Personality changes during adolescence predict young adult psychosis proneness and mediate gene-environment interplays of schizophrenia risk

Psychotic symptoms in adolescence are associated with social adversity and genetic risk for schizophrenia. This gene-environment interplay may be mediated by personality, which also develops during adolescence. We hypothesized that (i) personality development predicts later Psychosis Proneness Signs (PPS), and (ii) personality traits mediate the association between genetic risk for schizophrenia, social adversities, and psychosis.

A total of 784 individuals were selected within the IMAGEN cohort (Discovery Sample-DS: 526; Validation Sample-VS: 258); personality was assessed at baseline (13-15 years), follow-up-1 (FU1, 16-17 years), and FU2 (18-20 years). Latent growth curve models served to compute coefficients of individual change across 14 personality variables. A support vector machine algorithm employed these coefficients to predict PPS at FU3 (21-24 years). We computed mediation analyses, including personality-based predictions and self-reported bullying victimization as serial mediators along the pathway between polygenic risk score (PRS) for schizophrenia and FU3 PPS. We replicated the main findings also on 1132 adolescents recruited within the TRAILS cohort.

Growth scores in neuroticism and openness predicted PPS with 65.6% balanced accuracy in the DS, and 69.5% in the VS Mediations revealed a significant positive direct effect of PRS on PPS (confidence interval [CI] 0.01-0.15), and an indirect effect, serially mediated by personality-based predictions and victimization (CI 0.006-0.01), replicated in the TRAILS cohort (CI 0.0004-0.004).

Adolescent personality changes may predate future experiences associated with psychosis susceptibility. PPS personality-based predictions mediate the relationship between PRS and victimization toward adult PPS, suggesting that gene-environment correlations proposed for psychosis are partly mediated by personality.