| 1. BackgroundCompleted suicide is considered as a severe public health problem both at home and abroad. Completed suicide is defined as behavior to end one’s own lives, no matter whatever measures they have adopted. According to WHO, the incidence rate of completed suicide is16.7out of1million people, which means that one person died of suicide every40seconds and put suicide at14th place in the list of deaths in the world. For the huge population of China, it contributes large proportion of suicide to the world. In2002, Philips put forwards with suicide rate of23per1million people for China. Incidence rate of suicide in rural China is3times higher that in urban China, and90%of suicide is conservatively estimated to occur in rural areas. Attempted suicide is referred to as behavior that has been committed by oneself for suicide, with results of no death. Attempted suicide is considered as an important risk factors for completed suicide, as some meta-analysis demonstrated that the risk of attempted suicide to commit completed suicide was30to40times higher that that of ordinary population.Therefore it is obligatory to carry out study on uncompleted suicide.Some studies indicated that completed suicide depended on many factors such as hereditary factors, socio-psychological factors and so on, of which hereditary factors played a critical role. There were also studies showing that suicide was probably related to hereditary background or some specific genes.Human emotions are considered to be associated with catecholamine and dopamine. Catechol-O-methyltransferase (COMT) is both the main metabolism enzyme for catecholamine and degradation enzyme for dopamine, which plays an important role for the metabolism of this kind of neurotransmitters, therefore genes coding COMT have become the focus on the study of attempted suicide. Genes of human COMT are located in the chromosome of22q11.2, and can be cloned from cDNA completely. Substitution mutation of G to A can occur in the exon No.4of the gene, which triggers3to4times of activation changes of this enzyme. Some studies have demonstrated that gene type of GG is a risk factor for uncompleted suicide among the gene types of COMT. In our study, materials of subjects were collected from hospitals in6counties of Shandong diseases surveillance points to explore the association between COMT gene polymorphism and attempted suicide in rural China.2. Objectives2.1To indentify whether GG type of COMT gene was a risk factor for rural attempted suicide. To explore genotypes and gene frequencies of COMT in attempted suicide and corresponding controls. To analyze behavioral and psychological characteristics of attempted suicide of different genotypes. To carry out genetic epidemiology on behaviors of attempted suicide.2.2To explore the features of attempted suicide of different genotypes by method of classification tree.2.3To demonstrate the path relationship among genotypes, life satisfaction, hopelessness, depression, and attempted suicide by structural equation model (SEM).2.4To study the prevalence of attempted suicide in different population of different genotypes in the follow-up.To explore the psychological outcome of attempted suicide of different genotype and corresponding controls.3. Subjects and Methods3.1Subjects Cases of attempted suicide that committed suicide during the period of October1th,2009to March31th,2011were enrolled from6counties of Shandong diseases surveillance points, and their corresponding controls were matched by the same gender, age gap within3years and living in the same community.3.2MethodsSubjects were interviewed face to face by professional staff, by method of questionnaire, after giving written consent on this study. Strict quality control was carried out during the whole process of interview. The questionnaire was consisted of as follows:demographic factors such as age, gender, occupation, marital status, education, living lonely or not, religious belief, physical status, mental illness or not, suicidal history, negative events, domestic economy, details on the first degree relatives of subjects. Available scales were as follows:(1) SIS, Suicide Intent Scale,(2) LSI A, Life Satisfaction Index A,(3) IRLE, Interview for Recent Life Events,(4) SES,Self-Esteem Scale,(5) DSSI, Duke Social Support Index,(6) DⅡ, Dickman Impulsivity Inventory,(7) TAI, Trait Anxiety Inventory,(8) CES-D, Center for Epidemiologic Studies-Depression Scale,(9) BHS, Beck Hopelessness Scale,(10) SCID.3.3Statistical methodsAll datas were analyzed by software of SPSS16.0and Iisre18.7. Chi-square test,/-test and multivariate conditional logistic regression were selected to analyze the association between COMT genotype and attempted suicide. Penrose method was used to estimate heredity followed by Falconer method applied to estimate the effects of heritability. Method of classification tree was used to explore the features of uncompleted suicide of different genotypes. Structural equation model (SKM) was used to demonstrate the path relationship among genotypes and