Role of resilience in modifying the links between genetic propensity for mental disorders and irritability

We examined (1) whether polygenic risk scores for schizophrenia (PRS_SCZ), major depression (PRS_MDD), and posttraumatic stress disorder (PRS_PTSD) explain irritability between ages 20 and 50 and (2) whether these associations are modified by early psychosocial resilience.

Participants came from the prospective, population-based Young Finns Study (n = 1272-2212). The most recent available genome-wide association studies were used to calculate PRSs. Irritability was assessed over a 15-year follow-up (participants being 20-50 years old). Early resilience was assessed across five indices: psychological strength, social satisfaction, leisure time activities, responsible health behaviors, and school career. Covariates included early family environment, traumatic experiences, health behaviors, and socioeconomic factors.

PRS_MDD and PRS_PTSD showed robust positive associations with irritability, whereas PRS_SCZ was only modestly associated with higher disposition to behavioral form of irritability and only in earliest adulthood. We did not observe interactions between PRSs and most resilience indices (e.g., psychological strength, social satisfaction). However, school career and leisure time activities had interactions with PRSs, indicating a stronger protective effect against irritability in individuals with higher vs. lower PRSs. PRS_MDD and PRS_PTSD have clearly more robust associations with irritability compared to PRS_SCZ.

Polygenic liabilities for affective disorders but not schizophrenia are associated with higher irritability trajectories between ages 20 and 50 years. Individuals with higher or lower PRSs appeared to benefit from early resilience indices in a largely similar manner, except for school career and leisure time activities, which seemed to have particularly strong protective effects in individuals with high PRSs.