Association between BDNF Polymorphism and Hypothalamic-Pituitary-Adrenal Activity in Later Adulthood

Gerontology. 2020;66(2):131-137. doi: 10.1159/000502143. Epub 2019 Sep 5.


Stress exposure over the lifespan is robustly associated with accelerated cognitive decline in later life. Brain-derived neurotrophic factor (BDNF) is shown to regulate activity of the hypothalamic-pituitary-adrenal axis. The objective of this study was to evaluate the association betweenthe BDNF polymorphism and indices of stress among adults aged 50+. Community-dwelling middle-aged and older adults provided a blood sample for BDNF genotyping. Participants also sampled their saliva 5 times/day for 3 consecutive days for the measurement of diurnal cortisol and underwent the Trier Social Stress Test (TSST) for the measurement of stress reactivity. Among 121 adults aged 50-67 years (78% female; 89% Caucasian), 74 participants were Val/Val carriers and 47 carried 1 copy of the Met allele. Repeated-measures analyses did not reveal an association between BDNF genotype and diurnal salivary cortisol (p = 0.63); however, analyses revealed that Met+ carriers displayed lower levels of cortisol secretion in response to the TSST compared with Val/Val carriers; F(4.43, 496.238) = 2.57, p = 0.032. This is the first study to evaluate the role of the BDNF polymorphism in stress physiology among older adults. Future studies are needed to evaluate the lifespan interconnections between BDNF and stress physiology.

Keywords: Brain-derived neurotrophic factor; Diurnal cortisol; Older adults; Stress reactivity; Trier social stress test; Val66Met BDNF gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain-Derived Neurotrophic Factor / blood
  • Brain-Derived Neurotrophic Factor / genetics*
  • Female
  • Genotype
  • Humans
  • Hydrocortisone / analysis
  • Hypothalamo-Hypophyseal System / physiology*
  • Independent Living
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / physiology*
  • Polymorphism, Genetic
  • Saliva / chemistry
  • Stress, Psychological / physiopathology


  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human
  • Hydrocortisone

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