Structural brain age trajectories in antipsychotic-naive first episode psychosis

BACKGROUND: Psychotic disorders such as schizophrenia have been associated with older-appearing brain structure, commonly quantified using the brain-age paradigm. However, it remains unclear whether these alterations are present at illness onset and whether antipsychotic treatment modifies their trajectory. METHODS: In this study, 61 (28 females and 33 males) antipsychotic-naïve people with first-episode psychosis were randomized to receive either a second-generation antipsychotic (risperidone or paliperidone) or placebo over a 6-month treatment period, alongside intensive psychosocial therapy. A healthy control group (n = 27, 17 females, 10 males) was also recruited. Structural MRI scans were collected at baseline, 3 months, and 12 months. Brain age was estimated using two pretrained and validated models (Pyment and CentileBrain). RESULTS: = 0.81, p = 0.37). There were also no significant effects of time, treatment group (antipsychotic, placebo, healthy control), or their interaction on brain-PAD across the first year (all p > 0.26). Findings were consistent across both brain-age models, and brain-PAD was not associated with clinical and lifestyle measures. CONCLUSION: These findings suggest that altered structural brain aging is not evident during the earliest stages of psychosis and is not modified by early antipsychotic exposure over the first year of illness. Longer follow-up and approaches that account for illness heterogeneity may be needed to clarify when brain-age alterations emerge in psychotic disorders. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/; ACTRN12607000608460).

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Journal
Schizophrenia Research
Published
2026-11-06
DOI
https://doi.org/10.1016/j.schres.2026.10.020
Primary Topic
Schizophrenia research and treatment
Type
article
Field-Weighted Citation Impact
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article

Structural brain age trajectories in antipsychotic-naive first episode psychosis

Laura K. M. Han, Shona M. Francey, Christos Pantelis, Vicente Molina et al.
2 links
Schizophrenia Research
Schizophrenia research and treatment
article

Structural brain age trajectories in antipsychotic-naive first episode psychosis

Laura K. M. Han, Shona M. Francey, Christos Pantelis, Vicente Molina, Alex Fornito, Alejandro Roig-Herrero, Barnaby Nelson, Rodrigo de Luis-Garcı́a, Patrick D. McGorry, Sidhant Chopra, Hok Pan Yuen, Vanessa Cropley, Mario Álvarez‐Jiménez, Susy Harrigan, Brian N. O'Donoghue, Kelly Allot, Stephen Wood, Andrew Thompson
article en

Abstract

BACKGROUND: Psychotic disorders such as schizophrenia have been associated with older-appearing brain structure, commonly quantified using the brain-age paradigm. However, it remains unclear whether these alterations are present at illness onset and whether antipsychotic treatment modifies their trajectory. METHODS: In this study, 61 (28 females and 33 males) antipsychotic-naïve people with first-episode psychosis were randomized to receive either a second-generation antipsychotic (risperidone or paliperidone) or placebo over a 6-month treatment period, alongside intensive psychosocial therapy. A healthy control group (n = 27, 17 females, 10 males) was also recruited. Structural MRI scans were collected at baseline, 3 months, and 12 months. Brain age was estimated using two pretrained and validated models (Pyment and CentileBrain). RESULTS: = 0.81, p = 0.37). There were also no significant effects of time, treatment group (antipsychotic, placebo, healthy control), or their interaction on brain-PAD across the first year (all p > 0.26). Findings were consistent across both brain-age models, and brain-PAD was not associated with clinical and lifestyle measures. CONCLUSION: These findings suggest that altered structural brain aging is not evident during the earliest stages of psychosis and is not modified by early antipsychotic exposure over the first year of illness. Longer follow-up and approaches that account for illness heterogeneity may be needed to clarify when brain-age alterations emerge in psychotic disorders. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/; ACTRN12607000608460).

Schizophrenia ResearchVol. 299
University College Dublin (IE), Universidad de Valladolid (ES), The University of Melbourne (AU), Florey Institute of Neuroscience and Mental Health (AU), Orygen Youth Health (AU), Amsterdam Neuroscience (NL), Orygen (AU), St. Vincent's University Hospital (IE), Western Health (AU), Amsterdam Public Health (NL), Sunshine Hospital (AU), Hospital Clínico Universitario de Valladolid (ES), Monash University (AU), Swinburne University of Technology (AU), University of Birmingham (GB), Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
Ministerio de Ciencia, Innovación y Universidades, European Commission, University of Melbourne, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Medical Research Council, National Health and Medical Research Council, European Regional Development Fund, Agencia Estatal de Investigación, European Social Fund
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Openalex Percentile: Top 62%
Schizophrenia research and treatment
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