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
Open accessAbstract
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.
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Positive emotions can neutralize the moderating effects of the BDNF(Val66Met) genotype on social stress sensitivity.
“Studies on the genetic mechanisms underlying stress responses show that positive emotions can neutralize the moderating effects of the BDNF(Val66Met) genotype on social stress sensitivity, indicating a potential avenue for mitigating stress through emotional regulation.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [24]
Chronic social defeat (CSD) in mice reveals that while cis-regulatory mechanisms predominantly control gene expression in the prefrontal cortex and amygdala, trans-regulatory mechanisms become more prominent in the amygdala under stress.
“Chronic social defeat (CSD) in mice reveals that while cis-regulatory mechanisms predominantly control gene expression in these brain regions, trans-regulatory mechanisms become more prominent in the amygdala under stress.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [24]
Early life stress has been significantly associated with DNA methylation levels at the 5-HTTLPR site, correlating with decreased white matter integrity in individuals with panic disorder.
“In humans, early life stress has been significantly associated with DNA methylation levels at the 5-HTTLPR site, correlating with decreased white matter integrity in individuals with panic disorder.”
From Comprehensive review of chronic stress pathways and the efficacy of behavioral stress reduction programs (BSRPs) in managing diseases. (2024) · cites this paper as [24]
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- Authors
- van Winkel, M., Peeters, F., van Winkel, R., Kenis, G., Collip, D., Geschwind, N., Jacobs, N., Derom, C., Thiery, E., van Os, J., Myin-Germeys, I., & Wichers, M.
- Affiliations
- Maastricht University (NL)
- KU Leuven (BE)
- Ghent University Hospital (BE)
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 24
- Issue
- 6
- Pages
- 930-938
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W2137313006
- Cited by
- 41
- References
- 49
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 7 · 2015: 7 · 2014: 2
- FWCI
- 3.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- European Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion)
- Lirias (submittedVersion)
- DSpace (Open University in the Netherlands) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- BDNF Val66Met polymorphism, gene-environment interaction, positive emotions, buffering effect, depressive symptoms, ecological momentary assessment, genetic susceptibility
- MeSH terms
- Adult, Affect, Depression, Emotions, Female, Genotype, Heterozygote, Humans, Male, Social Behavior, Stress, Psychological, Brain-Derived Neurotrophic Factor, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Resilience, Psychological, Gene-Environment Interaction
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