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

Zoe  Hart; Anna Großbach; Andrew J Simpkin; Esther Walton

doi:10.1017/S003329172510055X

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

Zoe Hart, Anna Großbach, Andrew J Simpkin, Esther Walton

University of Galway

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	e182
Pages (from-to)	1-9
Journal	Psychological Medicine
Volume	55
Early online date	30 Jun 2025
DOIs	https://doi.org/10.1017/S003329172510055X
Publication status	Published - 30 Jun 2025

Data Availability Statement

ALSPAC data access is through a system of managed open access. The steps below highlight how to apply for access to the data included in the data note and all other ALSPAC data: (1) Please read the ALSPAC access policy (http://www.bristol.ac.uk/media-library/sites/alspac/documents/researchers/data-access/ALSPAC_Access_Policy.pdf), which describes the process of accessing the data and samples in detail and outlines the costs associated with doing so. (2) You may also find it useful to browse our fully searchable research proposals database (https://proposals.epi.bristol.ac.uk/?q=proposalSummaries), which lists all research projects that have been approved since April 2011. Please submit your research proposal (https://proposals.epi.bristol.ac.uk/) for consideration by the ALSPAC Executive Committee. You will receive a response within 10 working days to advise you whether your proposal has been approved.

Acknowledgements

We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses.

Funding

The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provided core support for ALSPAC. The ARIES sub-study was funded by BBSRC (BBI025751/1 and BB/I025263/1), NICHD (R01HD068437), NIH (5RO1AI121226–02), and the EU Seventh Framework Programme (CONTAMED, 212502). This publication is the work of the authors, and EW will serve as the guarantor for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). EW received funding from UK Research and Innovation (UKRI) under the UK government’s Horizon Europe/ERC Frontier Research Guarantee [BrainHealth, grant number EP/Y015037/1] and from Wellcome (315898/Z/24/Z). EW and AS also received funding from the National Institute of Mental Health of the National Institutes of Health (award number R01MH113930). AG was funded by Research Ireland through the Research Ireland Centre for Research Training in Genomics Data Science under Grant number 18/CRT/6214 and the EU’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant H2020-MSCA-COFUND-2019-945385.

Funders	Funder number
Medical Research Council	217065/Z/19/Z

Keywords

ALSPAC
DNA methylation
epigenetic age
longitudinal
psychosis

ASJC Scopus subject areas

Applied Psychology
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1017/S003329172510055XLicence: CC BY

Cite this

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

abstract = "BackgroundPsychotic-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.MethodsEpigenetic 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).ResultsResults 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.ConclusionsOur 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.",

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N2 - BackgroundPsychotic-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.MethodsEpigenetic 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).ResultsResults 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.ConclusionsOur 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.

AB - BackgroundPsychotic-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.MethodsEpigenetic 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).ResultsResults 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.ConclusionsOur 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.

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

Abstract

Data Availability Statement

Acknowledgements

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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