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Editorial Perspective: From schizophrenia polygenic risk score to vulnerability (endo-)phenotypes: translational pathways in child and adolescent mental health.

The Polygenic Risk Scores (PRS) approach is becoming increasingly prominent in psycho-behavioral research, however, its translational potential is still relatively underconceptualized. Indeed, PRS paradigm (which capitalizes on the combination of multiple genetic markers into a single proxy score to predict lifetime outcomes) has the potential to unravel some of the developmental complexities leading to severe mental disorders. With respect to schizophrenia, the application of PRS approach to child-adolescent cohorts from the general population, provides a crucial vantage point for understanding how presumed genetic predisposition is manifested during developmental years. Clearly, this is essential for etiological research as well as for the timely identification of the earliest stages of those specific psychopathological trajectories leading to psychosis. Therefore, the translational import of the PRS approach could improve our etiopathogenetic understanding of schizophrenia (e.g., allowing the disentanglement of the respective contribution of genetic and environmental risk factors along neurodevelopment) and further refine current staging models for early detection of vulnerability to psychosis (e.g., providing the rationale for more developmentally oriented reformulations of clinical high-risk criteria).

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