title: MicroRNA expression is down-regulated and reorganized in prefrontal cortex of depressed suicide subjects.
abstract: BACKGROUND
  Recent studies suggest that alterations in expression of genes, including those which regulate neural and structural plasticity, may be crucial in the pathogenesis of depression. MicroRNAs (miRNAs) are newly discovered regulators of gene expression that have recently been implicated in a variety of human diseases, including neuropsychiatric diseases.
  
  
  RESULTS
  The present study was undertaken to examine whether the miRNA network is altered in the brain of depressed suicide subjects. Expression of miRNAs was measured in prefrontal cortex (Brodmann Area 9) of antidepressant-free depressed suicide (n = 18) and well-matched non-psychiatric control subjects (n = 17) using multiplex RT-PCR plates. We found that overall miRNA expression was significantly and globally down-regulated in prefrontal cortex of depressed suicide subjects. Using individual tests of statistical significance, 21 miRNAs were significantly decreased at p = 0.05 or better. Many of the down-regulated miRNAs were encoded at nearby chromosomal loci, shared motifs within the 5'-seeds, and shared putative mRNA targets, several of which have been implicated in depression. In addition, a set of 29 miRNAs, whose expression was not pairwise correlated in the normal controls, showed a high degree of co-regulation across individuals in the depressed suicide group.
  
  
  CONCLUSIONS
  The findings show widespread changes in miRNA expression that are likely to participate in pathogenesis of major depression and/or suicide. Further studies are needed to identify whether the miRNA changes lead to altered expression of prefrontal cortex mRNAs, either directly (by acting as miRNA targets) or indirectly (e.g., by affecting transcription factors).
authors.affiliation: Department of Psychiatry, Psychiatric Institute, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Neil R
authors.initials: NR
authors.lastname: Smalheiser
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lugli
authors.forename: Hooriyah S
authors.initials: HS
authors.lastname: Rizavi
authors.forename: Vetle I
authors.initials: VI
authors.lastname: Torvik
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Dwivedi
mesh_terms: D000328:Adult; D015153:Blotting, Western; D016022:Case-Control Studies; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D003863:Depression / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D017397:Prefrontal Cortex / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011792:Quebec; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043244:Ribonuclease III / Q000378:metabolism; D018709:Statistics, Nonparametric; D013405:Suicide
chemical_list: C474043:DGCR8 protein, human; D017931:DNA Primers; D035683:MicroRNAs; D011506:Proteins; D016601:RNA-Binding Proteins; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases