本文選題：重性抑郁障礙　切入點(diǎn)：糖原合成酶激酶-3β　出處：《天津醫(yī)科大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的： 重性抑郁障礙(MDD)是一種常見的慢性復(fù)發(fā)性精神疾病,嚴(yán)重的危害人類健康。近年來病因?qū)W研究證實MDD發(fā)生與遺傳、環(huán)境因素密切相關(guān),但其發(fā)病機(jī)理復(fù)雜,至今尚未完全闡明。糖原合成酶激酶-3β(GSK-3β)是調(diào)節(jié)神經(jīng)生長與神經(jīng)可塑性的重要因素,研究顯示GSK-3β在MDD的病理生理和抗抑郁作用機(jī)制上發(fā)揮重要作用。本研究旨在探討GSK-3β基因多態(tài)性與MDD發(fā)病、嚴(yán)重程度以及臨床癥狀之間的關(guān)系,分析GSK-3β基因型和生活事件交互作用對MDD發(fā)病的影響,為其病理生理機(jī)制提供新的理論依據(jù)。方法： 采用病例-對照研究方法,嚴(yán)格按照DSM-IV診斷標(biāo)準(zhǔn),選取500例MDD患者和550例與之性別、年齡相匹配的正常對照作為研究對象。選用HAMD-17評定抑郁的嚴(yán)重程度,同時采用生活事件量表(LES)對兩組的生活事件進(jìn)行評定。實驗中抽取被試外周靜脈全血,提取基因組DNA,采用限制性片段長度多態(tài)性-聚合酶鏈反應(yīng)(RFLP-PCR)技術(shù)對GSK-3β基因上的rs334558單核苷酸多態(tài)性進(jìn)行分型。運(yùn)用SPSS19.0統(tǒng)計軟件包進(jìn)行數(shù)據(jù)分析。結(jié)果： 1.GSK-3p基因rs334558位點(diǎn)基因型有CC、CT、TT三種多態(tài)性。經(jīng)擬和優(yōu)度χ2檢驗,病例組和對照組各基因型觀察值與期望值間差異均無統(tǒng)計學(xué)意義(P0.05),符合Hardy-Weinberg定律。 2.病例組和對照組GSK-3p基因rs334558位點(diǎn)基因型和等位基因分布差異均無統(tǒng)計學(xué)意義(P0.05)。按性別進(jìn)行分層,結(jié)果顯示基因型和等位基因的分布在女性中有統(tǒng)計學(xué)意義(P0.05),而在男性中差異無統(tǒng)計學(xué)意義(P0.05)。僅在女性中,CC基因型與TT基因型存在統(tǒng)計學(xué)關(guān)聯(lián)(P0.05,OR=0.528,95%CI為0.323-0.861),CC基因型是MDD發(fā)病的保護(hù)性因素；T等位基因與C等位基因之間也存在統(tǒng)計學(xué)關(guān)聯(lián)(P0.05,OR=1.363,95%CI為1.100-1.688),攜帶T等位基因患MDD的危險是C等位基因的1.363倍。 3.分析GSK-3β基因rs334558位點(diǎn)不同基因型在人口學(xué)資料包括性別、婚姻、家族史、年齡、首發(fā)年齡上的分布,差異均無統(tǒng)計學(xué)意義(P0.05)。 4.GSK-3β基因rs334558位點(diǎn)不同基因型在HAMD量表“精神性焦慮”這 -條目上的差異存在統(tǒng)計學(xué)意義(P0.05),而在其余條目及HAMD總分、遲滯因子、睡眠因子、焦慮/軀體化因子、Maier癥狀因子、核心因子的評分中差異均無統(tǒng)計學(xué)意義(P0.05)。 5.病例組LES總分高于對照組,且差異具有統(tǒng)計學(xué)意義(P0.05)。對病例組不同基因型的LES總分進(jìn)行比較,差異無統(tǒng)計學(xué)意義(P0.05)。根據(jù)HAMD總分將病例組分為輕中度抑郁組和重度抑郁組,重度抑郁組LES總分明顯高于輕中度抑郁組(P0.05)。 6.多因素Logistic回歸模型分析顯示生活事件、基因型之間不存在和MDD的發(fā)病相關(guān)的交互作用(P0.05)。 結(jié)論： 1.GSK-3β基因rs334558位點(diǎn)多態(tài)性在MDD的發(fā)生過程中可能存在性別特異性,僅在女性患者中基因型和等位基因的分布存在統(tǒng)計學(xué)差異,因此推測該基因多態(tài)性可能與中國天津地區(qū)女性人群MDD的發(fā)病有關(guān),CC基因型可能降低MDD發(fā)生的危險性,攜帶T等位基因可能增加MDD發(fā)生的危險性。 2.GSK-3β基因rs334558位點(diǎn)的基因型分布與MDD患者的性別、婚姻、家族史、年齡、首發(fā)年齡等一般資料無關(guān)。 3.GSK-3β基因rs334558位點(diǎn)基因多態(tài)性對MDD的抑郁嚴(yán)重程度、遲滯癥狀、睡眠、焦慮/軀體化癥狀、Maier癥狀、核心癥狀等均無影響,但可能與MDD的精神性焦慮癥狀有關(guān)聯(lián)。 4.生活事件可能是MDD發(fā)病的一個危險因素,MDD患者在發(fā)病前比正常對照經(jīng)歷更多的生活事件,且生活事件能夠增加MDD的嚴(yán)重程度,生活事件越嚴(yán)重,患者的抑郁程度越嚴(yán)重。 5.基因-環(huán)境交互作用的研究發(fā)現(xiàn),GSK-3β基因rs334558位點(diǎn)不同基因型和生活事件對MDD的發(fā)病可能不存在交互作用。
[Abstract]:Objective:
Major depressive disorder (MDD) is a common chronic recurrent psychiatric diseases, serious harm to human health. In recent years, the etiology study confirmed that MDD occurrence and genetic, environmental factors are closely related, but its pathogenesis is complex, has not yet been fully clarified. Glycogen synthase kinase -3 beta (GSK-3 beta) is an important factor in the regulation of nerve with the growth of neural plasticity, studies show that GSK-3 beta plays an important role in the pathophysiology of MDD and the antidepressant mechanism. This study aimed to investigate the GSK-3 gene polymorphism and the pathogenesis of MDD, as well as the relationship between the severity of clinical symptoms, analysis of the impact of GSK-3 gene type and life event interaction on the pathogenesis of MDD. To provide a new theoretical basis for its pathophysiological mechanism:
In a case-control study, in strict accordance with the diagnostic criteria of DSM-IV, a total of 500 cases of MDD patients and 550 patients with gender, age matched normal control as the research object. The severity assessment of HAMD-17 depression, and the life events scale (LES) were assessed in two groups of life events. In the experiment of extraction the subjects of peripheral venous blood, extract genomic DNA, using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) typing of single nucleotide polymorphism of rs334558 GSK-3 gene on technology. Packet data were analyzed by SPSS19.0 statistical software:
