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

Aliza P. Wingo, Lynn M. Almli, Jennifer J. Stevens, Torsten Klengel, Monica Uddin, Yujing Li, Angela C. Bustamante, Adriana Lori, Nastassja Koen, Dan J. Stein, Alicia K. Smith, Allison E. Aiello, Karestan C. Koenen, Derek E. Wildman, Sandro Galea, Bekh Bradley, Elisabeth B. Binder, Peng Jin, Greg Gibson, Kerry J. Ressler

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number10106
JournalNature communications
Volume6
DOIs
StatePublished - Dec 3 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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