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

M. van Winkel*, F. Peeters, R. van Winkel, G. Kenis, D. Collip, N. Geschwind, N. Jacobs, C. Derom, E. Thiery, J. van Os, I. Myin-Germeys, M. Wichers

*Corresponding author for this work

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A previous study reported that social stress sensitivity is moderated by the brain-derived-neurotrophic-factorVal66Met (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 BDNFVal66Met 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 BDNFVal66Met compared to "Val/Val" carriers. Positive emotions neutralized the moderating effect of BDNFVal66Met 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.
Original languageEnglish
Pages (from-to)930-938
Number of pages9
JournalEuropean Neuropsychopharmacology
Issue number6
Early online date18 Feb 2014
Publication statusPublished - Jun 2014


  • BDNF genotype
  • Gene-environment interaction
  • Stress sensitivity
  • Experience sampling method (ESM)
  • Positive emotions
  • Major depressive disorder (MDD)
  • RISK
  • TWIN

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