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Lookup NU author(s): Emeritus Professor Jan Scott
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Importance: Transdiagnostic clinical staging models for mental disorders are receiving increased attention. However, their underlying assumptions are underresearched; for example, it is not clear whether the observed progression across stages occurs independently of preexisting risk factors. Objectives: To test the likelihood of progression from stage 0 (familial risk) in childhood to stage 1a (mild symptoms) in adolescence and subsequently to stage 1b (clinically significant symptoms) in young adulthood, accounting for confounders, and to explore potential mediators. Design, Setting, and Participants: This prospective cohort study included participants from the Avon Longitudinal Study of Parents and Children (ALSPAC). ALSPAC included pregnant women and their offspring residing in Avon, United Kingdom, between 1991 and 1992, with a proportion of offspring followed up into young adulthood. Eligible participants provided data on stage determinants and potential confounders from birth until age 24 years. Data were collected from 1991 to 2015 and analyzed from January 2002 to June 2025. Exposures: Exposures were clinical stages 0 and 1a in separate tests of association with stages 1a and 1b, respectively. Criteria for stage 0 were the presence of schizophrenia or severe depression in a first-degree relative. Criteria for stage 1a were the presence of 1 to 2 symptoms of depression, anxiety, or psychosis at ages 12 to 13 years. Main Outcomes and Measures: Outcomes were stage 1a in adolescence and stage 1b in young adulthood. Criteria for stage 1b were at least moderate symptoms of depression, anxiety, or psychosis, with associated functional impact at ages 18 to 24 years. Confounders were sex assigned at birth, obstetric risk, parental social class, ethnicity, family adversity, temperament, early life events, and neurocognition, measured in childhood. Results: Among those with complete data at all 3 time points (1375 participants; weighted, 7342), 796 participants (57.9%; weighted, 51.5%) were female and 579 (42.1%; weighted, 48.5%) were male. After adjusting for potential confounders, there was an association between stage 0 in childhood and stage 1a in adolescence (3860 participants; weighted, 7388 participants; odds ratio [OR], 1.65, 95% CI, 1.30-2.11) and between stage 1a in adolescence and stage 1b in young adulthood (1661 participants; weighted, 7466 participants; OR, 2.07; 95% CI, 1.07-4.01). Level of neuroticism in adolescence mediated 18% of the association between stage 1a in adolescence and stage 1b in young adulthood. Conclusions and Relevance: In this cohort study, young people with mental health problems meeting criteria for early clinical stages were at heightened risk of developing subsequent stages, independent of early life risk factors. This study supports the assumption of progression underlying clinical staging models for mental disorders.
Author(s): Ratheesh A, Chen Y, Hammond D, Aitken Z, Shah J, Iorfino F, Scott J, Hickie I, Davey C, Chanen A, Berk M, McGorry P, Marwaha S, Thompson A, Nelson B
Publication type: Article
Publication status: Published
Journal: JAMA Psychiatry
Year: 2025
Volume: 82
Issue: 11
Pages: 1113-1122
Print publication date: 01/11/2025
Online publication date: 24/09/2025
Acceptance date: 21/07/2025
ISSN (print): 2168-622X
ISSN (electronic): 2168-6238
Publisher: American Medical Association
URL: https://doi.org/10.1001/jamapsychiatry.2025.2648
DOI: 10.1001/jamapsychiatry.2025.2648
PubMed id: 40991272
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