Refining criteria for a neurodevelopmental sub-phenotype of bipolar disorders: a FondaMental Advanced Centers of Expertise for Bipolar Disorders study.
Biological Psychiatry. 2024-10-01; :
DOI: 10.1016/j.biopsych.2024.09.025
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1. Biol Psychiatry. 2024 Oct 10:S0006-3223(24)01654-8. doi:
10.1016/j.biopsych.2024.09.025. Online ahead of print.
Refining criteria for a neurodevelopmental sub-phenotype of bipolar disorders: a
FondaMental Advanced Centers of Expertise for Bipolar Disorders study.
Lefrere A(1), Godin O(2), Jamain S(2), Dansou Y(3), Samalin L(4), Alda M(5),
Aouizerate B(6), Aubin V(7), Rey R(8), Contu M(9), Courtet P(10), Dubertret
C(11), Haffen E(12), Januel D(13), Leboyer M(2), Llorca PM(4), Marlinge E(14),
Manchia M(9), Neilson S(15), Olié E(10), Paribello P(16), Pinna M(17), Polosan
M(18), Roux P(19), Schwan R(20), Tondo L(21), Walter M(22), Tzavara E(23),
Auzias G(15), Deruelle C(15), Etain B(2), Belzeaux R(24).
Author information:
(1)Pôle de Psychiatrie, Assistance Publique Hôpitaux de Marseille, Marseille,
France; Institut de Neurosciences de la Timone, Aix-Marseille Univ, UMR CNRS,
France; Fondation Fondamental, F-94010, Créteil, France.
(2)Univ Paris Est Créteil, INSERM, IMRB, Translational Neuro-Psychiatry, AP-HP,
DMU IMPACT, FHU ADAPT, Fondation Fondamental, F-94010; Fondation Fondamental,
F-94010, Créteil, France.
(3)Fondation Fondamental, F-94010, Créteil, France; Fondation Fondamental,
F-94010, Créteil, France.
(4)Department of Psychiatry, CHU Clermont-Ferrand, University of Clermont
Auvergne, CNRS, Clermont Auvergne INP, Institut Pascal (UMR 6602),
Clermont-Ferrand, France; Fondation Fondamental, F-94010; Fondation Fondamental,
F-94010, Créteil, France.
(5)Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada;
National Institute of Mental Health, Klecany, Czech Republic.
(6)Centre Hospitalier Charles Perrens, Laboratoire NutriNeuro (UMR INRA 1286),
Université de Bordeaux, Bordeaux, France; Fondation Fondamental, F-94010;
Fondation Fondamental, F-94010, Créteil, France.
(7)Pôle de Psychiatrie, Centre Hospitalier Princesse Grace, Monaco; Fondation
Fondamental, F-94010, Créteil, France; Fondation Fondamental, F-94010, Créteil,
France.
(8)Bipolar Disorder Expert Centre, Le Vinatier Hospital, Bron; University Lyon
1, Villeurbanne; INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research
Center, Psychiatric Disorders, Neuroscience Research and Clinical Research Team,
Lyon, F-69000, France; Fondation Fondamental, F-94010, Créteil, France.
(9)Section of Psychiatry, Department of Medical Sciences and Public Health,
University of Cagliari, Cagliari, Italy.
(10)CHU Montpellier, Hôpital Lapeyronie, Psychiatric Emergency and Post
Emergency Department, Pole Urgence; IGF, Université de Montpellier, CNRS,
INSERM, Montpellier, France; Fondation Fondamental, F-94010, Créteil, France;
Fondation Fondamental, F-94010, Créteil, France.
(11)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; Fondation Fondamental, F-94010, Créteil, France; Fondation Fondamental,
F-94010, Créteil, France.
(12)Service de Psychiatrie de l’Adulte, CIC-1431 INSERM, CHU de Besançon,
Laboratoire de Neurosciences, UFC, UBFC, Besançon, France; Fondation
Fondamental, F-94010, Créteil, France; Fondation Fondamental, F-94010, Créteil,
France.
(13)Unité de Recherche Clinique, EPS Ville-Evrard, 93332 Neuilly-sur-Marne,
France; Fondation Fondamental, F-94010, Créteil, France; Fondation Fondamental,
F-94010, Créteil, France.
