Meta-analysis of the brain-derived neurotrophic factor gene (BDNF) Val66Met polymorphism in anxiety disorders and anxiety-related personality traits

Neuropsychobiology. 2008;58(3-4):163-70. doi: 10.1159/000182892. Epub 2008 Dec 17.


Objective: Brain-derived neurotrophic factor (BDNF) is potentially involved in the pathogenesis of anxiety. We carried out meta-analyses to evaluate the relationship between the BDNF Val66Met (valine, methionine) polymorphism and anxiety disorders (AD) or anxiety-related personality traits (ARPT).

Methods: Medline, Embase and PsycINFO were searched up to December 2007. We investigated 3 outcomes related to BDNF Val66Met polymorphisms: (1) clinically diagnosed cases of AD; (2) ARPT in subjects without psychiatric diagnoses, assessed either by the Neuroticism scale of NEO-Personality Inventory forms (NEO-PI, NEO-PI-R, NEO-FFI), or by (3) the Harm Avoidance (HA) scale of Tridimensional Personality Questionnaire (TPQ) or its extended version Temperament and Character Inventory (TCI).

Results: Seven case-control studies were selected for AD, including 1,092 cases and 8,394 controls, while 5 cross-sectional studies for Neuroticism (n = 1,633) and 4 for HA (n = 607). Both Met/Met and Val/Met individuals, as compared to Val/Val, showed a statistically significant lower Neuroticism score [SMD = -0.24 (95% CI: -0.44, -0.04), and -0.11 (95% CI: -0.22, -0.01), respectively]. No significant association was found between BDNF Val66Met polymorphism and AD [OR = 1.13 (95% CI: 0.85-1.52) for Met/Met versus Val/Val] or HA [SMD = 0.11 (95% CI: -0.19, 0.42) for Met/Met vs. Val/Val].

Conclusions: The low number of studies on this topic and their limited sample size, along with the inner limits in the definition of anxiety phenotypes, suggest caution in the interpretation of these results. Larger additional studies possibly investigating the interaction with other genes and environmental exposures are required to confirm these results.

Publication types

  • Meta-Analysis

MeSH terms

  • Anxiety / genetics*
  • Anxiety Disorders / diagnosis
  • Anxiety Disorders / genetics*
  • Asian Continental Ancestry Group / genetics
  • Brain-Derived Neurotrophic Factor / genetics*
  • Case-Control Studies
  • Cross-Sectional Studies
  • European Continental Ancestry Group / genetics
  • Genetic Heterogeneity
  • Humans
  • Neuropsychological Tests
  • Odds Ratio
  • Personality / genetics*
  • Polymorphism, Single Nucleotide*
  • Surveys and Questionnaires


  • Brain-Derived Neurotrophic Factor