Diurnal activity and pulsatility of the hypothalamus-pituitary-adrenal system in male depressed patients and healthy controls
Abstract
There is only sparse and ambiguous information about circadian and pulsatile secretion features of the hypothalamus-pituitary-adrenocortical system in depression. We studied 15 severely depressed (Hamilton Depression Scale 30.4 +/- 6.7) male patients (age 22-72 yr; mean, 47.7 +/- 14.8) and 22 age-matched male controls (age 23-85 yr; mean, 53.1 +/- 18.2). Twenty-four-hour blood sampling from 0800-0800 h with 30-min sampling intervals was performed; from 1800-2400 h, blood was drawn every 10 min. Multivariate analysis of covariance, with the covariate being age, revealed mean 24-h cortisol (315.9 +/- 58.5 vs. 188.2 +/- 27.3 nmol/L) and mean ACTH (7.82 +/- 1.94 vs. 5.79 +/- 1.28 pmol/L) to be significantly increased in depressed patients. The frequency of cortisol (2.6 +/- 0.7 vs. 1.3 +/- 1.0 pulses/6 h) and ACTH (2.6 +/- 1.6 vs. 1.6 +/- 1.4 pulses/6 h) pulses during the evening were higher in patients compared to controls. The flattened circadian cortisol variation and reduced time of quiescence of cortisol secretory activity (140 +/- 116 vs. 305 +/- 184 min) in patients suggest disturbances of circadian functions. We conclude that increased hypothalamus-pituitary-adrenocortical activity in depression is related to a greater frequency of episodic hormone release, and we hypothesize that the observed circadian changes might be partly due to altered mineralocorticoid and glucocorticoid receptor capacity and function.
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?
Depression is commonly believed to be caused by malfunctions in the HPA axis.
“However, it is commonly believed that depression is caused by malfunctions in the Hypothalamic-Pituitary-Adrenal (HPA) axis - a coupled endocrine system [9, 12, 20, 40].”
From Patient specific modeling of the HPA axis related to clinical diagnosis of depression (2017) · cites this paper as [12]
Early attempts to establish objective markers for diagnosing depression based on HPA hormone levels and patterns have not been successful.
“Early attempts of establishing objective markers for diagnosing depression based on hormone levels and patterns produced by the HPA axis have not been successful [9, 12, 43].”
From Patient specific modeling of the HPA axis related to clinical diagnosis of depression (2017) · cites this paper as [12]
Cites
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817 · 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
Flagged first, then by citations
Cited by
Sorted by citations
Belmaker, R. H., & Agam, G. (2008) · New England Journal of Medicine · doi:10.1056/nejmra073096 · Cited by 2,166 · see citing works
Chronic stress and obesity: a new view of “comfort food”
Dallman, M. F., Pecoraro, N., Akana, S. F., la Fleur, S. E., Gomez, F., Houshyar, H., Bell, M. E., Bhatnagar, S., Laugero, K. D., & Manalo, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1934666100 · Cited by 1,369 · see citing works
Depression and cancer: mechanisms and disease progression
Spiegel, D., & Giese-Davis, J. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00566-3 · Cited by 874 · see citing works
The awakening cortisol response: methodological issues and significance
Clow, A., Thorn, L., Evans, P., & Hucklebridge, F. (2004) · Stress · doi:10.1080/10253890410001667205 · Cited by 856 · see citing works
Sex differences in stress-related psychiatric disorders: neurobiological perspectives
Bangasser, D. A., & Valentino, R. J. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.03.008 · Cited by 737 · see citing works
The evidence for a neurobiological model of childhood antisocial behavior
van Goozen, S. H. M., Fairchild, G., Snoek, H., & Harold, G. T. (2007) · Psychological Bulletin · doi:10.1037/0033-2909.133.1.149 · Cited by 475 · see citing works
Neuroendocrine aspects of hypercortisolism in major depression
Parker, K. J., Schatzberg, A. F., & Lyons, D. M. (2003) · Hormones and Behavior · doi:10.1016/s0018-506x(02)00016-8 · Cited by 455 · see citing works
Van den Bergh, B. R. H., Van Calster, B., Smits, T., Van Huffel, S., & Lagae, L. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301450 · Cited by 434 · see citing works
The crucial role of pulsatile activity of the HPA axis for continuous dynamic equilibration
Lightman, S. L., & Conway-Campbell, B. L. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2914 · Cited by 390 · see citing works
Circadian rhythms in the hypothalamo-pituitary-adrenal (HPA) axis
Kalsbeek, A., van der Spek, R., Lei, J., Endert, E., Buijs, R. M., & Fliers, E. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.06.042 · Cited by 380 · see citing works
Circadian disruption in cancer: A neuroendocrine-immune pathway from stress to disease?
