Abstract:

The extant findings showed 5-HTR1A 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 Children’s Depression Inventory (2008: a = 0.88; 2011: a = 0.89), and parenting behavior were rated by mother-report questionnaire (positive: a = 0.85; negative: a = 0.72). DNA was extracted from saliva. Genotype at rs6295 was performed in real time with MassARRAY RT software version 3.0.0.4 and analyzed using the MassARRAY 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 polymorphism and 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-HTR1A 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-HTR1A 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.

Key words: 5-HTR1A gene, rs6295 polymorphism, depression, parenting behavior, differential susceptibility model