【作者】 王长虹；

【导师】 苏林雁；

【作者基本信息】 中南大学 ， 精神病与精神卫生学， 2007， 博士

【摘要】 第一部分Barratt冲动量表的信效度研究目的采用Barratt冲动量表（Barratt Impulsiveness Scale，BIS）界定儿童冲动行为，对Barratt冲动量表进行信效度检验。方法BIS-11由美国学者Barratt编制，由作者翻译为中文版。采用系统抽样方法选取1200名7～12岁的学生完成BIS-11中文版的测试，使用修定后的BIS-11中文版量表进行探索性因素分析与验证性因素分析，并且用Cronbach a系数、分半信度系数和重测信度系数进行信度检验。结果1．BIS-11包括3个因素：注意力冲动性、运动冲动性和无计划冲动性。采用Lickter 4点量表记分，由1分（从不／很少）到4分（几乎总是／总是），总分在24-96分之间。2．BIS-11的Cronbach a系数为0.86，分半信度系数为0.82，重测信度系数为0.91。量表包括的3个因素共解释方差41.72％，验证性因素分析显示量表的结构效度较好，RMSEA=0.049。结论BIS-11中文版具有较好的信效度，是一种较好的儿童冲动行为测评工具。第二部分冲动行为儿童的心理社会因素对照研究目的探讨儿童冲动行为与心理社会因素的关系，为儿童冲动行为的干预提供依据。方法采用病例对照研究，对157例具有冲动行为的儿童和152例正常对照组的儿童，采用一般人口学指标、父母养育方式评价量表、Barratt冲动量表中文版、儿童气质问卷、Piers-Harris儿童自我意识量表、自尊调查量表、Conners教师问卷、家庭功能评定问卷进行评定。并对儿童冲动行为多种影响因素进行t检验、卡方检验和Binary Logestic回归分析。结果1、研究组儿童学习成绩欠佳者显著多于对照组（P=0.04）；研究组家庭关系中父母关系不良者显著多于对照组（P=0.00），且发生争执者较多（P=0.02）。2、研究组父母对孩子的情感温暖及理解分值显著低于对照组（依次P=0.01，P=0.02），父母对孩子的严厉及惩罚、否认及拒绝的分值显著高于对照组，两组差异有显著性（依次P=0.02，P=0.04，P=0.00，P=0.00）。3．研究组运动冲动性、无计划冲动性及冲动总分均比对照组严重，差异有显著性意义（依次P=0.00，P=0.00，P=0.00）；4、在气质特点方面，研究组在活动水平、预测性、反应强度、心境特征、持久性、注意分散维度分值较高，与对照组比较差异有显著性（依次P=0.00，P=0.00，P=0.00，P=0.03，P=0.01，P=0.00），研究组反应阈显著比对照组低（P=0.00）；而趋避性及适应性差异无显著性（P=0.35，P=0.06）。研究组的气质类型以麻烦型（Difficulty，D型）及中间近麻烦型（Intermediate-Difficuhy，I-D型）较多（P=0.00，P=0.00）。5、研究组在行为、焦虑、合群、幸福与满足、总分方面的评分较低，与对照组相比差异均有显著性（P=0.00）；而在智力与学校情况、躯体外貌与属性与对照组比较差异无显著性（依次P=0.15，P=0.44）。6、研究组自尊总分较低，与对照组比较差异有显著性（P=0.01）。7、研究组Conners教师问卷（Teacher Rating Scale，TRS）的3个因子分及多动指数均比对照组高，研究组在品行问题、多动、注意不集中-被动及多动指数与对照组相比差异均有显著性（依次P=0.02，P=0.00，P=0.03，P=0.00）8、研究组家庭功能（FAD）中，情感介入、行为控制和总的功能分值显著高于对照组（P=0.03，P=0.01，P=0.03）9、儿童冲动行为Binary Logestic回归分析，最终依次进入回归方程的是夫妻关系，父亲对孩子的情感温暖及理解，母亲的否认及拒绝，运动冲动性，活动水平，适应性，反应强度，反应阈，焦虑，注意不集中-被动，多动指数，问题解决和情感介入。其中夫妻关系、父亲对孩子的情感温暖及理解，母亲的否认及拒绝，运动冲动性、活动水平、适应性、反应强度、反应阈、注意不集中-被动、多动指数、问题解决、情感介入具有统计学意义（P＜0.05）。结论1、冲动行为的儿童学习成绩欠佳的较多；家庭关系中父母关系不良的较多，且易发生争执。2、冲动行为儿童具有一定的气质基础，父母不良的养育方式较多，自我意识及自尊普遍较低。3、冲动行为儿童家庭功能紊乱的较多，具有过度的情感介入及行为控制。4、儿童冲动行为与父母关系、父亲对孩子缺乏情感温暖及理解的养育方式、对新环境的适应能力、对新刺激的反应阈值、注意不集中、母亲的否认及拒绝、运动冲动性、活动水平、反应强度、多动指数、问题解决、情感介入有关。其中父母关系，父亲对孩子缺乏情感温暖及理解的养育方式、对新环境的适应能力、对新刺激的反应阈值及注意不集中均是危险因素，可增加儿童期发生冲动行为的危险。第三部分冲动行为儿童的分子生物学研究目的探讨儿童冲动行为可能的易感基因。方法采用病例对照研究的方法，对148例具有冲动行为的儿童和152例正常对照组，采用基因芯片杂交技术检测与TPH2基因功能密切关联的4个SNPs多态性位点：rs4570625、rs11178997、rs1386494和rs7305115，用RFLP技术检测两组5-HTTLPR和MAOA-uVNTR多态性，对所得基因型和等位基因频率进行关联分析，以探讨其与冲动行为的关联。结果①研究组rs4570625的基因型分布与对照组不同，基因型为纯合子T／T的显著较多，与对照组比较差异有显著性（x²=4.051，P=0.044），其OR值为1.708，即研究组儿童rs4570625基因型为纯合子T／T而产生冲动行为的危险度是对照组的1.708倍，其总体相对危险度的95％可信区间为1.012-2.884。rs11178997的基因型A／A、A／T、T／T两组间差异无显著性（依次P=0.642，P=0.257，P=0.218）。rs4570625及rs11178997的等位基因频率与对照组比较差异均无显著性（依次P=0.174，P=0.222）；②经rs4570625及rs11178997两个基因型联合风险比较显示：研究组rs4570625及rs11178997 SNPs位点TT-AT两个基因型联合风险与对照组不同，研究组的TT-AT联合显著比对照组多，两组比较差异有统计学意义（x²=4.197，P=0.040），rs4570625及rs11178997基因型为TT-AT联合形式的OR值为2.350，即研究组rs4570625及rs11178997基因型为TT-AT联合而产生冲动行为的危险度是对照组的2.350倍，其总体相对危险度的95％可信区间为1.018-5.424。其它SNPs位点两个基因型的八种联合形式的风险两组比较差异均无显著性（P均＞0.05）；③研究组rs1386494的基因型分别为AA、AG及GG，其三种基因型分布与对照组比较，差异无显著性（依次P=0.308，P=0.338，P=0.442）。研究组rs7305115的基因型亦分别为AA、AG及GG，其三种基因型分布与对照组比较，差异无显著性（P=0.291，P=0.843，P=0.201）。两组rs1386494及rs7305115等位基因频率及基因型联合风险均无统计学意义；④研究组5-HTTLPR多态性的基因型分别为LL、SS、SL、SL⁺及LL⁺，在研究组还发现了两例SL⁺⁺的特殊基因型，两组基因型比较均无统计学意义。