Genetic Differences in Reactivity to the Environment Impact Psychotic-Like and Affective Reactivity in Daily Life.

Abstract

Background and Hypothesis: Consistent with diathesis-stress models, psychosis research has focused on geneticmoderation of adverse environmental exposures. In con-trast, the Differential Susceptibility (DS) model suggeststhat the same genetic variants that increase risk-inducingeffects of adverse experiences also enhance beneficial ef-fects from positive experiences. This study examinedwhether individuals with high genetic susceptibility to theenvironment showed differential psychotic-like and affec-tive reactivity in response to positive and negative events indaily life. Study Design: Experience sampling methodologyassessed context (positive and stressful) and momentarylevels of paranoia, psychotic-like experiences (PLE), andpositive (PA) and negative affect (NA) in 217 non-clinicaladults oversampled for schizotypy. Linear mixed modelsexamined whether Polygenic Risk Scores of EnvironmentalSensitivity (PRS-ES) moderated the impact of current con-text on subsequent experiences. Study Results: PRS-ESmoderated positive, but not stressful, context on subsequentlevels of momentary paranoia, NA, and PA, but not PLE.Genetic and environmental (G × E) interactions indicateddiathesis-stress at lower thresholds of PRS-ES, but a DSmodel at the highest threshold of the PRS-ES. Participantswith elevated PRS-ES showed increased paranoia and NAand decreased PA in subsequent assessments when re-porting low levels of positive situations, but also decreasedparanoia and NA and increased PA when rating contextsas positive. Conclusions: Findings support the influence ofgenetic sensitivity to the environment on psychotic-like andaffective reactivity in daily life, particularly in response topositive contexts. This highlights the transdiagnostic pro-tective role of positive experiences and informs ecologicalmomentary interventions.