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

Cuesta, Manuel J.Papiol, S.Ibáñez Beroiz, BertaGarcía de Jalón, ElenaSánchez Torres, Ana MaríaGil Berrozpe, Gustavo JoséMoreno-Izco, LucíaZarzuela, AmaliaFañanás, LourdesPeralta Martín, VíctorSEGPEPs Group2024-04-162024-04-162023Cuesta, M. J., Papiol, S., Ibañez, B., García De Jalón, E., Sánchez-Torres, A. M., Gil-Berrozpe, G. J., Moreno-Izco, L., Zarzuela, A., Fañanás, L., Peralta, V. (2023) 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. Psychological Medicine, 53(14), 6838-6847. https://doi.org/10.1017/S0033291723000351.0033-291710.1017/S0033291723000351https://academica-e.unavarra.es/handle/2454/47977Background. 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 longterm 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.application/pdfapplication/mswordeng© The Author(s), 2023.Exposome risk score (ERS)First episode psychosisGene-environment interactionOutcomePolygenic risk score (PRS)SchizophreniaEffect of polygenic risk score, family load of schizophrenia and exposome risk score, and their interactions, on the long-term outcome of first-episode psychosisinfo:eu-repo/semantics/article2024-04-16info:eu-repo/semantics/openAccess