What does really matter in the premorbid background of psychosis leading to long-term disability? a 21-year follow-up cohort study of first-episode psychosis

Background: clinicians are currently unable to predict which patients are at higher risk of long-term disability based on premorbid factors. We aimed to determine the extent to which premorbid factors could prospectively predict long-term disability in patients with first-episode psychosis. Methods:...

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Autores: Peralta Martín, Víctor, García de Jalón, Elena, Moreno-Izco, Lucía, Sánchez Torres, Ana María, Gil Berrozpe, Gustavo José, Peralta, David, Janda-Galán, Lucía, Cuesta, Manuel J., SEGPEPs Group
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2025
País:España
Institución:Universidad Pública de Navarra
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/54420
Acceso en línea:https://hdl.handle.net/2454/54420
Access Level:acceso abierto
Palabra clave:Psychosis
Outcome
Disability
Premorbid
Risk factors
DAGs
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spelling What does really matter in the premorbid background of psychosis leading to long-term disability? a 21-year follow-up cohort study of first-episode psychosisPeralta Martín, VíctorGarcía de Jalón, ElenaMoreno-Izco, LucíaSánchez Torres, Ana MaríaGil Berrozpe, Gustavo JoséPeralta, DavidJanda-Galán, LucíaCuesta, Manuel J.SEGPEPs GroupPsychosisOutcomeDisabilityPremorbidRisk factorsDAGsBackground: clinicians are currently unable to predict which patients are at higher risk of long-term disability based on premorbid factors. We aimed to determine the extent to which premorbid factors could prospectively predict long-term disability in patients with first-episode psychosis. Methods: we assessed 12 potential premorbid risk factors in 243 individuals with first-episode psychosis reassessed 21 years later for several domains of psychosocial disability. Hierarchical multivariate regression and Directed Acyclic Graphs (DAGs) were used sequentially to investigate independent and causal associations between risk factors and long-term disability. Results: the familial load of schizophrenia, lower parental SES, obstetric complications, early neurodevelopmental delay, childhood adversity, and poor adolescence social networks were independent predictors of long-term disability, accounting for 40.6 % of the variability. The DAGs analysis showed that both familial risk of schizophrenia and lower SES had statistically significant direct and indirect effects on later disability. The indirect effects were mediated by the variables indexing impaired development, although childhood adversity and poor adolescence social networks also had significant direct effects on disability. Early neurodevelopmental delay was the only developmental marker present in all statistically significant indirect paths from familial background factors to long-term disability, suggesting that it is a key component of the causal chain that leads to later disability. Conclusions: in individuals with psychotic disorders, familial background factors appear to trigger a complex and multidetermined cascade of risk factors across developmental stages that interact iteratively, leading to long-term disability.This work was supported by the Spanish Ministry of Economy, Industry and Competitiveness (VP, grant numbers PI16/02148 ; EGJ and MJC, 19/01698), and the Regional Government of Navarra (VP, grant number 31/17), (LMI, grant number 41/18).ElsevierCiencias de la SaludOsasun ZientziakGobierno de Navarra / Nafarroako Gobernua2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/mswordhttps://hdl.handle.net/2454/54420reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarrainstname:Universidad Pública de NavarraInglésinfo:eu-repo/grantAgreement/MINECO//PI16%2F02148info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F01698info:eu-repo/grantAgreement/Gobierno de Navarra//© 2025 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:academica-e.unavarra.es:2454/544202026-06-17T12:41:47Z
dc.title.none.fl_str_mv What does really matter in the premorbid background of psychosis leading to long-term disability? a 21-year follow-up cohort study of first-episode psychosis
title What does really matter in the premorbid background of psychosis leading to long-term disability? a 21-year follow-up cohort study of first-episode psychosis
spellingShingle What does really matter in the premorbid background of psychosis leading to long-term disability? a 21-year follow-up cohort study of first-episode psychosis
Peralta Martín, Víctor
Psychosis
Outcome
Disability
Premorbid
Risk factors
DAGs
title_short What does really matter in the premorbid background of psychosis leading to long-term disability? a 21-year follow-up cohort study of first-episode psychosis
title_full What does really matter in the premorbid background of psychosis leading to long-term disability? a 21-year follow-up cohort study of first-episode psychosis
title_fullStr What does really matter in the premorbid background of psychosis leading to long-term disability? a 21-year follow-up cohort study of first-episode psychosis
title_full_unstemmed What does really matter in the premorbid background of psychosis leading to long-term disability? a 21-year follow-up cohort study of first-episode psychosis
title_sort What does really matter in the premorbid background of psychosis leading to long-term disability? a 21-year follow-up cohort study of first-episode psychosis
dc.creator.none.fl_str_mv Peralta Martín, Víctor
García de Jalón, Elena
Moreno-Izco, Lucía
Sánchez Torres, Ana María
Gil Berrozpe, Gustavo José
Peralta, David
Janda-Galán, Lucía
Cuesta, Manuel J.
SEGPEPs Group
author Peralta Martín, Víctor
author_facet Peralta Martín, Víctor
García de Jalón, Elena
Moreno-Izco, Lucía
Sánchez Torres, Ana María
Gil Berrozpe, Gustavo José
Peralta, David
Janda-Galán, Lucía
Cuesta, Manuel J.
SEGPEPs Group
author_role author
author2 García de Jalón, Elena
Moreno-Izco, Lucía
Sánchez Torres, Ana María
Gil Berrozpe, Gustavo José
Peralta, David
Janda-Galán, Lucía
Cuesta, Manuel J.
SEGPEPs Group
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ciencias de la Salud
Osasun Zientziak
Gobierno de Navarra / Nafarroako Gobernua
dc.subject.none.fl_str_mv Psychosis
Outcome
Disability
Premorbid
Risk factors
DAGs
topic Psychosis
Outcome
Disability
Premorbid
Risk factors
DAGs
description Background: clinicians are currently unable to predict which patients are at higher risk of long-term disability based on premorbid factors. We aimed to determine the extent to which premorbid factors could prospectively predict long-term disability in patients with first-episode psychosis. Methods: we assessed 12 potential premorbid risk factors in 243 individuals with first-episode psychosis reassessed 21 years later for several domains of psychosocial disability. Hierarchical multivariate regression and Directed Acyclic Graphs (DAGs) were used sequentially to investigate independent and causal associations between risk factors and long-term disability. Results: the familial load of schizophrenia, lower parental SES, obstetric complications, early neurodevelopmental delay, childhood adversity, and poor adolescence social networks were independent predictors of long-term disability, accounting for 40.6 % of the variability. The DAGs analysis showed that both familial risk of schizophrenia and lower SES had statistically significant direct and indirect effects on later disability. The indirect effects were mediated by the variables indexing impaired development, although childhood adversity and poor adolescence social networks also had significant direct effects on disability. Early neurodevelopmental delay was the only developmental marker present in all statistically significant indirect paths from familial background factors to long-term disability, suggesting that it is a key component of the causal chain that leads to later disability. Conclusions: in individuals with psychotic disorders, familial background factors appear to trigger a complex and multidetermined cascade of risk factors across developmental stages that interact iteratively, leading to long-term disability.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2454/54420
url https://hdl.handle.net/2454/54420
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MINECO//PI16%2F02148
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F01698
info:eu-repo/grantAgreement/Gobierno de Navarra//
dc.rights.none.fl_str_mv © 2025 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0
https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © 2025 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/msword
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
instname:Universidad Pública de Navarra
instname_str Universidad Pública de Navarra
reponame_str Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
collection Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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