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Assessment of the Dexamethasone/CRH Test as a State-Dependent Marker for Hypothalamic-Pituitary-Adrenal (HPA) Axis Abnormalities in Major Depressive Episode: A Multicenter Study
Open accessAbstract
There is compelling evidence for the involvement of hypothalamic-pituitary-adrenal (HPA) axis abnormalities in depression. Growing evidence has suggested that the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test is highly sensitive to detect HPA axis abnormalities. We organized a multicenter study to assess the DEX/CRH test as a state-dependent marker for major depressive episode in the Japanese population. We conducted the DEX/CRH test in 61 inpatients with major depressive episode (Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV)) and 57 healthy subjects. In all, 35 patients were repeatedly assessed with the DEX/CRH test on admission and before discharge. The possible relationships between clinical variables and the DEX/CRH test were also examined. Significantly enhanced pituitary-adrenocortical responses to the DEX/CRH test were observed in patients on admission compared with controls. Such abnormalities in patients were significantly reduced after treatment, particularly in those who underwent electroconvulsive therapy (ECT) in addition to pharmacotherapy. Age and female gender were associated with enhanced hormonal responses to the DEX/CRH test. Severity of depression correlated with DEX/CRH test results, although this was explained, at least in part, by a positive correlation between age and severity in our patients. Medication per se was unrelated to DEX/CRH test results. These results suggest that the DEX/CRH test is a sensitive state-dependent marker to monitor HPA axis abnormalities in major depressive episode during treatment. Restoration from HPA axis abnormalities occurred with clinical responses to treatment, particularly in depressed patients who underwent ECT.
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“The dexamethasone suppression test and its newer version, the dexamethasone– corticotropin releasing hormone (CRH) stimulation test, receive the most attention as biological markers for MDD diagnosis (Greden et al. 1983; Kunugi et al. 2006).”
BackgroundSelf-citationIgata, R., Katsuki, A., Kakeda, S., Watanabe, K., Igata, N., Hori, H., Konishi, Y., Atake, K., Kawasaki, Y., Korogi, Y., et al. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.100 · Cited by 46
Kingdon, D., & Young, A. H. (2007) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.107.035675 · Cited by 46
“The diagnostic use of the dexamethasone suppression test is of course outmoded; however, the evolution of this into the dexamethasone/corticotrophin-releasing hormone test (Watson et al, 2006) is on the threshold of allowing us to specifically target some physical treatments (Kunugi et al, 2006).”
BackgroundEarly life stress alters pituitary growth during adolescence—A longitudinal study
Ganella, D. E., Allen, N. B., Simmons, J. G., Schwartz, O., Kim, J. H., Sheeber, L., & Whittle, S. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.01.005 · Cited by 47
Fujii, T., Hori, H., Ota, M., Hattori, K., Teraishi, T., Sasayama, D., Yamamoto, N., Higuchi, T., & Kunugi, H. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.01.007 · Cited by 48
Self-citationMissing and Possible Link between Neuroendocrine Factors, Neuropsychiatric Disorders, and Microglia
Kato, T. A., Hayakawa, K., Monji, A., & Kanba, S. (2013) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2013.00053 · Cited by 43
“The HPA axis has also been suggested to have a strong linkage to psychiatric disorders such as mood disorders and post-traumatic stress disorder (PTSD) (Baker et al., 1999; Holsboer, 2000; Kunugi et al., 2006).”
BackgroundSelf-citationHabib, M. Z., Shaker, S. M., Elgayar, N., & Aboul‐Fotouh, S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0120559 · Cited by 45
Kajiyama, Y., Iijima, Y., Chiba, S., Furuta, M., Ninomiya, M., Izumi, A., Shibata, S., & Kunugi, H. (2009) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.10.018 · Cited by 40
“Such hyperactivity is, at least in part, state-dependent (Kunugi et al., 2006), and high levels of glucocorticoid might be involved in the pathogenesis of depression.”
Self-citationMatsuzaka, H., Maeshima, H., Kida, S., Kurita, H., Shimano, T., Nakano, Y., Baba, H., Suzuki, T., & Arai, H. (2013) · The International Journal of Psychiatry in Medicine · doi:10.2190/pm.46.2.g · Cited by 39
“However, several studies mentioned that medication per se was unrelated to DEX/CRH test results [36, 37, 41].”
