Genetic Sensitivity to the Environment Moderates the Impact of Positive and Negative Childhood Experiences on Psychological Adjustment “For Good and for Bad”

Background: The vulnerability-stress framework guiding gene-environment interaction (GxE) research overlooks the role of positive experiences. The Differential Susceptibility (DS) model offers a broader perspective, suggesting that individuals vary in sensitivity to both negative and positive environments. This study aimed at replicating previous DS research by examining interactions between Polygenic Scores for Environmental Sensitivity (PGS-ES) and positive and negative early exposures on subclinical psychosis and internalizing psychopathology, functioning, and wellbeing. Methods: The sample consisted of 638 twins from the first wave of the TwinssCan study, a general population twin cohort. PGS-ES and adversity, bullying and positive experiences in childhood were collected, along with assessments of psychotic, affective, functioning and positive mental health. GxE interactions were tested under a competitive-confirmatory approach. Results: DS effects were found for the interactions between PGS-ES and all environmental exposures on schizotypic eccentricity and functioning. Adolescents with high genetic sensitivity were rated as more eccentric and less functional under childhood adversity, but were rated as less eccentric and better adjusted under childhood favorable conditions. DS also resulted from the interaction between PGS-ES and positive childhood on social coping. No significant models emerged for internalizing or wellbeing. Conclusion: Findings overall supported DS, indicating that genetic sensitivity to the environment operates in a “for better and for worse” manner depending on the quality of environmental exposures. It extends initial evidence that DS applies to nonclinical psychosis expression and highlights the importance of considering the full spectrum of environmental conditions to understand both risk and opportunity factors in GxE.