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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Amygdala / diagnostic imaging
  • Amygdala / metabolism
  • Cohort Studies
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Depression / diagnostic imaging
  • Depression / enzymology*
  • Depression / genetics
  • Depression / metabolism
  • Depression / psychology
  • Down-Regulation
  • Fear
  • Female
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Radiography
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism*
  • Stress Disorders, Post-Traumatic / diagnostic imaging
  • Stress Disorders, Post-Traumatic / enzymology*
  • Stress Disorders, Post-Traumatic / genetics
  • Stress Disorders, Post-Traumatic / metabolism
  • Stress Disorders, Post-Traumatic / psychology

Substances

  • MicroRNAs
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases

Associated data

  • GEO/GSE67663
  • GEO/GSE74162