Skip to main content
PMC home page
Indian Journal of Psychiatry logoLink to Indian Journal of Psychiatry
. 2003 Apr-Jun;45(2):5–14.

Glucocorticoid receptor dysfunction: consequences for the pathophysiology and treatment of mood disorders

Aju Abraham *, Stuart Watson *,*, Allan H Young ‡
PMCID: PMC2952148  PMID: 21206827

Abstract

Background:

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction in mood disorders is one of the most robust findings in biological psychiatry. However, considerable debate surrounds the nature of the core abnormality, its cause, consequences and treatment implications.

Aims:

To review the evidence for the role of HPA axis dysfunction in the pathophysiology of mood disorders with particular reference to corticosteroid receptor pathology.

Methods:

A selective review of the published literature in this field, focusing on human studies.

Results:

The nature of basal HPA axis dysregulation described in both manic and depressed bipolars appears to be similar to those described in MDD. But studies using the dexamethasone/ corticotropin releasing hormone (dex/CRH) test and dexamethasone suppression test (DST) have shown that HPA axis dysfunction is more prevalent in bipolar than in unipolar disorder. There is robust evidence for corticotropin releasing hormone (CRH) hyperdrive and glucocorticoid receptor (GR) dysfunction in mood disorders, with increasing evidence for disorders within the AVP system.

Conclusion:

HPA axis dysfunction is prevalent in patients with mood disorder, particularly those with psychotic disorders and bipolar affective disorder. This may be secondary to genetic factors, early life adversities or both. Dysfunction of GR may be the underlying abnormality and preliminary findings suggest that it is a potential target for novel therapies.

Declaration of interest:

