Evidence map›Paper›PMID 40413177›Full record

Trial reportTranslational psychiatry2025

Major depressive disorder in children and adolescents is associated with reduced hair cortisol and anandamide (AEA): cross-sectional and longitudinal evidence from a large randomized clinical trial.

Andreas Walther, Lukas Eggenberger, Rudolf Debelak, Clemens Kirschbaum, Isabelle Häberling, Ester Osuna, Michael Strumberger, Susanne Walitza, Jeannine Baumgartner, Isabelle Herter-Aeberli and 1 more

Abstract readRandomized Controlled TrialClinical Trial, Phase III
In one paragraph

Trial report in Translational psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

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

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
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

11 authors.

Andreas WaltherClinical Psychology and Psychotherapy, University of Zurich, Zurich, Switzerland. a.walther@psychologie.uzh.ch.ORCID http://orcid.org/0000-0003-4516-1783
Lukas EggenbergerExperimental Pharmacopsychology and Psychological Addiction Research, Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-3826-723X
Rudolf DebelakPsychological Methods, Evaluation and Statistics, University of Zurich, Zurich, Switzerland.
Clemens KirschbaumBiological Psychology, TU Dresden, Dresden, Germany.
Isabelle HäberlingDepartment of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Ester OsunaLaboratory of Human Nutrition, Institute of Food, Nutrition and Health, ETH Zürich, Zürich, Switzerland.ORCID http://orcid.org/0000-0001-7706-6102
Michael StrumbergerResearch Department of Child and Adolescent Psychiatry, Psychiatric University Hospitals Basel, University of Basel, Basel, Switzerland.
Susanne WalitzaDepartment of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-8161-8683
Jeannine BaumgartnerDepartment of Nutritional Sciences, King's College London, London, United Kingdom.ORCID http://orcid.org/0000-0002-9107-4181
Isabelle Herter-AeberliLaboratroy of Nutrition and Metabolic Epigenetics, Institute of Food, Nutrition and Health, ETH Zürich, Zürich, Switzerland.ORCID http://orcid.org/0000-0003-0134-6217
Gregor BergerDepartment of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 33IC30_166826Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) PZPGP1_201757
6 · The paper itself

Abstract

Pediatric major depressive disorder (MDD) represents a leading cause of disability worldwide in children and adolescents, while its underlying pathophysiology remains largely elusive. The endocannabinoid system (ECS) and the hypothalamus-pituitary-adrenal (HPA) axis are considered intertwined regulatory systems crucially implicated in the pathophysiology of depressive disorders. This study explores the cross-sectional and longitudinal association between the ECS, specifically anandamide (AEA), and the HPA axis with its main effector cortisol and MDD status and severity in children and adolescents. Utilizing data from the omega-3-pMDD trial, a phase III Randomized Clinical Trial assessing the efficacy and safety of omega-3 fatty acid supplementation in pediatric MDD, we examined hair AEA and cortisol concentrations in 110 children and adolescents aged 8-17 years, with MDD. Associations between MDD, symptom severity and hair AEA and cortisol concentrations were explored across four measurement time points (baseline, week 6, 24 and 36). Additionally, 127 healthy children and adolescents were examined once to enable cross-sectional comparisons between MDD cases and healthy controls. Baseline comparisons for the 237 children and adolescents showed lower cortisol and AEA levels in hair of children and adolescents with MDD compared to healthy controls. Longitudinal multi-level analysis over all time-points further corroborated negative longitudinal associations between hair cortisol and depressive symptoms in children and adolescents with MDD. Taken together, reduced baseline AEA and cortisol levels emerge as robust biomarker in depressed youth, while the negative longitudinal association between hair cortisol and depression symptoms might provide useful for therapy monitoring purposes. These results hold implications for early detection, diagnosis, and therapeutic response prediction in pediatric MDD.

Indexed as

Arachidonic AcidsEndocannabinoidsHairHydrocortisoneMajor Depressive DisorderPolyunsaturated AlkamidesAdolescentChildCross-Sectional StudiesFatty Acids, Omega-3FemaleHumansHypothalamo-Hypophyseal SystemLongitudinal StudiesMalePituitary-Adrenal SystemanandamideArachidonic AcidsEndocannabinoidsFatty Acids, Omega-3HydrocortisonePolyunsaturated Alkamides

Identifiers

PMID40413177
PMCPMC12103555

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.