The association between epigenetic ageing from childhood to early adulthood and psychotic-like experiences in early adulthood

BACKGROUND: Psychotic-like experiences (PLEs) are associated with cognitive impairment and premature mortality, which may be indicative of accelerated biological ageing. Epigenetic clocks provide a measure of biological age based on DNA methylation, yet the long-term relationship between epigenetic ageing and PLEs remains largely unclear. We tested the relationship between epigenetic ageing and PLEs using a 17-year longitudinal approach. METHODS: Epigenetic ageing was calculated using four epigenetic clocks (DunedinPACE, Cortical EpiAge, Horvath, and PCGrimAge) in a sample from the Avon Longitudinal Study of Parents and Children (ALSPAC), a large population-based birth cohort (n = 1840, 56.8% females). We modeled epigenetic ageing from up to three repeated measures collected between ages 7 and 24 using a linear mixed-effects model to calculate (1) average epigenetic age [mean-centered intercept] and (2) rate of epigenetic ageing over this 17-year period [slope]. We then compared these two measures between individuals who developed PLEs in early adulthood (n = 95) against those who did not (n = 1745). RESULTS: Results showed that a faster rate (slope) of longitudinal PCGrimAge was predictive of PLEs (OR = 1.79, 95% CI [1.13-2.85], p = .014), although this association was no longer significant after adjusting for smoking. There was a non-significant effect in the same direction for other clocks. Average epigenetic age (mean-centered intercept) was not associated with PLEs. CONCLUSIONS: Our findings suggest that the observed association between accelerated rate of epigenetic ageing, measured with PCGrimAge, from childhood to early adulthood, and the development of PLEs in early adulthood may be explained by smoking.