A genetic variant BDNF polymorphism alters extinction learning in both mouse and human

Fatima Soliman, Charles E Glatt, Kevin G Bath, Liat Levita, Rebecca M Jones, Siobhan S Pattwell, Deqiang Jing, Nim Tottenham, Dima Amso, Leah H Somerville, Henning U Voss, Gary Glover, Douglas J Ballon, Conor Liston, Theresa Teslovich, Tracey Van Kempen, Francis S Lee, B J Casey

Research output: Contribution to journalArticlepeer-review


Mouse models are useful for studying genes involved in behavior, but whether they are relevant to human behavior is unclear. Here, we identified parallel phenotypes in mice and humans resulting from a common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which is involved in anxiety-related behavior. An inbred genetic knock-in mouse strain expressing the variant BDNF recapitulated the phenotypic effects of the human polymorphism. Both were impaired in extinguishing a conditioned fear response, which was paralleled by atypical frontoamygdala activity in humans. Thus, this variant BDNF allele may play a role in anxiety disorders showing impaired learning of cues that signal safety versus threat and in the efficacy of treatments that rely on extinction mechanisms, such as exposure therapy.
Original languageEnglish
Pages (from-to)863-6
Number of pages4
Issue number5967
Publication statusPublished - 12 Feb 2010


  • Adolescent
  • Adult
  • Alleles
  • Amygdala
  • Animals
  • Brain Mapping
  • Brain-Derived Neurotrophic Factor
  • Conditioning, Classical
  • Cues
  • Ethnic Groups
  • Extinction, Psychological
  • Fear
  • Female
  • Gene Knock-In Techniques
  • Genotype
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Polymorphism, Single Nucleotide
  • Prefrontal Cortex
  • Young Adult

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