Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder
Psychiatry Research. 2024-09-01; 339: 116063
DOI: 10.1016/j.psychres.2024.116063
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1. Psychiatry Res. 2024 Sep;339:116063. doi: 10.1016/j.psychres.2024.116063. Epub
2024 Jul 6.
Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder.
Zachos KA(1), Choi J(1), Godin O(2), Chernega T(3), Kwak HA(3), Jung JH(3),
Aouizerate B(4), Aubin V(5), Bellivier F(6), Belzeaux-R R(7), Courtet P(8),
Dubertret C(9), Etain B(6), Haffen E(10), Lefrere A A(11), Llorca PM(12), Olié
E(8), Polosan M(13), Samalin L(12), Schwan R(14), Roux P(15), Barau C(16),
Richard JR(17), Tamouza R(2), Leboyer M(18), Andreazza AC(19); FondaMental
Academic Centers of Expertise in Bipolar Disorders (FACE-BD) Collaborators.
Collaborators: Etain B(20), Olié E(21), Leboyer M(22), Haffen E(21), Llorca
PM(21), Barteau V(23), Bensalem S(23), Godin O(23), Laouamri H(23), Souryis
K(23), Hotier S(22), Pelletier A(22), Hergeta F(22), Petrucci J(22), Willaume
L(22), Bellivier F(24), Etain B(24), Hennion V(24), Marlinge E(24), Meheust
J(24), Richard A(24), Carminati M(24), Francisque H(24), Dubertret C(25), Mazer
N(25), Portalier C(25), Scognamiglio C(25), Bing A(25), Laurent P(25), Gard
S(26), M’Bailara K(26), Elkael C(26), Hoorelbeke F(26), Minois I(26), Sportich
J(26), Da Ros N(26), Boukhobza L(27), Courtet P(27), Denat S(27), Deffinis
B(27), Ducasse D(27), Gachet M(27), Lengvenyté A(27), Molière F(27), Nass L(27),
Olié E(27), Tarquini G(27), Lefrere A(28), Moreau E(28), Pastol J(28), Groppi
F(28), Polomeni H(28), Bauberg J(28), Lescalier L(28), Muraccioli I(28), Suray
A(28), Cohen R(29), Kahn JP(29), Milazzo M(29), Wajsbrot-Elgrabli O(29),
Bougerol T(30), Pouchon A(30), Bertrand A(30), Fredembach B(30), Suisse A(30),
Denoual Q(30), Polosan M(30), Galliot AM(31), Brehon L(31), Bonny G(31), Durand
L(31), Feuga V(31), Kayser N(31), Roux P(31), Aubin V(32), Cussac I(32), Dupont
MA(32), Loftus J(32), Medecin I(32), Dubertret C(33), Mazer N(33), Laurent
P(33), Samalin L(34), Llorca PM(34), Mennetrier M(34), Bonnet T(34), Lacelle
D(34), Vayssié M(34), Beal C(34), Blanc O(34).
Author information:
(1)Department of Pharmacology and Toxicology, Temerty Faculty of Medicine,
University of Toronto, Toronto, ON, Canada; Mitochondrial Innovation Initiative,
MITO2i, Toronto, ON, Canada.
(2)INSERM U955 IMRB, Translational Neuropsychiatry laboratory, AP-HP, Hôpital
Henri Mondor, DMU IMPACT, Fédération Hospitalo-Universitaire de Médecine de
Précision en Psychiatrie (FHU ADAPT), Paris Est Créteil University (UPEC), ECNP
Immuno-NeuroPsychiatry Network; Fondation FondaMental, Créteil, France.
(3)Department of Pharmacology and Toxicology, Temerty Faculty of Medicine,
University of Toronto, Toronto, ON, Canada.
(4)Fondation FondaMental, Créteil, France; Centre Hospitalier Charles Perrens,
Pôle de Psychiatrie Générale et Universitaire, Laboratoire NutriNeuro (UMR INRAE
1286), Université de Bordeaux, Bordeaux, France.
(5)Fondation FondaMental, Créteil, France; Pôle de Psychiatrie, Centre
Hospitalier Princesse Grace, Monaco.
