DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression

Aliza P. Wingo, Lynn M. Almli, Jennifer S. Stevens, Torsten Klengel, Monica Uddin, Yujing Li, Angela C. Bustamante, Adriana Lori, Nastassja Koen, Dan J. Stein, Alicia K. Smith, Allison E. Aiello, Karestan C. Koenen, Derek E. Wildman, Sandro Galea, Bekh Bradley, Elisabeth B. Binder, Peng Jin, Greg Gibson and Kerry J. Ressler ()
Additional contact information
Aliza P. Wingo: Atlanta VA Medical Center
Lynn M. Almli: School of Medicine, Emory University
Jennifer S. Stevens: School of Medicine, Emory University
Torsten Klengel: School of Medicine, Emory University
Monica Uddin: University of Illinois at Urbana-Champaign
Yujing Li: School of Medicine, Emory University
Angela C. Bustamante: University of Illinois at Urbana-Champaign
Adriana Lori: School of Medicine, Emory University
Nastassja Koen: University of Cape Town
Dan J. Stein: University of Cape Town
Alicia K. Smith: School of Medicine, Emory University
Allison E. Aiello: School of Global Public Health, University of North Carolina at Chapel Hill
Karestan C. Koenen: Harvard T.H. Chan School of Public Health
Derek E. Wildman: University of Illinois at Urbana-Champaign
Sandro Galea: School of Public Health, Boston University
Bekh Bradley: Atlanta VA Medical Center
Elisabeth B. Binder: School of Medicine, Emory University
Peng Jin: School of Medicine, Emory University
Greg Gibson: Center for Integrative Genomics, School of Biology, Georgia Institute of Technology
Kerry J. Ressler: School of Medicine, Emory University

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract DICER1 is an enzyme that generates mature microRNAs (miRNAs), which regulate gene expression post-transcriptionally in brain and other tissues and is involved in synaptic maturation and plasticity. Here, through genome-wide differential gene expression survey of post-traumatic stress disorder (PTSD) with comorbid depression (PTSD&Dep), we find that blood DICER1 expression is significantly reduced in cases versus controls, and replicate this in two independent cohorts. Our follow-up studies find that lower blood DICER1 expression is significantly associated with increased amygdala activation to fearful stimuli, a neural correlate for PTSD. Additionally, a genetic variant in the 3′ un-translated region of DICER1, rs10144436, is significantly associated with DICER1 expression and with PTSD&Dep, and the latter is replicated in an independent cohort. Furthermore, genome-wide differential expression survey of miRNAs in blood in PTSD&Dep reveals miRNAs to be significantly downregulated in cases versus controls. Together, our novel data suggest DICER1 plays a role in molecular mechanisms of PTSD&Dep through the DICER1 and the miRNA regulation pathway.

Date: 2015
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DOI: 10.1038/ncomms10106

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