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Refining Criteria for a Neurodevelopmental Subphenotype of Bipolar Disorders: A FondaMental Advanced Centers of Expertise for Bipolar Disorders Study
A. Lefrere, O. Godin, S. Jamain, Y. Dansou, L. Samalin, M. Alda, B. Aouizerate, V. Aubin, R. Rey, M. Contu, P. Courtet, C. Dubertret, E. Haffen, D. Januel, M. Leboyer, PM. Llorca, E. Marlinge, M. Manchia, S. Neilson, E. Olié, P. Paribello, M....
Biological psychiatry.
2025 ;
97 (8) :
806-815.
[pub] 20241010
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
Perzistentní odkaz
https://www.medvik.cz/link/bmc25009303
- MeSH
- bipolární porucha * genetika MeSH
- dospělí MeSH
- fenotyp * MeSH
- hyperkinetická porucha genetika MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- multifaktoriální dědičnost genetika MeSH
- neurovývojové poruchy genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. It has been suggested that neurodevelopmental factors contribute to the etiology of BD, but a specific neurodevelopmental phenotype (NDP) of the disorder has not been identified. Our objective was to define and characterize an NDP in BD and validate its associations with clinical outcomes, polygenic risk scores, and treatment responses. METHODS: We analyzed the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort of 4468 patients with BD, a validation cohort of 101 patients with BD, and 2 independent replication datasets of 274 and 89 patients with BD. Using factor analyses, we identified a set of criteria for defining NDP. Next, we 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 gender with bootstrap replications. RESULTS: Our study established an NDP in BD consisting of 9 clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention-deficit/hyperactivity disorder, early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, and 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 NDP load and polygenic risk score for attention-deficit/hyperactivity disorder, suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and attention-deficit/hyperactivity disorder. CONCLUSIONS: The proposed NDP constitutes a promising clinical tool for patient stratification in BD.
Bipolar Disorder Expert Centre Le Vinatier Hospital University Lyon Bron France
Centre National de la Recherche Scientifique UMR 8002 Paris France
Department of Psychiatry Dalhousie University Halifax Nova Scotia Canada
Department of Psychiatry Harvard Medical School Boston Massachusetts
Fondation Fondamental Créteil France
Lucio Bini Mood Disorder Centers Cagliari Italy
National Institute of Mental Health Klecany Czech Republic
Pôle de Psychiatrie Assistance Publique Hôpitaux de Marseille Marseille France
Pôle de Psychiatrie Centre Hospitalier Princesse Grace Monaco
Unité de Recherche Clinique Etablissement public de santé Ville Evrard Neuilly sur Marne France
Université de Versailles Saint Quentin En Yvelines Versailles France
Université Paris Cité Paris France
Citace poskytuje Crossref.org
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- $a Lefrere, Antoine $u Pôle de Psychiatrie, Assistance Publique Hôpitaux de Marseille, Marseille, France; Institut de Neurosciences de la Timone, Aix-Marseille University, Unité mixte de recherche (UMR) Centre National de la Recherche Scientifique, Marseille, France; Fondation Fondamental, Créteil, France
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- $a Refining Criteria for a Neurodevelopmental Subphenotype of Bipolar Disorders: A FondaMental Advanced Centers of Expertise for Bipolar Disorders Study / $c A. Lefrere, O. Godin, S. Jamain, Y. Dansou, L. Samalin, M. Alda, B. Aouizerate, V. Aubin, R. Rey, M. Contu, P. Courtet, C. Dubertret, E. Haffen, D. Januel, M. Leboyer, PM. Llorca, E. Marlinge, M. Manchia, S. Neilson, E. Olié, P. Paribello, M. Pinna, M. Polosan, P. Roux, R. Schwan, L. Tondo, M. Walter, E. Tzavara, G. Auzias, C. Deruelle, B. Etain, R. Belzeaux
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- $a BACKGROUND: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. It has been suggested that neurodevelopmental factors contribute to the etiology of BD, but a specific neurodevelopmental phenotype (NDP) of the disorder has not been identified. Our objective was to define and characterize an NDP in BD and validate its associations with clinical outcomes, polygenic risk scores, and treatment responses. METHODS: We analyzed the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort of 4468 patients with BD, a validation cohort of 101 patients with BD, and 2 independent replication datasets of 274 and 89 patients with BD. Using factor analyses, we identified a set of criteria for defining NDP. Next, we 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 gender with bootstrap replications. RESULTS: Our study established an NDP in BD consisting of 9 clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention-deficit/hyperactivity disorder, early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, and 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 NDP load and polygenic risk score for attention-deficit/hyperactivity disorder, suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and attention-deficit/hyperactivity disorder. CONCLUSIONS: The proposed NDP constitutes a promising clinical tool for patient stratification in BD.
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- $a Godin, Ophélia $u Fondation Fondamental, Créteil, France; University Paris Est Créteil, Institut National de la Santé et de la Recherche Médicale, Institut Mondor de Recherche Biomédicale, Translational Neuro-Psychiatry, Assistance Publique-Hôpitaux de Paris, Département Médico-Universitaire de Psychiatrie et d'Addictologie (DMU IMPACT), Fédération Hospitalo-Universitaire de Médecine de Précision en Psychiatrie (FHU ADAPT)
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- 700 1_
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- 700 1_
- $a Aubin, Valérie $u Fondation Fondamental, Créteil, France; Pôle de Psychiatrie, Centre Hospitalier Princesse Grace, Monaco
- 700 1_
- $a Rey, Romain $u Fondation Fondamental, Créteil, France; Bipolar Disorder Expert Centre, Le Vinatier Hospital, University Lyon, Bron, France; University Lyon 1, Institut National de la Santé et de la Recherche Médicale U1028, Centre National de la Recherche Scientifique, UMR 5292, Villeurbanne, Lyon, France; Lyon Neuroscience Research Center, Psychiatric Disorders, Neuroscience Research and Clinical Research Team, Villeurbanne, Lyon, France
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Tondo, Leonardo $u Lucio Bini Mood Disorder Centers, Cagliari, Italy; International Consortium for Mood & Psychotic Disorders Research, Mailman Research Center, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
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- 700 1_
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- 700 1_
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- 700 1_
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