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Record W4411540479 · doi:10.1038/s41386-025-02150-y

Fatty acid amide hydrolase in major depressive episodes: A [11C]CURB positron emission tomography study

2025· article· en· W4411540479 on OpenAlexafffund
Dorsa Rafiei, Michelle De Pol, Jeffrey H. Meyer, Kimberly L. Desmond, Ruth A. Ross, Isabelle Boileau, Jerry J. Warsh, Pablo Rusjan, Neil Vasdev, Ryan Aloysius, Lauren Gray, Nathan J. Kolla

Bibliographic record

VenueNeuropsychopharmacology · 2025
Typearticle
Languageen
FieldMedicine
TopicCannabis and Cannabinoid Research
Canadian institutionsMcGill UniversityUniversity of TorontoCentre for Addiction and Mental Health
FundersCanadian Institutes of Health ResearchUniversity of TorontoCanada Research ChairsGovernment of Canada
KeywordsPositron emission tomographyFatty acid amide hydrolasePsychologyMedicineInternal medicineNuclear medicine

Abstract

fetched live from OpenAlex

Abstract The role of the endocannabinoid system (ECS) in major depressive disorder (MDD) is under-investigated despite reports of increased activity and/or concentration of fatty acid amide hydrolase (FAAH), a key ECS enzyme, in fronto-limbic brain regions in some animal models of depressive behavior. We hypothesized that [11C]CURB λk 3, an index of FAAH density, would be elevated in the prefrontal cortex, hippocampus, and anterior cingulate cortex in major depressive episodes of MDD compared to healthy controls. Fifteen unmedicated MDD participants and 15 age- and sex-matched healthy controls underwent [11C]CURB positron emission tomography and FAAH genotyping. Psychological tests of depressive severity, apathy, and anxiety were administered and measurements were assessed as covariates in exploratory analyses. No significant group differences in [11C]CURB λk 3 were observed between MDD participants and controls (F 1,27 = 0.32; p = 0.58). A mixed effects model revealed that Marin Apathy Evaluation Scale scores in the MDD group had a significant main effect on [11C]CURB λk 3 binding across the collective regions of medial prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and midbrain (F 1,11 = 6.75; p = 0.02). Depressive severity and anxiety did not have a significant relationship to [11C]CURB λk 3 binding. The relationship of greater fronto-limbic [11C]CURB λk 3 to greater apathy along with the metabolic role of FAAH in the ECS, the latter which supports maintaining feelings of interest, initiative, and motivation, has important implications for the pathophysiology of apathy in MDD.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.342
Teacher spread0.332 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations3
Published2025
Admission routes2
Has abstractyes

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