MicroRNA132 Associated Multimodal Neuroimaging Patterns in Unmedicated Major Depressive Disorder

Brain. 2018 Mar 1;141(3):916-926. doi: 10.1093/brain/awx366.

Abstract

There is compelling evidence that epigenetic factors contribute to the manifestation of depression, in which microRNA132 (miR-132) is suggested to play a pivotal role in the pathogenesis and neuronal mechanisms underlying the symptoms of depression. Additionally, several depression-associated genes [MECP2, ARHGAP32 (p250GAP), CREB, and period genes] were experimentally validated as miR-132 targets. However, most studies regarding miR-132 in major depressive disorder are based on post-mortem, animal models or genetic comparisons. This work will be the first attempt to investigate how miR-132 dysregulation may impact covariation of multimodal brain imaging data in 81 unmedicated major depressive patients and 123 demographically-matched healthy controls, as well as in a medication-naïve subset of major depressive patients. MiR-132 values in blood (patients > controls) was used as a prior reference to guide fusion of three MRI features: fractional amplitude of low frequency fluctuations, grey matter volume, and fractional anisotropy. The multimodal components correlated with miR-132 also show significant group difference in loadings. Results indicate that (i) higher miR-132 levels in major depressive disorder are associated with both lower fractional amplitude of low frequency fluctuations and lower grey matter volume in fronto-limbic network; and (ii) the identified brain regions linked with increased miR-132 levels were also associated with poorer cognitive performance in attention and executive function. Using a data-driven, supervised-learning method, we determined that miR-132 dysregulation in major depressive disorder is associated with multi-facets of brain function and structure in fronto-limbic network (the key network for emotional regulation and memory), which deepens our understanding of how miR-132 dysregulation in major depressive disorders contribute to the loss of specific brain areas and is linked to relevant cognitive impairments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain / diagnostic imaging
  • Case-Control Studies
  • Cognition / physiology
  • Depressive Disorder, Major / blood*
  • Depressive Disorder, Major / diagnostic imaging*
  • Depressive Disorder, Major / genetics
  • Depressive Disorder, Major / metabolism
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Middle Aged
  • Oxygen / blood
  • Young Adult

Substances

  • MIRN132 microRNA, human
  • MicroRNAs
  • Oxygen