Sephton, S., & Spiegel, D. (2003) · Brain Behavior and Immunity · doi:10.1016/s0889-1591(03)00078-3 · Cited by 377 · see citing works
Pathophysiology of hypercortisolism in depression
Carroll, B. J., Cassidy, F., Naftolowitz, D., Tatham, N. E., Wilson, W. H., Iranmanesh, A., Liu, P. Y., & Veldhuis, J. D. (2007) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2007.00967.x · Cited by 317 · see citing works
Diurnal mood variation in major depressive disorder
Peeters, F., Berkhof, J., Delespaul, P., Rottenberg, J., & Nicolson, N. A. (2006) · Emotion · doi:10.1037/1528-3542.6.3.383 · Cited by 306 · see citing works
Cortisol and depression: three questions for psychiatry
Herbert, J. (2013) · Psychological Medicine · doi:10.1017/s0033291712000955 · Cited by 301 · see citing works
Interplay between the gut-brain axis, obesity and cognitive function
Agustí, A., García-Pardo, M. P., López-Almela, I., Campillo, I., Maes, M., Romaní-Pérez, M., & Sanz, Y. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00155 · Cited by 294 · see citing works
Lieverse, R., Van Someren, E. J. W., Nielen, M. M. A., Uitdehaag, B. M. J., Smit, J. H., & Hoogendijk, W. J. G. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.183 · Cited by 261 · see citing works
Social Support and Salivary Cortisol in Women With Metastatic Breast Cancer
Turner-Cobb, J. M., Sephton, S. E., Koopman, C., Blake-Mortimer, J., & Spiegel, D. (2000) · Psychosomatic Medicine · doi:10.1097/00006842-200005000-00007 · Cited by 259 · see citing works
Raison, C. L., Borisov, A. S., Woolwine, B. J., Massung, B., Vogt, G., & Miller, A. H. (2010) · Molecular Psychiatry · doi:10.1038/mp.2008.58 · Cited by 183 · see citing works
Sex differences in mood disorders: Perspectives from humans and rodent models
Seney, M. L., & Sibille, E. (2014) · Biology of Sex Differences · doi:10.1186/s13293-014-0017-3 · Cited by 181 · see citing works
Tata, D. A., & Anderson, B. J. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.09.008 · Cited by 173 · see citing works
“Further work is needed to understand whether the plasma elevations serve as an appropriate representation of those seen in Cushing's disease and major depressive disorder [85, 86].”
Alterations in arginine vasopressin neurons in the suprachiasmatic nucleus in depression
Zhou, J.-N., Riemersma, R. F., Unmehopa, U. A., Hoogendijk, W. J. G., van Heerikhuize, J. J., Hofman, M. A., & Swaab, D. F. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.7.655 · Cited by 172 · see citing works
Depression, cortisol, and suppressed cell-mediated immunity in metastatic breast cancer
Sephton, S. E., Dhabhar, F. S., Keuroghlian, A. S., Giese-Davis, J., McEwen, B. S., Ionan, A. C., & Spiegel, D. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.07.007 · Cited by 170 · see citing works
Corticosteroid–serotonin interactions in depression: a review of the human evidence
Porter, R. J., Gallagher, P., Watson, S., & Young, A. H. (2004) · Psychopharmacology · doi:10.1007/s00213-004-1774-1 · Cited by 169 · see citing works
Huang, G.-J., & Herbert, J. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.09.016 · Cited by 165 · see citing works
Sleep Disturbances in Women With Metastatic Breast Cancer
Koopman, C., Nouriani, B., Erickson, V., Anupindi, R., Butler, L. D., Bachmann, M. H., Sephton, S. E., & Spiegel, D. (2002) · The Breast Journal · doi:10.1046/j.1524-4741.2002.08606.x · Cited by 156 · see citing works
Glucocorticoid Dysregulations and Their Clinical Correlates: From Receptors to Therapeutics
Marques, A. H., Silverman, M. N., & Sternberg, E. M. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04987.x · Cited by 158 · see citing works
Biomarkers of depression in cancer patients
Jehn, C. F., Kuehnhardt, D., Bartholomae, A., Pfeiffer, S., Krebs, M., Regierer, A. C., Schmid, P., Possinger, K., & Flath, B. C. (2006) · Cancer · doi:10.1002/cncr.22294 · Cited by 139 · see citing works
Conway‐Campbell, B. L., Sarabdjitsingh, R. A., McKenna, M. A., Pooley, J. R., Kershaw, Y. M., Meijer, O. C., De Kloet, E. R., & Lightman, S. L. (2010) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2010.02051.x · Cited by 137 · see citing works
Penninx, B. W. J. H., Beekman, A. T. F., Corsi, A. M., Bremmer, M., Hoogendijk, W. J., Guralnik, J. M., Ferrucci, L., & Bandinelli, S. (2007) · The American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e318033ed80 · Cited by 134 · see citing works
Sex differences in stress regulation of arousal and cognition
