<p id="C2">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 (<italic>COMT</italic>) gene Val158Met polymorphism might be an important candidate gene of depression. Some researches have also investigated the moderating effect of <italic>COMT</italic> 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 <italic>COMT</italic> 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 <italic>COMT</italic> gene Val158Met polymorphism and parenting behavior on the association between negative life events and early adolescent depression, and its possible gender differences. <br/><p id="C60">In this study, 637 adolescents (<italic>M</italic><sub>age </sub>= 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. <br/><p id="C61">The results showed that negative life events significantly positively predicted early adolescent depression. Moreover, negative life events, <italic>COMT</italic> 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 <italic>COMT</italic> 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. <br/><p id="C62">Overall, our results suggested that the effects of negative life events on early adolescent depression were moderated by <italic>COMT</italic> 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.
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