Altered brain structure age gap estimation in major depressive disorder patients with and without anhedonia: a machine learning-based study

Abstract Previous studies have found that major depressive disorder (MDD) may accelerate overall structural brain aging. Nevertheless, it still remains unknown whether anhedonia, a critical negative prognostic indicator in MDD, further leads to advanced brain aging in specific regions. A total of 31...

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Main Authors: Qingli Mu, Kejing Zhang, Yue Chen, Yuwei Xu, Shaohua Hu, Manli Huang, Peng Zhang, Dong Cui, Shaojia Lu
Format: Article
Language:English
Published: Nature Publishing Group 2025-08-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-025-03555-5
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author Qingli Mu
Kejing Zhang
Yue Chen
Yuwei Xu
Shaohua Hu
Manli Huang
Peng Zhang
Dong Cui
Shaojia Lu
author_facet Qingli Mu
Kejing Zhang
Yue Chen
Yuwei Xu
Shaohua Hu
Manli Huang
Peng Zhang
Dong Cui
Shaojia Lu
author_sort Qingli Mu
collection DOAJ
description Abstract Previous studies have found that major depressive disorder (MDD) may accelerate overall structural brain aging. Nevertheless, it still remains unknown whether anhedonia, a critical negative prognostic indicator in MDD, further leads to advanced brain aging in specific regions. A total of 31 MDD with anhedonia (MDD-WA), 41 MDD without anhedonia (MDD-WoA), and 43 healthy controls (HCs) were recruited in this study. The difference between brain structure age (BSA) applied by support vector regression (SVR) and chronological age was calculated to derive the brain structure age gap estimation (BSAGE). Analyses of covariance (ANCOVAs) and intergroup comparisons were performed to obtain brain regions with significant BSAGE differences among three groups. Moreover, a support vector machine (SVM) classification model was used to verify the diagnostic value of altered BSAGE. ANCOVAs revealed significant BSAGE differences among three groups in the bilateral putamen (PU), left cerebellar white matter (CB), left cuneus (CUN), left fusiform gyrus (FuG), left subcallosal area (SCA), left superior occipital gyrus (SOG), left triangular inferior frontal gyrus (IFG-Tri), right lateral ventricle (L-V), right superior frontal gyrus medial segment (SFG-SM), right opercular inferior frontal gyrus (IFG-Oper), right precuneus (pre-CUN), right posterior insula (INS-Post), and right superior temporal gyrus (STG). Compared to HCs, the MDD-WA group showed significant BSAGE increase in all of the aforementioned brain regions, while the MDD-WoA group showed limited BSAGE increase in the CB, FuG, and SCA of left hemisphere only. However, no significant difference was found between MDD-WA and MDD-WoA. The altered BSAGE values showed promising discriminatory performance with an area under the curve (AUC) of 0.944 in classifying MDD-WA and HCs. The current findings emphasize that MDD with anhedonia may exhibit more extensive advanced brain aging, primarily in the frontal-limbic system, temporal lobe, and parietal lobe.
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spelling doaj-art-0ad1ccdcd5f74af78cc275805e6ff5b12025-08-24T11:51:38ZengNature Publishing GroupTranslational Psychiatry2158-31882025-08-011511910.1038/s41398-025-03555-5Altered brain structure age gap estimation in major depressive disorder patients with and without anhedonia: a machine learning-based studyQingli Mu0Kejing Zhang1Yue Chen2Yuwei Xu3Shaohua Hu4Manli Huang5Peng Zhang6Dong Cui7Shaojia Lu8Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang Key Laboratory of Precision Psychiatry, Zhejiang Engineering Center for Mathematical Mental HealthDepartment of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang Key Laboratory of Precision Psychiatry, Zhejiang Engineering Center for Mathematical Mental HealthDepartment of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang Key Laboratory of Precision Psychiatry, Zhejiang Engineering Center for Mathematical Mental HealthDepartment of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang Key Laboratory of Precision Psychiatry, Zhejiang Engineering Center for Mathematical Mental HealthDepartment of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang Key Laboratory of Precision Psychiatry, Zhejiang Engineering Center for Mathematical Mental HealthDepartment of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang Key Laboratory of Precision Psychiatry, Zhejiang Engineering Center for Mathematical Mental HealthDepartment of Psychiatry, Affiliated Xiaoshan Hospital, Hangzhou Normal UniversitySchool of Radiology, Shandong First Medical University & Shandong Academy of Medical SciencesDepartment of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang Key Laboratory of Precision Psychiatry, Zhejiang Engineering Center for Mathematical Mental HealthAbstract Previous studies have found that major depressive disorder (MDD) may accelerate overall structural brain aging. Nevertheless, it still remains unknown whether anhedonia, a critical negative prognostic indicator in MDD, further leads to advanced brain aging in specific regions. A total of 31 MDD with anhedonia (MDD-WA), 41 MDD without anhedonia (MDD-WoA), and 43 healthy controls (HCs) were recruited in this study. The difference between brain structure age (BSA) applied by support vector regression (SVR) and chronological age was calculated to derive the brain structure age gap estimation (BSAGE). Analyses of covariance (ANCOVAs) and intergroup comparisons were performed to obtain brain regions with significant BSAGE differences among three groups. Moreover, a support vector machine (SVM) classification model was used to verify the diagnostic value of altered BSAGE. ANCOVAs revealed significant BSAGE differences among three groups in the bilateral putamen (PU), left cerebellar white matter (CB), left cuneus (CUN), left fusiform gyrus (FuG), left subcallosal area (SCA), left superior occipital gyrus (SOG), left triangular inferior frontal gyrus (IFG-Tri), right lateral ventricle (L-V), right superior frontal gyrus medial segment (SFG-SM), right opercular inferior frontal gyrus (IFG-Oper), right precuneus (pre-CUN), right posterior insula (INS-Post), and right superior temporal gyrus (STG). Compared to HCs, the MDD-WA group showed significant BSAGE increase in all of the aforementioned brain regions, while the MDD-WoA group showed limited BSAGE increase in the CB, FuG, and SCA of left hemisphere only. However, no significant difference was found between MDD-WA and MDD-WoA. The altered BSAGE values showed promising discriminatory performance with an area under the curve (AUC) of 0.944 in classifying MDD-WA and HCs. The current findings emphasize that MDD with anhedonia may exhibit more extensive advanced brain aging, primarily in the frontal-limbic system, temporal lobe, and parietal lobe.https://doi.org/10.1038/s41398-025-03555-5
spellingShingle Qingli Mu
Kejing Zhang
Yue Chen
Yuwei Xu
Shaohua Hu
Manli Huang
Peng Zhang
Dong Cui
Shaojia Lu
Altered brain structure age gap estimation in major depressive disorder patients with and without anhedonia: a machine learning-based study
Translational Psychiatry
title Altered brain structure age gap estimation in major depressive disorder patients with and without anhedonia: a machine learning-based study
title_full Altered brain structure age gap estimation in major depressive disorder patients with and without anhedonia: a machine learning-based study
title_fullStr Altered brain structure age gap estimation in major depressive disorder patients with and without anhedonia: a machine learning-based study
title_full_unstemmed Altered brain structure age gap estimation in major depressive disorder patients with and without anhedonia: a machine learning-based study
title_short Altered brain structure age gap estimation in major depressive disorder patients with and without anhedonia: a machine learning-based study
title_sort altered brain structure age gap estimation in major depressive disorder patients with and without anhedonia a machine learning based study
url https://doi.org/10.1038/s41398-025-03555-5
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