BDNF Val66Met genotype and neuroticism predict life stress: A longitudinal study from childhood to adulthood

Eur Neuropsychopharmacol. 2016 Mar;26(3):562-9. doi: 10.1016/j.euroneuro.2015.12.029. Epub 2015 Dec 19.


The brain-derived neurotrophic factor gene (BDNF) Val66Met polymorphism and life stress have been associated with negative emotionality (e.g., neuroticism), but relevant evidence is far from unequivocal. Possible confounding factors include the type and timing of stressful events measured, such as childhood adversity vs. recent stressful events, and variable gene × environment interactions. The aim of this study was to longitudinally assess the BDNF Val66Met polymorphism and environment interaction effect on neuroticism in a population representative sample, depending upon the type of stress, gender and family relations. In the original older cohort of the Estonian Children Personality Behavior and Health Study (ECPBHS, n=593), neuroticism was measured at age 15 (parental assessment), 18 and 25 (self-assessments). Childhood stress was reported at age 15, quality of family relations was measured at age 18, and recent stressful life events at age 25. The BDNF Val66Met polymorphism interacted with recent stressful life events, but not with childhood adversities, to impact neuroticism. Interestingly, in female participants, neuroticism at age 18 predicted future stressful life events dependent upon genotype: individuals with Val/Val genotype and high neuroticism experienced higher, but Met-allele carriers with high neuroticism lower stress exposure at age 25. Similar tendencies were observed using parental assessments at age 15. The protective effect of Met-allele in the high stress exposure group could result from better early family environment. In conclusion, we herewith provide further evidence for a role of BDNF gene variance contributing to plasticity in response to environmental demands.

Keywords: BDNF genotype; Development; Gender; Gene–environment Interaction; Neuroticism; Stressful events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Analysis of Variance
  • Anxiety Disorders / genetics*
  • Anxiety Disorders / psychology*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Child
  • Family Relations
  • Female
  • Gene-Environment Interaction*
  • Genotype
  • Humans
  • Life Change Events
  • Longitudinal Studies
  • Male
  • Methionine / genetics
  • Neuroticism
  • Personality Inventory
  • Polymorphism, Genetic / genetics*
  • Stress, Psychological / complications*
  • Valine / genetics
  • Young Adult


  • Brain-Derived Neurotrophic Factor
  • Methionine
  • Valine