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

• Type of Material: Article
• Authors: Aliza Wingo, Emory University; Lynn Almli, Emory University; Jennifer J. Stevens, Emory University; Torsten Klengel, Emory University; Monica Uddin, University of Illinois at Urbana-Champaign; Yujing Li, Emory University; Angela C. Bustamante, University of Illinois at Urbana-Champaign; Adriana Lori, Emory University; Nastassja Koen, University of Cape Town; Dan J. Stein, University of Cape Town; Alicia Smith, Emory University; Allison E. Aiello, 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, Boston University; Bekh Bradley-Davino, Emory University; Elisabeth Binder, Emory University; Peng Jin, Emory University; Greg Gibson, Georgia Institute of Technology; Kerry Ressler, Emory University
• Language: English
• Date: 2015-12-01
• Publisher: Nature Publishing Group: Nature Communications
• Publication Version: Final Published Version
• Copyright Statement: © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/ncomms10106
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 6
• Start Page: 10106
• End Page: 10106
• Grant/Funding Information: Support was also received from Emory and Grady Memorial Hospital General Clinical Research Center, National Institutes of Health (NIH). The Drakenstein study was funded by the Bill and Melinda Gates Foundation (1017641), the NIH (R21 MH098662) and the Medical Research Council (MRC) of South Africa. The DNHS was funded by DA022720 and RC1MH088283 (to A.E.A.).; T.K. is supported by a NARSAD YI Grant and an EMBO Long-Term Fellowship. The contents do not represent the views of the Department of Veterans Affairs or the United States Government.; This study was supported in part by the Department of Veterans Affairs Career Development Award IK2CX000601 and the NARSAD Young Investigator Award (to A.P.W.). This work was primarily supported by the National Institutes of Mental Health (MH096764 and MH071537 to K.J.R.).
• Keywords: GENE-EXPRESSION; UP-REGULATION; IMMUNE-SYSTEM; Science & Technology - Other Topics; PSYCHIATRIC-DISORDERS; Science & Technology; SEQUENCING DATA; BRAIN; DNA-DAMAGE; GENOME-WIDE ASSOCIATION; Multidisciplinary Sciences; HEART-DISEASE; CHILDHOOD MALTREATMENT
• Research Categories: Psychology, General; Psychology, Behavioral

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.