An altered peripheral IL6 response in major depressive disorder

Kelli M. Money, Zita Olah, Zeljka Korade, Krassimira A. Garbett, Richard C. Shelton, Karoly Mirnics

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Major depressive disorder (MDD) is one of the most prevalent major psychiatric disorders with a lifetime prevalence of 17%. Recent evidence suggests MDD is not only a brain dysfunction, but a systemic disease affecting the whole body. Central and peripheral inflammatory changes seem to be a centerpiece of MDD pathology: a subset of patients show elevated blood cytokine and chemokine levels that partially normalize with symptom improvement over the course of anti-depressant treatment. As this inflammatory process in MDD is poorly understood, we hypothesized that the peripheral tissues of MDD patients will respond differently to inflammatory stimuli, resulting in an aberrant transcriptional response to elevated pro-inflammatory cytokines. To test this, we used MDD patient- and control-derived dermal fibroblast cultures to investigate their response to an acute treatment with IL6, IL1β, TNFα, or vehicle. Following RNA isolation and subsequent cDNA synthesis, quantitative PCR was used to determine the relative expression level of several families of inflammation-responsive genes. Our results showed comparable expression of the tested genes between MDD patients and controls at baseline. In contrast, MDD patient fibroblasts had a diminished transcriptional response to IL6 in all the gene sets tested (oxidative stress response, mitochondrial function, and lipid metabolism). We also found a significant increase in baseline and IL6 stimulated transcript levels of the IL6 receptor gene. This IL6 receptor transcript increase in MDD fibroblasts was accompanied by an IL6 stimulated increase in induction of SOCS3, which dampens IL6 receptor signaling. Altogether our results demonstrate that there is an altered transcriptional response to IL6 in MDD, which may represent one of the molecular mechanisms contributing to disease pathophysiology. Ultimately we hope that these studies will lead to validation of novel MDD drug targets focused on normalizing the altered IL6 response in patients.

Original languageEnglish (US)
Pages (from-to)46-54
Number of pages9
JournalNeurobiology of Disease
Volume89
DOIs
StatePublished - May 1 2016

Fingerprint

Major Depressive Disorder
Interleukin-6
Interleukin-6 Receptors
Fibroblasts
Cytokines
Genes
Lipid Metabolism
Chemokines
Psychiatry
Oxidative Stress
Complementary DNA
RNA
Pathology
Inflammation
Gene Expression
Polymerase Chain Reaction
Skin

Keywords

  • Cytokine
  • Fibroblasts
  • IL1b
  • IL6
  • Inflammation
  • Lipid metabolism
  • Major depressive disorder
  • Mitochondrial function
  • Oxidative stress
  • TNFa

ASJC Scopus subject areas

  • Neurology

Cite this

An altered peripheral IL6 response in major depressive disorder. / Money, Kelli M.; Olah, Zita; Korade, Zeljka; Garbett, Krassimira A.; Shelton, Richard C.; Mirnics, Karoly.

In: Neurobiology of Disease, Vol. 89, 01.05.2016, p. 46-54.

Research output: Contribution to journalArticle

Money, Kelli M. ; Olah, Zita ; Korade, Zeljka ; Garbett, Krassimira A. ; Shelton, Richard C. ; Mirnics, Karoly. / An altered peripheral IL6 response in major depressive disorder. In: Neurobiology of Disease. 2016 ; Vol. 89. pp. 46-54.
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