Study On Genetic Susceptibility, Environmental Factors And The Interactions Of Adolescent Aggression

Section 1 The prevalence and risk factors of adolescent aggression among Chinese rural areasObjectives: Our aim was to understand the prevalence and main influencing factors of adolescent aggression among Chinese rural areas and then to provide evidence for the prevention of adolescent aggression.Methods: A total of 8455 students in grade 4-6 from 26 primary schools in 15 rural areas among Anhui,Guangdong,Yunnan,Heilongjiang,Hubei provinces were recruited to complete the psychological behavioral survey using multistage stratified cluster sampling.Aggression was assessed by Buss-Warren's Aggression Questionnaire.The crude total scores were converted to T scores,and participants with ?56T scores were classified as high aggression group,according to the interpretation of BWAQ.Demographic characteristics,history of childhood maltreatment,loneliness,life stress events,resilience,social support were measured by a structured self-reported questionnaire.The t test and Pearson ?2 test were used to compare differences among two groups when it was appropriate.Univariate and multivariate logistic regression models were used to examine the risk factors of adolescent aggression.Structured equation models were used to explore the mediator effects of resilience on the association between life stress events and aggression.Results: 1.Boys were 4472(52.9%)and girls were 3983(47.1%)among total 8455 participants.The total prevalence of aggression was 29.0% and statistically significant gender differences were observed(P<0.05).Boys(32.5%)were more aggressive than girls(25.0%).2.The total scores of aggression were 68.61±16.85.Boys scored higher in total aggression,five subscales of aggression,loneliness,life stress events than girls.Furthermore,boys were more likely to experience neglect,physical abuse(mild,moderate,severe)than girls.However,girls scored higher in resilience and social support than boys.All the differences were statistically significant(P<0.05).3.The results of multivariate logistic aggression showed that girls were less likely to have aggressive behavior than boys(OR: 0.84;95%CI: 0.76-0.94).Students from grandparent family were more likely to have aggressive behavior than those from nuclear family(OR: 1.29;95%CI: 1.03-1.62).Students whose mothers' education level was college or above were more likely to have aggressive behavior(OR: 1.47;95%CI: 1.15-1.88)than those whose mothers' education level was less than primary school.The high level of loneliness were the risk factor of aggression(OR:6.61,95%CI: 5.51-7.94).The experience of neglect,mild physical abuse,moderate physical abuse and severe physical abuse were also negative risk factors for aggression(OR: 1.41,95%CI: 1.22-1.62;OR: 1.19,95%CI: 1.05-1.35;OR: 1.31,95%CI: 1.15-1.49;OR: 1.36,95%CI: 1.15-1.60,respectively).However,the high level of resilience and social support were the protective factor of aggression(OR: 0.79,95%CI: 0.64-0.98;OR: 0.70,95%CI: 0.59-0.84,respectively).4.The results of structured equation models showed that life stress events had a total effect on aggression(0.529)and a direct effect on aggression(0.505).And resilience partially mediates the association between life stress events and aggression(P<0.001).Conclusions: Living in grandparent family,college or above degree of mothers' education,the high level of loneliness and life stress events,experience of neglect,mild physical abuse,moderate physical abuse,severe physical abuse were risk factors of adolescent aggression among Chinese rural areas.However,female,the high level of resilience and social support were the protective factors of adolescent aggression.Section 2: Associations between OXTR,CRHBP,BDNF,and CREB1 genetic variations and adolescent aggressionObjectives: Our aim was to investigate the associations between OXTR,CRHBP,BDNF,and CREB1 genetic variations and adolescent aggression and to investigate the interaction between genes and the cumulative effect of risk genotypes on adolescent aggression.Methods: A total of 976 participants including 488 cases and 488 controls were selected in our present study using a 1:1 case-control study design.Cases were selected from Juvenile reformatory in Hubei province.Those who were prisoned for violent crime and whose total scores ?56T were selected as aggression group.At the same time,participants with ? 55 T scores in the control group were volunteers from high schools and universities among Hubei province.Buccal cells of all participants were collected for extracting DNA.Genotyping was performed using SNPscan.Multivariate logistic regression models were used to examine the association between OXTR,CRHBP,BDNF,and CREB1 genetic variation and adolescent aggression.The classification and regression tree were used to examine the interaction effectors between gene and gene.And the cumulative effectors of risk genotypes on adolescent aggression were also investigated.Results: 1.OXTRrs237885,CRHBPrs32897,CRHBPrs10062369,BDNFrs7940188,BDNFrs1519480,and CREB1rs4675690 polymorphisms were found to have statistically significant effects on adolescent aggression after adjusting for age.Participants who carried OXTRrs237885 TT genotypes were 1.31 times as likely as those who carried OXTRrs237885GT/GG genotypes to have aggressive behavior(OR:1.31,95%CI:1.02-1.69).Participants