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

Neuroimage. 2021 Jan 1:224:117428. doi: 10.1016/j.neuroimage.2020.117428. Epub 2020 Oct 7.

Abstract

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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Adult Survivors of Child Abuse / psychology*
  • Amygdala / diagnostic imaging*
  • Amygdala / physiopathology
  • Case-Control Studies
  • Depressive Disorder, Major / diagnostic imaging*
  • Depressive Disorder, Major / metabolism
  • Depressive Disorder, Major / physiopathology
  • Depressive Disorder, Major / psychology
  • Female
  • Functional Neuroimaging
  • Humans
  • Limbic System / diagnostic imaging
  • Limbic System / physiopathology
  • Magnetic Resonance Imaging
  • Male
  • Mediation Analysis
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neostriatum / diagnostic imaging*
  • Neostriatum / physiopathology
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / physiopathology
  • Prefrontal Cortex / diagnostic imaging*
  • Prefrontal Cortex / physiopathology
  • Severity of Illness Index
  • Support Vector Machine
  • Young Adult

Substances

  • MIRN92 microRNA, human
  • MicroRNAs