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

doi:10.1126/science.1181886

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

Psychology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	863-6
Number of pages	4
Journal	Science
Volume	327
Issue number	5967
DOIs	https://doi.org/10.1126/science.1181886
Publication status	Published - 12 Feb 2010

Keywords

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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10.1126/science.1181886

http://www.sciencemag.org/content/327/5967/863

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Soliman, F., Glatt, C. E., Bath, K. G., Levita, L., Jones, R. M., Pattwell, S. S., Jing, D., Tottenham, N., Amso, D., Somerville, L. H., Voss, H. U., Glover, G., Ballon, D. J., Liston, C., Teslovich, T., Van Kempen, T., Lee, F. S., & Casey, B. J. (2010). A genetic variant BDNF polymorphism alters extinction learning in both mouse and human. Science, 327(5967), 863-6. https://doi.org/10.1126/science.1181886

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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.",

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

year = "2010",

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day = "12",

doi = "10.1126/science.1181886",

language = "English",

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Soliman, F, Glatt, CE, Bath, KG, Levita, L, Jones, RM, Pattwell, SS, Jing, D, Tottenham, N, Amso, D, Somerville, LH, Voss, HU, Glover, G, Ballon, DJ, Liston, C, Teslovich, T, Van Kempen, T, Lee, FS & Casey, BJ 2010, 'A genetic variant BDNF polymorphism alters extinction learning in both mouse and human', Science, vol. 327, no. 5967, pp. 863-6. https://doi.org/10.1126/science.1181886

TY - JOUR

T1 - A genetic variant BDNF polymorphism alters extinction learning in both mouse and human

AU - Soliman, Fatima

AU - Glatt, Charles E

AU - Bath, Kevin G

AU - Levita, Liat

AU - Jones, Rebecca M

AU - Pattwell, Siobhan S

AU - Jing, Deqiang

AU - Tottenham, Nim

AU - Amso, Dima

AU - Somerville, Leah H

AU - Voss, Henning U

AU - Glover, Gary

AU - Ballon, Douglas J

AU - Liston, Conor

AU - Teslovich, Theresa

AU - Van Kempen, Tracey

AU - Lee, Francis S

AU - Casey, B J

PY - 2010/2/12

Y1 - 2010/2/12

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Alleles

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KW - Animals

KW - Brain Mapping

KW - Brain-Derived Neurotrophic Factor

KW - Conditioning, Classical

KW - Cues

KW - Ethnic Groups

KW - Extinction, Psychological

KW - Fear

KW - Female

KW - Gene Knock-In Techniques

KW - Genotype

KW - Humans

KW - Magnetic Resonance Imaging

KW - Male

KW - Mice

KW - Polymorphism, Single Nucleotide

KW - Prefrontal Cortex

KW - Young Adult

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U2 - 10.1126/science.1181886

DO - 10.1126/science.1181886

M3 - Article

C2 - 20075215

SN - 0036-8075

VL - 327

SP - 863

EP - 866

JO - Science

JF - Science

IS - 5967

ER -

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

Abstract

Keywords

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