Wang Meiping

The Interaction between rs6295 Polymorphism in the 5-HTR1A Gene and Parenting Behavior on Early Adolescents’ Depression: The Verification of Differential Susceptability Model

The extant findings showed 5-HTR1 A gene rs6295 polymorphism was associated with depression. However, most of them were mainly guided by the diathesis and stress model and typically focused on the interaction between risk alleles and adverse environments. According to the differential susceptibility model, the individuals exclusively affected by negative contexts can also respond more favorably to positive environments, but the positive environments interacting with the same genes have scarcely been investigated. It also remains unclear whether there is a moderating effect of gender on the way rs6295 polymorphism interacting with environments. This study aimed to test the hypothesis of differential susceptibility model by examining the interaction of rs6295 polymorphism with positive and negative parenting behavior on early adolescent depression, and explore the mediating effect of adolescents gender. Participants(n = 1323) were a subset of a 4-year longitudinal study(n = 2715) which investigated 14 primary schools in Jinan by random cluster sampling method. During the initial assessment(in 2008), adolescents(grade 5) were on average 11.31 years old(SD = 0.49), and mothers ranged in age from 35 to 40 years(M = 38.03, SD = 2.39). Adolescents depression were identified via self-rating on the Childrens Depression Inventory(2008: ? = 0.88; 2011: ? = 0.89), and parenting behavior were rated by mother-report questionnaire(positive: ? = 0.85; negative: ? = 0.72). DNA was extracted from saliva. Genotype at rs6295 was performed in real time with Mass ARRAY RT software version 3.0.0.4 and analyzed using the Mass ARRAY Typer software version 3.4(Sequenom). A series of linear regression analyses were conducted by SPSS 18.0. The results showed rs6295 polymorphism significantly interacted with positive parenting behaviors in predicting early adolescents depression, and furthermore this interaction was moderated by adolescents gender. Specifically, among female early adolescents, those with CC genotype reported lower levels of depression than their counterparts with G allele(including CG and GG genotypes) when they were experiencing higher levels of positive parenting behavior, but such effect was not observed among the female adolescents who were exposure to lower levels of positive parenting behaviors. The above mentioned interaction between rs6295 polymorphismand positive parenting behaviors was not obtained among male early adolescents. The results also showed that there existed no significant interaction between rs6295 polymorphism and negative parenting behaviors on depression among both male and female early adolescents. The main effect of 5-HTR1 A gene rs6295 polymorphism on depression was not found either. Taken together, the findings of the present study indicated that the CC genotype in the rs6295 locus, which was regarded as the risk genotype in some previous studies, could respond more favorably to positive parenting behavior among female early adolescents. This lends partial support for the viewpoint of the newly-developed differential susceptibility model, and contributes to 5-HTR1 A gene-depression literature by elaborating the moderating effect of gender and parenting behavior among early adolescents. Future research should add the clinical sample, which can enlarge the variation of the parenting behavior, and the indexes of the distal environmental factors to further examine the interaction between rs6295 polymorphism and environmental influences on adolescent depression.以＂不同易感性模型＂为理论基础,1323名青少年为被试（初次测评时M=11.31岁;SD=0.49）,考察了5-HTR1A基因rs6295多态性与父母教养行为对青少年早期抑郁的交互作用及其性别差异。结果表明：当父母积极教养行为水平较高时,携带CC基因型的女青少年抑郁水平显著低于G等位基因携带者,当父母积极教养行为水平较低时,携带不同基因型的女青少年的抑郁水平无显著差异,但rs6295多态性与父母教养行为对男青少年的抑郁无显著交互作用。此外,rs6295多态性对男女青少年早期抑郁均无显著主效应。研究结果提示,rs6295多态性与父母教养行为对青少年早期抑郁的交互作用部分支持不同易感性模型观点,且存在性别差异,主要表现于女青少年群体中。本研究发现能够为基因-环境交互作用设计研究提供一定启示,同时亦能推进有关抑郁发生机制的研究。

Interaction between COMT Gene rs6267 Polymorphism and Maternal Parenting Behavior on Adolescents' Physical and Relational Aggression

The influencing factors and underlying mechanisms of aggressive behavior are important fundamental issues in research on human aggression. With the advancement of molecular genetics, the research on the mechanisms of aggression has reached molecular level in recent years. Recent studies using candidate gene strategy have demonstrated that the COMT(catechol-O-methyltransferase) gene was significantly associated with human aggression. However, existing research mainly focused on physical aggression, while the genetics mechanism of relational aggression has scarcely been investigated. To our knowledge, only two studies examined the genetic underpinnings of the two specific subtypes of aggression by examining the direct associations between COMT gene Val158 Met polymorphism and both physical and relational aggression, but these studies failed to investigate the gene-environment interaction. Recent research has revealed a new functionally single nucleotide polymorphism rs6267 in the COMT gene which also plays an important role in individuals development, but its possible interaction with environment on aggressive behavior remains unclear. The present study aimed to extend the previous research by examining the association between COMT gene rs6267 polymorphism and both physical and relational aggression among Chinese children and adolescents, with a particular focus on the possible moderating effects of maternal parenting behavior and gender on the association.One thousand two hundred and fifty eight children(male = 649) from 40 classes of 14 primary schools in Jinan City were followed from grade 4 till to grade 7. The subjects physical and relational aggression were obtained through peer rating, and the maternal parenting behavior was measured by mother report. DNA was extracted from saliva. In detail, genotype at rs6267 polymorphism in the COMT gene was performed for each participant in real time with MassARRAY RT software version 3.0.0.4 and analyzed using the MassARRAY Typer software version 3.4(Sequenom). Pearson correlation and hierarchical regression analyses were conducted to examine the effect of rs6267 polymorphism and maternal parenting behavior on adolescent aggression. The main findings of the present study were as follows: Rs6267 polymorphism in the COMT gene significantly interacted with maternal parenting behavior in predicting adolescent physical aggression, but this interaction was observed only among males, such that maternal warmth negatively predicted male adolescent physical aggression among carriers of GG homozygote but not T allele. Similarly, maternal rejection and punishment only positively predicted male adolescent physical aggression among carriers of GG homozygote but not T allele. However, the interaction between rs6267 polymorphism in the COMT gene and maternal parenting behavior on adolescent relational aggression was not significant. The findings of the present study indicate that gene-environment interactions on adolescents aggression may vary across physical and relational aggression and across gender, and thereby provide additional support for the dichotomy of these two subtypes of aggression. Besides, by elaborating the moderating effect of maternal parenting behavior and gender, the present study enriches the literature of the relation between COMT gene and aggression.