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Definition of early age at onset in bipolar disorder according to distinctive neurodevelopmental pathways: insights from the FACE-BD study

Published online by Cambridge University Press:  28 February 2023

Filippo Corponi ,
Antoine Lefrere ,
Marion Leboyer ,
Frank Bellivier ,
Ophelia Godin ,
Josephine Loftus ,
Philippe Courtet ,
Caroline Dubertret ,
Emmanuel Haffen  and
Pierre Michel Llorca
...Show all authors
Filippo Corponi
Affiliation:
School of Informatics, University of Edinburgh, Edinburgh, UK
Antoine Lefrere
Affiliation:
Assistance Publique Hôpitaux de Marseille, Pôle de Psychiatrie, Marseille, France Fondation FondaMental, Créteil, France Institut de neurosciences de la Timone UMR 7289, Aix-Marseille Université & CNRS, Marseille, France
Marion Leboyer
Affiliation:
Fondation FondaMental, Créteil, France Assistance publique des hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, Département Médico-Universitaire de Psychiatrie et d'Addictologie (DMU IMPACT), Fédération Hospitalo-Universitaire de Médecine de Précision en Psychiatrie (FHU ADAPT), Créteil, France Translational NeuroPsychiatry Laboratory, Université Paris Est Créteil (UPEC), INSERM U955, IMRB, Paris, France
Frank Bellivier
Affiliation:
Fondation FondaMental, Créteil, France Université de Paris, INSERM UMR-S 1144, Optimisation Thérapeutique en Neuropsychopharmacologie OTeN, Paris, France Assistance publique des Hôpitaux de Paris, Groupe Hospitalo-universitaire AP-HP Nord, Hôpital Lariboisière, Département de Psychiatrie et de Médecine Addictologique, Paris, France
Ophelia Godin
Affiliation:
Fondation FondaMental, Créteil, France Translational NeuroPsychiatry Laboratory, Université Paris Est Créteil (UPEC), INSERM U955, IMRB, Paris, France
Josephine Loftus
Affiliation:
Fondation FondaMental, Créteil, France Pôle de Psychiatrie, Centre Hospitalier Princesse Grace, France, Monaco
Philippe Courtet
Affiliation:
Fondation FondaMental, Créteil, France IGF, Univ. Montpellier France, CNRS, INSERM, Montpellier, France Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France
Caroline Dubertret
Affiliation:
Fondation FondaMental, Créteil, France Assistance publique des hôpitaux de Paris, 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
Emmanuel Haffen
Affiliation:
Fondation FondaMental, Créteil, France Service de Psychiatrie, CIC-1431 INSERM, CHU de Besançon, France UR481 Neurosciences, UFC, Besançon, France
Pierre Michel Llorca
Affiliation:
Fondation FondaMental, Créteil, France CHU Clermont-Ferrand, Department of Psychiatry, University of Clermont Auvergne, UMR 6602 Institut Pascal (IP), Clermont-Ferrand, France
Paul Roux
Affiliation:
Centre Hospitalier de Versailles, Service Universitaire de Psychiatrie d'adulte et d'addictologie, Le Chesnay, France DisAP-DevPsy-CESP, INSERM UMR1018, Université de Versailles Saint-Quentin-En-Yvelines, Université Paris-Saclay, Villejuif, France
Mircea Polosan
Affiliation:
Fondation FondaMental, Créteil, France Grenoble Alpes University, Inserm U1216 Grenoble Institute of Neuroscience, CHU Grenoble Alpes, Grenoble, France
Raymund Schwan
Affiliation:
Fondation FondaMental, Créteil, France Université de Lorraine, Centre Psychothérapique de Nancy, Inserm U1254, Nancy, France
Ludovic Samalin
Affiliation:
Fondation FondaMental, Créteil, France CHU Clermont-Ferrand, Department of Psychiatry, University of Clermont Auvergne, UMR 6602 Institut Pascal (IP), Clermont-Ferrand, France
Emilie Olié
Affiliation:
Fondation FondaMental, Créteil, France IGF, Univ. Montpellier France, CNRS, INSERM, Montpellier, France Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France
Bruno Etain
Affiliation:
Fondation FondaMental, Créteil, France Université de Paris, INSERM UMR-S 1144, Optimisation Thérapeutique en Neuropsychopharmacologie OTeN, Paris, France Assistance publique des Hôpitaux de Paris, Groupe Hospitalo-universitaire AP-HP Nord, DMU Neurosciences, Hôpital Fernand Widal, Département de Psychiatrie et de Médecine Addictologique, Paris, France
Peggy Seriès
Affiliation:
School of Informatics, University of Edinburgh, Edinburgh, UK
Raoul Belzeaux*
Affiliation:
Pôle Universitaire de Psychiatrie, CHU de Montpellier, France
*
Author for correspondence: Raoul Belzeaux, E-mail: raoul.belzeaux@univ-amu
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Abstract

Background

Converging evidence suggests that a subgroup of bipolar disorder (BD) with an early age at onset (AAO) may develop from aberrant neurodevelopment. However, the definition of early AAO remains unprecise. We thus tested which age cut-off for early AAO best corresponds to distinguishable neurodevelopmental pathways.

