Interaction between 5-HTTLPR and BDNF Val66Met polymorphisms on HPA axis reactivity in preschoolers

Biol Psychol. 2010 Feb;83(2):93-100. doi: 10.1016/j.biopsycho.2009.10.009. Epub 2009 Nov 13.


This study examined whether the interaction between the serotonin transporter promoter region (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms was associated with hypothalamic-pituitary-adrenal (HPA) axis reactivity to stress. A community sample of 144 preschool-aged children was genotyped and exposed to stress-inducing laboratory tasks. Salivary cortisol was obtained at four time points during a standardized laboratory assessment before and after stressors involving separation from a parent and frustrating tasks. Children homozygous for the short-5-HTTLPR allele and carrying the Met-BDNF allele evidenced a significantly lower initial level of cortisol, followed by a positive increase in cortisol in response to the laboratory stressors. In contrast, children who were homozygous for the short-5-HTTLPR and the Val-BDNF alleles evidenced a greater decline in cortisol in response to the laboratory stressors. Findings indicated that the BDNF gene moderated the association between 5-HTTLPR and children's biological stress responses, suggesting that epistatic effects play a role in individual differences in stress regulation, and possibly genetic vulnerability to stress-related disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alleles
  • Brain-Derived Neurotrophic Factor / genetics*
  • Child, Preschool
  • Female
  • Humans
  • Hydrocortisone / analysis
  • Hypothalamo-Hypophyseal System / physiology*
  • Male
  • Pituitary-Adrenal System / physiology*
  • Polymorphism, Genetic / genetics*
  • Saliva / chemistry
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Stress, Physiological / genetics*
  • Surveys and Questionnaires
  • Temperament


  • Brain-Derived Neurotrophic Factor
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Hydrocortisone