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Effect of polygenic risk score, family load of schizophrenia and exposome risk score, and their interactions, on the long-term outcome of first-episode psychosis

Published online by Cambridge University Press:  06 March 2023

M. J. Cuesta Open the ORCID record for M. J. Cuesta [Opens in a new window] ,
S. Papiol ,
B. Ibañez ,
E. García de Jalón ,
A. M. Sánchez-Torres ,
G. J. Gil-Berrozpe ,
L. Moreno-Izco ,
A. Zarzuela ,
L. Fañanás  and
V. Peralta
...Show all authors
M. J. Cuesta*
Affiliation:
Department of Psychiatry, Hospital Universitario de Navarra, Pamplona, Spain Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
S. Papiol
Affiliation:
Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, 80336, Germany Max Planck Institute of Psychiatry, Munich, Germany
B. Ibañez
Affiliation:
Navarra Institute for Health Research (IdiSNA), Pamplona, Spain Navarrabiomed – Hospital Universitario de Navarra – UPNA, Pamplona, Spain Red de Investigación en Atención Primaria, Servicios Sanitarios y Cronicidad (RICAPPS), Barcelona, Spain
E. García de Jalón
Affiliation:
Navarra Institute for Health Research (IdiSNA), Pamplona, Spain Mental Health Department, Servicio Navarro de Salud, Pamplona, Spain
A. M. Sánchez-Torres
Affiliation:
Department of Psychiatry, Hospital Universitario de Navarra, Pamplona, Spain Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
G. J. Gil-Berrozpe
Affiliation:
Department of Psychiatry, Hospital Universitario de Navarra, Pamplona, Spain Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
L. Moreno-Izco
Affiliation:
Department of Psychiatry, Hospital Universitario de Navarra, Pamplona, Spain Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
A. Zarzuela
Affiliation:
Navarra Institute for Health Research (IdiSNA), Pamplona, Spain Mental Health Department, Servicio Navarro de Salud, Pamplona, Spain
L. Fañanás
Affiliation:
Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, University of Barcelona, Biomedicine Institute of the University of Barcelona (IBUB), Barcelona, Spain
V. Peralta
Affiliation:
Navarra Institute for Health Research (IdiSNA), Pamplona, Spain Mental Health Department, Servicio Navarro de Salud, Pamplona, Spain
SEGPEPs Group
Affiliation:
Red de Salud Mental de Álava, Vitoria-Gasteiz, Spain CSMIJ Ciutat Vella. Consorci Parc de Salut Mar, Barcelona, Spain
*
Author for correspondence: M. J. Cuesta, E-mail: mcuestaz@navarra.es
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Abstract

Background

Consistent evidence supports the involvement of genetic and environmental factors, and their interactions, in the etiology of psychosis. First-episode psychosis (FEP) comprises a group of disorders that show great clinical and long-term outcome heterogeneity, and the extent to which genetic, familial and environmental factors account for predicting the long-term outcome in FEP patients remains scarcely known.

Methods

The SEGPEPs is an inception cohort study of 243 first-admission patients with FEP who were followed-up for a mean of 20.9 years. FEP patients were thoroughly evaluated by standardized instruments, with 164 patients providing DNA. Aggregate scores estimated in large populations for polygenic risk score (PRS-Sz), exposome risk score (ERS-Sz) and familial load score for schizophrenia (FLS-Sz) were ascertained. Long-term functioning was assessed by means of the Social and Occupational Functioning Assessment Scale (SOFAS). The relative excess risk due to interaction (RERI) was used as a standard method to estimate the effect of interaction of risk factors.

Results

Our results showed that a high FLS-Sz gave greater explanatory capacity for long-term outcome, followed by the ERS-Sz and then the PRS-Sz. The PRS-Sz did not discriminate significantly between recovered and non-recovered FEP patients in the long term. No significant interaction between the PRS-Sz, ERS-Sz or FLS-Sz regarding the long-term functioning of FEP patients was found.

Conclusions

Our results support an additive model of familial antecedents of schizophrenia, environmental risk factors and polygenic risk factors as contributors to a poor long-term functional outcome for FEP patients.

Keywords

Exposome risk score (ERS)first episode psychosisgene-environment interactionoutcomepolygenic risk score (PRS)schizophrenia
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 14 , October 2023 , pp. 6838 - 6847
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Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press

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Footnotes

*

SEGPEPs Group: A. Ballesteros10, R. Hernández11, L. Janda2,8, R. Lorente2, D. Peralta2,8, M. Ribeiro1,2 and A. Rosero8

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