Association between smoking, nicotine dependence, and BDNF Val66Met polymorphism with BDNF concentrations in serum

Nicotine Tob Res. 2015 Mar;17(3):323-9. doi: 10.1093/ntr/ntu151. Epub 2014 Sep 2.


Introduction: Nicotine use is associated with the upregulation of brain-derived neurotrophic factor (BDNF) in serum. An association between smoking and the BDNF Val(66)Met polymorphism has also been found. The aim of this study is to examine the levels of serum BDNF in never-smokers, former smokers, and current smokers-with and without nicotine dependence-and to examine the interaction of the polymorphism and smoking status with serum BDNF.

Methods: We used baseline serum and gene data of BDNF on 2,088 participants from the Netherlands Study of Depression and Anxiety (NESDA) to investigate smoking-BDNF association while controlling for potential confounding variables. Nicotine dependence was assessed with the Fagerstrom Test for Nicotine Dependence (FTND).

Results: Smokers with and without nicotine dependence had higher levels of serum BDNF than former and never-smokers. Nicotine dependence and number of cigarettes smoked per day did not add to the prediction of serum BDNF; however, total number of smoking years was a significant predictor of serum BDNF. There was no association of BDNF Val(66)Met, nor an interaction of this polymorphism and smoking status, with serum BDNF.

Conclusions: Current smoking and higher number of smoking years are associated with higher levels of serum BDNF, and this is independent of the BDNF genotype. Nicotine dependence itself is not associated with a further increase or decrease of serum BDNF. Longitudinal investigations that address changes in serum BDNF in incident smokers and/or in quitters may be useful to understand the association of smoking with BDNF.

Publication types

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

MeSH terms

  • Adult
  • Brain-Derived Neurotrophic Factor / blood*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Genotype
  • Humans
  • Male
  • Methionine / genetics
  • Middle Aged
  • Netherlands / epidemiology
  • Polymorphism, Genetic / genetics*
  • Prospective Studies
  • Smoking / epidemiology
  • Smoking / genetics*
  • Smoking / metabolism
  • Tobacco Use Disorder / blood*
  • Tobacco Use Disorder / epidemiology
  • Tobacco Use Disorder / genetics*
  • Valine / genetics


  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human
  • Methionine
  • Valine