Dexamethasone stimulated gene expression in peripheral blood indicates glucocorticoid-receptor hypersensitivity in job-related exhaustion.
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.
Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, D-80804 Munich, Germany. Electronic address: menke@mpipsykl.mpg.de.
Andreas
A
Menke
Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, D-80804 Munich, Germany.
Janine
J
Arloth
Institute of Exercise and Health Sciences, University of Basel, Birsstrasse 320B, CH-4052 Basel, Switzerland.
Markus
M
Gerber
Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, D-80804 Munich, Germany.
Monika
M
Rex-Haffner
Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, D-80804 Munich, Germany.
Manfred
M
Uhr
Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, D-80804 Munich, Germany.
Florian
F
Holsboer
Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, D-80804 Munich, Germany.
Elisabeth B
EB
Binder
Psychiatric University Hospital Basel, Wilhelm Klein-Str. 27, CH-4012 Basel, Switzerland.
Edith
E
Holsboer-Trachsler
Psychiatric University Hospital Basel, Wilhelm Klein-Str. 27, CH-4012 Basel, Switzerland. Electronic address: Johannes.Beck@upkbs.ch.
Johannes
J
Beck
D000328:Adult; D002055:Burnout, Professional / Q000097:blood / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology*; D005221:Fatigue / Q000097:blood / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009790:Occupations; D011965:Receptors, Glucocorticoid / Q000235:genetics*
D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D006854:Hydrocortisone
Aerobic exercise; Burnout; Cortisol; Dexamethasone; Gene expression; Glucocorticoid receptor; Job-related exhaustion; Peripheral blood; RNA