Dexamethasone stimulated gene expression in peripheral blood indicates glucocorticoid-receptor hypersensitivity in job-related exhaustion
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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The mDST was able to identify HPA axis alterations in MDD, job-related exhaustion, anxious depression and childhood trauma, chronic stress, and healthy females compared to healthy men.
“The mDST was able to identify HPA axis alterations in MDD [67], job-related exhaustion [69], anxious depression and childhood trauma [70], chronic stress [31], and healthy females compared to healthy men [71].”
From The HPA Axis as Target for Depression (2024) · cites this paper as [69]
Cites
Statistical Power Analysis for the Behavioral Sciences
Muller, K. E., & Cohen, J. (1989) · Technometrics · doi:10.2307/1270020 · Cited by 99,588 · see citing works
Statistical power analysis for the behavioral sciences
Cohen, J. (1990) · Computers Environment and Urban Systems · doi:10.1016/0198-9715(90)90050-4 · Cited by 65,406 · see citing works
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610 · see citing works
(1998) · The Journal of Clinical Psychiatry · Cited by 19,139 · see citing works
Maslach, C., Schaufeli, W. B., & Leiter, M. P. (2001) · Annual Review of Psychology · doi:10.1146/annurev.psych.52.1.397 · Cited by 12,852 · see citing works
(2014) · Medical Entomology and Zoology · Cited by 9,400 · see citing works
Adjusting batch effects in microarray expression data using empirical Bayes methods
Johnson, W. E., Li, C., & Rabinovic, A. (2007) · Biostatistics · doi:10.1093/biostatistics/kxj037 · Cited by 8,658 · see citing works
Huang, D. W., Sherman, B. T., Tan, Q., Kir, J., Liu, D., Bryant, D., Guo, Y., Stephens, R. M., Baseler, M., Lane, H. C., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm415 · Cited by 2,216 · see citing works
The Corticosteroid Receptor Hypothesis of Depression
Holsboer, F. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00159-7 · Cited by 2,181 · see citing works
Self-citationGlucocorticoid receptors in major depression: relevance to pathophysiology and treatment
Pariante, C. M., & Miller, A. H. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(00)01088-x · Cited by 1,147 · see citing works
Maslach burnout inventory-general survey
김, 영. (2009) · Cited by 921 · see citing works
Burnout, Perceived Stress, and Cortisol Responses to Awakening
Pruessner, J. C., Hellhammer, D. H., & Kirschbaum, C. (1999) · Psychosomatic Medicine · doi:10.1097/00006842-199903000-00012 · Cited by 822 · see citing works
Carpenter, L. L., Carvalho, J. P., Tyrka, A. R., Wier, L. M., Mello, A. F., Mello, M. F., Anderson, G. M., Wilkinson, C. W., & Price, L. H. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.05.002 · Cited by 564 · see citing works
Model-based variance-stabilizing transformation for Illumina microarray data
Lin, S. M., Du, P., Huber, W. K., & Kibbe, W. A. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkm1075 · Cited by 515 · see citing works
The relationship between job stress, burnout and clinical depression
Iacovides, A., Fountoulakis, K. Ν., Kaprinis, S., & Kaprinis, G. S. (2002) · Journal of Affective Disorders · doi:10.1016/s0165-0327(02)00101-5 · Cited by 508 · see citing works
Burnout and risk factors for cardiovascular diseases
Melamed, S., Kushnir, T., & Shirom, A. (1992) · Behavioral Medicine · doi:10.1080/08964289.1992.9935172 · Cited by 490 · cited 2× · see citing works
“, 1996) and the Shirom-Melamed Burnout Measure (SMBM) (Melamed et al., 1992) that are valid measures of occupational burnout, a psychological consequence of prolonged job-related stress.”
Ahola, K., Honkonen, T., Isometsä, E. T., Kalimo, R., Nykyri, E., Aromaa, A., & Lönnqvist, J. K. (2005) · Journal of Affective Disorders · doi:10.1016/j.jad.2005.06.004 · Cited by 413 · see citing works
Status of Glucocorticoid Alterations in Post‐traumatic Stress Disorder
Yehuda, R. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04979.x · Cited by 409 · see citing works
Effect of childhood physical abuse on cortisol stress response
Carpenter, L. L., Shattuck, T. T., Tyrka, A. R., Geracioti, T. D., & Price, L. H. (2011) · Psychopharmacology · doi:10.1007/s00213-010-2007-4 · Cited by 307 · see citing works
Sex, trauma, stress hormones and depression
Young, E., & Korszun, A. (2010) · Molecular Psychiatry · doi:10.1038/mp.2009.94 · Cited by 235 · see citing works
Biomarkers in burnout: a systematic review.