Bangasser, D. A., Eck, S. R., Telenson, A. M., & Salvatore, M. (2018) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.09.025 · Cited by 133 · see citing works
Sarabdjitsingh, R. A., Conway-Campbell, B. L., Leggett, J. D., Waite, E. J., Meijer, O. C., de Kloet, E. R., & Lightman, S. L. (2010) · Endocrinology · doi:10.1210/en.2010-0832 · Cited by 116 · see citing works
Rayner, G., Jackson, G., & Wilson, S. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.09.022 · Cited by 104 · see citing works
Acculturation, Maternal Cortisol, and Birth Outcomes in Women of Mexican Descent
D’Anna-Hernandez, K. L., Hoffman, M. C., Zerbe, G. O., Coussons-Read, M., Ross, R. G., & Laudenslager, M. L. (2012) · Psychosomatic Medicine · doi:10.1097/psy.0b013e318244fbde · Cited by 102 · see citing works
Touma, C., Fenzl, T., Ruschel, J., Palme, R., Holsboer, F., Kimura, M., & Landgraf, R. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004325 · Cited by 77 · see citing works
Rudolf, S., Greggersen, W., Kahl, K. G., Hüppe, M., & Schweiger, U. (2014) · Psychiatry Research · doi:10.1016/j.psychres.2014.02.016 · Cited by 71 · see citing works
Basal cortisol levels in relation to dimensions and DSM-IV categories of depression and anxiety
Veen, G., van Vliet, I. M., DeRijk, R. H., Giltay, E. J., van Pelt, J., & Zitman, F. G. (2011) · Psychiatry Research · doi:10.1016/j.psychres.2009.07.013 · Cited by 58 · see citing works
Altered glucocorticoid receptor signaling cascade in lymphocytes of bipolar disorder patients
Spiliotaki, M., Salpeas, V., Malitas, P., Alevizos, V., & Moutsatsou, P. (2006) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2006.02.006 · Cited by 58 · see citing works
Christiansen, S., Bouzinova, E. V., Palme, R., & Wiborg, O. (2012) · Stress · doi:10.3109/10253890.2011.654370 · Cited by 55 · see citing works
Spiga, F., Harrison, L. R., Wood, S. A., Atkinson, H. C., MacSweeney, C. P., Thomson, F., Craighead, M., Grassie, M., & Lightman, S. L. (2007) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2007.01605.x · Cited by 53 · see citing works
Horstmann, S., Dose, T., Lucae, S., Kloiber, S., Menke, A., Hennings, J., Spieler, D., Uhr, M., Holsboer, F., & Ising, M. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.09.004 · Cited by 44 · see citing works
Howell, M. P., & Muglia, L. J. (2006) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2006.05.001 · Cited by 46 · see citing works
Patient specific modeling of the HPA axis related to clinical diagnosis of depression
Bangsgaard, E. O., & Ottesen, J. T. (2017) · Mathematical Biosciences · doi:10.1016/j.mbs.2016.10.007 · Cited by 31 · see citing works
Bais, B., Kamperman, A. M., van der Zwaag, M. D., Dieleman, G. C., Harmsen van der Vliet-Torij, H. W., Bijma, H. H., Lieverse, R., Hoogendijk, W. J. G., & Lambregtse-van den Berg, M. P. (2016) · BMC Psychiatry · doi:10.1186/s12888-016-1092-2 · Cited by 28 · see citing works
Psychosocial Influences in Oncology: An Expanded Model of Biobehavioral Mechanisms
LUTGENDORF, S. K., COSTANZO, E. S., & SIEGEL, S. D. (2007) · Psychoneuroimmunology · doi:10.1016/b978-012088576-3/50048-4 · Cited by 28 · see citing works
Bertholf, R. L., Jialal, I., & Winter, W. E. (2012) · Tietz Textbook of Clinical Chemistry and Molecular Diagnostics · doi:10.1016/b978-1-4160-6164-9.00054-8 · Cited by 5 · see citing works
Etiology and Diagnosis of Major Depression—A Novel Quantitative Approach
Ottesen, J. T. (2013) · Open Journal of Endocrine and Metabolic Diseases · doi:10.4236/ojemd.2013.32018 · Cited by 3 · see citing works
- Authors
- Deuschle, M., Schweiger, U., Weber, B., Gotthardt, U., Körner, A., Schmider, J., Standhardt, H., Lammers, C.-H., & Heuser, I.
- Affiliations
- Max Planck Institute of Psychiatry (DE)
- Corresponding author
- Deuschle, Michael
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1997-01
- Volume
- 82
- Issue
- 1
- Pages
- 234-238
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2021746160
- Cited by
- 344
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 4 · 2020: 7 · 2019: 13 · 2018: 9 · 2017: 7 · 2016: 13 · 2015: 10 · 2014: 10 · 2013: 15 · 2012: 21
- FWCI
- 4.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- depression, hypothalamic-pituitary-adrenal axis, cortisol, ACTH, circadian rhythm, diurnal cycle, pulsatile hormone secretion, mineralocorticoid receptor, glucocorticoid receptor, male patients
- MeSH terms
- Adrenal Glands, Adrenocorticotropic Hormone, Adult, Aged, Circadian Rhythm, Depression, Humans, Hydrocortisone, Hypothalamus, Male, Middle Aged, Periodicity, Pituitary Gland
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
