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Plasma acetyl-l-carnitine and l-carnitine in major depressive episodes: a case–control study before and after treatment

Published online by Cambridge University Press:  14 October 2021

Abd El Kader Ait Tayeb Open the ORCID record for Abd El Kader Ait Tayeb [Opens in a new window] ,
Romain Colle ,
Khalil El-Asmar ,
Kenneth Chappell ,
Cécile Acquaviva-Bourdain ,
Denis J. David ,
Séverine Trabado ,
Philippe Chanson ,
Bruno Feve  and
Laurent Becquemont
...Show all authors
Abd El Kader Ait Tayeb*
Affiliation:
CESP, MOODS Team, INSERM, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre F-94275, France Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre F-94275, France
Romain Colle
Affiliation:
CESP, MOODS Team, INSERM, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre F-94275, France Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre F-94275, France
Khalil El-Asmar
Affiliation:
CESP, MOODS Team, INSERM, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre F-94275, France Department of Epidemiology and Population Health, Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon
Kenneth Chappell
Affiliation:
CESP, MOODS Team, INSERM, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre F-94275, France
Cécile Acquaviva-Bourdain
Affiliation:
Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Centre de Biologie et Pathologie Est, Groupement Hospitalier Est (GHE), Hospices Civils de Lyon, Bron, France
Denis J. David
Affiliation:
CESP, MOODS Team, INSERM, Faculté de Pharmacie, Univ Paris-Saclay, Châtenay-Malabry, France
Séverine Trabado
Affiliation:
INSERM UMR-S U1185, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre F-94275, France Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre F-94275, France
Philippe Chanson
Affiliation:
INSERM UMR-S U1185, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre F-94275, France Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre F-94275, France
Bruno Feve
Affiliation:
Sorbonne Université-INSERM, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire ICAN, Service d'Endocrinologie, CRMR PRISIS, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris F-75012, France
Laurent Becquemont
Affiliation:
CESP, MOODS Team, INSERM, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre F-94275, France Centre de Recherche Clinique, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre F-94275, France
Céline Verstuyft
Affiliation:
CESP, MOODS Team, INSERM, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre F-94275, France Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre F-94275, France
Emmanuelle Corruble
Affiliation:
CESP, MOODS Team, INSERM, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre F-94275, France Service Hospitalo-Universitaire de Psychiatrie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre F-94275, France
*
Author for correspondence: Abd El Kader Ait Tayeb, E-mail: abdelkader.aittayeb@aphp.fr
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Abstract

Background

Major depressive disorder (MDD) is the main cause of disability worldwide, its outcome is poor, and its underlying mechanisms deserve a better understanding. Recently, peripheral acetyl-l-carnitine (ALC) has been shown to be lower in patients with major depressive episodes (MDEs) than in controls. l-Carnitine is involved in mitochondrial function and ALC is its short-chain acetyl-ester. Our first aim was to compare the plasma levels of l-carnitine and ALC, and the l-carnitine/ALC ratio in patients with a current MDE and healthy controls (HCs). Our second aim was to assess their changes after antidepressant treatment.

Methods

l-Carnitine and ALC levels and the carnitine/ALC ratio were measured in 460 patients with an MDE in a context of MDD and in 893 HCs. Depressed patients were re-assessed after 3 and 6 months of antidepressant treatment for biology and clinical outcome.

Results

As compared to HC, depressed patients had lower ALC levels (p < 0.00001), higher l-carnitine levels (p < 0.00001) and higher l-carnitine/ALC ratios (p < 0.00001). ALC levels increased [coefficient: 0.18; 95% confidence interval (CI) 0.12–0.24; p < 0.00001], and l-carnitine levels (coefficient: −0.58; 95% CI −0.75 to −0.41; p < 0.00001) and l-carnitine/ALC ratios (coefficient: −0.41; 95% CI −0.47 to −0.34; p < 0.00001), decreased after treatment. These parameters were completely restored after 6 months of antidepressant. Moreover, the baseline l-carnitine/ALC ratio predicted remission after 3 months of treatment (odds ratio = 1.14; 95% CI 1.03–1.27; p = 0.015).

Conclusions

Our data suggest a decreased mitochondrial metabolism of l-carnitine into ALC during MDE. This decreased mitochondrial metabolism is restored after a 6-month antidepressant treatment. Moreover, the magnitude of mitochondrial dysfunction may predict remission after 3 months of antidepressant treatment. New strategies targeting mitochondria should be explored to improve treatments of MDD.

Keywords

Acetyl-l-carnitineantidepressantsbiomarkersl-carnitinemajor depressive disordermajor depressive episodesmitochondria
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 6 , April 2023 , pp. 2307 - 2316
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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Footnotes

*

These two authors contributed equally to this work.

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