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

Mark van Winkel; Frenk Peeters; Ruud van Winkel; Gunter Kenis; Dina Collip; Nicole Geschwind; Nele Jacobs; Catherine Derom; Evert Thiery; Jim van Os; Inez Myin-Germeys; Marieke Wichers

doi:10.1016/j.euroneuro.2014.02.005

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

Eur Neuropsychopharmacol. 2014 Jun;24(6):930-8. doi: 10.1016/j.euroneuro.2014.02.005. Epub 2014 Feb 18.

Authors

Affiliations

¹ Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, PO Box 616 (DRT 10), Maastricht 6200 MD, The Netherlands; Riagg Maastricht, Parallelweg 45-47, 6221 BD, Maastricht, the Netherlands. Electronic address: mark.vanwinkel@maastrichtuniversity.nl.
² Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, PO Box 616 (DRT 10), Maastricht 6200 MD, The Netherlands.
³ Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, PO Box 616 (DRT 10), Maastricht 6200 MD, The Netherlands; University Psychiatric Centre, Catholic University Leuven, Kortenberg, Belgium.
⁴ Clinical Psychological Science, Maastricht University, The Netherlands.
⁵ Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, PO Box 616 (DRT 10), Maastricht 6200 MD, The Netherlands; Faculty of Psychology, Open University of the Netherlands, Heerlen, the Netherlands.
⁶ Centre of Human Genetics, University Hospitals Leuven, Department of Human Genetics, KU Leuven, Belgium.
⁷ Dept of Neurology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
⁸ Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, PO Box 616 (DRT 10), Maastricht 6200 MD, The Netherlands; King׳s College London, King׳s Health Partners, Department of Psychosis Studies, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.

PMID: 24613654
DOI: 10.1016/j.euroneuro.2014.02.005

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.

Keywords: BDNF genotype; Experience sampling method (ESM); Gene–environment interaction; Major depressive disorder (MDD); Positive emotions; Stress sensitivity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Affect
Brain-Derived Neurotrophic Factor / genetics*
Depression / genetics*
Emotions*
Female
Gene-Environment Interaction
Genetic Predisposition to Disease
Genotype
Heterozygote
Humans
Male
Polymorphism, Single Nucleotide*
Resilience, Psychological
Social Behavior*
Stress, Psychological / genetics*

Substances

Brain-Derived Neurotrophic Factor
BDNF protein, human