Evidence map›Paper›PMID 25731744›Full record

ArticleNature communications2015

FAAH genetic variation enhances fronto-amygdala function in mouse and human.

Iva Dincheva, Andrew T Drysdale, Catherine A Hartley, David C Johnson, Deqiang Jing, Elizabeth C King, Stephen Ra, J Megan Gray, Ruirong Yang, Ann Marie DeGruccio and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
168citing papers in PubMed, 3 pooled it
25.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

168 citing papers in PubMed, 3 syntheses or guidelines pooled it, 283 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  4. Trial
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  7. The effects of FAAH inhibition on the neural basis of anxiety-related processing in healthy male subjects: a randomized clinical trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021
    Trial
  8. Trial
  9. The fatty acid amide hydrolase C385A variant affects brain binding of the positron emission tomography tracer [11C]CURB.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2015
    Trial
  10. Review
  11. Article
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  13. Article
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  16. Genetic Tools in Rodents to Study Cannabinoid Functions.Current topics in behavioral neurosciences · 2026
    Review
  17. Article
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  19. Research Review: What we have learned about the endocannabinoid system in developmental psychopathology.Journal of child psychology and psychiatry, and allied disciplines · 2025
    Review
  20. Review

108 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 2 countries.

Iva Dincheva1] Department of Psychiatry, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA [2] Department of Pharmacology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Andrew T DrysdaleSackler Institute for Developmental Psychobiology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Catherine A HartleySackler Institute for Developmental Psychobiology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
David C JohnsonSackler Institute for Developmental Psychobiology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Deqiang JingDepartment of Psychiatry, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Elizabeth C King1] Department of Psychiatry, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA [2] Department of Pharmacology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Stephen RaDepartment of Psychiatry, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
J Megan GrayHotchkiss Brain Institute and Mathison Centre for Mental Health Research and Education, Departments of Cell Biology and Anatomy &Psychiatry, University of Calgary, 3330 Hospital Drive NW, Calgary AB Canada T2N4N1.
Ruirong YangDepartment of Psychiatry, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Ann Marie DeGruccioinGenious Targeting Laboratory, 2200 Smithtown Avenue, Ronkonkoma, New York 11779, USA.
Chienchun HuangDepartment of Psychiatry, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Benjamin F CravattDepartment of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Charles E GlattDepartment of Psychiatry, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Matthew N HillHotchkiss Brain Institute and Mathison Centre for Mental Health Research and Education, Departments of Cell Biology and Anatomy &Psychiatry, University of Calgary, 3330 Hospital Drive NW, Calgary AB Canada T2N4N1.
B J Casey1] Department of Psychiatry, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA [2] Department of Pharmacology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Francis S Lee1] Department of Psychiatry, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA [2] Department of Pharmacology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA [3] Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Cornell University · USUniversity of Calgary · CAIngenious Targeting Laboratory (United States) · USScripps Research Institute · US

Funding

Weill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1M
STRUCTURAL STUDIES OF FAAHP01DA017259 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI CRAVATT, BENJAMIN F · 2004 to 2013
$10.6M
Statistical Genetics Core: Impact of BDNF Genotype and Stress on LearningP50MH079513 · NIMH · WEILL MEDICAL COLL OF CORNELL UNIV · PI CASEY, BETTY J · 2008 to 2012
$9.4M
The Impact of the BDNF Val66Met Prodomain on Cognitive Function in a Mouse Model of Alzheimer's DiseaseR01NS052819 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HEMPSTEAD, BARBARA L, LEE, FRANCIS SANG YONG · 2005 to 2019
$5.3M
TRI-INSTITUTIONAL TRAINING PROGRAM IN VISION RESEARCHT32EY007138 · NEI · WEILL MEDICAL COLL OF CORNELL UNIV · PI RODRIGUEZ-BOULAN, ENRIQUE J · 1994 to 2013
$3.2M
Developing Researchers in Neuropsychiatric ImagingR25MH060478 · NIMH · WEILL MEDICAL COLL OF CORNELL UNIV · PI CASEY, BETTY J · 1999 to 2008
$2.3M
Canadian Institutes of Health ResearchNEI NIH HHS EY007138NEI NIH HHS T32 EY007138NIDA NIH HHS DA017259NIDA NIH HHS P01 DA017259NIGMS NIH HHS GM07739NIGMS NIH HHS T32 GM007739NIMH NIH HHS MH060478NIMH NIH HHS MH079513NIMH NIH HHS P50 MH079513NIMH NIH HHS R25 MH060478NINDS NIH HHS NS052819NINDS NIH HHS R01 NS052819
6 · The paper itself

Abstract

Cross-species studies enable rapid translational discovery and produce the broadest impact when both mechanism and phenotype are consistent across organisms. We developed a knock-in mouse that biologically recapitulates a common human mutation in the gene for fatty acid amide hydrolase (FAAH) (C385A; rs324420), the primary catabolic enzyme for the endocannabinoid anandamide. This common polymorphism impacts the expression and activity of FAAH, thereby increasing anandamide levels. Here, we show that the genetic knock-in mouse and human variant allele carriers exhibit parallel alterations in biochemisty, neurocircuitry and behaviour. Specifically, there is reduced FAAH expression associated with the variant allele that selectively enhances fronto-amygdala connectivity and fear extinction learning, and decreases anxiety-like behaviours. These results suggest a gain of function in fear regulation and may indicate for whom and for what anxiety symptoms FAAH inhibitors or exposure-based therapies will be most efficacious, bridging an important translational gap between the mouse and human.

Indexed as

AmidohydrolasesAmygdalaAnimalsBlotting, WesternExtinction, PsychologicalFatty Acid Amide HydrolasesFearFrontal LobeGene Expression Regulation, EnzymologicGene Knock-In TechniquesHumansImage Processing, Computer-AssistedImmunohistochemistryMagnetic Resonance ImagingMass SpectrometryMiceAmidohydrolasesFatty Acid Amide Hydrolases

Identifiers

PMID25731744
PMCPMC4351757
OpenAlexW2003159048

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.