Published online by Cambridge University Press: 28 February 2023
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.
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.
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.
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.
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