(6)Fondation FondaMental, Créteil, France; Université Paris Cité, INSERM
UMR-S1144, AP-HPm GH Saint-Louis-Bariboisière-Fernand Widal, Pôle Neurosciences,
Paris Optimisation Thérapeutique en Neuropsychopharmacologie OTeN, Paris,
France; AP-HP, Groupe Hospitalo-Universitaire AP-HP Nord, DMU Neurosciences,
Hôpital Fernand Widal, Département de Psychiatrie et de Médecine Addictologique,
Paris, France.
(7)Fondation FondaMental, Créteil, France; Univ. Montpellier & Department of
Psychiatry, CHU de Montpellier, France.
(8)Fondation FondaMental, Créteil, France; IGF, Univ. Montpellier, CNRS, INSERM,
Department of Emergency Psychiatry and Acute Care, CHU Montpellier, Montpellier,
France.
(9)Fondation FondaMental, Créteil, France; AP-HP, Groupe Hospitalo-Universitaire
AP-HP Nord, DMU ESPRIT, Service de Psychiatrie et Addictologie, Hôpital Louis
Mourier, Colombes, France, Université de Paris, Inserm UMR1266, Sorbonne Paris
Cité, Faculté de Médecine, Paris, France.
(10)Fondation FondaMental, Créteil, France; Université de Franche-Comté, UR 481
LINC, Service de Psychiatrie de l’Adulte, CIC-1431 INSERM, CHU de Besançon,
F-2500, France.
(11)Fondation FondaMental, Créteil, France; Pôle de Psychiatrie, Assistance
Publique Hôpitaux de Marseille, Marseille, France, INT-UMR7289, CNRS
Aix-Marseille Université, Marseille, France.
(12)Fondation FondaMental, Créteil, France; Department of Psychiatry, CHU
Clermont-Ferrand, University of Clermont Auvergne, CNRS, Clermont Auvergne INP,
Institut Pascal (UMR 6602), Clermont-Ferrand, France.
(13)Fondation FondaMental, Créteil, France; Univ. Grenoble Alpes, Inserm, U1216,
CHU Grenoble Alpes, Grenoble Institut Neurosciences, Grenoble, France.
(14)Université de Lorraine, Centre Psychothérapique de Nancy, Inserm U1254,
Nancy, France.
(15)Fondation FondaMental, Créteil, France; Centre Hospitalier de Versailles,
Service Universitaire de Psychiatrie d’Adulte et d’Addictologie, Le Chesnay,
France; Université Paris-Saclay & Université Versailles
Saint-Quentin-En-Yvelines, INSERM UMR1018, Centre de recherche en Épidémiologie
et Santé des Populations, Equipe DevPsy-DisAP, Paris, France.
(16)Plateforme de Ressources Biologiques, HU Henri Mondor, Créteil, France.
(17)INSERM U955 IMRB, Translational Neuropsychiatry laboratory, AP-HP, Hôpital
Henri Mondor, DMU IMPACT, Fédération Hospitalo-Universitaire de Médecine de
Précision en Psychiatrie (FHU ADAPT), Paris Est Créteil University (UPEC), ECNP
Immuno-NeuroPsychiatry Network.
(18)INSERM U955 IMRB, Translational Neuropsychiatry laboratory, AP-HP, Hôpital
Henri Mondor, DMU IMPACT, Fédération Hospitalo-Universitaire de Médecine de
Précision en Psychiatrie (FHU ADAPT), Paris Est Créteil University (UPEC), ECNP
Immuno-NeuroPsychiatry Network; Fondation FondaMental, Créteil, France.
Electronic address: .
(19)Department of Pharmacology and Toxicology, Temerty Faculty of Medicine,
University of Toronto, Toronto, ON, Canada; Mitochondrial Innovation Initiative,
MITO2i, Toronto, ON, Canada; Department of Psychiatry, University of Toronto,
Toronto, ON, Canada.
(20)FACE-BD Clinical Coordinating Center (Fondation FondaMental); FACE-BD
Clinical Sites and Principal Collaborators in France.
