=0.043; r=0.158, P=0.026)。結(jié)論在本研究中兒童期創(chuàng)傷經(jīng)歷可能不是影響抗抑郁劑療效的獨(dú)立因素,但兒童期創(chuàng)傷尤其是情感虐待可能是抑郁癥首發(fā)年齡提前的關(guān)鍵因素；IL1B基因rs16944位點(diǎn)多態(tài)性及其與兒童期創(chuàng)傷經(jīng)歷相互作用可能影響抑郁患者臨床療效。
[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.

【學(xué)位授予單位】：東南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R749.4

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