研究组5-HTTLPR等位基因L频率显著较少，与对照组比较差异有显著性（x²=4.092，P=0.043）；⑤发现了MAOA-uVNTR的4.5R、5.5R两种新的基因型。研究组4.5／4.5基因型显著较对照组少（P=0.004）；等位基因为5R的频率显著较对照组多，与对照组比较差异有显著性（P=0.004），其OR值为1.979，即研究组儿童MAOA-uVNTR多态性的等位基因为5R而产生冲动行为的危险度是对照组的1.979倍，其总体相对危险度的95％可信区间为1.244-3.150；⑥研究组男童MAOA-uVNTR基因型为5／5较多，与对照组比较差异有显著性（P=0.006），其OR值为3.997，即研究组儿童MAOA-uVNTR多态性的等位基因为5R而产生冲动行为的危险度是对照组的3.997倍，其总体相对危险度的95％可信区间为1.400-11.405。研究组男童MAOA-uVNTR等位基因5R的频率较多，与对照组比较差异有显著性（P=0.000）。其OR值为3.991，即研究组男性儿童MAOA-uVNTR多态性的等位基因为5R而产生冲动行为的危险度是对照组的3.991倍，其总体相对危险度的95％可信区间为1.956-8.144。结论①rs4570625基因型为纯合子T／T时增加了儿童冲动行为的风险，其危险度是对照组的1.708倍。rs4570625与rs11178997基因型为TT-AT的联合可增加了儿童冲动行为的风险，其危险度是对照组的2.350倍；②冲动行为儿童5-HTTLPR等位基因L频率显著较少；③发现了MAOA-uVNTR的4.5R、5.5R两种新的基因型。冲动行为儿童4.5／4.5基因型显著较少、等位基因为5R的频率显著较多，分析认为当等位基因为5R时可增加儿童冲动行为的风险，其危险度是对照组的1.979倍；④研究组男童MAOA-uVNTR基因型为5／5较多，其发生冲动行为的危险度是对照组的3.997倍。⑤以上结果提示TPH2基因SNP多态性、5-HTTLPR和MAOA-uVNTR基因多态性与儿童冲动行为有直接和／或间接联系。更多还原

【Abstract】 PartⅠResearch of Reliability and Validity for BarrattImpulsiveness Scale （BIS-11）ObjectivesTo explore the reliability and validity of Barratt Impulsiveness Scalein order to select the children with impulsive behaviour.MethodsBarratt Impulsiveness Scale （BIS-11） was compiled by Americanscholar Barratt, it was translated into Chinese by author. 1200 studentswhich age range from 7 to 12 years old were selected by systematicsampling. All of them tested by revised Chinese BIS-11. The explosivefactor analysis and the confirmative factor analysis were made on revisedChinese BIS-11. And the reliability testing was made with Cronbach acoefficient, split-half reliability coefficient and test-retest reliabilitycoefficient.Results1. The BIS-11 include three factors, they are attentionalimpulsiveness （Iat）, motor impulsiveness （Im） and non-planningimpulsiveness （Inp）. We used the four-point variable method of Lickter todesign the scale, from 1 （never/rarely） to 4 （almost/always）, the total score is from 24 to 96.2. The Cronbach a coefficient of BIS-11’s is 0.86, the split-halfreliability coefficient is 0.82, and the test-retest reliability coefficient is0.91. The three factors of scale explained 41.72％of the variance. Theresults of confirmative factor analysis showed satisfactory constructionvalidity （RMSEA=0.067）.ConclusionsThe BIS-11 Chinese Revision is a better children impulsivenessscale which achieves satisfactory reliability and validity. PartⅡContrast Research of Social PsychologicalFactors For Impulsive ChildrenObjectivesTo explore the relationship between children impulsiveness andsocial psychological factors, in order to provide a basis for interventionof impulsiveness.Methods157 impulsive children and 152 normal children were researched bycase-control study with the demography index, the Egm Minnen avBardnosnauppforstran （EMBU）, the Barratt Impulsiveness Scale-11Chinese Revision （BIS-11CR）, Behavioral Style questionnaire （BSQ）,Piers-Harris Children’s Self-concept Scale （PHCSS）, The Self-esteemInventory （SEI）, Conners Teacher Rating Scale （TRS） and FmamilyAsessment Device （FAD）. The multiple influence factors were analysisedby t-test, x² test and Binary Logestic regression analysis.Results1. The number of