(14)GHU Paris Nord, DMU Neurosciences, Hôpital Fernand Widal AP-HP, Paris,
France; Fondation Fondamental, F-94010, Créteil, France; Fondation Fondamental,
F-94010, Créteil, France.
(15)Institut de Neurosciences de la Timone, Aix-Marseille Univ, UMR CNRS,
France.
(16)Lucio Bini Mood Disorder Centers, Cagliari, Italy.
(17)Section of Psychiatry, Department of Medical Sciences and Public Health,
University of Cagliari, Cagliari, Italy; Lucio Bini Mood Disorder Centers,
Cagliari, Italy.
(18)Université Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble
Institut Neurosciences, Grenoble, France; Fondation Fondamental, F-94010,
Créteil, France; Fondation Fondamental, F-94010, Créteil, France.
(19)Centre Hospitalier de Versailles, Service Hospitalo-Universitaire de
Psychiatrie d’Adultes et d’Addictologie, Le Chesnay; Université Paris-Saclay;
Université de Versailles Saint-Quentin-En-Yvelines; DisAP-DevPsy-CESP, INSERM
UMR1018, Villejuif, France; Fondation Fondamental, F-94010, Créteil, France;
Fondation Fondamental, F-94010, Créteil, France.
(20)Université de Lorraine, Centre Psychothérapique de Nancy, Inserm U1254,
Nancy, France; Fondation Fondamental, F-94010, Créteil, France; Fondation
Fondamental, F-94010, Créteil, France.
(21)Lucio Bini Mood Disorder Centers, Cagliari and Rome, Italy; International
Consortium for Mood & Psychotic Disorders Research, Mailman Research Center,
McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical
School, Boston, MA, USA.
(22)Service Hospitalo-Universitaire de Psychiatrie Générale et de Réhabilitation
Psycho Sociale 29G01 et 29G02, CHRU de Brest, Hôpital de Bohars, Brest, France;
Fondation Fondamental, F-94010, Créteil, France; Fondation Fondamental, F-94010,
Créteil, France.
(23)Université Paris Cité, 75005 Paris, France; CNRS, UMR 8002, 75006 Paris,
France; Pôle de Psychiatrie, Assistance Publique Hôpitaux de Marseille,
Marseille, France.
(24)CHU Montpellier, Hôpital Lapeyronie, Psychiatric Emergency and Post
Emergency Department, Pole Urgence; IGF, Université de Montpellier, CNRS,
INSERM, Montpellier, France; Fondation Fondamental, F-94010, Créteil, France;
Fondation Fondamental, F-94010, Créteil, France. Electronic address:
.
BACKGROUND: Bipolar disorder (BD) is a complex and heterogeneous psychiatric
disorder. Neurodevelopmental factors were suggested to contribute to the
etiology of BD, yet a specific neurodevelopmental phenotype of the disorder
remains unidentified. Our objective was to define and characterize a
neurodevelopmental phenotype (NDP) in BD and validate its associations with
clinical outcomes, polygenic risk scores (PGS), and treatment responses.
METHOD: We analyzed the FACE-BD cohort of 4,468 BD patients, a validation cohort
of 101 BD patients, and two independent replication datasets of 274 and 89 BD
patients. Using factor analyses, we identified a set of criteria for defining
NDP. We next developed a scoring system for NDP-load and assessed its
association with prognosis, neurological soft signs, polygenic risk scores for
neurodevelopmental disorders, and responses to treatment using multiple
regressions, adjusted for age and sex with bootstrap replications.
RESULTS: Our study established a NDP in BD consisting of nine clinical features:
advanced paternal age, advanced maternal age, childhood maltreatment, attention
deficit hyperactivity disorder (ADHD), early onset of BD, early onset of
substance use disorders, early onset of anxiety disorders, early onset of eating
disorders, specific learning disorders. Patients with higher NDP-load showed a
worse prognosis and increased neurological soft signs. Notably, these
individuals exhibited a poorer response to lithium treatment. Furthermore, a
significant positive correlation was observed between the NDP-load and PGS for
ADHD suggesting potential overlapping genetic factors or pathophysiological
mechanisms between BD and ADHD.
CONCLUSIONS: The proposed NDP constitutes a promising clinical tool for patient
stratification in BD.
Copyright © 2024. Published by Elsevier Inc.
DOI: 10.1016/j.biopsych.2024.09.025
PMID: 39395474