Genetic Heterogeneity in Adolescents’ Depressive Symptoms in Response to Victimization

Abstract

Objective This study had two objectives: first, to determine the degree to which experiences of victimization by peers during adolescence led to a subsequent rise in depressive symptoms; second, to identify genetic markers that predict depressive reactivity to victimization. Method We used a cohort sequential design to obtain a longitudinal sample of 1,475 adolescents (3,263 observations) in grades 8 to 12 (56% female; 47% Black, 46% White). Multilevel growth curve models were used to assess whether victimization predicted depressive symptoms six months later, beyond baseline trajectories for depressive symptoms. We modeled the interactive effects of peer victimization with three genetic polymorphisms (on 5-HTTLPR, DRD2 TaqIA, and BDNF Val66Met) on depressive symptoms. Results While victimization predicted subsequent depressive symptoms, there was substantial heterogeneity in the magnitude of the effect of victimization. Val alleles, associated with higher brain-derived neurotrophic factor (BDNF) functioning, predicted more sensitivity to victimization. Neither DRD2 TaqIA, a marker associated with dopaminergic functioning, nor 5-HTTLPR, a marker associated with serotonin activity, was associated with sensitivity to victimization. Conclusions The social stress of peer victimization triggers depressive symptoms most strongly in individuals who are homozygous for the Val allele on the BDNF Val/Met polymorphism. This polymorphism has been linked with sensitivity to social defeat in animal models. Future research should explore behavioral, cognitive, and emotional explanations of the effects of BDNF Val/Met on responsivity to victimization.

The BDNF Val66Met Polymorphism Interacts with Maternal Parenting Influencing Adolescent Depressive Symptoms: Evidence of Differential Susceptibility Model

“…Notably, though, a study of Chinese adolescents found that it was Val-BDNF carriers who proved most susceptible to depressive symptoms in the face of stressful life events (Chen et al 2012). Such results would seem to be in line with work with Mexican adolescents (12-17 years) showing BDNF Val/Val homozygotes to be most at risk of depression when facing cumulative psychosocial adversities (Cruz-Fuentes et al 2014), and with U.S. adolescents indicating that Val-BDNF carriers manifested the most depressive symptoms when victimized by their peers (Gottfredson et al 2014). Collectively, the work just cited points to potential developmental, cultural, and ethnic variation in how the BDNF Val66Met polymorphism interacts with the environment in predicting depression.…”

“…We focused on adolescence because most previous G 9 E studies focused on depression were of adults, with earlier reviewed research suggesting that the interaction between BDNF gene and environment may vary across development (e.g., Casey et al 2009;Lenroot and Giedd 2011). Our findings, together with prior adolescent studies (Chen et al 2012;Cruz-Fuentes et al 2014;Gottfredson et al 2014), support the propostion that BDNF Val66Met 9 Environment might vary between adolescents and adults. Specifically, the Val version of BDNF appears to confer heightened susceptibility to environmental influences in the case of youth, whereas the Met version of BDNF operates in this manner with regard to depression and adversity in the case of adults (see meta-analysis in Hosang et al 2014).…”

Social defeat stress induces depression-like behavior and alters spine morphology in the hippocampus of adolescent male C57BL/6 mice

“…To gain insight into the neural mechanisms associated with the negative impact of adolescent bullying and the expression of depression-related symptomatology, we used the social defeat stress model of depression (Gottfredson et al., 2015, Kudryavtseva et al., 1991). We selected this preclinical behavioral approach because it can mimic some of the negative emotional and physical aspects of bullying (Bjorkqvist, 2001), resulting in depression-related behavior (Krishnan et al., 2007, Yu et al., 2011).…”

Harsh Parenting and Serotonin Transporter and BDNF Val66Met Polymorphisms as Predictors of Adolescent Depressive Symptoms

“…A recent meta-analysis shows that the BDNF Val66Met polymorphism serves as a moderator of the life stress-depression association; individuals with the Met allele, in the presence of environmental risk, have higher rates of depression (Hosang, Shiles, Tansey, McGuffin, & Uher, 2014). Similar to adult research, the BDNF Val66Met has been found to interact with environmental stressors in the prediction of adolescent depressive symptoms; however, the particular allele (Val versus Met) associated with conferring greater risk varies across different investigations during adolescence (Carver, Johnson, Joormann, LeMoult, & Cuccaro, 2011; Chen, Li, McGue, 2012; 2013; Gottfredson, Foshee, Ennett, Haberstick, & Smolen, 2015). It has been posited that which allele of the BDNF Val66Met polymorphism that is associated with poorer phenotype outcomes may vary as a function of development (Casey et al, 2009).…”