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Structure-function coupling and hierarchy-specific antidepressant response in major depressive disorder

Published online by Cambridge University Press:  04 April 2024

Xinyi Wang ,
Li Xue ,
Lingling Hua ,
Junneng Shao ,
Rui Yan ,
Zhijian Yao  and
Qing Lu Open the ORCID record for Qing Lu [Opens in a new window]
Xinyi Wang
Affiliation:
School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, China Child Development and Learning Science, Key Laboratory of Ministry of Education, Southeast University, Nanjing, China
Li Xue
Affiliation:
School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, China Child Development and Learning Science, Key Laboratory of Ministry of Education, Southeast University, Nanjing, China
Lingling Hua
Affiliation:
Department of Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
Junneng Shao
Affiliation:
School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, China Child Development and Learning Science, Key Laboratory of Ministry of Education, Southeast University, Nanjing, China
Rui Yan
Affiliation:
Department of Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
Zhijian Yao*
Affiliation:
Department of Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China Nanjing Brain Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Nanjing, China
Qing Lu*
Affiliation:
School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, China Child Development and Learning Science, Key Laboratory of Ministry of Education, Southeast University, Nanjing, China
*
Corresponding author: Qing Lu; Email: luq@seu.edu.cn; Zhijian Yao; Email: zjyao@njmu.edu.cn
Corresponding author: Qing Lu; Email: luq@seu.edu.cn; Zhijian Yao; Email: zjyao@njmu.edu.cn
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Abstract

Background

Extensive research has explored altered structural and functional networks in major depressive disorder (MDD). However, studies examining the relationships between structure and function yielded heterogeneous and inconclusive results. Recent work has suggested that the structure-function relationship is not uniform throughout the brain but varies across different levels of functional hierarchy. This study aims to investigate changes in structure-function couplings (SFC) and their relevance to antidepressant response in MDD from a functional hierarchical perspective.

Methods

We compared regional SFC between individuals with MDD (n = 258) and healthy controls (HC, n = 99) using resting-state functional magnetic resonance imaging and diffusion tensor imaging. We also compared antidepressant non-responders (n = 55) and responders (n = 68, defined by a reduction in depressive severity of >50%). To evaluate variations in altered and response-associated SFC across the functional hierarchy, we ranked significantly different regions by their principal gradient values and assessed patterns of increase or decrease along the gradient axis. The principal gradient value, calculated from 219 healthy individuals in the Human Connectome Project, represents a region's position along the principal gradient axis.

Results

Compared to HC, MDD patients exhibited increased SFC in unimodal regions (lower principal gradient) and decreased SFC in transmodal regions (higher principal gradient) (p < 0.001). Responders primarily had higher SFC in unimodal regions and lower SFC in attentional networks (median principal gradient) (p < 0.001).

Conclusions

Our findings reveal opposing SFC alterations in low-level unimodal and high-level transmodal networks, underscoring spatial variability in MDD pathology. Moreover, hierarchy-specific antidepressant effects provide valuable insights into predicting treatment outcomes.

Keywords

antidepressant responsebrain hierarchyfunctional connectivity gradientstructure-function coupling
Type
Original Article
Information
Psychological Medicine , Volume 54 , Issue 10 , July 2024 , pp. 2688 - 2697
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Copyright
Copyright © The Author(s), 2024. Published by Cambridge University Press

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