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Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior.

A common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met), is associated with alterations in brain anatomy and memory, but its relevance to clinical disorders is unclear. We generated a variant BDNF mouse (BDNF(Met/Met)) that reproduces the phenotypic hallmarks in humans with the variant allele. BDNF(Met) was expressed in brain at normal levels, but its secretion from neurons was defective. When placed in stressful settings, BDNF(Met/Met) mice exhibited increased anxiety-related behaviors that were not normalized by the antidepressant, fluoxetine. A variant BDNF may thus play a key role in genetic predispositions to anxiety and depressive disorders.

Pubmed ID: 17023662


  • Chen ZY
  • Jing D
  • Bath KG
  • Ieraci A
  • Khan T
  • Siao CJ
  • Herrera DG
  • Toth M
  • Yang C
  • McEwen BS
  • Hempstead BL
  • Lee FS


Science (New York, N.Y.)

Publication Data

October 6, 2006

Associated Grants

  • Agency: NIMH NIH HHS, Id: MH060478
  • Agency: NIMH NIH HHS, Id: MH068850
  • Agency: NINDS NIH HHS, Id: NS052819
  • Agency: NINDS NIH HHS, Id: NS30687
  • Agency: NINDS NIH HHS, Id: R01 NS052819

Mesh Terms

  • Alleles
  • Animals
  • Anxiety
  • Behavior, Animal
  • Brain-Derived Neurotrophic Factor
  • Conditioning (Psychology)
  • Dendrites
  • Dentate Gyrus
  • Fear
  • Fluoxetine
  • Hippocampus
  • Memory
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Activity
  • Neurons
  • Organ Size
  • Polymorphism, Single Nucleotide
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Uptake Inhibitors