Danhof-Pont, M. B., van Veen, T., & Zitman, F. (2011) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2010.10.012 · Cited by 234 · see citing works
van Zuiden, M., Geuze, E., Willemen, H. L. D. M., Vermetten, E., Maas, M., Amarouchi, K., Kavelaars, A., & Heijnen, C. J. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.10.026 · Cited by 201 · see citing works
Bellingrath, S., Weigl, T., & Kudielka, B. M. (2008) · Biological Psychology · doi:10.1016/j.biopsycho.2008.01.006 · Cited by 192 · see citing works
Menke, A., Arloth, J., Pütz, B., Weber, P., Klengel, T., Mehta, D., Gonik, M., Rex-Haffner, M., Rubel, J., Uhr, M., et al. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.331 · Cited by 177 · see citing works
Self-citationMaslach Burnout Inventory-General Survey (MBIGS)
Schaufeli, W. B. (1996) · Medical Entomology and Zoology · Cited by 136 · see citing works
Aerobic exercise training and burnout: a pilot study with male participants suffering from burnout
Gerber, M., Brand, S., Elliot, C., Holsboer‐Trachsler, E., Pühse, U., & Beck, J. (2013) · BMC Research Notes · doi:10.1186/1756-0500-6-78 · Cited by 126 · see citing works
Self-citationn, I. A., & Arnetz, B. B. (2005) · Journal of Occupational and Environmental Medicine · doi:10.1097/01.jom.0000167259.03247.1e · Cited by 118 · see citing works
Sonnenschein, M., Mommersteeg, P. M. C., Houtveen, J. H., Sorbi, M. J., Schaufeli, W. B., & van Doornen, L. J. P. (2007) · Biological Psychology · doi:10.1016/j.biopsycho.2007.02.001 · Cited by 103 · see citing works
Hatzinger, M., Brand, S., Perren, S., von Wyl, A., von Klitzing, K., & Holsboer‐Trachsler, E. (2006) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2006.07.012 · Cited by 92 · see citing works
Self-citationvan Zuiden, M., Heijnen, C. J., Maas, M., Amarouchi, K., Vermetten, E., Geuze, E., & Kavelaars, A. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.03.018 · Cited by 91 · see citing works
Grossi, G., Theorell, T., Jürisoo, M., & Setterlind, S. (1999) · Integrative Psychological and Behavioral Science · doi:10.1007/bf02688708 · Cited by 62 · see citing works
Beck, J., Gerber, M., Brand, S., Pühse, U., & Holsboer‐Trachsler, E. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.08.009 · Cited by 48 · see citing works
Self-citationPhysical Exercise-Associated Gene Expression Signatures in Peripheral Blood
Kawai, T., Morita, K., Masuda, K., Nishida, K., Sekiyama, A., Teshima-Kondo, S., Nakaya, Y., Ohta, M., Saito, T., & Rokutan, K. (2007) · Clinical Journal of Sport Medicine · doi:10.1097/jsm.0b013e31814c3e4f · Cited by 17 · see citing works
Flagged first, then by citations
2 of the 36 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
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Menke, A. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00101 · Cited by 240 · see citing works
Self-citationStress, burnout and depression: A systematic review on DNA methylation mechanisms
Bakusic, J., Schaufeli, W., Claes, S., & Godderis, L. (2017) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2016.11.005 · Cited by 223 · see citing works
The HPA Axis as Target for Depression
Menke, A. (2024) · Current Neuropharmacology · doi:10.2174/1570159x21666230811141557 · Cited by 131 · see citing works
“The mDST was able to identify HPA axis alterations in MDD [67], job-related exhaustion [69], anx-ious depression and childhood trauma [70], chronic stress [31], and healthy females compared to healthy men [71].”
BackgroundSelf-citationExercise and the cortisol awakening response: a systematic review
Anderson, T., & Wideman, L. (2017) · Sports Medicine - Open · doi:10.1186/s40798-017-0102-3 · Cited by 100 · see citing works
Rothe, N., Steffen, J., Penz, M. S., Kirschbaum, C., & Walther, A. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.02.024 · Cited by 83 · see citing works
Physical activity and cortisol regulation: A meta-analysis
Moyers, S. A., & Hagger, M. S. (2023) · Biological Psychology · doi:10.1016/j.biopsycho.2023.108548 · Cited by 83 · see citing works
Leistner, C., & Menke, A. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.01.023 · Cited by 69 · see citing works
Self-citationChildhood trauma dependent anxious depression sensitizes HPA axis function
Menke, A., Lehrieder, D., Fietz, J., Leistner, C., Wurst, C., Stonawski, S., Reitz, J., Lechner, K., Busch, Y., Weber, H., et al. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.07.025 · Cited by 55 · see citing works
Self-citationMenke, A. (2018) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s146110 · Cited by 41 · see citing works
Self-citationMeyer, T., & Wirtz, P. H. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7186 · Cited by 40 · see citing works
Blood-based biomarkers predicting response to antidepressants
Busch, Y., & Menke, A. (2018) · Journal of Neural Transmission · doi:10.1007/s00702-018-1844-x · Cited by 36 · see citing works
Self-citationMenke, A., Arloth, J., Best, J., Namendorf, C., Gerlach, T., Czamara, D., Lucae, S., Dunlop, B. W., Crowe, T. M., Garlow, S. J., et al. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.04.003 · Cited by 35 · see citing works
Self-citationGenome‐wide DNA methylation investigation of glucocorticoid exposure within buccal samples
Braun, P., Tanaka‐Sahker, M., Chan, A. C., Jellison, S. S., Klisares, M. J., Hing, B. W. Q., Shabbir, Y., Gaul, L. N., Nagahama, Y., Robles, J., et al. (2019) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12835 · Cited by 29 · see citing works
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Bakusic, J., Ghosh, M., Polli, A., Bekaert, B., Schaufeli, W. B., Claes, S. J., & Godderis, L. (2021) · Journal of Affective Disorders · doi:10.1016/j.jad.2021.08.081 · Cited by 28 · see citing works
In vivo effects of dexamethasone on blood gene expression in ataxia telangiectasia
Menotta, M., Biagiotti, S., Orazi, S., Rossi, L., Chessa, L., Leuzzi, V., D’Agnano, D., Plebani, A., Soresina, A., & Magnani, M. (2017) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-017-3122-x · Cited by 23 · see citing works
Tao, N., Zhang, J., Song, Z., Tang, J., & Liu, J. (2015) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph121214977 · Cited by 21 · see citing works
ATM splicing variants as biomarkers for low dose dexamethasone treatment of A-T
Menotta, M., Biagiotti, S., Spapperi, C., Orazi, S., Rossi, L., Chessa, L., Leuzzi, V., D’Agnano, D., Soresina, A., Micheli, R., et al. (2017) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-017-0669-2 · Cited by 19 · see citing works
Jahangard, L., Hedayati, M., Abbasalipourkabir, R., Haghighi, M., Ahmadpanah, M., Faryadras, M., Mikoteit, T., Bahmani, D. S., & Brand, S. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.104384 · Cited by 19 · see citing works
Possible association between phantom vibration syndrome and occupational burnout
Lin, Chen, C.-P., Wu, C.-C., & Chang, L. (2014) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s73038 · Cited by 15 · see citing works
The effect of pilates training on hormonal and psychophysical function in older women
FARZANE, A., & Jahromi, M. K. (2022) · The Journal of Sports Medicine and Physical Fitness · doi:10.23736/s0022-4707.21.12089-4 · Cited by 13 · see citing works
Luik, A. I., Direk, N., Zuurbier, L. A., Albert Hofman, D., Someren, E. J. W. V., & Tiemeier, H. W. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.01.011 · Cited by 13 · see citing works
Emotions and Steroid Secretion in Aging Men: A Multi—Study Report
Walther, A., Waldvogel, P., Noser, E., Schoch-Ruppen, J., & Ehlert, U. (2017) · Frontiers in Psychology · doi:10.3389/fpsyg.2017.01722 · Cited by 11 · see citing works
Archer, S. N., Möller‐Levet, C. S., Laing, E., & Dijk, D. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.946444 · Cited by 12 · see citing works
Rothe, N., Vogel, S., Schmelzer, K., Kirschbaum, C., Penz, M. S., Wekenborg, M., Gao, W., & Walther, A. (2021) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2021.100051 · Cited by 11 · see citing works
Lichter, K., Klüpfel, C., Stonawski, S., Hommers, L. G., Blickle, M., Burschka, C., Das, F., Heißler, M., Hellmuth, A., Helmel, J., et al. (2023) · Journal of Neural Transmission · doi:10.1007/s00702-023-02615-8 · Cited by 8 · see citing works
Self-citationRotvig, D. H., Jorgensen, A., Jensen, J. H., Hansen, A. R., Eller, N. H., Jonsson, S. H., Knorr, U. B., Klose, M., Feldt‐Rasmussen, U., Menke, A., et al. (2024) · Stress · doi:10.1080/10253890.2024.2353781 · Cited by 1 · see citing works
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Menke, A., Dusi, N., & Brambilla, P. (2016) · Springer eBooks · doi:10.1007/978-3-319-27040-1_5
Self-citationLv, J., Xu, J., Lv, S., Zheng, Q., Chen, Y., & Wang, Q. (2026) · Microorganisms · doi:10.3390/microorganisms14102384
- Authors
- Menke, A., Arloth, J., Gerber, M., Rex-Haffner, M., Uhr, M., Holsboer, F., Binder, E. B., Holsboer-Trachsler, E., & Beck, J.
- Affiliations
- Max Planck Society (DE)
- Max Planck Institute of Psychiatry (DE)
- University of Basel (CH)
- University Hospital of Basel (CH)
- Corresponding author
- Menke, Andreas
- Beck, Johannes
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 44
- Pages
- 35-46
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W2145983444
- Cited by
- 28
- References
- 36
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 2 · 2014: 1
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- European Commission
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Social Psychology › Stress and Burnout Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- burnout, gene expression, whole blood transcriptome, plasma cortisol, cortisol suppression, aerobic exercise training, occupational stress, neuroendocrine regulation, biomarkers
- MeSH terms
- Adult, Burnout, Professional, Dexamethasone, Fatigue, Humans, Hydrocortisone, Male, Middle Aged, Occupations, Receptors, Glucocorticoid, Gene Expression
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