The genotype of rs334558 locus of 1.GSK-3p gene has three polymorphisms of CC, CT and TT. There was no significant difference between the observed values and the expected values of genotypes between the case group and the control group (P0.05), which was in accordance with Hardy-Weinberg law by the quasi goodness of fit 2 test.
2. in case group and control group GSK-3p rs334558 gene distribution difference of genotype and allele were not statistically significant (P0.05). Divided by sex, the results showed that the distribution of genotypes and alleles were statistically significant in women (P0.05), but there was no significant difference in men (P0.05). In women, CC and TT genotype was significantly associated (P0.05, OR=0.528,95%CI, 0.323-0.861) CC genotype is a protective factor in the pathogenesis of MDD; there is also a statistical association between T alleles and C alleles (P0.05, OR= 1.363,95%CI, 1.100-1.688) carrying dangerous T allele with MDD it is 1.363 times of the C allele.
3., there was no significant difference in the distribution of rs334558 genotype of GSK-3 beta gene in demographic data, including gender, marriage, family history, age and first age (P0.05).
The different genotypes of the 4.GSK-3 beta gene rs334558 loci are in the HAMD scale "mental anxiety"
The difference in items was statistically significant (P0.05), but there was no statistically significant difference in other items and HAMD total score, such as sluggish factor, sleep factor, anxiety / somatization factor, Maier symptom factor and core factor score (P0.05).
5. cases of group LES score higher than the control group, and the difference was statistically significant (P0.05). The cases of different genotypes of LES scores were compared, the difference was not statistically significant (P0.05). According to the HAMD scores of the patients were divided into mild to moderate depression group and severe depression group, severe depression group LES score was significantly higher than that of mild to moderate the depression group (P0.05).
6. multiple factor Logistic regression model analysis showed that there was no interaction between the genotypes and the pathogenesis of MDD (P0.05).
Conclusion:
1.GSK-3 gene rs334558 polymorphism may have gender specificity in the process of MDD, there were significant differences in the distribution only in female patients with genotype and allele, suggesting that this gene polymorphism may be associated with the incidence of female population in Tianjin area Chinese MDD, CC genotype may reduce the risk of MDD the T allele may increase the risk of MDD.
The genotype distribution of the 2.GSK-3 beta gene rs334558 loci is independent of the general data of sex, marriage, family history, age, and the first age of the MDD patients.
The rs334558 polymorphism of 3.GSK-3 beta gene has no effect on the severity of depression, delayed symptoms, sleep, anxiety / somatization symptoms, Maier symptoms and core symptoms of MDD, but it may be related to the mental anxiety symptoms of MDD.
4., life events may be a risk factor for the onset of MDD. MDD patients experience more life events before onset than normal controls, and life events can increase the severity of MDD. The more severe life events, the more severe the patients' depression is.
The study of 5. gene - environmental interaction has found that different genotypes and life events at the GSK-3 beta gene rs334558 locus may not interact with the pathogenesis of MDD.

