The polygenic basis of relapse after a first episode of schizophrenia
Àlex G. Segura, L. Prohens, Patricia Gassó, Natàlia Rodríguez, Clemente García‐Rizo, Lucía Moreno-Izco, Álvaro Andreu-Bernabeu, Iñaki Zorrilla, Anna Mané, Natàlia Rodríguez, Alexandra Roldán, Salvador Sarró, Ángela Ibáñez, Judith Usall, Pilar A. Sáiz, Manuel J. Cuesta, Mara Parellada, Ana González‐Pinto, Ester Berrocoso, Miquel Bernardo, Sergi Mas, Gisela Mezquida, Néstor Arbelo, Mario De Matteis, Joaquín Galvañ, Alejandra Duque Guerra, Laia Arias i Queralt, Maria Perez-Bacigalupe, Itxaso González–Ortega, Alba Toll, Francesc Roma i Casanovas, Luis Sánchez-Pastor, Mercedes Valtueña, Edith Pomarol‐Clotet, María Ángeles García‐León, Ana Butjosa, Elena Rubio‐Abadal, María Ribeiro, Jose M. López-Ilundain, Pilar A. Sáiz, Luis León-Quismondo, Olga Rivero, Pedro Ruiz, Rafael Segarra Echevarría, María Paz García‐Portilla
Abstract
Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI [0.11-0.73]) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse.