Evidence mapPaperPMID 41310856Full record

ArticleJournal of eating disorders2025

Coordinated epigenetic dysregulation of CNR1 and FAAH genes drives endocannabinoid system dysfunction in anorexia nervosa.

Federica Gilardini, Francesca Mercante, Annalaura Sabatucci, Mariangela Pucci, Carlo Cifani, Cristina Segura-Garcia, Marianna Rania, Claudio D'Addario

Abstract read
In one paragraph

Article in Journal of eating disorders, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
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

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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

2 citing papers in PubMed.

  1. Review
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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

8 authors.

Federica GilardiniDepartment of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Via Renato Balzarini 1, 64100, Teramo, Italy.ORCID http://orcid.org/0009-0009-5806-9995
Francesca MercanteDepartment of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Via Renato Balzarini 1, 64100, Teramo, Italy.ORCID http://orcid.org/0000-0002-2260-5049
Annalaura SabatucciDepartment of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Via Renato Balzarini 1, 64100, Teramo, Italy.ORCID http://orcid.org/0000-0002-8004-2547
Mariangela PucciDepartment of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Via Renato Balzarini 1, 64100, Teramo, Italy.ORCID http://orcid.org/0000-0003-4657-6075
Carlo CifaniPharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy.ORCID http://orcid.org/0000-0001-6180-828X
Cristina Segura-GarciaDepartment of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy.ORCID http://orcid.org/0000-0002-5756-3045
Marianna RaniaOutpatient Unit for Clinical Research and Treatment of Eating Disorders, University Hospital Renato Dulbecco, Viale Pio X, 83, 88100, Catanzaro, Italy. marianna.rania@aourenatodulbecco.it.ORCID http://orcid.org/0000-0001-7742-7086
Claudio D'AddarioDepartment of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Via Renato Balzarini 1, 64100, Teramo, Italy. cdaddario@unite.it.ORCID http://orcid.org/0000-0002-1275-098X

Funding

Ministero dell'Università e della Ricerca 2022K7YKTY
6 · The paper itself

Abstract

backgroundAnorexia nervosa (AN) is a severe psychiatric disorder with limited biomarkers for diagnosis and treatment monitoring. We investigated endocannabinoid system (ECS) dysregulation in AN through integrated epigenetic and genetic analysis of saliva.

methodsWe analyzed DNA methylation patterns of cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes, characterized genetic polymorphisms, and quantified expression of exosomal microRNAs targeting these genes in AN patients versus healthy controls.

resultsWe discovered a novel bidirectional epigenetic dysregulation of the ECS: CNR1 promoter hypermethylation coupled with FAAH promoter hypomethylation. This dual-target mechanism systematically impairs endocannabinoid signaling by simultaneously reducing receptor availability while increasing endocannabinoid degradation. Compensatory miRNA responses (upregulated miR-342-3p, miR-23b-3p targeting CNR1; upregulated miR-4505, miR-1275 targeting FAAH) revealed dynamic regulatory attempts to counterbalance these primary epigenetic changes. This convergent pathway dysfunction demonstrates how multiple molecular mechanisms work in concert to dysregulate appetite regulation in AN. Combined biomarker panels showed superior diagnostic precision compared to individual markers.

conclusionsOur findings establish this bidirectional epigenetic dysregulation as a central mechanism underlying ECS dysfunction in AN, providing mechanistic insights that identify novel therapeutic targets and advance precision medicine approaches for this challenging disorder.

Indexed as

Anorexia nervosaDNA methylationEndocannabinoid systemEpigeneticsMicroRNAsMolecular biologyPsychiatric disordersSalivaTranscription factors

Identifiers

PMID41310856
PMCPMC12771889

What Socratic holds

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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 Socratic graph.