Shiqi Di1,2,3 · Na Luo1,2 · Weiyang Shi1,2 · Zhengyi Yang1,2  · Jing Sui4  · Rongtao Jiang5  · Yue Cui2,3  · Zongchang Du1,2,3 · Jiaqi Zhang1,2,3 · Yawei Ma1,2,6 · Haiyan Wang1,2  · Congying Chu1,2  · Yuejia Zhong1,2,3 · Wen Li1,2 · Yuheng Lu1,2,3 · Hao Yan7,8  · Jinmin Liao7,8 · Dai Zhang7,8,9  · Vince Calhoun10 · Ming Song1,2 · Tianzi Jiang1,2,3,11

1 Beijing Key Laboratory of Brainnetome and Brain‑Computer Interface, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China 

2 Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China 

3 School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 100049, China 

4 IDG/McGovern Institute for Brain Research, State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China 

5 Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT 06520, USA 

6 Sino‑Danish College, University of Chinese Academy of Sciences, Beijing 100049, China 

7 Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing 100191, China 

8 Key Laboratory of Mental Health, Ministry of Health, National Clinical Research Center for Mental Disorders, Peking University, Beijing 100191, China 

9 Center for Life Sciences/PKU‑IDG/McGovern Institute for Brain Research, Peking University, Beijing 100191, China 

10 Tri‑Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS): Georgia State University, Georgia Institute of Technology, and Emory University, Atlanta, GA 30303, USA 

11 Xiaoxiang Institute for Brain Health an

Abstract

In various studies, exercise has been revealed to have a positive effect on alleviating depressive symptoms. However, the neural basis behind this phenomenon remains unknown, as well as its underlying biological mechanism. In this study, we used a large neuroimaging cohort [n = 1,027, major depressive disorder (MDD)/healthy controls (HCs) = 492/535] from the UK Biobank to identify structural connectivity (SC) patterns simultaneously linked with physical activity and depression, as well as the biological interpretation. An SC pattern linked with exercise was identified to be both significantly correlated with depressive mood and group discrimination between MDDs and HCs, primarily located between the motor-related regions and reward-related regions. This pattern was associated with multiple neurotransmitter receptors, such as serotonin and GABA receptors, and enriched in pathways like synaptic signaling and the astrocyte cell type. The SC pattern and genetic results were also replicated in another independent MDD dataset (n = 3,496) and present commonalities with bipolar disorder (n = 81). Overall, these findings not only initially identified a reproducible shared SC pattern between physical activity and depressive mood, but also elucidated the underlying biological mechanisms, which enhance our understanding of how exercise helps alleviate depression and may inform the development of novel neuromodulation targets.

Keywords

Physical activity; Depression; Structural connectivity; Replicable association; Biological mechanisms

[SpringerLink]