The effect of polygenic risk score and childhood adversity experiences on transdiagnostic symptom dimensions at first-episode psychosis: evidence for an affective pathway to psychosis

Abstract Background Childhood adversity is associated with various clinical dimensions in psychosis; however, how genetic vulnerability shapes the adversity associated psychopathological signature is yet to be clarified. Methods Using data from the EU-GEI study, in 376 First Episode Psychosis (FEP) cases, we evaluated the interaction between polygenic risk scores for schizophrenia (SZ-PRS), bipolar disorder (BD-PRS) and major depressive disorder (MDD-PRS), and childhood adversity on the transdiagnostic clinical dimensions of psychosis (positive, negative, depressive, and manic). The moderating effect of high, intermediate, and low PRSs on the relation between childhood adversity and psychotic dimensions was examined. Results: No analysis remained significant after adjusting for Bonferroni correction (p<0.004). However, a trend-level interaction was observed between levels of childhood adversity and MDD-PRS on the predominance of depressive (β=.12, p=.005), and positive dimension (β=.15, p=.006). No association was observed for BDD-PRS. For SZ-PRS, a trend-level negative interaction was observed for the manic dimension (β=-.17, p=.006). All analyses were adjusted for age, sex, 10 PCA, and country of recruitment. Conclusions This underpowered study suggests that genetic liability for MDD may have a differential effect on the relationship between childhood adversity and psychotic symptom dimensions. This supports the hypothesis of an affective pathway to psychosis in those exposed to childhood adversity; findings should be replicated in independent samples.