【作者】 寇长贵；

【导师】 于雅琴；

【作者基本信息】 吉林大学 ， 医学基因组学， 2009， 博士

【摘要】 神经症是影响大学生身心健康的重要精神疾病,严重影响了大学生的学习与生活。探讨大学生神经症的环境危险因素、易感基因以及基因与环境间的交互作用,是目前精神疾病流行病学研究的重要议题。本研究将现场调查与实验室、现况调查与病例对照研究相结合探讨大学生神经症的患病情况及其遗传与环境危险因素,并基于多因素Logistic回归模型探讨COMT基因多态性与环境危险因素交互作用对大学生神经症发病的影响,是基因与环境交互作用研究的有益尝试,为神经症的病因学研究提供了重要线索,研究结果对于大学生神经症的有效防制具有重要意义。本研究采用WHO-CIDI-3.0对在校本科大学生进行一对一面对面访谈,按ICD-10的神经症性障碍诊断标准筛查大学生中神经症患者,并以现况调查所筛查到的大学生神经症患者为病例组,选择此次调查中排除神经症等精神疾病诊断的健康大学生为对照,采用PCR-LDR的方法检测两组样本COMT基因上8个tag SNPs的基因多态性,经关联分析探讨8个tag SNPs基因多态性与大学生神经症的关联;将筛查到的环境危险因素分别与检测的COMT基因8个tag SNPs多态性进行基于多因素Logistic回归模型的交互作用分析,探讨COMT基因多态性与环境因素交互作用对大学生神经症发病的影响。研究结果显示目前在校大学生神经症的终生患病率为25.61%,12个月患病率为15.74%,30天患病率为6.84%,大学生神经症的分布存在年级差异,多因素分析发现母亲的心理状况差和童年时期父母对其的照看程度不够为大学生神经症的重要危险因素;关联分析结果显示COMT基因上rs737865、rs174675、rs5993883、rs5992500、rs165656、rs2239393、rs4646316和rs165774共8个tag SNPs位点的多态性与大学生神经症无关联,提示COMT可能不是大学生神经症的主要易感基因;基因与环境交互作用分析发现rs5993883位点的多态性与母亲的心理状况存在超相乘和正相加交互作用。本研究结果提示神经症是大学生的主要心理健康问题,应积极促进大学生心理健康,有效控制大学生精神疾病的发生。对母亲心理状况不好、童年时期缺少父母照看的大学生应加大防制力度,有效防止神经症的发生或病情的进一步加重。更多还原

