The Interaction of Polygenic Susceptibility to Stress and Childhood Adversity Dimensions Predicts Longitudinal Trajectories of Stress‐Sensitivity in Stress and Health

Stress-sensitivity (SS) is considered a psychobiological trait possibly resulting from the interaction of genetic and environmental factors (GxE). This study examined whether the interaction of SS-related genetic markers with interview-based dimensions of childhood adversity predicted longitudinal trajectories of low versus high SS. Participants were nonclinically-ascertained young adults comprising normative and elevated scores on schizotypy. SS trajectories were defined in a previous report based on three prospective assessments (23.5, 25, 28 years-old) of both retrospective (Perceived Stress Scale; PSS) and momentary (Experience Sampling Methodology; ESM) stress ratings. A total of n = 177 and n = 165 participants with PSS and ESM stress-sensitivity trajectories, respectively, as well as genetic data, were included in the study. GxE effects between a SS Polygenic Risk Score (PRS-SS) and a Genetic Risk Score of the Hypothalamic Pituitary Adrenal axis (GRS-HPA) with childhood adversity dimensions (Intrafamilial Adversity, Threat and Deprivation) on SS trajectories were examined. Threat was the most consistent predictor of persistently high SS. PRS-SS moderated the association of Threat with high-PSS. GRS-HPA moderated the effects of all adversity dimensions on high-PSS. The interaction of PRS-SS with Deprivation and GRS-HPA with Intrafamilial Adversity predicted trajectories of momentary social stress, but the effects were driven by those with lower genetic susceptibility. Genetic-HPA-axis moderates the effects of all adversity dimensions on persistent SS trajectories, as well as PRS-SS and Threat, particularly for retrospective stress measure. The findings highlight the complex interplay between GxE factors and suggest that PSS may better capture SS trait. Including biologically-meaningful GRS indexing SS and adversity dimensions in future studies using comprehensive stress measures would enhance our knowledge on high SS susceptibility and its relationship with diverse psychopathological outcomes.