Interacting effect of BDNF Val66Met polymorphism and stressful life events on adolescent depression

Abstract

There is a strong etiological link between brainderived neurotrophic factor and depression, but the neurocellular mechanisms and gene-environment interactions remain obscure. This study investigated whether one functional polymorphism in the brain-derived neurotrophic factor gene (BDNF Val66Met) modulates the influence of stressful life events on adolescent depressive symptoms. A total of 780 pairs of ethnic Han Chinese adolescent twins, 11-17 years of age, were randomly assigned to one of two subgroups (twin1 and twin2). All subjects were genotyped as Val/Val, Val/Met or Met/Met, and assessed for depressive symptoms using the Children's Depression Inventory. The level of environmental stress was estimated by the frequency of stressful life events using the Life Events Checklist. The frequency of stressful life events was significantly correlated with depressive symptoms (twin1: β = 0.21, P = 0.01; twin2: β = 0.27, P < 0.01), but there was no significant main effect of the BDNF Val66Met genotype on depressive symptoms. In both subgroups, however, the interaction between the BDNF Val66Met genotype and stressful life event frequency was significant (twin1: β = 0.19, P = 0.01; twin2: β = 0.15, P = 0.04); individuals with one or two Val alleles demonstrated a greater susceptibility to both the detrimental effects of higher stress and the beneficial effects of lower stress compared to the Met/Met genotype. These findings support the 'differential-susceptibility' hypothesis, whereby the BDNF Val allele modulates the influence of environmental stress on depression by enhancing the neuroplastic response to all life events.

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

“…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).…”

“…It should be noted that the G 9 E work presented herein focused on parenting extends prior research on the current sample that examined the G 9 E interaction of BDNF Val66Met and stressful life events in predicting adolescent depression (Chen et al 2012). Because the environmental parameter used in that earlier report was likely related to the parenting predictors used in the current inquiry, the parenting measures used here were residualized (i.e., statistically adjusted) for stressful life events.…”

“…We examined whether and how BDNF Val66Met polymorphism interacted with both negative and positive maternal parenting in predicting adolescent depressive symptoms, while evaluating which of two theoretical G 9 E models (differential susceptibility or diathesisstress) fit the data better. Recall that we sought to extend prior depression-related, G 9 E research on this sample that proved consistent with the differential-susceptibility model when using stressful life events as the environmental predictor (Chen et al 2012). Recall, too, that to distinguish the putative influence of parenting in the current inquiry from that of life events evaluated in the prior research, we adjusted the measures of parenting for their association with life events.…”

“…A meta-analysis of G 9 E studies of mostly even if not exclusively adult participants revealed that it was Met-BDNF carriers who were most prone to depression in the face of life stress (Hosang et al 2014). 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).…”

“…Each item in the checklist was scored ''1'' if the target adolescent indicated a specific event had occurred and ''0'' if the event had not occurred during the past 12 months. The number of events reported were summed; for purposes of this report, scores ranged from 0 (no SLE) to 6 or more, as done in Chen et al (2012).…”