【Abstract】 Neuroses are a group of mental diseases which seriously affect mental and physical health of university students. To explore the environmental risk factors, susceptibility genes and the interactions between genes and environment is an important subject in epidemiological mental disease research. In this study the prevalence of neuroses and its genetics and environment risk factors were conducted in university students based on the combination of field survey with laboratory investigation and case-control study. The interactions between COMT gene polymorphism and environmental risk factors in the development of neuroses in the university students were analyzed based on the multi-factor logistic regression model. The results may provide the important clue for etiology of neuroses and will be very useful for control of neuroses in university students..ObjectiveTo investigate the prevalence and distribution of neuroses characteristatics and analyze environmental risk factors, and relationship between COMT gene polymorphism and neuroses based on case-control study and interactions between COMT gene and environmental factors on neuroses in undergraduates of a comprehensive university. The present study will provide clue for further etiology study and theoretical basis for control neuroses.Methods①We sampled 2,046 undergraduates in a comprehensive university as subjects using a proportional stratified sample method and adopted the WHO-CIDI-3.0 as tool to collect information through face-to-face interview method and meanwhile collected their saliva for laboratory research. Data entry and diagnosis of neuroses according to the ICD-10 were done with CIDI-3.0 attached software. The SPSS12.0 software was used to analyze the prevalence, population distribution characteristics and related risk factors of neuroses in undergraduates.②In case-control study, both cases and controls came from the field survey. Cases were undergraduates who had been diagnosed as neuroses through the survey and controls were those who are healthy and without any mental illness. We extracted the genomic DNA from the saliva samples and detection the polymorphism of eight tag SNPs in COMT gene using PCR-LDR method. We analyzed the relationship of polymorphism of eight tag SNPs in COMT gene and neuroses using the method of correlation analysis based on case-control study, thereby researched the association of COMT gene and neuroses in university students.③Based on②we analyzed the environmental factors obtained from field survey again and got potential environmental influenced factors. Then we studied the interactions between COMT gene polymorphism and the screening environmental influenced factors in causation of neuroses by using multi-factor Logistic regression model method.Results①There are 1,848 completed interview questionnaires in 2,046 samples and 1,843 questionnaires are eligible. The response rate is 90.32% (1,848/2,046), the qualification rate is 99.73% (1,843/1,848), and the effective response rate is 90.08% (1,843/2,046). The results show that according to the diagnostic criterion for neuroses of ICD-10 the lifetime prevalence is 25.60%, the 12-month prevalence is 15.74% and 30-day prevalence is 6.84% in 1843 undergraduates who we interviewed. Among the various clinical subtypes of neuroses, the 12-month prevalence of obsessive-compulsive disorder is the highest (9.88%), the second is specific phobia (4.94%) and the third is social phobia (2.39%). The 12-month prevalence with more than two kinds of subtypes of neuroses is 2.71%.②In male college students the lifetime prevalence rate, 12-month prevalence rate and 30-day prevalence rate of neurosis is respectively 26.25% (326/1,242), 15.70% (195/1,242) and 7.09% (88/1,242), while in female college students the lifetime prevalence rate, 12-month prevalence rate and 30-day prevalence rate of neurosis is respectively 24.29 (146/601), 15.81% (95/601) and 6.32% (38/601). The difference of three kinds of prevalence rate of neuroses in male and female students has no statistical significance (P> 0.05). In different grades the 12-month prevalence rate of neuroses is 16.88% in freshmen, 19.29% in sophomores, 11.76% in juniors and 14.67% in seniors (including the fifth year students majoring in medicine). The difference of 12-month prevalence rate of neuroses in different grades has statistically significance (x~2 = 10.648, P <0.05).③In the field survey, the results of multi-factor non-conditional logistic regression analysis show that juniors have lower risk to neuroses than freshmen (OR = 0.602), the students whose fathers having poor psychological state have 1.545 times risk of neuroses than those whose fathers having good psychological state, the students whose mothers with poor psychological state have 1.565 times risk of neuroses than those whose mothers with good psychological state, the students suffering more quarrel between their parents have 1.546 times risk of neuroses than those suffering less quarrel, and lacking of parents’ care in childhood increases risk to neuroses (OR = 1.905).④Genotype distribution of eight tag SNPs in COMT gene(rs737865, rsl74675, rs5993883, rs5992500, rsl65656, rs2239393, rs4646316 and rs165774) do not deviate from the Hardy-Weinberg equilibrium both in case group and control group (P> 0.05), The association analyses found that genotype and allele distribution had no significant difference between case and control group (P>0.05). Both genotype and allele association with clinical subtypes were tested and only tag SNP rs174675 showed association with phobia neuroses (P< 0.05). The haplotype analysis was done using UNPHASED software and showed no haplotypic association between any certain haplotype and neuroses in university students (P> 0.05).⑤The potential environmental factors mining by using multi-factor non-conditional logistic regression analysis finds that family environmental factors including mother’s poor psychological state, lacking of parents care in childhood and father’s severe restriction are risk factors of neuroses in university students. In interaction study, interaction only exists between rs5993883 polymorphism and the mother’s psychological state (P<0.05), which is super multiplicative and positive plus interaction, and there are no interactions between other tag SNPs and the three environmental risk factors of neuroses (P>0.05).Conclusions①The lifetime prevalence rate, 12-month prevalence rate and 30-day prevalence rate of neuroses is respectively 25.61%, 15.74% and 6.84% in undergraduates. Among various clinical subtypes of neuroses, the 12-month prevalence of obsessive-compulsive disorder is the highest. There is no significantly statistical difference in the three kinds of prevalence rate of neuroses between male and female students. The 12-month prevalence rate of neuroses in lower grade students is higher than that in upper grade students. All above results suggest that neuroses may influence the mental health condition of college students. We should act mental health promotion to university students and effectively control the occurrence of mental illness in university students.②The mother’s poor psychological condition and lack of parents care in childhood are important risk factors for neuroses in undergraduates, and other factors, such as father’s psychological state, quarrel between parents and father’s severe restriction, also have a certain impact on neuroses in undergraduates.③The genetic polymorphisms of eight tag SNPs in COMT gene have no association with neuroses in undergraduates and association analysis between tag SNPs and clinical subtypes finds only rs174675 shows association with phobia neuroses. All these results indicate that COMT gene is not the major susceptibility gene for neuroses but can’t be excluded micro effect on neuroses.④There is super multiplicative and positive plus interaction between rs5993883 polymorphism and the mother’s psychological state, and there are no interactions between other tag SNPs and the three environmental risk factors of neuroses.更多还原