title: A genetic variant BDNF polymorphism alters extinction learning in both mouse and human.
abstract: 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.
authors.affiliation: The Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College, New York, NY 10065, USA. fas2002@med.cornell.edu
authors.forename: Fatima
authors.initials: F
authors.lastname: Soliman
authors.forename: Charles E
authors.initials: CE
authors.lastname: Glatt
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Bath
authors.forename: Liat
authors.initials: L
authors.lastname: Levita
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Jones
authors.forename: Siobhan S
authors.initials: SS
authors.lastname: Pattwell
authors.forename: Deqiang
authors.initials: D
authors.lastname: Jing
authors.forename: Nim
authors.initials: N
authors.lastname: Tottenham
authors.forename: Dima
authors.initials: D
authors.lastname: Amso
authors.forename: Leah H
authors.initials: LH
authors.lastname: Somerville
authors.forename: Henning U
authors.initials: HU
authors.lastname: Voss
authors.forename: Gary
authors.initials: G
authors.lastname: Glover
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Ballon
authors.forename: Conor
authors.initials: C
authors.lastname: Liston
authors.forename: Theresa
authors.initials: T
authors.lastname: Teslovich
authors.forename: Tracey
authors.initials: T
authors.lastname: Van Kempen
authors.forename: Francis S
authors.initials: FS
authors.lastname: Lee
authors.forename: B J
authors.initials: BJ
authors.lastname: Casey
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000679:Amygdala / Q000502:physiology; D000818:Animals; D001931:Brain Mapping; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000502:physiology*; D003214:Conditioning, Classical; D003463:Cues; D005006:Ethnicity / Q000235:genetics; D005108:Extinction, Psychological; D005239:Fear; D005260:Female; D055879:Gene Knock-In Techniques; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000502:physiology; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor