A genetic variant BDNF polymorphism alters extinction learning in both mouse and human.
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.
Soliman
Fatima
F
The Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College, New York, NY 10065, USA. fas2002@med.cornell.edu
Glatt
Charles E
CE
Bath
Kevin G
KG
Levita
Liat
L
Jones
Rebecca M
RM
Pattwell
Siobhan S
SS
Jing
Deqiang
D
Tottenham
Nim
N
Amso
Dima
D
Somerville
Leah H
LH
Voss
Henning U
HU
Glover
Gary
G
Ballon
Douglas J
DJ
Liston
Conor
C
Teslovich
Theresa
T
Van Kempen
Tracey
T
Lee
Francis S
FS
Casey
B J
BJ
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
D019208:Brain-Derived Neurotrophic Factor