本文選題：心理應(yīng)激 + 社會(huì)環(huán)境　； 參考：《新疆醫(yī)科大學(xué)》2012年博士論文

【摘要】：目的：研究不同程度的應(yīng)激對(duì)心理健康的影響。系統(tǒng)的闡述心理應(yīng)激過(guò)程，影響心理應(yīng)激的社會(huì)（環(huán)境）因素以及遺傳因素，結(jié)合結(jié)構(gòu)方程模型（SEM）以及遺傳流行病學(xué)的統(tǒng)計(jì)方法（多因子降維法）綜合分析心理應(yīng)激的影響因素以及與候選基因多態(tài)性的關(guān)聯(lián)，包括社會(huì)（環(huán)境）因素與基因的交互作用以及基因與基因的交互作用，全面揭示心理應(yīng)激的作用機(jī)制。方法：1）以新疆野外作業(yè)石油工人為例，利用癥狀自評(píng)量表、社會(huì)支持量表、人格特征量表、職業(yè)倦怠問(wèn)卷、職業(yè)緊張問(wèn)卷結(jié)合結(jié)構(gòu)方程模型探討影響輕度心理應(yīng)激的社會(huì)（環(huán)境）因素，以及各因素間的相互作用；2）以交通事故導(dǎo)致創(chuàng)傷人群為例探討中度心理應(yīng)激及過(guò)程，利用PCL-C量表及臨床表現(xiàn)篩查創(chuàng)傷后應(yīng)激障礙陽(yáng)性癥狀患者，基于結(jié)構(gòu)方程模型分析影響中度心理應(yīng)激反應(yīng)的社會(huì)（環(huán)境）因素與遺傳易感性的交互作用；3）基于病例對(duì)照研究利用問(wèn)卷調(diào)查和實(shí)驗(yàn)室方法結(jié)合Logistic回歸、MDR分析影響重度心理應(yīng)激的社會(huì)（環(huán)境）因素與基因交互作用以及基因－基因交互作用。結(jié)果：1）野外石油工人SCL-90量表得分與全國(guó)常模比較，敵對(duì)因子和偏執(zhí)因子得分與全國(guó)常模比較差異無(wú)統(tǒng)計(jì)學(xué)意義，除人際敏感外，其他各因子得分均高于全國(guó)常模，且P＜0.05。與新疆地區(qū)部分漢族職業(yè)人群SCL-90常模比較石油工人抑郁因子得分（1.63±0.54）、精神病性因子得分（1.48±0.44）均高于職業(yè)人群常模得分，分別為：（1.57±0.61）、（1.41±0.50），P均＜0.05；2）多因素Logistic回歸分析發(fā)現(xiàn)影響輕度心理應(yīng)激的因素為：心理緊張反應(yīng)（PSY）、自我保�。⊿C）、神經(jīng)質(zhì)（N）、精神質(zhì)（P）、支持利用度以及情感耗竭；3）利用SEM建立影響輕度心理應(yīng)激的多因素模型，結(jié)果表明模型擬和符合理論，擬和優(yōu)度指數(shù)較好（RMSEA＝0.048，NFI＝0.949，GFI＝0.906）。各個(gè)觀測(cè)指標(biāo)和潛變量之間的因子載荷較高，且具有統(tǒng)計(jì)學(xué)意義；4）以PCL-C得分分值38分為臨界值，PTSD陽(yáng)性篩查率為15%（25人發(fā)生）；25例創(chuàng)傷后應(yīng)激障礙患者分?jǐn)?shù)在38～52分之間，20例集中在38～46之間；5）創(chuàng)傷初期精神健康狀況（SCL-90）與創(chuàng)傷后應(yīng)激障礙的總分以及各癥狀得分均存在著顯著正相關(guān)，提示創(chuàng)傷初期心理健康水平可以預(yù)測(cè)后期PTSD的發(fā)生；人格特征因素神經(jīng)質(zhì)（N）和精神質(zhì)（P）與創(chuàng)傷后應(yīng)激障礙總得分、各癥狀得分具有正相關(guān)，社會(huì)支持總分與PTSD總分呈負(fù)相關(guān)；6）影響中度心理應(yīng)激的多元線性回歸分析，結(jié)果表明強(qiáng)迫癥狀、精神質(zhì)（P）、主觀支持、人際關(guān)系敏感、內(nèi)外向（E）等因素進(jìn)入回歸方程，5個(gè)變量解釋PTSD陽(yáng)性發(fā)生程度變異的65.0%，估計(jì)值的標(biāo)準(zhǔn)誤為4.758；7）利用SNP-SHOT方法共檢測(cè)了4個(gè)基因：糖皮質(zhì)激素受體（GCCR）基因、多巴胺D2受體（DRD2）基因、五羥色胺轉(zhuǎn)運(yùn)體（SLC6A4）基因、CRHR1（促腎上腺皮質(zhì)釋放激素受體-1）基因的10個(gè)tag SNPs位點(diǎn)的多態(tài)性，其中GCCR基因的rs6189位點(diǎn)沒(méi)有突變，故未將其列入后期數(shù)據(jù)分析。其他9個(gè)SNPs位點(diǎn)經(jīng)X2檢驗(yàn)，基因型及等位基因頻率均分布符合Hardy-Weinberg平衡定律，各P值均大于0.05，表明其基因頻率已達(dá)到遺傳平衡有群體代表性；8）影響中度心理應(yīng)激反應(yīng)遺傳易感因素分析：①GCCR基因：rs258747突變純合子GG基因型在闖入/重復(fù)體驗(yàn)癥狀得分高于雜合子AG型和野生純合子AA型。rs10482605位點(diǎn)，血漿皮質(zhì)醇水平突變雜合子AG型高于野生純合子AA型；rs41423247位點(diǎn)血漿皮質(zhì)醇水平突變純合子GG型高于突變雜合子GC型和野生純合子CC型。rs258747可能是一個(gè)具有重要生物學(xué)功能的SNP位點(diǎn)，應(yīng)進(jìn)一步結(jié)合臨床病例證實(shí)G等位基因的個(gè)體在受到創(chuàng)傷性事件后發(fā)展成PTSD的危險(xiǎn)性相對(duì)較高，對(duì)PTSD可能是一個(gè)易感因子，可作為PTSD相關(guān)疾病易感性的一個(gè)重要指標(biāo)。②DRD2基因：rs1800497位點(diǎn)突變純合子AA型在闖入/重復(fù)體驗(yàn)癥狀上的得分高于雜合子GA型和野生純合子GG型得分。DRD2受體濃度的測(cè)定發(fā)現(xiàn)rs1800497突變純合子的濃度高于雜合子和野生純合子的濃度。rs6275位點(diǎn)攜帶突變純合子AA基因型的創(chuàng)傷患者在支持利用度方面得分低于雜合子GA基因型和野生純合子GG型。rs1076560位點(diǎn)攜帶雜合子AC基因型在主觀支持上的得分低于野生純合子CC基因型。rs1800497位點(diǎn)攜帶突變純合子AA基因型支持利用度低于野生純合子GG基因型。③SLC6A4基因：rs1042173位點(diǎn)突變純合子AA基因型在警覺(jué)因子上的得分高于雜合子AC型和野生純合子CC基因型。rs242948位點(diǎn)突變純合子GG基因型的創(chuàng)傷患者血漿多巴胺D2受體濃度高于雜合子GT基因型個(gè)體和野生純合子TT基因型個(gè)體；9）利用結(jié)構(gòu)方程模型對(duì)基因與社會(huì)（環(huán)境）相互作用對(duì)PTSD陽(yáng)性癥狀影響進(jìn)行模型擬和，通過(guò)對(duì)模型擬和發(fā)現(xiàn)，在增加了遺傳易感因素后整體模型擬和更好（與第一部分圖1-1比較，RMSEA＝0.041，NFI＝0.951，GFI＝0.914）大多數(shù)指標(biāo)的因子荷載提高；10）LES總分比較顯示，應(yīng)激障礙組得分高于對(duì)照組，應(yīng)激障礙組的負(fù)性生活事件高于對(duì)照組，差異有統(tǒng)計(jì)學(xué)意義，P＜0.05，OR＝9.650；社會(huì)支持總分、主觀支持、支持利用度在應(yīng)激障礙組和對(duì)照組間具有差異，P＜0.05，OR分別＝0.035，0.027，0.025；消極應(yīng)對(duì)方式在應(yīng)激障礙組和對(duì)照組之間得分有差別，差別具有統(tǒng)計(jì)學(xué)意義，OR＝1.014；應(yīng)激精神障礙組和對(duì)照組人格特征進(jìn)行T檢驗(yàn)發(fā)現(xiàn)，兩組在P（精神質(zhì)）量表的得分差異顯著，應(yīng)激障礙組得分高于對(duì)照組，進(jìn)一步進(jìn)行趨勢(shì)卡方檢驗(yàn)發(fā)現(xiàn)隨著P量表得分增加，OR值顯著增加，P的T分大于60分，OR＝8.741；11）影響應(yīng)激精神障礙的遺傳因素分析：①GCCR基因上的rs10482605位點(diǎn)和rs258747與應(yīng)激精神障礙有關(guān)聯(lián)（P＜0.05）。rs10482605位點(diǎn)攜帶有G突變型等位基因是應(yīng)激精神障礙的危險(xiǎn)因素（OR＝1.431，，95%CI＝1.186～1.999）；rs258747位點(diǎn)攜帶有G突變型等位基因是應(yīng)激精神障礙的危險(xiǎn)因素（OR＝1.781，95%CI＝1.567～2.0782）；由3個(gè)位點(diǎn)組成的2個(gè)單倍體型（AGC和AGG）與應(yīng)激精神障礙的發(fā)生有關(guān)聯(lián)（P＜0.05）。OR分別＝1.468，1.419。②DRD2基因：應(yīng)激障礙組rs1800497位點(diǎn)突變純合子AA基因型和雜合子GA基因型基因頻率高于對(duì)照組，OR＝1.434，1.766，并且攜帶有A突變型等位基因是應(yīng)激精神障礙的危險(xiǎn)因素（OR＝1.211，95%CI＝0.890～1.647）；由3個(gè)位點(diǎn)組成的1個(gè)單倍體型（GAA）與應(yīng)激精神障礙的發(fā)生有關(guān)聯(lián)（P＜0.05）。OR分別＝1.233。③SLC6A4基因2個(gè)位點(diǎn)、CRHR1基因1個(gè)位點(diǎn)，其基因頻率和等位基因頻率在應(yīng)激障礙組和對(duì)照組間無(wú)差異（P＞0.05）；12）通過(guò)MDR軟件分析后，選擇了由5個(gè)位點(diǎn)組成的交互模型作為最佳基因-基因交互模型來(lái)說(shuō)明基因交互作用對(duì)應(yīng)激精神障礙的影響。該5個(gè)位點(diǎn)組成的交互模型其具有最大的檢測(cè)準(zhǔn)確度（67.48）和最大的交叉驗(yàn)證一致性（CV＝10/10），此最佳的基因-基因交互模型由rs10482605，rs258747，rs242948，rs1800497和rs4142324五個(gè)多態(tài)性位點(diǎn)組成；13）應(yīng)激精神障礙的基因環(huán)境交互作用顯示：顯示GCCR基因的rs258747位點(diǎn)與N（神經(jīng)質(zhì)）有交互作用，OR＝3.304；rs41423247與主觀支持有交互作用OR＝0.269；DRD2基因的rs1076560位點(diǎn)與消極應(yīng)對(duì)方式有交互作用，OR＝2.320；rs1800497位點(diǎn)與主觀支持有交互作用，OR＝0.397。結(jié)論：1）影響輕度心理應(yīng)激的社會(huì)環(huán)境因素有心理緊張反應(yīng)（PSY），自我保�。⊿C），神經(jīng)質(zhì)（N）精神質(zhì)（P）、支持利用度。預(yù)測(cè)總符合率為62.70%；2）輕度心理應(yīng)激模型擬和較好，SEM量化了社會(huì)環(huán)境因素對(duì)心理應(yīng)激的影響，職業(yè)任務(wù)、個(gè)體緊張反應(yīng)、社會(huì)支持、人格特征對(duì)心理應(yīng)激的影響分別為：0.165、0.139、0.077、0.189；3）創(chuàng)傷初期的精神健康狀況（SCL-90）與PTSD癥狀嚴(yán)重程度成正相關(guān)，具有神經(jīng)質(zhì)和精神質(zhì)人格特征的人群更易患PTSD，社會(huì)支持是其保護(hù)性因素；4）影響中度心理應(yīng)激的社會(huì)環(huán)境因素有強(qiáng)迫癥狀、精神質(zhì)（P）、主觀支持、人際關(guān)系敏感、內(nèi)外向，預(yù)測(cè)總符合率為65.0%；5）GCCR基因rs258747位點(diǎn)以及DRD2基因rs1800497位點(diǎn)是2個(gè)具有重要生物學(xué)功能的SNP位點(diǎn)，可作為PTSD相關(guān)疾病易感性的重要TagSnp；6）SEM構(gòu)建的社會(huì)環(huán)境與遺傳交互作用模型擬和較好，大多數(shù)指標(biāo)的因子荷載提高。血漿皮質(zhì)醇和多巴胺D2受體濃度與精神狀況（SCL-90）和PTSD的發(fā)生以及癥狀嚴(yán)重程度具有相關(guān)性，路徑系數(shù)分別為0.09和0.21，且對(duì)PTSD的預(yù)測(cè)能力較大；7）過(guò)強(qiáng)的負(fù)性生活事件刺激可使患應(yīng)激精神障礙的風(fēng)險(xiǎn)增大9倍；社會(huì)支持總分、主觀支持、支持利用度使患應(yīng)激精神障礙的風(fēng)險(xiǎn)分別降低73%，75%，65%具有精神質(zhì)傾向的人格可以增加應(yīng)激精神障礙的患病風(fēng)險(xiǎn)；8）病例對(duì)照研究GCCR基因上的rs10482605和rs258747位點(diǎn)以及DRD2基因rs1800497位點(diǎn)與應(yīng)激精神障礙有關(guān)聯(lián)；9）最佳的基因-基因互模型由rs10482605，rs258747，rs242948，rs1800497和rs4142324多態(tài)性位點(diǎn)組成。
