The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress

Psychoneuroendocrinology. 2010 Jul;35(6):949-53. doi: 10.1016/j.psyneuen.2009.12.008. Epub 2010 Jan 15.


Background: Growing evidence suggests that individual differences in HPA-axis reactivity to psychosocial stress are partly due to heritable influences. However, knowledge about the role of specific genetic variants remains very limited to date. Since brain-derived neurotrophic factor (BDNF) not only exhibits neurotrophic actions but is also involved in the regulation of hypothalamic neuropeptides, we investigated the role of a common functional polymorphism within the BDNF gene (BDNF Val66Met) in the context of endocrine and cardiovascular stress reactivity.

Methods: Healthy male adults (N=100) were genotyped and exposed to a standardized laboratory stress task (Public Speaking). Saliva cortisol and self-reported mood levels were obtained at 6 time points prior to the stressor and during an extended recovery period. Furthermore, heart rate reactivity as an indicator of sympathetic activation was monitored continuously during the experimental procedure.

Results: We report a small, but significant effect of the BDNF Val66Met polymorphism on stress reactivity. More precisely, carriers of the met-allele showed a significantly attenuated HPA-axis and cardiovascular reactivity to the psychosocial stressor compared to subjects with the val/val genotype. Furthermore, the diminished physiological response in met-allele carriers was also attended by significantly lower self-reported ratings of perceived stress and nervousness.

Conclusion: Our findings of a diminished endocrine and cardiovascular stress response in healthy male adults is consistent with a previously published study and adds further evidence for a crucial role of the BDNF Val66Met polymorphism in the modulation of stress reactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affect / physiology
  • Alleles
  • Brain-Derived Neurotrophic Factor / genetics*
  • Genotype
  • Heart Rate / physiology
  • Humans
  • Hydrocortisone / metabolism
  • Hypothalamo-Hypophyseal System / metabolism*
  • Male
  • Pituitary-Adrenal System / metabolism*
  • Polymorphism, Genetic*
  • Saliva / metabolism
  • Stress, Psychological / genetics*
  • Stress, Psychological / physiopathology


  • Brain-Derived Neurotrophic Factor
  • Hydrocortisone