Refining Criteria for a Neurodevelopmental Subphenotype of Bipolar Disorders: A FondaMental Advanced Centers of Expertise for Bipolar Disorders Study
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
39395474
DOI
10.1016/j.biopsych.2024.09.025
PII: S0006-3223(24)01654-8
Knihovny.cz E-resources
- Keywords
- Bipolar disorder, Genomics, Lithium response, Neurodevelopment, Neurologic soft sign, Stratification,
- MeSH
- Bipolar Disorder * genetics diagnosis classification drug therapy MeSH
- Adult MeSH
- Phenotype MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Multifactorial Inheritance MeSH
- Neurodevelopmental Disorders * diagnosis MeSH
- Risk Factors MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article 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.
Fondation Fondamental Créteil France
Fondation Fondamental Créteil France; Pôle de Psychiatrie Centre Hospitalier Princesse Grace Monaco
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