[Abstract]:Objective: To study the influence of different degrees of stress on mental health. The systematic exposition of psychological stress process, social (environmental) factors and genetic factors affecting psychological stress, combined with structural equation model (SEM) and the statistical method of genetic epidemiology (multi factor reduction method) to analyze the influencing factors of psychological stress and their candidates. The association of genetic polymorphisms, including the interaction of social (environmental) factors and genes, and the interaction of genes and genes, comprehensively reveals the mechanism of psychological stress. Method: 1) taking the field working oil workers in Xinjiang as an example, using the symptom checklist, social support scale, personality scale, job burnout questionnaire, occupational stress. The questionnaire combined with the structural equation model to explore the social (environmental) factors affecting mild psychological stress and the interaction among the factors. 2) to explore the moderate psychological stress and process by the traffic accident caused by the trauma crowd, and to screen the patients with positive symptoms of post traumatic stress disorder using the PCL-C scale and clinical manifestation, based on the structural equation model. Analysis of the interaction between social (environmental) factors and genetic susceptibility to moderate psychological stress; 3) a case-control study, based on a combination of questionnaires and laboratory methods, combined with Logistic regression, and MDR analysis of social (environmental) factors and gene interaction and gene gene interaction in severe psychological stress. Results: 1 Compared with the national norm, the scores of the SCL-90 scale of the field oil workers and the national norm were not statistically significant compared with the national norm. Except for interpersonal sensitivity, the scores of all the other factors were higher than the national norm, and the scores of P < 0.05. and the SCL-90 norm of the Han ethnic group in Xinjiang were compared with the depression factor scores of the oil workers. (1.63 + 0.54), the scores of psychosis factors (1.48 + 0.44) were higher than those of the occupational group, respectively: (1.57 + 0.61), (1.41 + 0.50), P < 0.05; 2.) multiple factor Logistic regression analysis found that the factors affecting mild psychological stress were psychological stress reaction (PSY), self health care (SC), neuroticism (P), support utilization, and support utilization. Emotional exhaustion; 3) using SEM to establish a multi factor model that affects mild psychological stress. The results show that the model is fit for the theory, and the pseudo sum index is better (RMSEA = 0.048, NFI = 0.949, GFI = 0.906). The factor load between the observed and the latent variables is higher and has statistical significance; 4) is divided into the critical value of the PCL-C score score of 38 as the critical point. The positive screening rate of PTSD was 15% (25 people), 25 patients with posttraumatic stress disorder were between 38~52, 20 and 38~46; 5) there were significant positive correlations between the mental health status (SCL-90) and the total score of posttraumatic stress disorder and the scores of all the symptoms, suggesting that the mental health level in the early stage of trauma could be found. The occurrence of PTSD in the later period was predicted; the personality factors neuroticism (N) and mental quality (P) were positively correlated with the total score of posttraumatic stress disorder, the score of each symptom, the total score of social support and the total score of PTSD were negatively correlated; 6) multiple linear regression analysis of moderate psychological stress showed that the symptoms of compulsion, mental quality (P), subjective support and interpersonal relationship were the result. Sensitive, internal and external (E) and other factors entered the regression equation, 5 variables explained 65% of the PTSD positive occurrence variation, the estimated value was 4.758; 7) 4 genes were detected by the SNP-SHOT method: the glucocorticoid receptor (GCCR) gene, the dopamine D2 receptor (DRD2) gene, the five serotonin transporter (SLC6A4) gene, and the CRHR1 (suprarenal). The polymorphism of the 10 tag SNPs loci of the adenocorticocorticosteroid receptor -1 gene, in which the rs6189 site of the GCCR gene is not mutated, is not included in the late data analysis. The other 9 SNPs loci are tested by X2, and the distribution of genotype and alleles conforms to the law of Hardy-Weinberg balance, and the P values are more than 0.05, indicating the frequency of their genes. Genetic balance has a population representation; 8) analysis of genetic susceptibility factors affecting moderate psychological stress: (1) GCCR gene: rs258747 mutant homozygous GG genotypes are higher than heterozygote AG and wild homozygote AA.Rs10482605 locus, and plasma cortisol level mutation heterozygote AG type is higher than wild Homozygous AA type; rs41423247 site plasma cortisol level mutation homozygous GG higher than mutant heterozygote GC and Nobu Juriko CC.Rs258747 may be an important biological function of SNP locus, which should be further combined with the risk of developing PTSD after a traumatic event in individuals with a clinically proven G allele. Relatively high, it may be a susceptible factor to PTSD, and can be an important indicator of susceptibility to PTSD related diseases. (2) DRD2 gene: the score of rs1800497 site mutant homozygous AA in intruding / repeated experience symptoms is higher than that of heterozygote GA and the determination of.DRD2 receptor concentration in the wild homozygote GG type score of.DRD2, and the discovery of rs1800497 mutation homozygosity The concentration of the child was higher than the heterozygote and the Nobu Juriko concentration.Rs6275 site carrying the mutant homozygote AA genotype. The score of the trauma patients in the support utilization was lower than the heterozygote GA genotype and the wild homozygote GG type.Rs1076560 locus carrying the heterozygote AC genotypes in subjective support lower than the wild homozygote CC genotype.Rs18. The 00497 loci carrying mutant homozygote AA genotype was