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DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression
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DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression
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Journal Article
DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression
2015
Overview
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.
DICER1 is required for the maturation of miRNAs which regulate expression of thousands of genes. Here the authors show significantly reduced levels of
DICER1
in individuals having post-traumatic stress disorder and comorbid depression suggestive of a role in the molecular mechanism of the condition.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 38/39
/ 38/43
/ 38/61
/ 38/91
/ 59/36
/ Adult
/ Amygdala - diagnostic imaging
/ Blood
/ DEAD-box RNA Helicases - genetics
/ DEAD-box RNA Helicases - metabolism
/ Depression - diagnostic imaging
/ Fear
/ Female
/ Humanities and Social Sciences
/ Humans
/ Male
/ Polymorphism, Single Nucleotide
/ Post traumatic stress disorder
/ Ribonuclease III - metabolism
/ Science
/ Stress Disorders, Post-Traumatic - diagnostic imaging
/ Stress Disorders, Post-Traumatic - enzymology
/ Stress Disorders, Post-Traumatic - genetics
