How to measure glucocorticoid receptor’s sensitivity in patients with stress-related psychiatric disorders
Abstract
Stress is a state of derailed homeostasis and a main environmental risk factor for psychiatric diseases. Chronic or uncontrollable stress may lead to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which is a common feature of stress-related psychiatric disorders. One of the key mechanisms underlying a disturbed HPA axis is an impaired function of the glucocorticoid receptor (GR) with an enhanced or reduced feedback sensitivity for glucocorticoids and subsequently altered concentrations of peripheral cortisol. GR function is regulated by a multiprotein complex including the different expression of the hsp90 co-chaperone FK 506 binding protein 51 (FKBP5) that may be genetically determined or acquired in response to stressful stimuli. Specific patterns of a dysregulation of the HPA axis and GR function are found in different stress-related psychiatric entities e.g. major depression, job-related exhaustion or posttraumatic stress disorder. GR challenge tests like the dexamethasone-suppression test (DST), the dexamethasone-corticotropin-releasing hormone (dex-CRH) test or most recently the analysis of the dexamethasone-induced gene expression are employed to sensitively measure HPA axis activity in these disorders. They provide information for a stratification of phenotypic similar but neurobiological diverse psychiatric disorders. In this review we present a synopsis of GR challenge tests with a focus on the application of the DST, the CRH test and the dex-CRH test as well as the dexamethasone-induced gene expression in stress-related psychiatric entities.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
To match the patient with the right treatment approach in terms of individualized treatment, it is necessary to apply tests that assess HPA axis function, such as dex-CRH or molecular DST.
“To match the patient with the right treatment approach in terms of an individualized treatment, it is necessary to apply tests that assess the function of the HPA axis, such as the dex-CRH test or the molecular DST [14, 47].”
From The HPA Axis as Target for Depression (2024) · cites this paper as [47]
Cites
The role of inflammation in depression: from evolutionary imperative to modern treatment target
Miller, A. H., & Raison, C. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2015.5 · Cited by 3,942 · see citing works
Stress signalling pathways that impair prefrontal cortex structure and function
Arnsten, A. F. T. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2648 · Cited by 3,299 · see citing works
Otte, C., Gold, S. M., Penninx, B. W., Pariante, C. M., Etkin, A., Fava, M., Mohr, D. C., & Schatzberg, A. F. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.65 · Cited by 2,269 · see citing works
The HPA axis in major depression: classical theories and new developments
Pariante, C. M., & Lightman, S. L. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.06.006 · Cited by 2,009 · see citing works
Stress and the General Adaptation Syndrome
Selye, H. (1950) · BMJ · doi:10.1136/bmj.1.4667.1383 · Cited by 1,481 · see citing works
Peripheral cytokine and chemokine alterations in depression: a meta‐analysis of 82 studies
Köhler, C. A., Freitas, T. H., Maes, M., de Andrade, N. Q., Liu, C. S., Fernandes, B. S., Stubbs, B., Solmi, M., Veronese, N., Herrmann, N., et al. (2017) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12698 · Cited by 1,443 · see citing works
The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission
Popoli, M., Yan, Z., McEwen, B. S., & Sanacora, G. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3138 · Cited by 1,393 · see citing works
Cytokine-Associated Emotional and Cognitive Disturbances in Humans
Reichenberg, A., Yirmiya, R., Schuld, A., Kraus, T., Haack, M., Morag, A., & Pollmächer, T. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.5.445 · Cited by 1,365 · see citing works
Post-Traumatic Stress Disorder
Yehuda, R. (2002) · New England Journal of Medicine · doi:10.1056/nejmra012941 · Cited by 1,134 · see citing works
Stetler, C., & Miller, G. E. (2011) · Psychosomatic Medicine · doi:10.1097/psy.0b013e31820ad12b · Cited by 1,123 · see citing works
Binder, E. B. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.05.021 · Cited by 968 · see citing works
Melamed, S., Shirom, A., Toker, S., Berliner, S., & Shapira, I. (2006) · Psychological Bulletin · doi:10.1037/0033-2909.132.3.327 · Cited by 943 · see citing works
Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids.
Czock, D., Keller, F., Rasche, F. M., & H??ussler, U. (2005) · Clinical Pharmacokinetics · doi:10.2165/00003088-200544010-00003 · Cited by 886 · see citing works
Post-traumatic stress disorder.
