@article{b7125e1a75d249a59754a999a02e8e59,
title = "DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression",
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.",
author = "Wingo, {Aliza P.} and Almli, {Lynn M.} and Stevens, {Jennifer J.} and Torsten Klengel and Monica Uddin and Yujing Li and Bustamante, {Angela C.} and Adriana Lori and Nastassja Koen and Stein, {Dan J.} and Smith, {Alicia K.} and Aiello, {Allison E.} and Koenen, {Karestan C.} and Wildman, {Derek E.} and Sandro Galea and Bekh Bradley and Binder, {Elisabeth B.} and Peng Jin and Greg Gibson and Ressler, {Kerry J.}",
note = "Funding Information: We appreciate the technical support of all of the staff and volunteers of the Grady Trauma Project, particularly Kimberly Kerley, BA, Jennifer Leveille, BA, Kristina Mercer, MS, Jordan Laird, BS, Allen W. Graham, BA, Angelo Brown and Claudia Klengel, MD. We thank Charles Gillespie, MD/PhD, Ann Schwartz, MD and Tamara Weiss, MD for medical support, Divya Mehta, PhD for contributing to generation of gene expression data, Abigail Lott, PhD for maintaining the database. Additionally, we thank Nirav Patel, MS, and Gregory Tharp, MS at the Emory Yerkes Genomics Core for technical support with the small RNA sequencing and data analysis. We thank the participants of the Grady Trauma Project for their time and effort. 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.). 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.",
year = "2015",
month = dec,
day = "3",
doi = "10.1038/ncomms10106",
language = "English (US)",
volume = "6",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Research",
}