Fibroblasts from patients with major depressive disorder show distinct transcriptional response to metabolic stressors

Translational Psychiatry
Krassimira A GarbettKároly Mirnics

Abstract

Major depressive disorder (MDD) is increasingly viewed as interplay of environmental stressors and genetic predisposition, and recent data suggest that the disease affects not only the brain, but the entire body. As a result, we aimed at determining whether patients with major depression have aberrant molecular responses to stress in peripheral tissues. We examined the effects of two metabolic stressors, galactose (GAL) or reduced lipids (RL), on the transcriptome and miRNome of human fibroblasts from 16 pairs of patients with MDD and matched healthy controls (CNTR). Our results demonstrate that both MDD and CNTR fibroblasts had a robust molecular response to GAL and RL challenges. Most importantly, a significant part (messenger RNAs (mRNAs): 26-33%; microRNAs (miRNAs): 81-90%) of the molecular response was only observed in MDD, but not in CNTR fibroblasts. The applied metabolic challenges uncovered mRNA and miRNA signatures, identifying responses to each stressor characteristic for the MDD fibroblasts. The distinct responses of MDD fibroblasts to GAL and RL revealed an aberrant engagement of molecular pathways, such as apoptosis, regulation of cell cycle, cell migration, metabolic control and energy production. In conclusion, ...Continue Reading

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Citations

Feb 9, 2016·Neuroscience·S KálmánK Mirnics
Jan 26, 2016·Neurobiology of Disease·Kelli M MoneyKaroly Mirnics
Feb 27, 2016·Critical Reviews in Oncology/hematology·Valentina FlaminiYu-Xin Cui
Sep 8, 2015·Journal of Psychiatric Research·Mehmet Akif CamkurtLülüfer Tamer
Jan 17, 2017·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Elena MilanesiLuisella Bocchio-Chiavetto
Aug 30, 2017·Frontiers in Molecular Neuroscience·Mylène HervéEl Chérif Ibrahim
Jul 6, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xinyi GuMingmei Zhou
Jul 7, 2021·Psychiatry and Clinical Neurosciences·Shinji SakamotoAtsushi Kamiya

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Methods Mentioned

BETA
biopsies
PCR
MDD

Software Mentioned

GSEA
SAS
BioCarta
miRNome
GenePattern

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