【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R749.4

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 徐林;;抑郁癥的神經(jīng)可塑性機(jī)制[J];中南大學(xué)學(xué)報(醫(yī)學(xué)版);2008年04期

2 陽德華;大學(xué)生抑郁和人格關(guān)系初探[J];健康心理學(xué)雜志;2004年03期

3 崔春青;陳紅梅;劉翠欣;張亞紅;屈建新;于慧靜;;河北省抑郁癥的流行病學(xué)調(diào)查[J];臨床精神醫(yī)學(xué)雜志;2009年02期

4 陳明軍;于劍鋒;柴繼俠;徐理;王中平;李瑞錫;彭裕文;;Wnt通路信號蛋白β-catenin和GSK-3β在孤獨(dú)癥模型大鼠腦中表達(dá)的變化[J];神經(jīng)解剖學(xué)雜志;2009年04期

5 鄭朝盾;鄭洪波;黎娟花;何柱國;陸惠紅;黃淑儀;韋紅梅;;兒茶酚胺氧位甲基轉(zhuǎn)移酶基因多態(tài)性與抑郁癥的關(guān)聯(lián)性研究[J];實用醫(yī)學(xué)雜志;2008年03期

6 杜巧琳,王小云;抑郁癥病因研究[J];現(xiàn)代中西醫(yī)結(jié)合雜志;2003年01期

7 魏立瑩,趙介城;抑郁癥患者認(rèn)知方式與人格類型[J];中國臨床康復(fù);2003年15期

8 吳澤俊;張洪波;許娟;王君;王堅杰;;女大學(xué)生焦慮、抑郁與人格特征的相關(guān)性研究[J];中國學(xué)校衛(wèi)生;2007年03期

9 張月娟,閻克樂,王進(jìn)禮;生活事件、負(fù)性自動思維及應(yīng)對方式影響大學(xué)生抑郁的路徑分析[J];心理發(fā)展與教育;2005年01期

10 王海民,趙榮霞,閻克樂,楊玉忠;軍校學(xué)員應(yīng)付方式與抑郁、個性的相關(guān)研究[J];中國行為醫(yī)學(xué)科學(xué);2003年05期

，

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