Yehuda, R., Hoge, C. W., McFarlane, A. C., Vermetten, E., Lanius, R. A., Nievergelt, C. M., Hobfoll, S. E., Koenen, K. C., Neylan, T. C., & Hyman, S. E. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.57 · Cited by 870 · see citing works
Inflamed moods: A review of the interactions between inflammation and mood disorders
Rosenblat, J. D., Cha, D. S., Mansur, R. B., & McIntyre, R. S. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2014.01.013 · Cited by 609 · see citing works
The glucocorticoid receptor: Pivot of depression and of antidepressant treatment?
Anacker, C., Zunszain, P. A., Carvalho, L. A., & Pariante, C. M. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.03.007 · Cited by 592 · see citing works
(1993) · American Journal of Psychiatry · doi:10.1176/ajp.150.1.83 · Cited by 517 · see citing works
Stress Hormone Regulation: Biological Role and Translation into Therapy
Holsboer, F., & Ising, M. (2010) · Annual Review of Psychology · doi:10.1146/annurev.psych.093008.100321 · Cited by 473 · see citing works
Morris, M. C., Compas, B. E., & Garber, J. (2012) · Clinical Psychology Review · doi:10.1016/j.cpr.2012.02.002 · Cited by 466 · see citing works
Rohleder, N., Joksimovic, L., Wolf, J. M., & Kirschbaum, C. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2003.11.018 · Cited by 393 · see citing works
HPA axis and aging in depression: Systematic review and meta-analysis
Belvederi Murri, M., Pariante, C., Mondelli, V., Masotti, M., Atti, A. R., Mellacqua, Z., Antonioli, M., Ghio, L., Menchetti, M., Zanetidou, S., et al. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.12.004 · Cited by 367 · see citing works
DST Studies in Psychotic Depression: A Meta-Analysis
Nelson, J. C., & Davis, J. M. (1997) · American Journal of Psychiatry · doi:10.1176/ajp.154.11.1497 · Cited by 356 · see citing works
Ising, M., Horstmann, S., Kloiber, S., Lucae, S., Binder, E. B., Kern, N., Künzel, H. E., Pfennig, A., Uhr, M., & Holsboer, F. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.07.039 · Cited by 341 · see citing works
Roy, A., Gorodetsky, E., Yuan, Q., Goldman, D., & Enoch, M.-A. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.236 · Cited by 282 · see citing works
Resistance to Suppression by Dexamethasone of Plasma 11-O.H.C.S. Levels in Severe Depressive Illness
Carroll, B. J., Martin, F. I. R., & Davies, B. (1968) · BMJ · doi:10.1136/bmj.3.5613.285 · Cited by 279 · see citing works
Rinne, T., de Kloet, E. R., Wouters, L., Goekoop, J. G., DeRijk, R. H., & van den Brink, W. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01395-1 · Cited by 279 · see citing works
Zimmermann, P., Brückl, T., Nocon, A., Pfister, H., Binder, E. B., Uhr, M., Lieb, R., Moffitt, T. E., Caspi, A., Holsboer, F., et al. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10111577 · Cited by 262 · see citing works
Review: Replication of cortisol circadian rhythm: new advances in hydrocortisone replacement therapy
Chan, S., & Debono, M. (2010) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018810380214 · Cited by 243 · see citing works
Holsboer, F., von Bardeleben, U., Wiedemann, K., Müller, O. A., & Stalla, G. K. (1987) · Biological Psychiatry · doi:10.1016/0006-3223(87)90237-x · Cited by 221 · see citing works
Kunugi, H., Ida, I., Owashi, T., Kimura, M., Inoue, Y., Nakagawa, S., Yabana, T., Urushibara, T., Kanai, R., Aihara, M., et al. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300868 · Cited by 200 · see citing works
Pace, T. W. W., Wingenfeld, K., Schmidt, I., Meinlschmidt, G., Hellhammer, D. H., & Heim, C. M. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.07.232 · Cited by 184 · 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-citationHow can we realize the promise of personalized antidepressant medicines?