uncompleted suicide.4. Results4.1Reliability analysis of scales and consistency test among investigatorsCronhach’s a of all scales ranged from0.546to0.954. most of which were bigger than0.7. Paired t-test was applied to test the consistency among investigators, and no significant differences were found with all intra-group correlation coefficients above0.8004.2Risk factors of attempted suicides, behavioral and psychological characteristics among different genotypes of attempted suicideResults of univariate and multivariate analyses showed that genotype GG of COMT was related to attempted suicide. There were no significant differences of behavioral and psychological characteristics among different genotypes of attempted suicide.4.3Hereditary analysisThe attempted suicide rate was higher in the first degree relatives of attempted suicide than that in controls (22vs.6, x-=9.597, P=0.002, OR=3.67); The attempted suicide rate was also higher in the second degree relatives of attempted suicide than that in controls(7vs.4), but there was no significant difference(x2=0.954,P=:0.329); The attempted suicide rate was also higher in the first degree relatives of uncompleted suicide than that in second degree relatives (22vs.7,x2=15.520,P=0.000,OR=4.73). The Penrose estimation of genetic mode concluded that s and q were both closely approximate to1/(?).Heredity of28.8%±4.98%for the first degree relatives of uncompleted suicide was obtained by method of Falconer regression, with that of21.2%±14.84%for the second degree relative. The heredity for the first degree relatives was bigger than that for the second degree relatives. And the heredity for the first degree relatives varied according to different characteristic group.4.4Comparison of genotypes of COMT and gene frequencies between attempted suicide and their corresponding controls.Distribution of genotypes of COMT was significantly different (x2=6.376, P=0.041). but no significant differences were found on distribution of gene frequencies (x2=1.181, P=0.277). 4.5The features of attempted suicide with different genotypes.Characteristics of uncompleted suicide of genotype GG:(1) people with depression and no social supports;(2) people with depression and social supports;(3) people with no depression but negative life events;(4) people with no depression, negative life events and social supports. The risk estimation of classification tree was demonstrated as0.258with accordance rate of0.779and sensitivity of0.931, by evaluating the Gain curve and Index curve. All of the values indicated that the classification model was good. Results of10-fold cross-validation showed that the risk estimation of final model established by training samples was0.258, and the mean of risk estimations for models established by random samples was0.263, which indicated that this method was good.Characteristics of attempted suicide of genotype AA and GG:(1) people with depression and mental illness;(2) people with depression and no mental illness;(3) people with no depression but negative life events. The risk estimation of classification tree was demonstrated as0.287with accordance rate of0.740and sensitivity of0.940, by evaluating the Gain curve and Index curve. All of the values indicated that the classification model was good. Results of10-fold cross-validation showed that the risk estimation of final model established by training samples was0.287, and the mean of risk estimations for models established by random samples was0.315, which indicated that this method was good.4.6Results of structural equation model (SEM)COMT genes played an indirect role on uncompleted suicide by mediation of depression and hopelessness, and positive relations were found between COMT genes and life satisfaction.4.7Resluts of follow-upThere were significant differences in the psychology of attempted suicide among different genotypes of COMT in the follow-up.There were significant differences between psychological characteristics of uncompleted suicide and their corresponding controls. Subjects with different genotypes were followed up respectively, and the results showed that distribution of reoccurrence of attempted suicide was not statistically different between these two groups.5. Conclusions(1) Genotype GG of COMT was a risk factor for attempted suicide, and there was significant difference in the distributions between attmepted suicide and their controls.The heredity of the first degree relatives was higher than that of the second degree relatives, and it indicated that suicide had the features of familial aggregation.(2) Different features of attempted suicide were found according to different genotypes of CMOT.(3) COMT genes played an indirect role on attempted suicide by mediation of depression and hopelessness.(4) According to different genotypes of CMOT, psychology of attempted suicide recovered in the follow-up respectively, while there was still significant difference in psychology between uncompleted suicide and their controls in the follow-up. |
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