(Cambridge University Press, 2023) Cuesta, Manuel J.; Papiol, S.; Ibáñez Beroiz, Berta; García de Jalón, Elena; Sánchez Torres, Ana María; Gil Berrozpe, Gustavo José; Moreno-Izco, Lucía; Zarzuela, Amalia; Fañanás, Lourdes; Peralta Martín, Víctor; SEGPEPs Group; Ciencias de la Salud; Osasun Zientziak
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 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.
