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Montanari, S.* ; Jansen, R.* ; Schranner, D. ; Kastenmüller, G. ; Arnold, M. ; Janiri, D.* ; Sani, G.* ; Bhattacharyya, S.* ; Mahmoudian Dehkordi, S.* ; Dunlop, B.W.* ; Rush, A.J.* ; Penninx, B.W.H.J.* ; Kaddurah-Daouk, R.* ; Milaneschi, Y.*

Acylcarnitines metabolism in depression: Association with diagnostic status, depression severity and symptom profile in the NESDA cohort.

Transl. Psychiatry 15:65 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Acylcarnitines (ACs) are involved in bioenergetics processes that may play a role in the pathophysiology of depression. Previous genomic evidence identified four ACs potentially linked to depression risk. We carried forward these ACs and tested the association of their circulating levels with Major Depressive Disorder (MDD) diagnosis, overall depression severity and specific symptom profiles. The sample from the Netherlands Study of Depression and Anxiety included participants with current (n = 1035) or remitted (n = 739) MDD and healthy controls (n = 800). Plasma levels of four ACs (short-chain: acetylcarnitine C2 and propionylcarnitine C3; medium-chain: octanoylcarnitine C8 and decanoylcarnitine C10) were measured. Overall depression severity as well as atypical/energy-related (AES), anhedonic and melancholic symptom profiles were derived from the Inventory of Depressive Symptomatology. As compared to healthy controls, subjects with current or remitted MDD presented similarly lower mean C2 levels (Cohen's d = 0.2, p ≤ 1e-4). Higher overall depression severity was significantly associated with higher C3 levels (ß = 0.06, SE = 0.02, p = 1.21e-3). No associations were found for C8 and C10. Focusing on symptom profiles, only higher AES scores were linked to lower C2 (ß = -0.05, SE = 0.02, p = 1.85e-2) and higher C3 (ß = 0.08, SE = 0.02, p = 3.41e-5) levels. Results were confirmed in analyses pooling data with an additional internal replication sample from the same subjects measured at 6-year follow-up (totaling 4141 observations). Small alterations in levels of short-chain acylcarnitine levels were related to the presence and severity of depression, especially for symptoms reflecting altered energy homeostasis. Cellular metabolic dysfunctions may represent a key pathway in depression pathophysiology potentially accessible through AC metabolism.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Acetyl-l-carnitine; Stress; Ids; Acetylcarnitine; Inflammation; Metaanalysis; Reliability; Inventory; Disease; Roles
ISSN (print) / ISBN 2158-3188
e-ISSN 2158-3188
Zeitschrift Translational Psychiatry
Quellenangaben Band: 15, Heft: 1, Seiten: , Artikelnummer: 65 Supplement: ,
Verlag Nature Publishing Group
Verlagsort Campus, 4 Crinan St, London, N1 9xw, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Förderungen National Institutes of Health/National Institute on Aging
Netherlands Organisation for Health Research and Development (ZonMw)
NIMH
Alzheimer Gut Microbiome Project - NIA
NIA
Amsterdam UMC
Y. Milaneschi received funding from Amsterdam UMC (Starter Grant 2023) and Amsterdam Neuroscience (PoC funding 2024-2026).