lower than the wild homozygote GG genotype. (3) SLC6A4 gene: rs1042173 locus mutation homozygous AA genotypes were higher than heterozygote AC and wild homozygous CC genotype.Rs242948 site mutated homozygous GG genotyping of dopamine D2 The receptor concentration is higher than the heterozygote GT genotype individual and the wild homozygote TT genotype individual; 9) using the structural equation model to model the effect of the gene and social (environment) interaction on the PTSD positive symptoms, the whole model of the genetic predisposing factor is proposed and better (with the first part of figure 1-1). Comparison, RMSEA = 0.041, NFI = 0.951, GFI = 0.914) the factor load of most indexes increased; 10) LES total score comparison showed that the score of stress disorder group was higher than that of the control group, the negative life events in the stress disorder group were higher than the control group, the difference was statistically significant, P < 0.05, OR = 9.650; social support total score, subjective support, support utilization in should There was a difference between the irritable and the control groups, P < 0.05, OR = 0.035,0.027,0.025, and the scores of the negative coping styles between the stress disorder group and the control group were different, the difference was statistically significant, OR = 1.014; the personality characteristics of the stress mental disorder group and the control group were detected by T, and the difference between the two groups in the P (psychotic) scale was different. Significantly, the score of the stress disorder group was higher than that of the control group. Further trend chi square test found that with the increase of the P scale, the OR value increased significantly, the T score of P was greater than 60, OR = 8.741; 11) the genetic factors affecting stress mental disorders were analyzed: (1) the rs10482605 sites and rs258747 on GCCR gene were associated with stress mental disorders (P < 0.05).R. The s10482605 locus with G mutational allele was a risk factor for stress disorder (OR = 1.431,95%CI = 1.186 ~ 1.999); the rs258747 locus with G mutational allele was a risk factor for stress disorder (OR = 1.781,95%CI = 1.567 ~ 2.0782), and 2 haplotypes (AGC and AGG) and stress sperm consisting of 3 loci. The occurrence of deity disorders was associated with (P < 0.05).OR = 1.468,1.419. 2 DRD2 gene: the frequencies of the homozygous AA genotypes and heterozygote GA genotypes in the rs1800497 site of the stress disorder group were higher than those of the control group, OR = 1.434,1.766, and the A mutant allele was a risk factor for stress disorder (OR = 1.211,95%CI = 0.890) To 1.647), 1 haplotypes (GAA) composed of 3 loci were associated with the occurrence of stress mental disorders (P < 0.05).OR = 2 loci of 1.233. (SLC6A4) gene and 1 loci of the CRHR1 gene, and the frequency and allele frequency of the allele were no difference between the stress disorder group and the control group (P > 0.05); 12) selected by MDR software analysis. The interaction model composed of 5 loci was used