Coordinated messenger RNA/microRNA changes in fibroblasts of patients with major depression

Krassimira A. Garbett, Andrea Vereczkei, Sára Kálmán, Jacquelyn A. Brown, Warren D. Taylor, Gábor Faludi, Zeljka Korade, Richard C. Shelton, Karoly Mirnics

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)256-265
Number of pages10
JournalBiological Psychiatry
Volume77
Issue number3
DOIs
StatePublished - Feb 1 2015

Fingerprint

MicroRNAs
Fibroblasts
Depression
Messenger RNA
Major Depressive Disorder
Skin
Biomarkers
Molecular Models
Adaptive Immunity
Mood Disorders
Innate Immunity
Cell Communication
Psychiatry
Signal Transduction
Cell Proliferation
Genome
Gene Expression
Polymerase Chain Reaction

Keywords

  • Biomarker
  • DNA microarray
  • Gene expression
  • Human fibroblasts
  • Major depression
  • miRNA

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Coordinated messenger RNA/microRNA changes in fibroblasts of patients with major depression. / Garbett, Krassimira A.; Vereczkei, Andrea; Kálmán, Sára; Brown, Jacquelyn A.; Taylor, Warren D.; Faludi, Gábor; Korade, Zeljka; Shelton, Richard C.; Mirnics, Karoly.

In: Biological Psychiatry, Vol. 77, No. 3, 01.02.2015, p. 256-265.

Research output: Contribution to journalArticle

Garbett, KA, Vereczkei, A, Kálmán, S, Brown, JA, Taylor, WD, Faludi, G, Korade, Z, Shelton, RC & Mirnics, K 2015, 'Coordinated messenger RNA/microRNA changes in fibroblasts of patients with major depression', Biological Psychiatry, vol. 77, no. 3, pp. 256-265. https://doi.org/10.1016/j.biopsych.2014.05.015
Garbett, Krassimira A. ; Vereczkei, Andrea ; Kálmán, Sára ; Brown, Jacquelyn A. ; Taylor, Warren D. ; Faludi, Gábor ; Korade, Zeljka ; Shelton, Richard C. ; Mirnics, Karoly. / Coordinated messenger RNA/microRNA changes in fibroblasts of patients with major depression. In: Biological Psychiatry. 2015 ; Vol. 77, No. 3. pp. 256-265.
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AB - 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.

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