poor-school record children in study group werehigher than control group （P=0.04）, and the number of children whichparents’ relationship was not good were significantly higher than incontrol group （P=0.00）, especially argument （P=0.02）.2. The scores of feeling warmness and understanding in study groupwere significantly lower than control group （P=0.01, P=0.02）. The severity, over-punishment, denial and refusal scores of study group weresignificantly higher than control group （P=0.02, P=0.04, P=0.00, P=0.00）.3. The scores of attentional impulsiveness and non-planningimpulsiveness and the total scores in study group were significantlyhigher than control group （P=0.00, P=0.00, P=0.00）.4. On the temperament characteristic, the activity level,predictability and rhythmicity, intensity of reaction, feature of mood,persistency, attention-dispersal scores of study group were significantlyhigher than control group （P=0.00, P=0.00, P=0.00, P=0.03, P=0.01, P=0.00）. The score of threshold of reaction in study group wassignificantly lower than control group （P=0.00）. There were nosignificant differences in approach-withdrawal and adaptability scoresbetween study group and control group （P=0.35, P=0.06）. Mostchildren’s temperament in study group were Difficulty （D） andIntermediate-Difficulty （I-D） type, and there were significant differencesbetween study group and control group （P=0.00, P=0.00）.5. The scores of behavior, anxiety, gregariousness, happiness andsatisfaction and total scores in study group were significantly lower thancontrol group （P=0.00）. There were no significant differences in thescores of intelligence and school situation, body and appearance betweenstudy group and control group （P=0.15, P=0.44）. 6. The total scores of self-esteem in study group were significantlylower than control group （P=0.01）.7. The scores of Teacher Rating Scale’ s three factors which includeconduct, hyperactivity, impaired concentration and passive as well ashyperactivity index in study group were significantly higher than controlgroup（P=0.02, P=0.00, P=0.03, P=0.00）.8. On the FAD, the scores of affective involvement, behaviorcontrol and general functioning in study group were significantly higherthan control group （P=0.03, P=0.01, P=0.03）.9. The children impulsiveness were analyzed by Binary Logesticregression analysis, whom entered the regression equation arerelationship of husband and wife, father’s feeling warmness andunderstanding, mother’s denial and refusal, motor impulsiveness, activitylevel, adaptability, intensity of reaction, threshold of reaction, anxiety,impaired concentration and passive, hyperactivity index, problem solvingand affective involvement. In addition to anxiety, the other factors hadstatistical significance （P＜0.05）.Conclusions1. Most impulsiveness children had poor-school record, and theirparents’ relationship were not good, especially argument.2. Impulsiveness children had temperament basis. They had lowerself-awareness and self-esteem than normal and their parents had harmful parental rearing patterns.3. The family of impulsiveness children were more dysfunction thannormal, and they had excessivly affective