DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression vol 6, 10106, 2015Report as inadecuate

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Journal Title:

Nature Communications


Volume 7


Nature Publishing Group: Nature Communications | 2016-03-01, Pages 10958-10958

Type of Work:

Article | Final Publisher PDF

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 PTSDandDep, 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 PTSDandDep, and the latter is replicated in an independent cohort. Furthermore, genome-wide differential expression survey of miRNAs in blood in PTSDandDep reveals miRNAs to be significantly downregulated in cases versus controls. Together, our novel data suggest DICER1 plays a role in molecular mechanisms of PTSDandDep through the DICER1 and the miRNA regulation pathway.

Subjects: Psychology, General - Psychology, Behavioral - Research Funding: This study was supported in part by the Department of Veterans Affairs Career Development Award IK2CX000601 and the NARSAD Young Investigator Award to A.P.W

This work was primarily supported by the National Institutes of Mental Health MH096764 and MH071537 to K.J.R

Support was also received from Emory and Grady Memorial Hospital General Clinical Research Center, National Institutes of Health NIH. The Drakenstein study was funded by the Bill and Melinda Gates Foundation 1017641, the NIH R21 MH098662 and the Medical Research Council MRC of South Africa. The DNHS was funded by DA022720 and RC1MH088283 to A.E.A

T.K. is supported by a NARSAD YI Grant and an EMBO Long-Term Fellowship. The contents do not represent the views of the Department of Veterans Affairs or the United States Government.

Keywords: Science and Technology - Multidisciplinary Sciences - Science and Technology - Other Topics - CHILDHOOD MALTREATMENT - PSYCHIATRIC-DISORDERS - GENE-EXPRESSION - SEQUENCING DATA - IMMUNE-SYSTEM - HEART-DISEASE - UP-REGULATION - BRAIN - None - None -

Author: Aliza Wingo, Lynn Almli, Alicia Smith, Jennifer Stevens, Torsten Klengel, Monica Uddin, Yujing Li, Angela C. Bustamante, Adriana

Source: https://open.library.emory.edu/


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