BackgroundHageman, I., Nielsen, M., Wörtwein, G., Diemer, N. H., & Jørgensen, M. B. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.07.037 · Cited by 40
Aberrant REST-mediated transcriptional regulation in major depressive disorder
Otsuki, K., Uchida, S., Wakabayashi, Y., Matsubara, T., Hobara, T., Funato, H., & Watanabe, Y. (2009) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2009.09.009 · Cited by 38
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Ruksee, N., Tongjaroenbuangam, W., Mahanam, T., & Govitrapong, P. (2014) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.02.011 · Cited by 36
Antiglucocoticoid Treatments for Depression
Young, A. H. (2006) · Australian & New Zealand Journal of Psychiatry · doi:10.1080/j.1440-1614.2006.01813.x · Cited by 36
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
The DEX/CRH test for major depression: A potentially useful diagnostic test
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Adachi, N., Numakawa, T., Kumamaru, E., Itami, C., Chiba, S., Iijima, Y., Richards, M., Katoh‐Semba, R., & Kunugi, H. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhs074 · Cited by 34
“We have also revealed that glucocor- ticoid, a stress hormone closely linked to depression (e.g., Kunugi et al. 2006), hampers the synaptic function of BDNF in cortical neurons (Numakawa et al. 2009).”
BackgroundSelf-citationCortisol Stress Response and in Vivo PET Imaging of Human Brain Serotonin 1A Receptor Binding
Steinberg, L. J., Rubin‐Falcone, H., Galfalvy, H., Kaufman, J., Miller, J. M., Sublette, M. E., Cooper, T. B., Min, E., Keilp, J. G., Stanley, B., et al. (2019) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyz009 · Cited by 34
Owashi, T., Otsubo, T., Oshima, A., Nakagome, K., Higuchi, T., & Kamijima, K. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2007.10.011 · Cited by 33
“Furthermore, the results of the DEX/CRH test appear to be a state-dependent marker of major depressive episode (Kunugi et al., 2006).”
BackgroundSelf-citationGlucocorticoids as Predictors of Treatment Response in Depression
Horstmann, S., & Binder, E. B. (2011) · Harvard Review of Psychiatry · doi:10.3109/10673229.2011.586550 · Cited by 31
Fuß, J., Claro, L., Ising, M., Biedermann, S. V., Wiedemann, K., Stalla, G. K., Briken, P., & Auer, M. K. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.02.023 · Cited by 32
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Hori, H., Teraishi, T., Ota, M., Hattori, K., Matsuo, J., Kinoshita, Y., Ishida, I., Nagashima, A., Koga, N., Higuchi, T., et al. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2013.10.013 · Cited by 33
Self-citation
Metadata
- Authors
- Kunugi, H., Ida, I., Owashi, T., Kimura, M., Inoue, Y., Nakagawa, S., Yabana, T., Urushibara, T., Kanai, R., Aihara, M., Yuuki, N., Otsubo, T., Oshima, A., Kudo, K., Inoue, T., Kitaichi, Y., Shirakawa, O., Isogawa, K., Nagayama, H., Kamijima, K., Nanko, S., Kanba, S., Higuchi, T., & Mikuni, M.
- Affiliations
- Teikyo University (JP)
- Gunma University (JP)
- SHOWA Medical University (JP)
- Nippon Medical School (JP)
- University of Yamanashi (JP)
- Hokkaido University (JP)
- National Center of Neurology and Psychiatry (JP)
- Kobe University (JP)
- Oita University (JP)
- Kyushu University (JP)
- Corresponding author
- Kunugi, Hiroshi
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2005-08-17
- Volume
- 31
- Issue
- 1
- Pages
- 212-220
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2165668731
- Cited by
- 200
- References
- 52
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 9 · 2020: 11 · 2019: 11 · 2018: 14 · 2017: 8 · 2016: 12 · 2015: 15 · 2014: 8 · 2013: 7 · 2012: 18
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- dexamethasone/corticotropin-releasing hormone test, hypothalamic-pituitary-adrenal axis, major depressive episode, depression, electroconvulsive therapy, depression severity, age and sex differences, treatment response monitoring, Japanese patients
- MeSH terms
- Adult, Age Factors, Corticotropin-Releasing Hormone, Major Depressive Disorder, Depressive Disorder, Major, Dexamethasone, Female, Humans, Hypothalamo-Hypophyseal System, Male, Middle Aged, Pituitary-Adrenal System, Psychiatric Status Rating Scales, Sex Characteristics
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