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Development and validation of a prognostic model and risk calculator for the estimation of bipolar-spectrum disorder risk in hospitalised adolescents with non-psychotic/non-bipolar mental disorders

Lookup NU author(s): Dr Aditya SharmaORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© The Author(s) 2025.We aimed to develop and validate a risk estimation model for developing bipolar-spectrum disorders (BSD) in psychiatrically hospitalized adolescents based on clinical characteristics, including putatively prodromal symptoms. Adolescent inpatients (ages = 12–18 years) with non-psychotic/non-BSD diagnoses were recruited for the Adolescent Mood Disorder and Psychosis Study (AMDPS), a longitudinal, prospective 5-year follow-up cohort. We assessed prevalence and severity of syndromal/subsyndromal psychopathology at baseline using the validated Bipolar Prodrome Symptom Interview and Scale–Prospective. We carried out machine learning analyses (Lasso-Cox regression analyses, LCR) to create a calculator to estimate the risk of developing BSD based on baseline demographic/comorbidity/illness/treatment characteristics. Of 105 adolescents (age = 15.6 ± 1.3 years, females = 72.4%), we observed that 18 developed BSD. The cumulated estimated risk of BSD was 5/22/29/36% at 1/2/3/4 years. BSD development was associated with presence of persistent depressive disorder (HR = 4.0, p < 0.018) at baseline, treatment with mood stabilizers (hazard ratio (HR) = 3.9, p = 0.006), and ADHD medications (HR = 3.3, p = 0.023). BSD development risk estimation calculator included the prevalence of inflated self-esteem/grandiosity (β = 0.83) and racing thoughts (β = 0.08) and the severity of overtalkativeness (β = 0.03) and increased energy (β = 0.04). For predicting BSD onset within the first 20 months, the area under the receiver operating characteristic curve (AUC) indicated acceptable to strong discrimination (cross-validation AUC = 0.72; bootstrap out-of-bag validation AUC = 0.86). Codes used in this study are provided in the R package “easy.glmnet”. In conclusion, in this prognostic model/calculator, presence and severity of subthreshold (hypo)mania-like symptoms conferred increased risk of BSD development in youth, informing preventive efforts to identify individuals at risk for BSD and improve their outcomes.

Publication metadata

Author(s): Salazar de Pablo G, Radua J, Frearson G, Young AH, Arango C, Kelleher I, Sharma A, Uhlhaas PJ, Solmi M, Fusar-Poli P, Guinart D, Correll CU

Publication type: Article

Publication status: Published

Journal: Molecular Psychiatry

Year: 2026

Volume: 31

Pages: 1333–1342

Print publication date: 01/03/2026

Online publication date: 29/09/2025

Acceptance date: 05/09/2025

Date deposited: 13/10/2025

ISSN (print): 1359-4184

ISSN (electronic): 1476-5578

Publisher: Springer Nature

URL: https://doi.org/10.1038/s41380-025-03244-1

DOI: 10.1038/s41380-025-03244-1

Data Access Statement: Data is available upon request to the corresponding author.

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