负性生活事件与青少年早期抑郁的关系：COMT基因Val158Met多态性与父母教养行为的调节作用

Association between negative life events and early adolescents’ depression: The moderating effects of Catechol-O-methyltransferase(COMT) Gene Val158Met polymorphism and parenting behavior

采用环境×基因×环境(E×G×E)研究设计,以637名青少年为被试,考察了负性生活事件、COMT基因Val158Met多态性和父母教养行为对青少年早期抑郁的影响.结果发现:负性生活事件对青少年早期抑郁具有显著正向预测作用,且COMT基因Val158Met多态性和父亲积极教养行为在其中起调节作用,但该调节作用仅存在于男青少年群体中:在携带Val/Val基因型的男青少年中,当父亲积极教养行为水平较低时,青少年的抑郁水平随负性生活事件的增多而显著上升,当父亲积极教养行为水平较高时,负性生活事件对抑郁无显著预测作用;在携带Met等位基因的男青少年中,上述交互作用不显著.

Early adolescence is a critical period for examining the development of depression in that there is a sharp increase in the prevalence. Existing studies suggested that depression was significantly associated with negative life events. However, it is well-known that not all adolescents who experienced negative life events would become depressed. Findings from molecular genetics indicated that catechol-O-methyltransferase (COMT) gene Val158Met polymorphism might be an important candidate gene of depression. Some researches have also investigated the moderating effect of COMT gene Val158Met polymorphism on the association between negative life events and depression. However, the findings still remain inconsistent. According to developmental system theory, family factors, such as parental rearing behavior, may also play an important role on adolescent depression. However, whether and how COMT gene Val158Met polymorphism with parenting behavior moderate the association between negative life events and early adolescent depression remain unclear. Moreover, extant evidence has demonstrated that there is a significant gender difference in the interaction between gene and environment on depression. The aim of this study was to investigate the moderating role of COMT gene Val158Met polymorphism and parenting behavior on the association between negative life events and early adolescent depression, and its possible gender differences. In this study, 637 adolescents (Mage = 13.50 years, male = 344) of two middle schools in Jinan were selected as subjects. Adolescent depressive symptoms, negative life events and parenting behavior were accessed using self-rated children’s depression inventory (CDI), adolescent life events scale and parental rearing behavior questionnaire. All measures showed good reliability. DNA was extracted from saliva. Genotype at Val158Met polymorphism was performed for each participant with MassARRAY RT software version 3.0.0.4 and analyzed using the MassARRAY Typer software version 3.4 (Sequenom). A series of hierarchical regressions, internal replication analyses and meta-analyses were conducted to examine the effects of negative life events, Val158Met polymorphism and parenting behavior on adolescent depression. The results showed that negative life events significantly positively predicted early adolescent depression. Moreover, negative life events, COMT gene Val158Met polymorphism and positive paternal behavior had a significant three-way interaction on adolescent depression, which only existed in male adolescents. Specifically, for male adolescents with Val/Val genotype, positive paternal behavior played a significant moderating effect on the association between negative life events and depression. When the level of positive paternal behavior was lower, negative life events could positively predict male adolescent depression, whereas its effect was not significant when the level of positive paternal behavior was higher. Additionally, the above mentioned interaction was not observed among male adolescents with Met allele. The findings also indicated that both positive and negative maternal behaviors had marginally significant interactions with COMT gene Val158Met polymorphism and negative life events, and were also manifested only in male adolescents. In the further simple effect analysis of the three-way interactions, male adolescents with Val/Val genotype were still more sensitive to the environment. Overall, our results suggested that the effects of negative life events on early adolescent depression were moderated by COMT gene Val158Met polymorphism and parenting behavior, and there were gender differences in the moderating effect. More importantly, this study emphasizes the effects of genes and multiple environments on depression, which lends a reference for future studies on the interaction between genes and multiple environments. Besides, the findings provide important implications for the theoretical construction and intervention of adolescent depression.