Identification of microRNA-9 linking the effects of childhood maltreatment on depression using amygdala connectivity

NeuroImage

Dandan Fan¹  Chunming Xie²  Zhijun Zhang³  Haisan Zhang⁴  Xinyi Liu⁴  Zan Wang⁴  Cancan He⁴  Qing Wang⁴  Ying Bai⁵  Honghong Yao⁶  Hongxing Zhang⁷ 

[1] Institute of Neuropsychiatry, Affiliated ZhongDa Hospital, Southeast University, Nanjing, Jiangsu 210009, China;Psychology School of Xinxiang Medical University, Xinxiang, Henan 453003, China;Xinxiang Key Laboratory of Multimodal Brain Imaging, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453002, China;Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China;Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China;Department of Psychiatry, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453002, China;Department of Radiology, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453002, China;

关键词: Major depressive disorder;    Childhood maltreatment;    microRNA-9;    Resting-state fMRI;    Amygdala functional connectivity;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown