Schizophrenia polygenic risk score: Zooming-in on early, non-psychotic developmental expressions of vulnerability

Polygenic Risk Scores (PRS) are proxy values generated combining multiple genetic markers into a single score indicative of specific lifetime risk for a disease. The PRS approach has been increasingly implemented in psychiatry, especially for the study of schizophrenia. Although the majority of studies on PRS focused on possible associations with overt clinical features in patients with already diagnosed schizophrenia spectrum disorders, an emerging trend involves early phenotypic expression of genetic risk for schizophrenia in the general population. This article offers an update on this emerging trend, focusing on how the genetic risk for schizophrenia is early expressed at an endophenotypic level, through a broad range of soft non-psychotic neurocognitive and behavioral manifestations. These features might be integrated with other prediction paradigms, such as familial-high-risk, neurodevelopmental and clinical staging models, to empower and refine early detection strategies.