TY - JOUR
T1 - MicroRNA132 associated multimodal neuroimaging patterns in unmedicated major depressive disorder
AU - Qi, Shile
AU - Yang, Xiao
AU - Zhao, Liansheng
AU - Calhoun, Vince D.
AU - Perrone-Bizzozero, Nora
AU - Liu, Shengfeng
AU - Jiang, Rongtao
AU - Jiang, Tianzi
AU - Sui, Jing
AU - Ma, Xiaohong
N1 - Funding Information:
This study was funded by the National High-Tech Development Program (863 plan, No. 2015AA020513), ‘100 Talents Plan’ of Chinese Academy of Sciences, the Chinese National Natural Science Foundation No. 81471367, No. 81671344 and No. 61773380, the Strategic Priority Research Program of the Chinese Academy of Sciences (grant No. XDB02060005), the National Science and Technology Support plan (2015BAI13B02), and NIH grants R01EB005846, 1R01MH094524 and P20GM103472.
Publisher Copyright:
© The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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.
AB - 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.
KW - Fronto-limbic network
KW - Major depressive disorder
KW - MicroRNA132
KW - Supervised multimodal fusion
KW - Unmedicated
UR - http://www.scopus.com/inward/record.url?scp=85042906398&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042906398&partnerID=8YFLogxK
U2 - 10.1093/brain/awx366
DO - 10.1093/brain/awx366
M3 - Article
C2 - 29408968
AN - SCOPUS:85042906398
SN - 0006-8950
VL - 141
SP - 916
EP - 926
JO - Brain
JF - Brain
IS - 3
ER -