Dynamic changes in hemispheric lateralization in major depressive disorder correlate with neurotransmitter and genetic profiles: a DIRECT consortium study

Hemispheric lateralization, recognized as a pivotal feature in both the structural and functional organization of the human brain, may undergo alterations in specific psychiatric disorders. However, the time-varying patterns of hemispheric lateralization in individuals with major depressive disorder (MDD) and the relationship between these patterns and gene expression profiles remain largely unexplored thus far. Using a large multi-site resting-state functional magnetic resonance imaging (rs-fMRI) data encompassing 2611 participants (1660 MDD patients and 1341 healthy controls), we examined MDD-related abnormalities in dynamic laterality and its association with clinical symptoms, meta-analytic cognitive functions, and neurotransmitter receptor profiles, respectively. And the biological basis behind these changes was investigated through gene enrichment analysis and cell-specific analysis. Here we found revealed pronounced fluctuations in lateralization primarily in the regions in default mode network, attention network and control network in MDD patients when compared to healthy controls. In addition, these fluctuations exhibited significant correlations with higher-order cognition terms and the distributions of disease related neurotransmitters. Further, through gene enrichment and cell-specific analysis, we identified a molecular genetic basis for these changes, highlighting synaptic function-related genes and neuronal cells. Collectively, these results demonstrated robust altered brain lateralization patterns in MDD and its molecular genetic basis, providing new clues to understand the pathophysiology of MDD.

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Publication Details

Journal
Translational Psychiatry
Published
2025-11-10
DOI
https://doi.org/10.1038/s41398-025-03715-7
Primary Topic
Functional Brain Connectivity Studies
Type
article
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article

Dynamic changes in hemispheric lateralization in major depressive disorder correlate with neurotransmitter and genetic profiles: a DIRECT consortium study

Shi‐Xian Cui, Yicheng Long, Chao‐Gan Yan, Wenbin Guo et al.
Translational Psychiatry
Functional Brain Connectivity Studies
article

Dynamic changes in hemispheric lateralization in major depressive disorder correlate with neurotransmitter and genetic profiles: a DIRECT consortium study

Shi‐Xian Cui, Yicheng Long, Chao‐Gan Yan, Wenbin Guo, Xiaoxiao Shan, Zhaosong Chu, Shan Sun, Yu‐Feng Zang, Baojuan Li, Xinlei Ji, Minlan Yuan, Yonggui Yuan, Dianjianyi Sun, Ai-Xia Zhang, Cong Zhou, Zhao‐Yu Deng, Xi‐Nian Zuo, Yongqiang Yu, Mengxin He, Tianmei Si, Chunming Xie, Zijing Zhang, Ke-Rang Zhang, Guanmao Chen, Jun‐Juan Zhu, Daihui Peng, Liping Cao, Xinran Wu, Zheng-Jia-Yi Hu, Zhenpeng Xue, Qiyong Gong, Xiaoping Wu, Feng-Nan Jia, Huaning Wang, Jiajia Zhu, Zonglin Shen, Yiru Fang, Peng-Feng Sun, Jian Xu, Zhening Liu, Ching‐Po Lin, Xilong Cui, Jiangshan Chen, Liangliang Ping, Yifan Liao, Chuanyue Wang, Yan-Kun Wu, Wei Chen, Ying Wang, Tao Chen, Xiao Chen, Zihan Wang, Zhijun Zhang, Xiang Wang, Yuwei Wang, Kai You Wang, Tao Li, Fei Wang, Xueying Li, Li Kuang, Wei Zhang, Bin Lü, Peng Xie, Xiaoyun Liu, Jian Yang, Jianping Lu, Hong Yang, Jiang Qiu, Guangrong Xie, Yanqing Tang, Li Feng, Yuqi Cheng, Yuedi Shen, Qing-Hua Luo, Hua Yu, Qian Huang, Tao Lian, Huaqing Meng, Xiufeng Xu, Jingping Zhao, Hui-Xian Li, Cancan He, Shu-Qiao Yao, Yan‐Song Liu
article en

Abstract

Hemispheric lateralization, recognized as a pivotal feature in both the structural and functional organization of the human brain, may undergo alterations in specific psychiatric disorders. However, the time-varying patterns of hemispheric lateralization in individuals with major depressive disorder (MDD) and the relationship between these patterns and gene expression profiles remain largely unexplored thus far. Using a large multi-site resting-state functional magnetic resonance imaging (rs-fMRI) data encompassing 2611 participants (1660 MDD patients and 1341 healthy controls), we examined MDD-related abnormalities in dynamic laterality and its association with clinical symptoms, meta-analytic cognitive functions, and neurotransmitter receptor profiles, respectively. And the biological basis behind these changes was investigated through gene enrichment analysis and cell-specific analysis. Here we found revealed pronounced fluctuations in lateralization primarily in the regions in default mode network, attention network and control network in MDD patients when compared to healthy controls. In addition, these fluctuations exhibited significant correlations with higher-order cognition terms and the distributions of disease related neurotransmitters. Further, through gene enrichment and cell-specific analysis, we identified a molecular genetic basis for these changes, highlighting synaptic function-related genes and neuronal cells. Collectively, these results demonstrated robust altered brain lateralization patterns in MDD and its molecular genetic basis, providing new clues to understand the pathophysiology of MDD.

Translational PsychiatryVol. 15(1)
Central South University (CN), Southwest University (CN), Shanxi Medical University (CN), Shanghai Jiao Tong University (CN), Capital Medical University (CN), Anhui Medical University (CN), Chinese Academy of Sciences (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Peking University (CN), Sichuan University (CN), Beijing Normal University (CN), Kunming Medical University (CN), Renji Hospital (CN), Sir Run Run Shaw Hospital (CN), Shanghai Mental Health Center (CN), Soochow University (CN), First Affiliated Hospital of Xiamen University (CN), Xian Central Hospital (CN), West China Hospital of Sichuan University (CN), Affiliated Hospital of Hangzhou Normal University (CN), Zhongda Hospital Southeast University (CN), 174th hospital of the People's Liberation Army (CN), Suzhou Guangji Hospital (CN), Nanjing Brain Hospital (CN), Beijing Anding Hospital (CN), Chinese Institute for Brain Research (CN), Shenzhen KangNing Hospital (CN), First Affiliated Hospital of Kunming Medical University (CN), Zhejiang Lab (CN), First Hospital of Shanxi Medical University (CN), Anhui Provincial Hospital (CN), The Affiliated Yongchuan Hospital of Chongqing Medical University (CN), Institute of Psychology, Chinese Academy of Sciences (CN), Hangzhou Seventh Peoples Hospital (CN), First Affiliated Hospital of Anhui Medical University (CN), Xiamen Chang Gung Hospital (CN), Second Xiangya Hospital of Central South University (CN), Xijing Hospital (CN), Children's Hospital of Chongqing Medical University (CN), Peking University Sixth Hospital (CN), First Affiliated Hospital of Jinan University (CN), First Hospital of Xi'an (CN), Fujian Fisheries Research Institute (CN), University of Chinese Academy of Sciences (CN), Jining Medical University (CN), Zhejiang University (CN), Nanjing Medical University (CN), Chongqing Medical University (CN), China Medical University (CN), Guangzhou Medical University (CN)
National Natural Science Foundation of China, Recruitment Program of Global Experts, National Ten Thousand Talent Program, NIH Clinical Center
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Functional Brain Connectivity Studies
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