MicroRNA132 associated multimodal neuroimaging patterns in unmedicated major depressive disorder

Shile Qi, Xiao Yang, Liansheng Zhao, Vince Daniel Calhoun, Nora Perrone-Bizzozero, Shengfeng Liu, Rongtao Jiang, Tianzi Jiang, Jing Sui, Xiaohong Ma

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)916-926
Number of pages11
JournalBrain
Volume141
Issue number3
DOIs
StatePublished - Mar 1 2018
Externally publishedYes

Keywords

  • Fronto-limbic network
  • Major depressive disorder
  • MicroRNA132
  • Supervised multimodal fusion
  • Unmedicated

ASJC Scopus subject areas

  • Clinical Neurology

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  • Cite this

    Qi, S., Yang, X., Zhao, L., Calhoun, V. D., Perrone-Bizzozero, N., Liu, S., Jiang, R., Jiang, T., Sui, J., & Ma, X. (2018). MicroRNA132 associated multimodal neuroimaging patterns in unmedicated major depressive disorder. Brain, 141(3), 916-926. https://doi.org/10.1093/brain/awx366