(21)FACE-BD Clinical Coordinating Center (Fondation FondaMental).
(22)AP-HP, DHU PePSY, Pôle de Psychiatrie et d’Addictologie des Hôpitaux
Universitaires H Mondor, Créteil.
(23)FACE-BD Data Coordinating Center (Fondation FondaMental).
(24)AP-HP, GH Saint-Louis-Lariboisière-Fernand Widal, Pôle Neurosciences, Paris.
(25)APHP, Groupe Hospitalo-universitaire AP-HP Nord, DMU ESPRIT, Service de
Psychiatrie et Addictologie, Hôpital Louis Mourier, Colombes, France.
(26)Hôpital C. Perrens, Centre Expert Trouble Bipolaire, Pôle de Psychiatrie
Générale et Universitaire.
(27)Département d’Urgence et Post Urgence Psychiatrique, CHRU Montpellier,
Montpellier.
(28)Pôle de Psychiatrie, addictologie et pédopsychiatrie, Hôpital Sainte
Marguerite, Marseille.
(29)Service de Psychiatrie et Psychologie Clinique, CHU de Nancy, Hôpitaux de
Brabois, Vandoeuvre Les Nancy.
(30)Service Universitaire de Psychiatrie, CHU de Grenoble et des Alpes,
Grenoble.
(31)Centre Hospitalier de Versailles, Service U niversitaire de Psychiatrie
d’adultes et d’addictologie, Le Chesnay.
(32)Centre Hospitalier Princesse Grace, Monaco.
(33)AHPH, Departement de Psychiatrie, Hopital Louis Mourier, Colombes, France.
(34)Service de Psychiatrie d’adultes B, Centre Expert Trouble Bipolaire, CHU de
Clermont-Ferrand, Clermont-Ferrand, France.
The object of this study is test whether mitochondrial blood-based biomarkers
are associated with markers of metabolic syndrome in bipolar disorder,
hypothesizing higher lactate but unchanged cell-free circulating mitochondrial
DNA levels in bipolar disorder patients with metabolic syndrome. In a cohort
study, primary testing from the FondaMental Advanced Centers of Expertise for
bipolar disorder (FACE-BD) was conducted, including 837 stable bipolar disorder
patients. The I-GIVE validation cohort consists of 237 participants: stable and
acute bipolar patients, non-psychiatric controls, and acute schizophrenia
patients. Multivariable regression analyses show significant lactate association
with triglycerides, fasting glucose and systolic and diastolic blood pressure.
Significantly higher levels of lactate were associated with presence of
metabolic syndrome after adjusting for potential confounding factors.
Mitochondrial-targeted metabolomics identified distinct metabolite profiles in
patients with lactate presence and metabolic syndrome, differing from those
without lactate changes but with metabolic syndrome. Circulating cell-free
mitochondrial DNA was not associated with metabolic syndrome. This thorough
analysis mitochondrial biomarkers indicate the associations with lactate and
metabolic syndrome, while showing the mitochondrial metabolites can further
stratify metabolic profiles in patients with BD. This study is relevant to
improve the identification and stratification of bipolar patients with metabolic
syndrome and provide potential personalized-therapeutic opportunities.
Copyright © 2024. Published by Elsevier B.V.
DOI: 10.1016/j.psychres.2024.116063
PMID: 39003800 [Indexed for MEDLINE]
Conflict of interest statement: Declaration of competing interest Kassandra A.
Zachos: none Jaehyoung Choi: none Ophelia Godin: none Timofei Chernega: none
Haejin Angela Kwak: none Jae H. Jung: none Bruno Aouizerate: none Valérie Aubin:
none Frank Bellivier: none Raoul Belzeaux R: none Philippe Courtet: none
Caroline Dubertret: none Bruno Etain: none Emmanuel Haffen: none Antoine Lefrere
A: none Pierre-Michel Llorca: none Emilie Olié: none Mircea Polosan: none
Ludovic Samalin: none Raymund Schwan: none Paul Roux: none Caroline Barau: none
Jean Romain Richard: none Ryad Tamouza: none Ana C. Andreazza: none Marion
Leboyer: none