Journal of affective disorders · 2026
Using machine learning to reveal two distinct neuroanatomical subtypes of first-episode, drug-naïve major depressive disorder: Evidence from the REST-meta-MDD project.
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Hu Songhao, Zuo Xingyue, Huang Jiaqi, Hou Tao, Hong Yufeng, Xu Li, Wu Ming, Yu Dairui, Xiao Jiping, Cheng Li, Zhang Mian, Liu Dandan, Zhu Li, Zhang Xiangyang
Аннотация
BACKGROUND: Major depressive disorder (MDD) is a highly heterogeneous condition, complicating biomarker discovery and precision medicine. Identifying biologically distinct subtypes using structural MRI (sMRI) offers a promising approach to address this heterogeneity. This study employed sMRI features to define neuroimaging-based subtypes in first-episode, drug-naïve (FEDN) MDD patients.
METHODS: In this study, we analyzed T1-weighted anatomical images from 169 first-episode, drug-naïve (FEDN) MDD patients and 169 healthy controls (HCs) obtained from the rest-meta-MDD project. Patient symptom severity was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) and its subscales. We employed region-specific gray matter volume (GMV) feature-based heterogeneity through discriminant analysis (HYDRA) to explore neuroanatomical subtypes of FEDN MDD patients and validate their stability. Furthermore, we examined demographic and symptomatic differences between identified subtypes.
RESULTS: We identified two distinct neuroanatomical subtypes of FEDN MDD patients (FEDN MDD 1: n = 85, FEDN MDD 2: n = 84), which exhibited significant differences in GMV alterations. Compared with HCs, FEDN MDD 1 showed widespread GMV increases, while FEDN MDD 2 demonstrated significant GMV reductions. These two subtypes also demonstrated significant differences in HAMD anxiety/somatization subscale scores (t = 2.845, p < 0.01) and age distribution (t = 3.886, p < 0.001). Furthermore, reproducibility analyses confirmed the robustness of these subtypes.
CONCLUSIONS: Our findings revealed two clinically significant neuroanatomical subtypes of MDD, providing new insights into the neurobiological heterogeneity of this disorder. These findings may serve as a valuable reference for future precision diagnosis and treatment strategies.
METHODS: In this study, we analyzed T1-weighted anatomical images from 169 first-episode, drug-naïve (FEDN) MDD patients and 169 healthy controls (HCs) obtained from the rest-meta-MDD project. Patient symptom severity was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) and its subscales. We employed region-specific gray matter volume (GMV) feature-based heterogeneity through discriminant analysis (HYDRA) to explore neuroanatomical subtypes of FEDN MDD patients and validate their stability. Furthermore, we examined demographic and symptomatic differences between identified subtypes.
RESULTS: We identified two distinct neuroanatomical subtypes of FEDN MDD patients (FEDN MDD 1: n = 85, FEDN MDD 2: n = 84), which exhibited significant differences in GMV alterations. Compared with HCs, FEDN MDD 1 showed widespread GMV increases, while FEDN MDD 2 demonstrated significant GMV reductions. These two subtypes also demonstrated significant differences in HAMD anxiety/somatization subscale scores (t = 2.845, p < 0.01) and age distribution (t = 3.886, p < 0.001). Furthermore, reproducibility analyses confirmed the robustness of these subtypes.
CONCLUSIONS: Our findings revealed two clinically significant neuroanatomical subtypes of MDD, providing new insights into the neurobiological heterogeneity of this disorder. These findings may serve as a valuable reference for future precision diagnosis and treatment strategies.