Childhood Trauma Mediates the effects of Genetic Risk for Schizophrenia on Personality Traits

Abstract

Schizophrenia is a severely debilitating psychiatric disorder that is typically presented with phases of relapse and remission. Despite being widely known, schizophrenia remains one of the top causes of disability in the world, causing severe personal and societal burden from long term disability. The symptoms and etiology of schizophrenia remain poorly understood, but recent developments in our understanding of psychiatric genetic risk are beginning to contribute to our grasp of psychiatric conditions, including schizophrenia. One of these developments are Polygenic Risk Scores (PRS), which are a measure of an individual’s inherited liability to developing a trait, disease or disorder. Previous studies have shown that Schizophrenia Polygenic Risk Scores (SZ-PRS) and childhood trauma (CT) have strong associations with the Five-Factor Model (FFM) of Personality. This model, better known as the Big Five, divides personality into five traits: openness, conscientiousness, extraversion, agreeableness, and neuroticism. This thesis aims to examine the relationship between SZ-PRS and personality traits in a non-diagnosed population, subsequently looking into the possible gene-environment correlation between SZ-PRS and CT and examining the mediating role of CT in the relationship between SZ-PRS and personality traits. The analyses were performed using participants from the Utrecht Cannabis Cohort (N = 910). SZ-PRS were computed from the most recent Genome Wide Association Studies. The relationships between SZ-PRS, the FFM of personality and CT were first examined using linear regressions. Subsequently, mediation analyses of CT were performed to link the pathway of SZ-PRS to the FFM of personality. All analyses were corrected for age and sex. Our results are in line with previous research findings indicating that openness, conscientiousness, agreeableness and neuroticism are associated with SZ-PRS (B = .083, p = .020; B = -.112, p = .007; B = -.070, p = .039; B = .361, p = .017, respectively). No significant effect for extraversion was reported (B = -.073, p = .079). Furthermore, SZ-PRS was significantly associated with CT (B = .183, p = <.001), and CT was significantly associated with conscientiousness, extraversion, agreeableness and neuroticism (B = -.168, p = <.001; B = -.192, p = <.001; B = -.226, p = <.001; B = 1.215, p = <.001, respectively). Openness was not significantly affected by CT, thereby eliminating the possibility of a significant mediation effect. (B = .026, p = .253). The mediation analyses yielded results that indicate that CT fully mediated the relationship between SZ-PRS and agreeableness, extraversion and neuroticism and partially mediated the relationship between SZ-PRS and conscientiousness. Overall, age and sex displayed numerous group level differences across almost all analyses. Additional research is needed to support the current findings, but our results indicate that a genetic predisposition for developing schizophrenia influences the development of personality traits through the mechanisms of CT even before a clinical diagnosis.