The Interactive Effects of Monoamine Oxidase A (MAOA) Gene and Peer Victimization on Depressive Symptoms in Early Adolescent Boys: The Moderating Role of Catechol-O-methyltransferase (COMT) Gene
【Abstract】The monoamine oxidase A (MAOA) gene, as an important candidate gene of depressive symptoms, has been demonstrated to interact with environmental factors, especially stressful life events and family environments, in predicting adolescent depressive symptoms. Peer victimization serves as a significant source of stress particularly during early adolescence and can lead to a series of psychosocial adjustment problems that even persist long after the experience of being harassed. However, it still remains unknown about whether or not the MAOA gene interacts with peer victimization on adolescent depressive symptoms. There is evidence about the significant interaction between the catechol-O-methyltransferase (COMT) gene and the MAOA gene on depressive symptoms. However, whether or not the COMT gene plays a moderating role on the interactive effects between MAOA gene and environmental factors is still unclear. Therefore, the present study aimed to examine (i) the interaction between the MAOA T94 G polymorphism and peer victimization on adolescent depressive symptoms and (ii) the moderating role of the COMT Val158 Met polymorphism in the aforementioned associations.The original participants (1440 adolescents, male = 757, 52.6%) were drawn from an ongoing longitudinal study, which recruiting children from 40 classes of 14 primary schools in Jinan, China. Because of the uncertain X-inactivation and resulting MAOA activity among females, this study limited our analyses on the male subsample. Using a 2-year longitudinal design, we first assessed adolescent depressive symptoms and peer victimization by self-rated Children’s Depression Inventory (CDI) and Peer Victimization Scale (PVS), respectively, at Time 1 (Mage= 11.32 years, SD = 0.49). At time 2 (Mage = 12.32 years, SD = 0.48), saliva samples of adolescents were collected and genotyped for the MAOA T941 and COMT Val158 Met polymorphisms using the Mass ARRAY Typer software version 3.4 (Sequenom), and the adolescent depressive symptoms were tested again using CDI. A series of hierarchical regressions were conducted to analyze the effects of genes and peer victimization on adolescent depressive symptoms. The results showed that, after depressive symptoms at Time 1 was controlled for, the MAOA T941 G polymorphism significantly interacted with peer victimization (i.e., physical victimization and relational victimization, respectively) in predicting depressive symptoms at Time 2. Among MAOA G allele carriers, the peer victimization positively predicted depressive symptoms; however, among MAOA T allele carriers, the peer victimization was not associated with depressive symptoms. More importantly, this interaction between the MAOA gene and the peer victimization was moderated by the COMT Val158 Met polymorphism, such that the aforementioned interaction only existed among COMT Met allele carriers, but not among Val/Val homozygotes. That is, among all the combined genotypes of the MAOA and COMT genes, only G-Met genotype carriers were susceptible to peer victimization. In summary, our results demonstrated that the peer victimization also served as an important candidate environmental factor and interacted with the MAOA gene in predicting depressive symptoms during early adolescence. Of particular note, such interactive effect between the MAOA gene and peer victimization was further moderated by the COMT Val158 Met polymorphism. These findings highlight the importance of investigating the moderating role of peer victimization in the association between genes and depressive symptoms during early adolescence. More importantly, this study underscores complex polygenic underpinnings of depressive symptoms and lends support for the multi-genes by environment interactions on the etiology of depressive symptoms.
【Keywords】 MAOA gene; COMT gene; peer victimization; depressive symptoms; multi-genes by environment interaction;
. 1 Considering the nested structure in the sampling of this research, the zero-model of multilevel linear models (where no independent variables are inserted) was applied to examine the difference of adolescent depression in different classes at T1 (N = 2 199) and T2 (N = 2 157). The result showed that the intraclass correlation coefficients (icc) of the zero-model at T1 and T2 were 0.017 and 0.019, respectively. According to the multilevel correlation standards proposed by Cohen (1988), when the multilevel correlation was less than 0.059, the correlation was so small, indicating that a single-level model was likely to possess a relatively more stable standard error estimation, that the impact of the nested structure could be neglected. Thus, the subsequent data analysis applied the single-level model.
. 2 Factor synthesis method was applied to combine the educational background of parents, the employment of parents, and the monthly household income to get the social and economic family conditions (SES) score. The higher the score was, the better the SES was (Cao et al., 2016). According to the multilevel regression, after SES and depression at T1 were controlled, the interaction of the MAOA gene T941G polymorphism, the COMT gene VAL158Met polymorphism and the physical victimization still significantly estimated the adolescent depression at T2 (β = −0.24, t = −4.134, p < 0.001); only with the carriers of T941G G alleles and Val158Met Met alleles, physical victimization significantly and positively predicted adolescent depression at T2 (β = 0.21, t = 4.35, p < 0.001). Similarly, when SES and depression at T1 were controlled, the interaction of T941G, Val158Met polymorphism and relationship victimization was significant (β = −0.15, t = −2.73, p < 0.01); only the combination of T941G G alleles and Val158Met Met alleles was sensitive to relationship victimization (β = 0.19, t = 3.81, p < 0.001). This meant that when the controlled variable of SES was added, this research found that the interactive effect of G × G × E was still significant, and the significance was smaller than the threshold of multiple adjustments.
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