None

Keywords: Mood disorders, pathophysiology, Glncocorticoid Receptor

Full Text

The Full Text of this article is available as a PDF (568.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amsterdam J. D., Maislin G., Winokur A., Berwish N., Kling M., Gold P. The oCRH stimulation test before and after clinical recovery from depression. J Affect Disord. 1988 May-Jun;14(3):213–222. doi: 10.1016/0165-0327(88)90037-7. [DOI] [PubMed] [Google Scholar]
  2. Amsterdam J. D., Winokur A., Abelman E., Lucki I., Rickels K. Cosyntropin (ACTH alpha 1-24) stimulation test in depressed patients and healthy subjects. Am J Psychiatry. 1983 Jul;140(7):907–909. doi: 10.1176/ajp.140.7.907. [DOI] [PubMed] [Google Scholar]
  3. Antoni F. A. Hypothalamic control of adrenocorticotropin secretion: advances since the discovery of 41-residue corticotropin-releasing factor. Endocr Rev. 1986 Nov;7(4):351–378. doi: 10.1210/edrv-7-4-351. [DOI] [PubMed] [Google Scholar]
  4. Arana G. W., Barreira P. J., Cohen B. M., Lipinski J. F., Fogelson D. The dexamethasone suppression test in psychotic disorders. Am J Psychiatry. 1983 Nov;140(11):1521–1523. doi: 10.1176/ajp.140.11.1521. [DOI] [PubMed] [Google Scholar]
  5. Arborelius L., Owens M. J., Plotsky P. M., Nemeroff C. B. The role of corticotropin-releasing factor in depression and anxiety disorders. J Endocrinol. 1999 Jan;160(1):1–12. doi: 10.1677/joe.0.1600001. [DOI] [PubMed] [Google Scholar]
  6. Belanoff J. K., Flores B. H., Kalezhan M., Sund B., Schatzberg A. F. Rapid reversal of psychotic depression using mifepristone. J Clin Psychopharmacol. 2001 Oct;21(5):516–521. doi: 10.1097/00004714-200110000-00009. [DOI] [PubMed] [Google Scholar]
  7. Brown E. S., Bobadilla L., Rush A. J. Ketoconazole in bipolar patients with depressive symptoms: a case series and literature review. Bipolar Disord. 2001 Feb;3(1):23–29. doi: 10.1034/j.1399-5618.2001.030103.x. [DOI] [PubMed] [Google Scholar]
  8. Cardno Alastair G., Rijsdijk Frühling V., Sham Pak C., Murray Robin M., McGuffin Peter. A twin study of genetic relationships between psychotic symptoms. Am J Psychiatry. 2002 Apr;159(4):539–545. doi: 10.1176/appi.ajp.159.4.539. [DOI] [PubMed] [Google Scholar]
  9. Carroll B. J., Curtis G. C., Mendels J. Neuroendocrine regulation in depression. II. Discrimination of depressed from nondepressed patients. Arch Gen Psychiatry. 1976 Sep;33(9):1051–1058. doi: 10.1001/archpsyc.1976.01770090041003. [DOI] [PubMed] [Google Scholar]
  10. Cervantes P., Gelber S., Kin F. N., Nair V. N., Schwartz G. Circadian secretion of cortisol in bipolar disorder. J Psychiatry Neurosci. 2001 Nov;26(5):411–416. [PMC free article] [PubMed] [Google Scholar]
  11. Cole T. J., Blendy J. A., Monaghan A. P., Krieglstein K., Schmid W., Aguzzi A., Fantuzzi G., Hummler E., Unsicker K., Schütz G. Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation. Genes Dev. 1995 Jul 1;9(13):1608–1621. doi: 10.1101/gad.9.13.1608. [DOI] [PubMed] [Google Scholar]
  12. Cole T. J., Myles K., Purton J. F., Brereton P. S., Solomon N. M., Godfrey D. I., Funder J. W. GRKO mice express an aberrant dexamethasone-binding glucocorticoid receptor, but are profoundly glucocorticoid resistant. Mol Cell Endocrinol. 2001 Feb 28;173(1-2):193–202. doi: 10.1016/s0303-7207(00)00407-x. [DOI] [PubMed] [Google Scholar]
  13. Coplan J. D., Andrews M. W., Rosenblum L. A., Owens M. J., Friedman S., Gorman J. M., Nemeroff C. B. Persistent elevations of cerebrospinal fluid concentrations of corticotropin-releasing factor in adult nonhuman primates exposed to early-life stressors: implications for the pathophysiology of mood and anxiety disorders. Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1619–1623. doi: 10.1073/pnas.93.4.1619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Davis M. The role of the amygdala in fear and anxiety. Annu Rev Neurosci. 1992;15:353–375. doi: 10.1146/annurev.ne.15.030192.002033. [DOI] [PubMed] [Google Scholar]
  15. De Kloet E. R., Reul J. M. Feedback action and tonic influence of corticosteroids on brain function: a concept arising from the heterogeneity of brain receptor systems. Psychoneuroendocrinology. 1987;12(2):83–105. doi: 10.1016/0306-4530(87)90040-0. [DOI] [PubMed] [Google Scholar]
  16. De Kloet E. R., Vreugdenhil E., Oitzl M. S., Joëls M. Brain corticosteroid receptor balance in health and disease. Endocr Rev. 1998 Jun;19(3):269–301. doi: 10.1210/edrv.19.3.0331. [DOI] [PubMed] [Google Scholar]
  17. DeBattista C., Posener J. A., Kalehzan B. M., Schatzberg A. F. Acute antidepressant effects of intravenous hydrocortisone and CRH in depressed patients: a double-blind, placebo-controlled study. Am J Psychiatry. 2000 Aug;157(8):1334–1337. doi: 10.1176/appi.ajp.157.8.1334. [DOI] [PubMed] [Google Scholar]
  18. Dean C. E. Prasterone (DHEA) and mania. Ann Pharmacother. 2000 Dec;34(12):1419–1422. doi: 10.1345/aph.10115. [DOI] [PubMed] [Google Scholar]
