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Accelerated ageing unfolds along the sensorimotor–association cortical axis in schizophrenia: multi-site study

Published online by Cambridge University Press:  01 October 2025

Haonan Pei Open the ORCID record for Haonan Pei [Opens in a new window] ,
Sisi Jiang Open the ORCID record for Sisi Jiang [Opens in a new window] ,
Changyue Hou ,
Hechun Li ,
Zhihuan Yang ,
Roberto Rodriguez-Labrada ,
Mingjun Duan ,
Dezhong Yao Open the ORCID record for Dezhong Yao [Opens in a new window]  and
Cheng Luo Open the ORCID record for Cheng Luo [Opens in a new window]
Haonan Pei
Affiliation:
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
Sisi Jiang
Affiliation:
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China China–Cuba Belt and Road Joint Laboratory on Neurotechnology and Brain-Apparatus Communication, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
Changyue Hou
Affiliation:
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
Hechun Li
Affiliation:
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
Zhihuan Yang
Affiliation:
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
Roberto Rodriguez-Labrada
Affiliation:
Cuban Centre for Neurosciences, Havana, Cuba
Mingjun Duan
Affiliation:
Department of Psychiatry, The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
Dezhong Yao
Affiliation:
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China China–Cuba Belt and Road Joint Laboratory on Neurotechnology and Brain-Apparatus Communication, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China Research Unit of NeuroInformation, Chinese Academy of Medical Sciences, Chengdu, People’s Republic of China
Cheng Luo*
Affiliation:
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China China–Cuba Belt and Road Joint Laboratory on Neurotechnology and Brain-Apparatus Communication, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China Research Unit of NeuroInformation, Chinese Academy of Medical Sciences, Chengdu, People’s Republic of China
*
Correspondence: Cheng Luo. Email: chengluo@uestc.edu.cn.
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Abstract

Background

Schizophrenia is associated with a reduced average lifespan due to accelerated ageing. Early studies have predominantly focused on the global brain age gap, limiting our understanding of region-specific ageing. Moreover, the relationship between accelerated ageing and schizophrenia disease progression has not been directly examined.

Aims

Our aim was to investigate the cortical spatiotemporal patterns in ageing and disease progression in schizophrenia.

Method

Using multi-site, resting-state functional magnetic resonance imaging data, we analysed intrinsic activity fluctuations in 2353 healthy controls and 546 subjects with schizophrenia. We assessed normative models of ageing trajectories in brain activities in healthy controls, and examined the developmental trajectory of deviations from normative reference ranges with disease progression in schizophrenia.

Results

The ageing trajectories of both groups demonstrated spatiotemporal variability unfolding along the sensorimotor–association cortical axis, characterised by a rapid decline in transmodal association cortices at younger ages and followed by an accelerated decline in primary cortices at older ages. However, schizophrenia exhibited a more rapid rate of decline across the entire cerebral cortex, particularly during the short-duration stage. Further analysis revealed that the spatial variability of disease-induced ageing deviations persisted along the sensorimotor–association cortical axis throughout disease progression. The premature involvement of neurotransmitter systems, including dopamine and serotonin, may underlie accelerated ageing.

Conclusions

Our work uncovers regional ageing trajectories organised along the sensorimotor–association cortical axis, and provides new insights into the mechanisms of atypical ageing and disease progression in schizophrenia.

Keywords

Schizophreniaaccelerated ageingnormative modelsmulti-site analysissensorimotor–association cortical axis

Information

Type
Original Article
Information
The British Journal of Psychiatry , First View , pp. 1 - 9
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Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of Royal College of Psychiatrists

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