Journal Article

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

Zhu, Jia-Jia, Ping, Liang-Liang, Sun, Shan, Wang, Zi-Han, Kuang, Li, Wang, Chuan-Yue, Xu, Jian, Wang, Ying, Chen, Tao, Yu, Hua, Yuan, Yong-Gui, Wu, Yan-Kun, Xu, Xiu-Feng, Gong, Qi-Yong, Li, Tao, Huang, Qian, Zhang, Ai-Xia, He, Meng-Xin, Liao, Yi-Fan, Shan, Xiao-Xiao, Liu, Yan-Song, Bin Lu, Zhou, Cong, Hu, Zheng-Jia-Yi, Xie, Guang-Rong, Guo, Wen-Bin, Chu, Zhao-Song, Chen, Xiao, Li, Xue-Ying, Zhao, Jing-Ping, Zhang, Zi-Jing, Chen, Guan-Mao, Xue, Zhen-Peng, Cao, Li-Ping, Cui, Shi-Xian, Wu, Xiao-Ping, Jia, Feng-Nan, Yang, Jian, Ji, Xin-Lei, Li, Hui-Xian, Sun, Peng-Feng, Cheng, Yu-Qi, Wang, Hua-Ning, He, Can-Can, Wang, Yu-Wei, Xie, Peng, Yuan, Min-Lan, Deng, Zhao-Yu, Yu, Yong-Qiang, Zhang, Ke-Rang, Liu, Xiao-Yun, Sun, Duo, Liu, Zhe-Ning, Cui, Xi-Long, Wu, Xin-Ran, Shen, Zong-Lin, Lian, Tao, Si, Tian-Mei, Chen, Jian-Shan, Yang, Hong, Xie, Chun-Ming, Long, Yi-Cheng, Qiu, Jiang, Zhang, Wei, Li, Feng, Yan, Chao-Gan, Chen, Tao-Lin, Li, Bao-Juan, Wang, Xiang, Lu, Jian-Ping

2025

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 59/36 / 59/57 / 631/477/2811 / 692/699/476/1414 / Adult / Asymmetry / Behavioral Sciences / Biological Psychology / Brain - diagnostic imaging / Brain - physiopathology / Brain research / Case-Control Studies / Datasets / Default Mode Network - diagnostic imaging / Default Mode Network - physiopathology / Depressive Disorder, Major - diagnostic imaging / Depressive Disorder, Major - genetics / Depressive Disorder, Major - metabolism / Depressive Disorder, Major - physiopathology / Female / Functional Laterality - genetics / Functional Laterality - physiology / Gene expression / Humans / Magnetic Resonance Imaging / Male / Medical imaging / Medicine / Medicine & Public Health / Mental depression / Mental disorders / Middle Aged / Neuroimaging / Neurosciences / Neurotransmitter Agents - metabolism / Pharmacotherapy / Psychiatry