miR‐9 could mediate the relationship between childhood maltreatment and depression

• Published in: Alzheimer's & dementia Vol. 16
• Main Authors: He, Cancan, Wang, Qing, Xie, Chunming
• Format: Journal Article
• Language: English
• Published: 01.12.2020
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.043590

Background Childhood maltreatment (CM) is regarded as an important risk factor for major disorder depression (MDD). However, the neural links corresponding to the process of early CM experience producing brain alterations and then leading to depression later remain unclear. Purpose To explore the neural basis of the effects of CM on MDD and the potential effects of microRNA‐9 (miR‐9) in mediating these processes. Method Forty unmedicated MDD patients and 34 healthy controls (HCs) completed 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) network 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. Result 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 separately mediated the effects of CM severity on the miR‐9 levels, and 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%). Conclusion 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.