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Nat Commun. 2015 Dec 3;6:10106. doi: 10.1038/ncomms10106.

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

Author information

1
Atlanta VA Medical Center, Atlanta, Georgia 30033, USA.
2
Department of Psychiatry, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
3
McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA.
4
Department of Psychology, University of Illinois at Urbana-Champaign, Illinois 61820, USA.
5
Carl R. Woese Institute for Genomic Biology, Illinois 61820, USA.
6
Department of Human Genetics, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
7
Department of Psychiatry and MRC Unit on Anxiety and Stress Disorders, University of Cape Town, Cape Town, South Africa.
8
School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
9
Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
10
School of Public Health, Boston University, Boston, Massachusetts 02118, USA.
11
Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.

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.

PMID:
26632874
PMCID:
PMC4686835
DOI:
10.1038/ncomms10106
[Indexed for MEDLINE]
Free PMC Article

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