as the best gene gene interaction model to illustrate the effect of gene interaction on psychotic disorders. The interactive model of the 5 loci has the maximum detection accuracy (67.48) and the largest cross validation conformance (CV = 10/10), and the best gene gene interaction model is rs10482605 Five polymorphic loci of rs258747, rs242948, rs1800497 and rs4142324; 13) the genetic environmental interaction of stress disorder showed that the rs258747 locus of the GCCR gene had interaction with N (neuroticism), OR = 3.304; rs41423247 and the subjective support were interacting with OR = 0.269, rs1076560 sites and negative responses of DRD2 genes. Interaction, OR = 2.320; rs1800497 locus and subjective support interaction, OR = 0.397. conclusion: 1) social environmental factors affecting mild psychological stress (PSY), self health care (SC), neuroticism (P), support utilization, predictive total coincidence rate of 62.70%; 2) mild psychological stress model and Better, SEM quantified the influence of social environmental factors on psychological stress. Occupational tasks, individual stress reactions, social support, and personality characteristics were respectively the effects of 0.165,0.139,0.077,0.189; 3) mental health status (SCL-90) in the early stage of trauma was positively related to the severity of PTSD symptoms, with neuroticism and psychotic personality traits. The social support is a protective factor for PTSD, and social support is a protective factor. 4) social environmental factors affecting moderate psychological stress include compulsive symptoms, mental quality (P), subjective support, interpersonal sensitivity, internal and external, and the total coincidence rate is 65%; 5) the rs258747 locus of GCCR gene and the rs1800497 locus of DRD2 gene are of important biological merits. The SNP locus can be used as an important TagSnp for susceptibility to PTSD related diseases; 6) the social environment and genetic interaction model constructed by SEM is well planned and better, and the factor load of most indicators is improved. The concentration of plasma cortisol and dopamine D2 receptor is related to the occurrence of SCL-90 and PTSD and the severity of the symptoms, and the path is related. The coefficients were 0.09 and 0.21 respectively, and the predictive ability of PTSD was greater; 7) too strong negative life event stimulation could increase the risk of stress mental disorder by 9 times; social support total score, subjective support, support utilization to reduce the risk of stress mental disorder by 73%, 75%, 65% with psychotic personality can increase stress essence. The risk of deity disorders; 8) the rs10482605 and rs258747 loci in the case-control study GCCR gene and the rs1800497 locus of the DRD2 gene were associated with stress mental disorders; 9) the best gene gene cross model was composed of rs10482605, rs258747, rs242948, rs1800497 and rs4142324 polymorphisms.
【學(xué)位授予單位】：新疆醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類號(hào)】：R395

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