Identification of microRNA-9 linking the effects of childhood maltreatment on depression using amygdala connectivity
Cancan He,
Ying Bai,
Zan Wang,
Dandan Fan,
Qing Wang,
Xinyi Liu,
Haisan Zhang,
Hongxing Zhang,
Zhijun Zhang,
Honghong Yao,
Chunming Xie
Affiliations
Cancan He
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China
Ying Bai
Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China
Zan Wang
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China; Institute of Neuropsychiatry, Affiliated ZhongDa Hospital, Southeast University, Nanjing, Jiangsu 210009, China
Dandan Fan
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China
Qing Wang
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China
Xinyi Liu
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China
Haisan Zhang
Department of Radiology, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453002, China; Xinxiang Key Laboratory of Multimodal Brain Imaging, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453002, China
Hongxing Zhang
Department of Psychiatry, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453002, China; Psychology School of Xinxiang Medical University, Xinxiang, Henan 453003, China
Zhijun Zhang
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China; Institute of Neuropsychiatry, Affiliated ZhongDa Hospital, Southeast University, Nanjing, Jiangsu 210009, China; Corresponding authors at: Department of Neurology, Institute of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.
Honghong Yao
Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China; Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, Jiangsu 210096, China; Corresponding author at: Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.
Chunming Xie
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China; Institute of Neuropsychiatry, Affiliated ZhongDa Hospital, Southeast University, Nanjing, Jiangsu 210009, China; Corresponding authors at: Department of Neurology, Institute of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.
Childhood maltreatment (CM) is regarded as an important risk factor for major depressive disorder (MDD). However, the neural links corresponding to the process of early CM experience producing brain alterations and then leading to depression later remain unclear. To explore the neural basis of the effects of CM on MDD and the potential role of microRNA-9 (miR-9) in these processes, we recruited 40 unmedicated MDD patients and 34 healthy controls (HCs) to complete resting-state fMRI scans and peripheral blood miR-9 tests. The neural substrates of CM, miR-9, and depression, as well as their interactive effects on intrinsic amygdala functional connectivity (AFC) networks were investigated in MDD patients. Two-step mediation analysis was separately employed to explore whether AFC strength mediates the association among CM severity, miR-9 levels, and depression. A support vector classifier (SVC) model of machine learning was used to distinguish MDD patients from HCs. MDD patients showed higher miR-9 levels that were negatively correlated with CM scores and depressive severity. Overlapping effects of CM, miR-9, and depressive severity on bilateral AFC networks in MDD patients were primarily located in the prefrontal-striatum pathway and limbic system. The connection of amygdala to prefrontal-limbic circuits could mediate the effects of CM severity on the miR-9 levels, as well as the impacts of miR-9 levels on the severity of depression in MDD patients. Furthermore, the SVC model, which integrated miR-9 levels, CM severity, and AFC strength in prefrontal-limbic regions, had good power in differentiating MDD patients from HCs (accuracy 85.1%). MiR-9 may play a crucial role in the process of CM experience-produced brain changes targeting prefrontal-limbic regions and that subsequently leads to depression. The present neuroimaging-epigenetic results provide new insight into our understanding of MDD pathophysiology.
