Psychosis as a multisystem disorder of aberrant aging

Rachel Upthegrove; Amalie C. M. Couch; Antonio de Marvao; Benjamin I. Perry; Fabiana Corsi-Zuelli; Jack Rogers; Lahiru Handunnetthi; Nicholas M. Barnes; Nikolaos Koutsouleris; Paris A. Lalousis; Toby Pillinger; Zachary Freyberg

doi:10.1038/s41514-026-00409-2

Psychosis as a multisystem disorder of aberrant aging

Rachel Upthegrove^*
, Amalie C. M. Couch
, Antonio de Marvao
, Benjamin I. Perry
, Fabiana Corsi-Zuelli
, Jack Rogers
, Lahiru Handunnetthi
, Nicholas M. Barnes
, Nikolaos Koutsouleris
, Paris A. Lalousis
, Toby Pillinger
, Zachary Freyberg

^*Corresponding author for this work

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

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Abstract

Psychotic disorders, including schizophrenia and affective psychosis, affect ~3% of the population and typically emerge in early adulthood. Cardiometabolic disease accounts for much of the 20-year life-expectancy gap in psychosis. Evidence indicates potentially causal processes, often seen in aging, act within and beyond the brain, and before the onset of treatment; these include inflammation, metabolic and mitochondrial dysfunction. Here we synthesize evidence and propose a framework that proposes psychosis as a multisystem disorder of accelerated aging, and outline implications for aging-targeted interventions.

Original language	English
Journal	npj Aging
Early online date	29 May 2026
DOIs	https://doi.org/10.1038/s41514-026-00409-2
Publication status	E-pub ahead of print - 29 May 2026

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SDG 3 Good Health and Well-being

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title = "Psychosis as a multisystem disorder of aberrant aging",

abstract = "Psychotic disorders, including schizophrenia and affective psychosis, affect \textasciitilde{}3\% of the population and typically emerge in early adulthood. Cardiometabolic disease accounts for much of the 20-year life-expectancy gap in psychosis. Evidence indicates potentially causal processes, often seen in aging, act within and beyond the brain, and before the onset of treatment; these include inflammation, metabolic and mitochondrial dysfunction. Here we synthesize evidence and propose a framework that proposes psychosis as a multisystem disorder of accelerated aging, and outline implications for aging-targeted interventions.",

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AU - Upthegrove, Rachel

AU - Couch, Amalie C. M.

AU - de Marvao, Antonio

AU - Perry, Benjamin I.

AU - Corsi-Zuelli, Fabiana

AU - Rogers, Jack

AU - Handunnetthi, Lahiru

AU - Barnes, Nicholas M.

AU - Koutsouleris, Nikolaos

AU - Lalousis, Paris A.

AU - Pillinger, Toby

AU - Freyberg, Zachary

PY - 2026/5/29

Y1 - 2026/5/29

N2 - Psychotic disorders, including schizophrenia and affective psychosis, affect ~3% of the population and typically emerge in early adulthood. Cardiometabolic disease accounts for much of the 20-year life-expectancy gap in psychosis. Evidence indicates potentially causal processes, often seen in aging, act within and beyond the brain, and before the onset of treatment; these include inflammation, metabolic and mitochondrial dysfunction. Here we synthesize evidence and propose a framework that proposes psychosis as a multisystem disorder of accelerated aging, and outline implications for aging-targeted interventions.

AB - Psychotic disorders, including schizophrenia and affective psychosis, affect ~3% of the population and typically emerge in early adulthood. Cardiometabolic disease accounts for much of the 20-year life-expectancy gap in psychosis. Evidence indicates potentially causal processes, often seen in aging, act within and beyond the brain, and before the onset of treatment; these include inflammation, metabolic and mitochondrial dysfunction. Here we synthesize evidence and propose a framework that proposes psychosis as a multisystem disorder of accelerated aging, and outline implications for aging-targeted interventions.

U2 - 10.1038/s41514-026-00409-2

DO - 10.1038/s41514-026-00409-2

M3 - Article

SN - 2731-6068

JO - npj Aging

JF - npj Aging

ER -

Psychosis as a multisystem disorder of aberrant aging

Abstract

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