involvement and behaviorcontrol.4. Impulsiveness was related to some factors which include children’parents relationship, father’s lack of feeling warmness and understanding,adaptability for new surroundings, threshold of reaction for newstimulation, impaired concentration, mother’s denial and refusal, motorimpulsiveness, activity level, intensity of reaction, hyperactivity index,problem solving, affective involvement. Among which, parentsrelationship, father’s lack of feeling warmness and understanding,adaptability for new surroundings, threshold of reaction for newstimulation and impaired concentration were dangerous factors, theycontributed to children impulsiveness. PartⅢMolecular-biollgical study on childrenimpulsive behaviourObjectivesTo detect the potential predisposing genes of children who sufferedfrom impulsive behaviour.Methods148 impulsiveness children and 152 healthy control subjects werestudied by the approach of case control. Gene chip hybridizationtechnique were performed to detect polymorphic sites of 4 singlenucleotide polymorphisms （SNPs）: rs4570625、rs11178997、rs1386494and rs7305115, which was associated with TPH-2 gene. To detect thepolymorphism of two sets 5-HTTLPR and MAOA-uVNTR withrestriction fragment length polymorphism technology （RFLP）, and thenthe genotype and allele frequency were analyzed by association analysisin order to detect the association of impulsive behaviour and predisposinggenes.Results①There is difference in genotype distribution of rs4570625,that thegenotype is homozygote T/T is much higher in the investigated group.Compared with the control group, there is a signifcantdifference（x²=4.051, P=0.044）, the OR is 1.708.That is, in the investigatedgroup, the risk of suffering from impulsive behaviour is 1.708 times than the control group when the genotype of rs4570625 is homozygote T/T,the popular relative risk’s 95％confidence interval is 1.012-2.884. In thetwo groups, there is no difference in genotype A/A,A/T,T/T ofrs11178997（by turns P=0.642, P=0.257, P=0.218）.Also there is nodifference in the allele frequency of rs4570625 and rs11178997 in the twogroups（by turns P=0.174,P=0.222）.②Through risky comparison of the combination of the twogenotypes in rs4570625 and rs11178997, it shows: compared with thecontrol group, there is a difference in the locus TT-AT combination ofrs4570625 and rs11178997 in the investigated group, the TT-ATcombination of the investigated group is significantly higher than thecontrol group, there is statistic significance in the two groups’comparison（x²=4.197, P=0.040）, the OR is 2.350 in the genotype TT-ATcombinations of rs4570625 and rs11178997. That is, in the investigatedgroup, because of the genotype TT-AT combinations of rs4570625 andrs11178997, the risk suffering from impulsive behaviour is 2.350 timesthan the control group, the popular relative risk’s 95％confidence intervalis 1.018-5.424.There is no difference in the eight combination forms ofthe two genotypes in other SNPs locus in the two groups（all P＞0.05）.