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Published on: April 27, 2021
Dexamethasone stimulated gene expression in peripheral blood indicates glucocorticoid-receptor hypersensitivity in
Andreas Menke1, Janine Arloth1, Markus Gerber2
1Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, D-80804 Munich, Germany.
Abstract:
Work-related stress can lead to various health problems ranging from job-related exhaustion to psychiatric and somatic diseases. Biomarkers of job-related exhaustion could help to improve our understanding of the biological mechanisms and might be useful to guide prevention and treatment strategies. The present study included 12 male cases suffering from job-related exhaustion and 12 matched healthy controls. Severity of exhaustion was assessed with the Maslach Burnout Inventory (MBI) and the Shirom-Melamed Burnout Measure (SMBM). Whole genome expression profiles derived from whole blood cells (baseline and following glucocorticoid-receptor (GR) stimulation with 1.5mg dexamethasone p.o.) and corresponding plasma cortisol levels were analyzed. All cases participated in regular aerobic exercise for 12 consecutive weeks and were then re-assessed at follow-up for exhaustion symptoms as well as for cortisol levels and gene expression profiles. At baseline, we found increased basal cortisol levels and an enhanced suppression of plasma cortisol concentrations following dexamethasone in cases suffering from job-related exhaustion. Gene expression analysis revealed that 1.6-fold more transcripts were significantly regulated by dexamethasone in cases as compared to controls. At follow-up after 12 weeks of regular exercise training which was accompanied by significantly improved exhaustion severity scores, cortisol levels and gene expression profiles of cases normalized to the levels observed in controls. In conclusion, we detected GR-induced neuroendocrine and gene expression changes in cases suffering from job-related exhaustion which are in line with an increased sensitivity of GR function. This GR dysregulation normalized with symptom recovery.
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