The British journal of psychiatry : the journal of mental science
April 22, 2026 · via Europe PMC
Schizophrenia and accelerated ageing: systematic review and future research directions.
Fernandez-Egea E, Garcia-Rizo C, Kirkpatrick B.
AI summary — for doctors, generated from the abstract only
This systematic review supports a multisystem, advanced ageing phenotype in schizophrenia, most consistently involving telomere shortening and oxidative and inflammatory stress, rather than uniformly accelerated ageing.
What was studied
PRISMA systematic review (PROSPERO CRD42024574059) of studies since 2009 testing the accelerated ageing hypothesis of schizophrenia across molecular, neuroimaging, cognitive and epidemiological markers, synthesized narratively with emphasis on meta-analyses and minimally treated longitudinal cohorts.
Key findings
- Of 923 manuscripts identified, 170 were included; schizophrenia showed a reproducible ageing phenotype with increased mortality, higher dementia risk, brain-predicted age elevation and cognitive decline
- BrainAGE studies reported mean age gaps of 3-4 years, often already present at first episode
- Meta-analyses reported consistent telomere shortening (standardised mean difference approximately -0.4 to -0.5) and modest acceleration of selected epigenetic clocks; oxidative stress, inflammation, mitochondrial and IGF-1 dysregulation were frequent and partly preceded antipsychotic exposure
Clinical relevance
The findings reinforce attention to physical health, cardiometabolic risk and cognitive monitoring in people with schizophrenia from early in illness, and suggest biomarkers of ageing as research targets.
Who should care
Limitations
The review is narrative rather than quantitatively pooled, searched only PubMed and Google Scholar, and covers heterogeneous measures. Medication, lifestyle and illness-related confounding are hard to separate, as the abstract implies.
Schizophrenia shows early biological deviation consistent with advanced ageing that runs in parallel rather than steeper decline, with telomere attrition and oxidative or inflammatory stress the most consistent mechanisms.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Background
Schizophrenia has been proposed to be a disorder of accelerated ageing, characterised by a mismatch between biological and chronological age. Evidence accumulated over the past 15 years has examined this model using molecular, neuroimaging, cognitive and epidemiological markers.
Aims
To evaluate whether schizophrenia shows evidence of an accelerated or advanced ageing phenotype across biological systems and to assess the consistency of the underlying molecular mechanisms.
Method
A systematic review (PROSPERO CRD42024574059) was conducted following PRISMA guidelines. PubMed and Google Scholar were searched for studies published after 2009 that cited the original accelerated ageing hypothesis publication or investigated ageing in the context of schizophrenia and/or psychosis. Evidence was synthesised narratively by domain, with emphases on meta-analyses and minimally treated, longitudinal cohorts.
Results
A total of 923 manuscripts were identified, and a final 170 were included in the systematic review. Schizophrenia showed a reproducible ageing phenotype, as evidenced by in increased mortality, higher dementia risk, brain-predicted age elevation and cognitive decline. BrainAGE studies revealed mean age gaps of 3-4 years, often present at first episode. At the mechanistic level, meta-analyses reported consistent telomere shortening (standardised mean difference approximately -0.4 to -0.5) and modest acceleration of selected epigenetic clocks. Dysregulation of oxidative stress, inflammation, mitochondrial function and insulin-like growth factor-1 signalling were frequent and partly preceded antipsychotic exposure.
Conclusions
Schizophrenia is associated with a multisystem ageing phenotype underpinned by convergent biological mechanisms, most consistently involving telomere attrition and oxidative and/or inflammatory stress. The overall pattern supports a model of advanced rather than uniformly accelerated ageing, reflecting early biological deviation with parallel rather than steeper decline.
DOI
10.1192/bjp.2026.10606
PMID
42015596
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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