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Study on Psychosocial Factors and the Gene Polymorphisms of TPH2、5-HTTLPR、MAOA of Impulsive Behavior in Children Suffered with ODD and ADHD

Author: WangChangHong
Tutor: SuLinYan
School: Central South University
Course: Psychiatry and Mental Health
Keywords: Child Impulsive behavior The BIS- 11 Reliability Validity Psychological and social factors Logestic regression analysis TPH2 MAOA-uVNTR 5-HTTLPR
CLC: R749.94
Type: PhD thesis
Year: 2007
Downloads: 345
Quote: 1
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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.

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