Cellular senescence changes and their association with brain structure in schizophrenia and major depressive disorder

Individuals with schizophrenia (SZ) and major depressive disorder (MDD) may experience accelerated biological aging, potentially linked to cellular senescence and the senescence-associated secretory phenotype (SASP). While the SASP index has been reported to be elevated in MDD, its status in SZ and its relationship with brain structure remain unclear. This study investigated whether the SASP index, a composite biomarker-based measure, is elevated in SZ and MDD, and examined its associations with brain-predicted age difference (brain-PAD) and regional brain morphology across SZ, MDD, and healthy controls (HCs). A total of 119 subjects (29 individuals with SZ, 40 individuals with MDD, and 50 HCs) underwent both peripheral blood collection and MRI scanning. First, across all subjects, the effects of diagnostic groups on SASP indices were assessed. Second, associations between age-adjusted SASP indices and brain-PAD were examined within each diagnostic group. Third, exploratory analyses tested associations between SASP indices and subcortical volumes as well as cortical thickness and surface area in each diagnostic group. We found a significant main effect of diagnostic group on SASP indices and significantly elevated SASP indices in both SZ and MDD. Although no significant associations were observed between SASP indices and brain-PAD in any diagnostic group, negative associations were identified in SZ between SASP indices and the surface area of the left transverse temporal gyrus and the right inferior frontal gyrus pars triangularis, regions that play pivotal roles in auditory and language processing alterations observed in SZ. These findings suggest that SASP-related processes may contribute to the neural underpinnings of SZ through localized, rather than global, alterations in brain structure.

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Publication Details

Journal
Translational Psychiatry
Published
2026-11-07
DOI
https://doi.org/10.1038/s41398-026-04538-w
Primary Topic
Schizophrenia research and treatment
Type
article
Field-Weighted Citation Impact
0.00

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article

Cellular senescence changes and their association with brain structure in schizophrenia and major depressive disorder

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2 links
Translational Psychiatry
Schizophrenia research and treatment
article

Cellular senescence changes and their association with brain structure in schizophrenia and major depressive disorder

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article en

Abstract

Individuals with schizophrenia (SZ) and major depressive disorder (MDD) may experience accelerated biological aging, potentially linked to cellular senescence and the senescence-associated secretory phenotype (SASP). While the SASP index has been reported to be elevated in MDD, its status in SZ and its relationship with brain structure remain unclear. This study investigated whether the SASP index, a composite biomarker-based measure, is elevated in SZ and MDD, and examined its associations with brain-predicted age difference (brain-PAD) and regional brain morphology across SZ, MDD, and healthy controls (HCs). A total of 119 subjects (29 individuals with SZ, 40 individuals with MDD, and 50 HCs) underwent both peripheral blood collection and MRI scanning. First, across all subjects, the effects of diagnostic groups on SASP indices were assessed. Second, associations between age-adjusted SASP indices and brain-PAD were examined within each diagnostic group. Third, exploratory analyses tested associations between SASP indices and subcortical volumes as well as cortical thickness and surface area in each diagnostic group. We found a significant main effect of diagnostic group on SASP indices and significantly elevated SASP indices in both SZ and MDD. Although no significant associations were observed between SASP indices and brain-PAD in any diagnostic group, negative associations were identified in SZ between SASP indices and the surface area of the left transverse temporal gyrus and the right inferior frontal gyrus pars triangularis, regions that play pivotal roles in auditory and language processing alterations observed in SZ. These findings suggest that SASP-related processes may contribute to the neural underpinnings of SZ through localized, rather than global, alterations in brain structure.

Translational Psychiatry
Brigham and Women's Hospital (US), Harvard University (US), Massachusetts General Hospital (US), Toho University Omori Medical Center (JP), The University of Tokyo Institutes for Advanced Study (JP), UTokyo Institute for Diversity and Adaptation of Human Mind (JP), Center for Diversity in Medical Education and Research, The University of Tokyo (JP), Center for Disease Biology and Integrative Medicine, The University of Tokyo (JP), International Research Center for Neurointelligence, The University of Tokyo (JP), The University of Tokyo (JP)
Brain and Behavior Research Foundation, Japan Agency for Medical Research and Development, Ministry of Education, Culture, Sports, Science and Technology, Brigham Research Institute, Japan Society for the Promotion of Science, Japan Science and Technology Agency, International Research Center for Neurointelligence, University of Tokyo, Moonshot Research and Development Program
Good health and well-being
Openalex Percentile: Top 22%
Schizophrenia research and treatment
DOIOpen Access PDFOpenAlex
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