title: Coordinated messenger RNA/microRNA changes in fibroblasts of patients with major depression.
abstract: BACKGROUND
  Peripheral biomarkers for major psychiatric disorders have been an elusive target for the last half a century. Dermal fibroblasts are a simple, relevant, and much underutilized model for studying molecular processes of patients with affective disorders, as they share considerable similarity of signal transduction with neuronal tissue.
  
  
  METHODS
  Cultured dermal fibroblast samples from patients with major depressive disorder (MDD) and matched control subjects (n = 16 pairs, 32 samples) were assayed for genome-wide messenger RNA (mRNA) expression using microarrays. In addition, a simultaneous quantitative polymerase chain reaction-based assessment of >1000 microRNA (miRNA) species was performed. Finally, to test the relationship between the mRNA-miRNA expression changes, the two datasets were correlated with each other.
  
  
  RESULTS
  Our data revealed that MDD fibroblasts, when compared with matched control subjects, showed a strong mRNA gene expression pattern change in multiple molecular pathways, including cell-to-cell communication, innate/adaptive immunity, and cell proliferation. Furthermore, the same patient fibroblasts showed altered expression of a distinct panel of 38 miRNAs, which putatively targeted many of the differentially expressed mRNAs. The miRNA-mRNA expression changes appeared to be functionally connected, as the majority of the miRNA and mRNA changes were in the opposite direction.
  
  
  CONCLUSIONS
  Our data suggest that combined miRNA-mRNA assessments are informative about the disease process and that analyses of dermal fibroblasts might lead to the discovery of promising peripheral biomarkers of MDD that could be potentially used to aid the diagnosis and allow mechanistic testing of disturbed molecular pathways.
authors.affiliation: Department of Psychiatry, Vanderbilt University, Nashville, Tennessee.
authors.forename: Krassimira A
authors.initials: KA
authors.lastname: Garbett
authors.affiliation: Department of Psychiatry, Vanderbilt University, Nashville, Tennessee; Institute for Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vereczkei
authors.affiliation: Department of Psychiatry, Vanderbilt University, Nashville, Tennessee; Department of Psychiatry, University of Szeged, Szeged.
authors.forename: Sára
authors.initials: S
authors.lastname: Kálmán
authors.affiliation: Department of Psychiatry, Vanderbilt University, Nashville, Tennessee.
authors.forename: Jacquelyn A
authors.initials: JA
authors.lastname: Brown
authors.affiliation: Department of Psychiatry, Vanderbilt University, Nashville, Tennessee.
authors.forename: Warren D
authors.initials: WD
authors.lastname: Taylor
authors.affiliation: Department of Psychiatry, Kútvölgyi Clinical Centre, Semmelweis University, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Faludi
authors.affiliation: Department of Psychiatry, Vanderbilt University, Nashville, Tennessee; Vanderbilt Kennedy Center for Research on Human Development (ZK, KM), Vanderbilt University, Nashville, Tennessee.
authors.forename: Željka
authors.initials: Ž
authors.lastname: Korade
authors.affiliation: Department of Psychiatry, University of Alabama, Birmingham, Alabama.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Shelton
authors.affiliation: Department of Psychiatry, Vanderbilt University, Nashville, Tennessee; Department of Psychiatry, University of Szeged, Szeged; Vanderbilt Kennedy Center for Research on Human Development (ZK, KM), Vanderbilt University, Nashville, Tennessee.. Electronic address: karoly.mirnics@vanderbilt.edu.
authors.forename: Károly
authors.initials: K
authors.lastname: Mirnics
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003865:Major Depressive Disorder / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Biomarker; DNA microarray; Gene expression; Human fibroblasts; Major depression; miRNA