A Genetic Variant BDNF Polymorphism Alters Extinction Learning in Both Mouse and Human
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Of Mice and Men: Just how closely must mouse models replicate the known features of human disorders to be accepted as useful for mechanistic and therapeutic studies? Soliman et al. (p. 863 , published online 14 January) compared mice that vary only in their allelic composition at one position within the gene encoding brain-derived neurotrophic factor (BDNF) with humans exhibiting the same range of allelic variation. Individuals (mice and humans) carrying the allele that codes for a methionine-containing variant of BDNF retained a fearful response to a threatening stimulus even after its removal in comparison to those with the valine variant. Furthermore, in both cases, this linkage was mediated by diminished activity in the ventral-medial region of the prefrontal cortex. This deficit in extinction learning may contribute to differential responses to extinction-based therapies for anxiety disorders.
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Both rodents and humans with BDNF Val66Met polymorphisms exhibit impaired fear extinction learning and reduced mPFC activity during extinction.
“Both rodents and humans with BDNF Val66Met polymorphisms exhibit impaired fear extinction learning and reduced mPFC activity during extinction (138)”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [138]
The paper reports impaired fear extinction in both mice and humans carrying the Met allele, and significantly reduced vmPFC activity during extinction in human carriers (section labeled Abstract; page unavailable). For mice, it reports only a trend toward blunted vmPFC c-Fos expression after extinction, not an established reduction in mPFC activity during extinction. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThe Met allele of BDNF Val66Met has been implicated in impaired extinction of conditioned fear response and atypical frontoamygdala activity in humans.
“and has been implicated in impaired extinction of conditioned fear response and atypical frontoamygdala activity in humans (Soliman et al. 2010)”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Soliman et al. 2010
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Lost in translation: How to upgrade fear memory research
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- Authors
- 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.
- Affiliations
- Weill Cornell Medicine (US)
- Citigroup (US)
- Stanford Medicine (US)
- The Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College, New York, NY 10065, USA.
- Corresponding author
- Soliman, Fatima
- Lee, Francis S.
- Casey, B. J.
- ORCID
- Venue
- Science
- Published
- 2010-02-12
- Volume
- 327
- Issue
- 5967
- Pages
- 863-866
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2829261
- OpenAlex
- W1998261300
- Cited by
- 585
- References
- 33
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 10 · 2023: 18 · 2022: 25 · 2021: 27 · 2020: 26 · 2019: 39 · 2018: 36 · 2017: 35 · 2016: 36 · 2015: 48 · 2014: 71 · 2013: 63 · 2012: 65
- FWCI
- 38.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (P50MH079513, MH079513, R01MH091864, R25MH060478, MH060478)
- National Institute of General Medical Sciences (GM 07739, T32GM007739)
- National Institute of Neurological Disorders and Stroke (NS052819, R01NS052819)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD055177, T32HD055177)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- brain-derived neurotrophic factor, single nucleotide polymorphisms, extinction learning, anxiety disorders, knock-in mice, exposure therapy, fear conditioning
- MeSH terms
- Adolescent, Adult, Alleles, Amygdala, Animals, Brain Mapping, Conditioning, Classical, Cues, Ethnicity, Extinction, Psychological, Fear, Female, Genotype, Humans, Magnetic Resonance Imaging, Male, Prefrontal Cortex, Brain-Derived Neurotrophic Factor, Polymorphism, Single Nucleotide, Mice, Young Adult, Gene Knock-In Techniques
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