③In the investigated group, the genotype of rs1386494 isrespectively AA, AG and GG, the distribution of the three genotypes hasno signifecance compared with the control group（by turns P=0.308, P=0.338, P=0.442）. Also the genotype of rs7305115 is AA, AG and GG,there is no significance compared with the control group（by turnsP=0.291, P=0.843, P=0.201）. The allele frequency and genotypecombination risk of the two rs1386494 and rs7305115 in the two groupsalso have no statistical significance.④In the investigated group, the genotype of 5-HTTLPRpolymorphism is respectively LL,SS,SL,SL⁺ and LL⁺, we also discoveredtwo samples whose genotype was special SL⁺⁺, there is no statisticalsignificance in the comparison of genotype in the two groups. Thefrequency of 5-HTTLPR allelomorphic gene L is significantly lower inthe investigated group, compared with the control group, there is asignificant difference（x²=4.092, P=0.043）.⑤We also discovered two new genotypes 4.5R and 5.5R inMAOA-uVNTR. In the investigated group, the genotype 4.5/4.5 issignificantly lower compared with the control group（P=0.004）;Thefrequency of allele 5R is significantly higher in the investigated group,there is a statistical significance in the two groups（P=0.004）,the OR is1.979. That is, in the investigated group, the risk is 1.979 times than thecontrol group in children whose allelomorphic gene of MAOA-uVNTRpolymorphism is 5R may suffer from impulsive behaviour, the popularrelative risk’s 95％confidence interval is 1.244-3.150.⑥In the boys of the investigated group, the genotype 5/5 of MAOA-uVNTR is much higher, there is a statistical significance in thetwo groups（P=0.006）,the OR is 3.997.That is, the risk is 3.997 times thanthe control group in children whose allelomorphic gene ofMAOA-uVNTR polymorphism is 5R may suffer from impulsivebehaviour, the popular relative risk’s 95％confidence interval is1.400-11.405. In the boys of investigated group, the frequency ofallelomorphic gene 5R of MAOA-uVNTR is much higher, there is astatistical significance in the two groups（P=0.000）, the OR is 3.991That is, the risk is 3.991 times than the control group in children whoseallelomorphic gene of MAOA-uVNTR polymorphism is 5R may sufferfrom impulsive behaviour, the popular relative risk’s 95％confidenceinterval is 1.956-8.144.Conclusions①That the genotype of rs4570625 is homozygote T/T added therisk of impulsive behaviour in children, and the risk is 1.708 times thanthe control group; It may also add the risk when the genotype ofrs4570625 and rs11178997 is a combination of TT-AT.②The frequency of 5-HTTLPR allelomorphic gene L issignificantly lower in children who suffered from impulsive behaviour.③We discovered two new genotypes of MAOA-uVNTR:4.5R and5.5R.The 4.5/4.5 genotype is significantly lower in children who sufferedfrom impulsive behaviour, while the frequency of allele 5R is much higher. We consider it adds the risk of impulsive behaviour when thegenotype is 5R.,the risk 1.979 times over the control group.④In the boys of the investigated group, it is much higher whengenotype of MAOA-uVNTR is 5/5,the risk is 3.997 times than the controlgroup.⑤The upper results indicate there is a direct and/or indirectassociation about SNP polymorphism of TPH2,5HTTLPR, MAOA-uVNTR and children’s impulsive behaviour.更多还原