https://doi.org/10.1140/epjs/s11734-025-02052-6
Regular Article
High-order segregation of brain functional networks in major depressive disorder patients with and without suicide
1
College of Science, Xi’an University of Science and Technology, 710054, Xi’an, China
2
State Key Laboratory for Strength and Vibration of Mechanical Structures, School of Aerospace Engineering, Xi’an Jiaotong University, 710049, Xi’an, China
3
Medical Psychological Center, the Second Xiangya Hospital, Central South University, 410011, Changsha, China
4
National Clinical Research Center for Mental Disorders (the Second Xiangya Hospital), 410011, Changsha, China
5
Department of Psychology, Hunan Normal University, Changsha, China
6
Cognition and Human Behavior Key Laboratory of Hunan Province, Hunan Normal University, Changsha, China
a
tiger.lin9906@gmail.com
b
wangxiang0916@csu.edu.cn
Received:
28
July
2025
Accepted:
28
October
2025
Published online:
19
November
2025
Major depressive disorder (MDD) is a complex psychiatric condition frequently accompanied by suicidal ideation and behavior, yet its underlying neural mechanisms remain unclear. Here, we studied the high-order segregation of brain functional networks in MDD patients with suicide attempt (SA) and without suicide attempt (DEP). First, compared to healthy controls, both DEP and SA patients exhibited increased segregation, particularly in the parietal, occipital and precentral gyrus regions. SA patients had significantly decreased segregation in the left dorsomedial prefrontal cortex and right precentral gyrus, relative to DEP patients. Second, more severe depression symptoms were linked to higher segregation in the left parietal operculum and left dorsomedial prefrontal cortex in DEP patients, whereas they were associated with the left occipital cortex, bilateral prefrontal cortex, left parietal cortex, and right precentral gyrus in SA patients. Then, we predicted the suicide symptom with a machine learning model and found that the right occipital cortex, pre/postcentral gyrus, right lateral prefrontal cortex, and left parietal cortex contributed to severe suicide symptom. Finally, we provided that the high-order segregation contributed to the classification of DEP and SA patients, outperforming traditional graph theory measures. Our findings revealed the neurobiological differences between suicidal and non-suicidal MDD patients, suggesting that increased high-order brain network segregation may serve as a potential biomarker for MDD diagnosis and suicide risk prediction.
Supplementary Information The online version contains supplementary material available at https://doi.org/10.1140/epjs/s11734-025-02052-6.
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© The Author(s), under exclusive licence to EDP Sciences, Springer-Verlag GmbH Germany, part of Springer Nature 2025
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
