Impact of variation in the BDNF gene on social stress sensitivity and the buffering impact of positive emotions: Replication and extension of a gene–environment interaction

Abstract

A previous study reported that social stress sensitivity is moderated by the brain-derived-neurotrophic-factor(Val66Met) (BDNF rs6265) genotype. Additionally, positive emotions partially neutralize this moderating effect. The current study aimed to: (i) replicate in a new independent sample of subjects with residual depressive symptoms the moderating effect of BDNF(Val66Met) genotype on social stress sensitivity, (ii) replicate the neutralizing impact of positive emotions, (iii) extend these analyses to other variations in the BDNF gene in the new independent sample and the original sample of non-depressed individuals. Previous findings were replicated in an experience sampling method (ESM) study. Negative Affect (NA) responses to social stress were stronger in "Val/Met" carriers of BDNF(Val66Met) compared to "Val/Val" carriers. Positive emotions neutralized the moderating effect of BDNF(Val66Met) genotype on social stress sensitivity in a dose-response fashion. Finally, two of four additional BDNF SNPs (rs11030101, rs2049046) showed similar moderating effects on social stress-sensitivity across both samples. The neutralizing effect of positive emotions on the moderating effects of these two additional SNPs was found in one sample. In conclusion, ESM has important advantages in gene-environment (GxE) research and may attribute to more consistent findings in future GxE research. This study shows how the impact of BDNF genetic variation on depressive symptoms may be explained by its impact on subtle daily life responses to social stress. Further, it shows that the generation of positive affect (PA) can buffer social stress sensitivity and partially undo the genetic susceptibility.

BDNF ValMet polymorphism tunes frontolimbic circuitry during affective contextual learning

“…Because of the role of the vMPFC in cognitive and affective processes (Montag et al 2008; Mühlberger et al 2014; van Winkel et al 2014) as well as in BDNF-dependent extinction learning in preclinical and human studies (Chhatwal et al 2006; Soliman et al 2010; Milad & Quirk 2012; Park & Poo 2013), we performed post-hoc ROI analyses on this region in order to assess effects of interest across the various experimental questions addressed here. A bilateral vMPFC ROI based on Milad & Quirk’s 2012 vMPFC human analog of the infralimbic cortex was drawn using the anatomical ROI toolbox, ITK SNAP (see insert in Fig.…”

“…In line with these findings, in both transgenic mice and healthy humans, impairments in fear extinction learning and altered amygdala-vMPFC function has been demonstrated in BDNF Met carriers, relative to BDNF Val homozygotes (Soliman et al 2010). Additionally, the BDNF Val 66 Met polymorphism is involved in neural responses to visual observation of positive and negative emotional stimuli in humans (Montag et al 2008; van Winkel et al 2014). However, the role of this genotype in the neural mediation of socially relevant higher-order aversive and reward-related learning is not well defined in humans, despite the fact that such learning is proximate to the maintenance of well-being by means of the adaptive capacity to flexibly adapt to both threatening and favorable contexts in our modern, socially-complex environment.…”

Daily life stress reactivity in remitted versus non-remitted depressed individuals

“…Further, in favour of a pre-morbid vulnerability, there is emerging evidence that increased NA-reactivity to social stress is indicative of a genetic predisposition to respond with more NA to small social stressors and may function as an intermediate endophenotype of MDD [43,42,29,27]. More specifically, specific variations of the BDNF gene, Met carriers of the BDNF Val66Met genotype, are associated with a higher NAreactivity to social stress [43,42]. This is in line with evidence that sensitivity to perceived social stress is an important vulnerability factor in teenagers that develop depression at a later stage [39].…”

Population difference in the association of BDNF promoter methylation with mild cognitive impairment in the Xinjiang Uygur and Han populations

“…BDNF level has been linked to healthy lifestyle factors (Chan et al, 2008). In addition, serum BDNF levels and environmental pressure are also closely related (Chen et al, 2013;van Winkel et al, 2014). Our results showed that BDNF promoter methylation in the Xinjiang Han elderly is significantly higher than in the Ningbo Han elderly.…”