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

Alessandra Frustaci, Gino Pozzi, Francesco Gianfagna, Lamberto Manzoli, Stefania Boccia

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)163-170
Number of pages8
Issue number3-4
Publication statusPublished - 2008


  • Anxiety disorders
  • Brain-derived neurotrophic factor
  • Genetic susceptibility
  • Harm avoidance
  • Meta-analysis
  • Neuroticism

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Neuropsychology and Physiological Psychology
  • Biological Psychiatry


Dive into the research topics of 'Meta-analysis of the brain-derived neurotrophic factor gene (BDNF) Val66Met polymorphism in anxiety disorders and anxiety-related personality traits'. Together they form a unique fingerprint.

Cite this