who carried CRHBPrs32897 CC genotypes had a lower risk for aggression compared with those who carried CRHBPrs32897CT/TT genotypes(OR:0.47,95%CI: 0.25-0.86).Participants who carried CRHBPrs10062367AG/GG genotypes had a higher risk for aggression compared with those who carried CRHBPrs10062367 AA genotypes(OR:2.15,95%CI:1.00-4.61).Participants who carried BDNFrs7940188 GG genotypes had a lower risk for aggression compared with those who carried BDNFrs7940188GC/CC genotypes(OR:0.70,95%CI:0.53-0.91).Participants who carried BDNFrs1519480 TT genotypes had a lower risk for aggression compared with those who carried BDNFrs1519480CT/CC genotypes(OR:0.73,95%CI:0.57-0.95).Participants who carried CREB1rs4675690CT/TT genotypes had a 0.61 times higher risk for aggression compared with those who carried CREB1rs4675690 CC genotypes(OR:1.61,95%CI:1.12-2.30).2.The results of the classification and regression tree showed that a high-order interaction existed among BDNFrs7940188,OXTRrs237885,and CREB1rs4675690.Compared with those who carried BDNFrs7940188GG-OXTRrs237885GG/GT-CREB1rs4675690 CC genotypes,participants who carried BDNFrs7940188GC/CC-CREB1rs4675690CT/TT genotypes were more likely to have aggressive behavior(OR:3.02;95% CI:1.56-5.85).3.The accumulative effects of OXTRrs237885,CRHBPrs32897,CRHBPrs10062367,BDNFrs7940188,BDNFrs1519480,and CREB1rs4675690 polymorphisms on adolescent aggression were observed.With the increase of the number of risk genotypes,the risk of aggression increases gradually.Compared with participants who carried no more than 2 risk genotypes,participants who carried 5 risk genotypes had a 1.92 times increased risk for aggression(OR:2.92;95%CI:1.63-5.23)and participants who carried 6 risk genotypes had a 2.33 times increased risk for aggression(OR:3.33;95%CI:1.75-6.34).Conclusions: OXTRrs237885,CRHBPrs32897,CRHBPrs10062367,BDNFrs7940188,BDNFrs1519480,and CREB1rs4675690 polymorphisms may be associated with adolescent aggression.And there were significantly interaction effect between BDNFrs7940188,OXTRrs237885 and CREB1rs4675690,and adolescent aggression.Furthermore,With the increase of the number of risk genotypes,the risk of aggression increases gradually.Section 3: interactions between genetic variants and environmental factors on adolescent aggressionObjectives: Our aim was to investigate the interactions between OXTRrs237885,CRHBPrs32897,CRHBPrs10062367,BDNFrs7940188,BDNFrs1519480,and CREB1rs4675690 polymorphisms and childhood physical abuse,sexual abuse,emotional abuse,physical neglect and emotional neglect on adolescent aggression.Methods: Participants in this section were the same as those in the second section.OXTRrs237885,CRHBPrs32897,CRHBPrs10062367,BDNFrs7940188,BDNFrs1519480,and CREB1rs4675690 polymorphisms were considered as genetic variants in this section.Childhood physical abuse,sexual abuse,emotional abuse,physical neglect and emotional neglect were evaluated by the corresponding scores in five subscales of childhood maltreatment questionnaire.If individual's scores in subscales exceed 5,then individuals have the corresponding type of neglect or abuse.Multivariate logistic regression models were used to estimate the multiplicative interactions between genetic variants and childhood maltreatment on adolescent aggression.And the additive interactions between genetic variants and childhood maltreatment were evaluated using specific Excel sheet made by Andersson.Results: 1.The statistically significant additive interactions between OXTRrs237885 polymorphisms and childhood physical abuse were observed(RERI:6.69,95%CI:0.41-12.96;AP:0.59,95%CI:0.33-0.84;S:2.81,95%CI:1.37-5.77).Participants who carried OXTRrs237885 TT genotypes and have experienced childhood physical abuse had a 9.42 times increased risk to have aggressive behavior compared with those who carried OXTRrs237885GT/GG genotypes and have not experienced childhood physical abuse(OR:10.42;95% CI:5.99-18.13).2.The statistically significant additive interactions between CREB1rs4675690 polymorphisms and childhood sexual abuse were observed(RERI:6.74,95%CI:0.73-12.74;AP:0.62,95%CI:0.31-0.94;S:3.18,95%CI:1.10-9.24).Participants who carried CREB1rs4675690CT/TT genotypes and have experienced childhood sexual abuse had a 9.83 times higher risk to have aggressive behavior compared with those who carried CREB1rs4675690 CC genotypes and have not experienced childhood sexual abuse(OR:10.83;95%CI:6.01-19.49).3.The statistically significant additive interactions between CREB1rs4675690 polymorphisms and childhood emotional neglect were observed(RERI:2.61,95%CI:0.67-4.54;AP:0.52,95%CI:0.24-0.81;S:2.90,95%CI:1.01-8.49).Participants who carried CREB1rs4675690CT/TT genotypes and have experienced childhood emotional neglect had a 3.98 times increased risk to have aggressive behavior compared with those who carried CREB1rs4675690 CC genotypes and have not experienced childhood emotional neglect(OR:4.98;95%CI:3.01-8.24).Statistically significant multiplicative interactions were not observed in our present study.Conclusions: This is the first study to report significant interactive effects of OXTRrs237885 polymorphism and childhood physical abuse on adolescent aggression.The significant interactive effects of CREB1rs4675690 polymorphism and childhood sexual abuse and emotional neglect on adolescent aggression were also observed in our present study.