Abstract
Research on gene-environment interactions in psychosis has been guided by diathesis-stress models, which emphasize the role of negative experiences. In contrast, the Differential Susceptibility (DS) model indicates that individuals differ in sensitivity to both adverse and supportive environments. This study replicates and expands an initial proof-of-concept DS study on psychosis by examining whether genetic sensitivity to the environment, indexed by polygenic scores of environmental sensitivity (PGS-ES) and psychotic-like experiences (PGS-PLE), moderated the impact of early-life positive and negative experiences on trans-syndromic outcomes, including subclinical psychotic features and positive mental health, in a DS manner. PGS and measures of early environmental, psychopathology, positive outcomes, and functioning were collected from 941 nonclinical young adults. A comprehensive factorial analysis of positive and negative environmental measures resulted in a general exposome score and four specific factors. A competitive-confirmatory approach examined DS patterns using LEGIT R package. Individuals with higher PGS-ES reported greater psychopathology, poorer functioning, and lower positive mental health outcomes when exposed to fewer positive experiences or poorer paternal parenting; but also exhibited less symptoms and more positive outcomes when exposed to supportive environments compared to individuals with lower PGS-ES. PGS-PLE only predicted psychopathology in a diathesis-stress manner. Findings support the trans-syndromic validity of the DS model, indicating that genetic susceptibility to the environment operated "for better and for worse" by impacting both ill and positive mental health. This highlights the importance of positive experiences and underscores the need to integrate risk and resilience models in psychosis.