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.
authors.affiliation: Atlanta VA Medical Center, Atlanta, Georgia 30033, USA.|Department of Psychiatry, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Aliza P
authors.initials: AP
authors.lastname: Wingo
authors.affiliation: Department of Psychiatry, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Almli
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Stevens
authors.affiliation: Department of Psychiatry, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Stevens
authors.affiliation: Department of Psychiatry, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.|McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA.
authors.forename: Torsten
authors.identifier: http://orcid.org/0000-0001-7045-9229
authors.initials: T
authors.lastname: Klengel
authors.affiliation: Department of Psychology, University of Illinois at Urbana-Champaign, Illinois 61820, USA.|Carl R. Woese Institute for Genomic Biology, Illinois 61820, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Uddin
authors.affiliation: Department of Human Genetics, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Psychology, University of Illinois at Urbana-Champaign, Illinois 61820, USA.
authors.forename: Angela C
authors.initials: AC
authors.lastname: Bustamante
authors.affiliation: Department of Psychiatry, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Lori
authors.affiliation: Department of Psychiatry and MRC Unit on Anxiety and Stress Disorders, University of Cape Town, Cape Town, South Africa.
authors.forename: Nastassja
authors.initials: N
authors.lastname: Koen
authors.affiliation: Department of Psychiatry and MRC Unit on Anxiety and Stress Disorders, University of Cape Town, Cape Town, South Africa.
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Stein
authors.affiliation: Department of Psychiatry, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Smith
authors.affiliation: School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Allison E
authors.initials: AE
authors.lastname: Aiello
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Karestan C
authors.initials: KC
authors.lastname: Koenen
authors.affiliation: Department of Psychology, University of Illinois at Urbana-Champaign, Illinois 61820, USA.
authors.forename: Derek E
authors.initials: DE
authors.lastname: Wildman
authors.affiliation: School of Public Health, Boston University, Boston, Massachusetts 02118, USA.
authors.forename: Sandro
authors.initials: S
authors.lastname: Galea
authors.affiliation: Atlanta VA Medical Center, Atlanta, Georgia 30033, USA.|Department of Psychiatry, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Bekh
authors.initials: B
authors.lastname: Bradley
authors.affiliation: Department of Psychiatry, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Elisabeth B
authors.initials: EB
authors.lastname: Binder
authors.affiliation: Department of Human Genetics, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.affiliation: Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Gibson
authors.affiliation: Department of Psychiatry, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.|McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
mesh_terms: D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000378:metabolism; D015331:Cohort Studies; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D003863:Depression / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D015536:Down-Regulation; D005239:Fear; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D013313:Stress Disorders, Post-Traumatic / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000523:psychology
chemical_list: D035683:MicroRNAs; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases