Accelerated Pace of Aging in Schizophrenia: Five Case-Control Studies

Avshalom Caspi; Gemma Shireby; Jonathan Mill; Terrie E Moffitt; Karen Sugden; Eilis Hannon

doi:10.1016/j.biopsych.2023.10.023

Accelerated Pace of Aging in Schizophrenia: Five Case-Control Studies

Biol Psychiatry. 2024 Jun 1;95(11):1038-1047. doi: 10.1016/j.biopsych.2023.10.023. Epub 2023 Nov 2.

Authors

Avshalom Caspi¹, Gemma Shireby², Jonathan Mill³, Terrie E Moffitt⁴, Karen Sugden⁵, Eilis Hannon³

Affiliations

¹ Department of Psychology & Neuroscience, Duke University, Durham, North Carolina; Social, Genetic and Developmental Psychiatry, Institute of Psychiatry, Psychology, & Neuroscience, King's College London, London, United Kingdom; PROMENTA, Department of Psychology, University of Oslo, Oslo, Norway. Electronic address: ac115@duke.edu.
² Centre of Longitudinal Studies, University College London, Exeter, United Kingdom.
³ University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.
⁴ Department of Psychology & Neuroscience, Duke University, Durham, North Carolina; Social, Genetic and Developmental Psychiatry, Institute of Psychiatry, Psychology, & Neuroscience, King's College London, London, United Kingdom; PROMENTA, Department of Psychology, University of Oslo, Oslo, Norway.
⁵ Department of Psychology & Neuroscience, Duke University, Durham, North Carolina.

PMID: 37924924
PMCID: PMC11063120 (available on 2025-06-01)
DOI: 10.1016/j.biopsych.2023.10.023

Abstract

Background: Schizophrenia is associated with increased risk of developing multiple aging-related diseases, including metabolic, respiratory, and cardiovascular diseases, and Alzheimer's and related dementias, leading to the hypothesis that schizophrenia is accompanied by accelerated biological aging. This has been difficult to test because there is no widely accepted measure of biological aging. Epigenetic clocks are promising algorithms that are used to calculate biological age on the basis of information from combined cytosine-phosphate-guanine sites (CpGs) across the genome, but they have yielded inconsistent and often negative results about the association between schizophrenia and accelerated aging. Here, we tested the schizophrenia-aging hypothesis using a DNA methylation measure that is uniquely designed to predict an individual's rate of aging.

Methods: We brought together 5 case-control datasets to calculate DunedinPACE (Pace of Aging Calculated from the Epigenome), a new measure trained on longitudinal data to detect differences between people in their pace of aging over time. Data were available from 1812 psychosis cases (schizophrenia or first-episode psychosis) and 1753 controls. Mean chronological age was 38.9 (SD = 13.6) years.

Results: We observed consistent associations across datasets between schizophrenia and accelerated aging as measured by DunedinPACE. These associations were not attributable to tobacco smoking or clozapine medication.

Conclusions: Schizophrenia is accompanied by accelerated biological aging by midlife. This may explain the wide-ranging risk among people with schizophrenia for developing multiple different age-related physical diseases, including metabolic, respiratory, and cardiovascular diseases, and dementia. Measures of biological aging could prove valuable for assessing patients' risk for physical and cognitive decline and for evaluating intervention effectiveness.

Keywords: Biological aging; DNA methylation; DunedinPACE; Epigenetics; Mental health and aging; Schizophrenia.

MeSH terms

Adult
Aging*
Case-Control Studies
DNA Methylation*
Female
Humans
Male
Middle Aged
Schizophrenia* / genetics
Young Adult

Abstract

MeSH terms

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