Methods

We analyzed data from the FondaMental Advanced Center of Expertise-Bipolar Disorder cohort, a naturalistic sample of 4421 patients. First, a supervised learning framework was applied in binary classification experiments using neurodevelopmental history to predict early AAO, defined either with Gaussian mixture models (GMM) clustering or with each of the different cut-offs in the range 14 to 25 years. Second, an unsupervised learning approach was used to find clusters based on neurodevelopmental factors and to examine the overlap between such data-driven groups and definitions of early AAO used for supervised learning.

Results

A young cut-off, i.e. 14 up to 16 years, induced higher separability [mean nested cross-validation test AUROC = 0.7327 (± 0.0169) for ⩽16 years]. Predictive performance deteriorated increasing the cut-off or setting early AAO with GMM. Similarly, defining early AAO below 17 years was associated with a higher degree of overlap with data-driven clusters (Normalized Mutual Information = 0.41 for ⩽17 years) relatively to other definitions.

Conclusions

Early AAO best captures distinctive neurodevelopmental patterns when defined as ⩽17 years. GMM-based definition of early AAO falls short of mapping to highly distinguishable neurodevelopmental pathways. These results should be used to improve patients' stratification in future studies of BD pathophysiology and biomarkers.

Keywords

Age at onsetbipolar disordermachine learningneurodevelopment
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 14 , October 2023 , pp. 6724 - 6732
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Copyright
Copyright © Institut de Neurosciences de la Timone, 2023. Published by Cambridge University Press

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Footnotes

*

List of FondaMental Advanced Center of Expertise for Bipolar Disorders (FACE-BD) collaborators:

FACE-BD Clinical Coordinating Center (Fondation FondaMental): B. Etain, E. Olié, M. Leboyer, P.M. Llorca; FACE-BD Data Coordinating Center (Fondation FondaMental): V. Barteau, S. Bensalem, O. Godin, H. Laouamri, and K. Souryis; FACE-BD Clinical Sites and Principal Collaborators in France; AP-HP, DHU PePSY, Pôle de Psychiatrie et d’Addictologie des Hôpitaux Universitaires H Mondor, Créteil, France: S. Hotier, A. Pelletier; APHP, Groupe Hospitalo-universitaire AP-HP Nord, DMU Neurosciences, Département de Psychiatrie et Médecine Addictologie, Hôpital Fernand Widal, Paris, France: F. Bellivier, B. Etain, V. Hennion, E. Marlinge; Hôpital C. Perrens, Centre Expert Trouble Bipolaire, Service de Psychiatrie Adulte, Pôle 3-4-7, Bordeaux: B. Aouizerate, A. Desage, S. Gard; Département d’Urgence et Post Urgence Psychiatrique, CHRU Montpellier, Montpellier, France: P. Courtet, D. Ducasse, F. Molière, E. Olié; Pôle de Psychiatrie, addictologie et pédopsychiatrie, Hôpital Sainte Marguerite, Marseille, France: A. Lefrere, E.Moreau, J. Pastol; Pôle Hospitalo-Universitaire de Psychiatrie du Grand Nancy, Centre Psychothérapique de Nancy, Laxou, France: G. Gross, R. Schwan, T. Schwitzer; Service Universitaire de Psychiatrie, CHU de Grenoble et des Alpes, Grenoble, France: T. Bougerol, A. Pouchon and M. PolosanCentre Hospitalier de Versailles, Centre Hospitalier de Versailles, Service Universitaire de Psychiatrie d’Adultes et d’Addictologie, Le Chesnay: G. Bonny, L. Brehon, L. Durand, V. Feuga, A.M. Galliot, N. Kayser, C. Passerieux, and P. Roux; Service de Psychiatrie, Centre Hospitalier Princesse Grace, Monaco: V. Aubin, I. Cussac, J. Loftus; APHP, Groupe Hospitalo-universitaire AP-HP Nord, DMU ESPRIT, Service de psychiatrie et addictologie, Hôpital Louis Mourier, Colombes, France: C. Dubertret, N. Mazer. Service de Psychiatrie de l’adulte B, Centre Expert Trouble Bipolaire, CHU de Clermont-Ferrand, Clermont-Ferrand, France: P.M. Llorca, L. Samalin, O. Blanc. Service de Psychiatrie, Centre Expert Bipolaire, CHU de Besançon F-25030: E. Haffen, D. Bennabi

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