Holsboer, F. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2453 · Cited by 177 · see citing works
von Bardeleben, U., & Holsboer, F. (1989) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.1989.tb00150.x · Cited by 161 · see citing works
Holsboer-Trachsler, E., Stohler, R., & Hatzinger, M. (1991) · Psychiatry Research · doi:10.1016/0165-1781(91)90041-m · Cited by 160 · see citing works
Stress-induced glucocorticoids as a neuroendocrine alarm signal of danger
Frank, M. G., Watkins, L. R., & Maier, S. F. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2013.02.004 · Cited by 160 · see citing works
Menke, A., Klengel, T., Rubel, J., Brückl, T., Pfister, H., Lucae, S., Uhr, M., Holsboer, F., & Binder, E. B. (2013) · Genes, Brain and Behavior · doi:10.1111/gbb.12026 · Cited by 151 · see citing works
Self-citationGlucocorticoid Receptor Function<i>In Vitro</i>in Patients with Major Depression
Pariante, C. M. (2004) · Stress · doi:10.1080/10253890500069650 · Cited by 147 · see citing works
Bevilacqua, L. (2012) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.152 · Cited by 137 · see citing works
Mommersteeg, P. M. C., Heijnen, C. J., Verbraak, M. J. P. M., & van Doornen, L. J. P. (2006) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2005.07.003 · Cited by 111 · see citing works
de Kloet, C. S., Vermetten, E., Bikker, A., Meulman, E., Geuze, E., Kavelaars, A., Westenberg, H. G. M., & Heijnen, C. J. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001934 · Cited by 98 · see citing works
Wirtz, P. H., Von KÄnel, R., Schnorpfeil, P., Ehlert, U., Frey, K., & Fischer, J. E. (2003) · Psychosomatic Medicine · doi:10.1097/01.psy.0000062529.39901.c7 · Cited by 75 · see citing works
Fischer, S., Macare, C., & Cleare, A. J. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.10.012 · Cited by 70 · see citing works
Schatzberg, A. F. (2015) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2014.916414 · Cited by 51 · see citing works
Matić, G., Milutinović, D. V., Nestorov, J., Elaković, I., Jovanović, S. M., Perišić, T., Dunđerski, J., Damjanović, S., Knežević, G., Špirić, Ž., et al. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2013.01.005 · Cited by 43 · see citing works
Menke, 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-citationMenke, A., Arloth, J., Gerber, M., Rex-Haffner, M., Uhr, M., Holsboer, F., Binder, E. B., Holsboer-Trachsler, E., & Beck, J. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.02.013 · Cited by 28 · see citing works
Self-citationMuhtz, C., Wester, M., Yassouridis, A., Wiedemann, K., & Kellner, M. (2008) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2007.08.006 · Cited by 27 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Is the HPA Axis as Target for Depression Outdated, or Is There a New Hope?
Menke, A. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00101 · Cited by 240 · see citing works
Self-citationThe HPA Axis as Target for Depression
Menke, A. (2024) · Current Neuropharmacology · doi:10.2174/1570159x21666230811141557 · Cited by 131 · see citing works
“Thus, a companion test would be needed to identify the patients who would benefit from these compounds, such as the dex-CRH test or the modified molecular mDST [15, 36, 47, 67, 84].”
BackgroundMethodInfluentialSelf-citationMenke, A. (2018) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s146110 · Cited by 41 · see citing works
Self-citationSomvanshi, P. R., Mellon, S. H., Flory, J. D., Abu-Amara, D., PTSD Systems Biology Consortium;, Wolkowitz, O. M., Yehuda, R., Jett, M., Hood, L., Marmar, C., et al. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00065.2019 · Cited by 40 · see citing works
Stress impairs response to antidepressants via HPA axis and immune system activation
Menke, A., Nitschke, F., Hellmuth, A., Helmel, J., Wurst, C., Stonawski, S., Blickle, M., Weiß, C., Weber, H., Hommers, L., et al. (2021) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.12.033 · Cited by 40 · see citing works
Self-citationZou, Z., Huang, Y., Maes, M., Wang, J., He, Y., Min, W., & Zhou, B. (2024) · BMC Psychiatry · doi:10.1186/s12888-024-05704-4 · Cited by 4 · see citing works
Hypothalamic–pituitary–adrenal axis and stress
(2020) · Handbook of Clinical Neurology · doi:10.1016/b978-0-444-64123-6.00004-7 · Cited by 279 · see citing works
- Authors
- Leistner, C., & Menke, A.
- Affiliations
- Universitätsklinikum Würzburg (DE)
- Corresponding author
- Menke, Andreas
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 91
- Pages
- 235-260
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W2794229663
- Cited by
- 69
- References
- 48
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 8 · 2021: 8 · 2020: 12 · 2019: 10 · 2018: 9
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- glucocorticoid receptor, HPA axis dysregulation, stress-related psychiatric disorders, dexamethasone suppression test, dexamethasone/corticotropin-releasing hormone test, FKBP5, major depressive disorder, post-traumatic stress disorder, cortisol
- MeSH terms
- Tacrolimus Binding Protein 5, Adrenocorticotropic Hormone, Mental Disorders, Corticotropin-Releasing Hormone, Dexamethasone, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Pituitary-Adrenal System, Receptors, Glucocorticoid, Stress, Psychological, Gene Expression, Tacrolimus Binding Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