  19. Dubrovsky B. Effects of adrenal cortex hormones on limbic structures: some experimental and clinical correlations related to depression. J Psychiatry Neurosci. 1993 Jan;18(1):4–16. [PMC free article] [PubMed] [Google Scholar]
  20. Dunn A. J., Berridge C. W. Physiological and behavioral responses to corticotropin-releasing factor administration: is CRF a mediator of anxiety or stress responses? Brain Res Brain Res Rev. 1990 May-Aug;15(2):71–100. doi: 10.1016/0165-0173(90)90012-d. [DOI] [PubMed] [Google Scholar]
  21. Erkut Z. A., Pool C., Swaab D. F. Glucocorticoids suppress corticotropin-releasing hormone and vasopressin expression in human hypothalamic neurons. J Clin Endocrinol Metab. 1998 Jun;83(6):2066–2073. doi: 10.1210/jcem.83.6.4881. [DOI] [PubMed] [Google Scholar]
  22. Ferrier I. N., Stanton B. R., Kelly T. P., Scott J. Neuropsychological function in euthymic patients with bipolar disorder. Br J Psychiatry. 1999 Sep;175:246–251. doi: 10.1192/bjp.175.3.246. [DOI] [PubMed] [Google Scholar]
  23. GIBBONS J. L. CORTISOL SECRETION RATE IN DEPRESSIVE ILLNESS. Arch Gen Psychiatry. 1964 Jun;10:572–575. doi: 10.1001/archpsyc.1964.01720240026004. [DOI] [PubMed] [Google Scholar]
  24. Gold P. W., Chrousos G., Kellner C., Post R., Roy A., Augerinos P., Schulte H., Oldfield E., Loriaux D. L. Psychiatric implications of basic and clinical studies with corticotropin-releasing factor. Am J Psychiatry. 1984 May;141(5):619–627. doi: 10.1176/ajp.141.5.619. [DOI] [PubMed] [Google Scholar]
  25. Goodwin F. K. The biology of depression: conceptual issues. Adv Biochem Psychopharmacol. 1984;39:11–26. [PubMed] [Google Scholar]
  26. Gould E., Tanapat P., Rydel T., Hastings N. Regulation of hippocampal neurogenesis in adulthood. Biol Psychiatry. 2000 Oct 15;48(8):715–720. doi: 10.1016/s0006-3223(00)01021-0. [DOI] [PubMed] [Google Scholar]
  27. Graham P. M., Booth J., Boranga G., Galhenage S., Myers C. M., Teoh C. L., Cox L. S. The dexamethasone suppression test in mania. J Affect Disord. 1982 Sep;4(3):201–211. doi: 10.1016/0165-0327(82)90004-0. [DOI] [PubMed] [Google Scholar]
  28. Greden J. F., DeVigne J. P., Albala A. A., Tarika J., Buttenheim M., Eiser A., Carroll B. J. Serial dexamethasone suppression tests among rapidly cycling bipolar patients. Biol Psychiatry. 1982 Apr;17(4):455–462. [PubMed] [Google Scholar]
  29. Harris T. O., Borsanyi S., Messari S., Stanford K., Cleary S. E., Shiers H. M., Brown G. W., Herbert J. Morning cortisol as a risk factor for subsequent major depressive disorder in adult women. Br J Psychiatry. 2000 Dec;177:505–510. doi: 10.1192/bjp.177.6.505. [DOI] [PubMed] [Google Scholar]
  30. Heim C., Newport D. J., Bonsall R., Miller A. H., Nemeroff C. B. Altered pituitary-adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. Am J Psychiatry. 2001 Apr;158(4):575–581. doi: 10.1176/appi.ajp.158.4.575. [DOI] [PubMed] [Google Scholar]
  31. Heim C, Newport DJ, Miller AH, Nemeroff CB. Long-term neuroendocrine effects of childhood maltreatment. JAMA. 2000 Nov 8;284(18):2321–2321. [PubMed] [Google Scholar]
  32. Heuser I. J., Schweiger U., Gotthardt U., Schmider J., Lammers C. H., Dettling M., Yassouridis A., Holsboer F. Pituitary-adrenal-system regulation and psychopathology during amitriptyline treatment in elderly depressed patients and normal comparison subjects. Am J Psychiatry. 1996 Jan;153(1):93–99. doi: 10.1176/ajp.153.1.93. [DOI] [PubMed] [Google Scholar]
  33. Heuser I., Yassouridis A., Holsboer F. The combined dexamethasone/CRH test: a refined laboratory test for psychiatric disorders. J Psychiatr Res. 1994 Jul-Aug;28(4):341–356. doi: 10.1016/0022-3956(94)90017-5. [DOI] [PubMed] [Google Scholar]
  34. Inskip H. M., Harris E. C., Barraclough B. Lifetime risk of suicide for affective disorder, alcoholism and schizophrenia. Br J Psychiatry. 1998 Jan;172:35–37. doi: 10.1192/bjp.172.1.35. [DOI] [PubMed] [Google Scholar]
  35. Jacobson L., Sapolsky R. The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis. Endocr Rev. 1991 May;12(2):118–134. doi: 10.1210/edrv-12-2-118. [DOI] [PubMed] [Google Scholar]
  36. Jaeckle R. S., Kathol R. G., Lopez J. F., Meller W. H., Krummel S. J. Enhanced adrenal sensitivity to exogenous cosyntropin (ACTH alpha 1-24) stimulation in major depression. Relationship to dexamethasone suppression test results. Arch Gen Psychiatry. 1987 Mar;44(3):233–240. doi: 10.1001/archpsyc.1987.01800150041006. [DOI] [PubMed] [Google Scholar]
  37. Jones M. T., Gillham B., Campbell E. A., Al-Taher A. R., Chuang T. T., Di Sciullo A. Pharmacology of neural pathways affecting CRH secretion. Ann N Y Acad Sci. 1987;512:162–175. doi: 10.1111/j.1749-6632.1987.tb24958.x. [DOI] [PubMed] [Google Scholar]
  38. Kaminska M., Harris J., Gijsbers K., Dubrovsky B. Dehydroepiandrosterone sulfate (DHEAS) counteracts decremental effects of corticosterone on dentate gyrus LTP. Implications for depression. Brain Res Bull. 2000 Jun;52(3):229–234. doi: 10.1016/s0361-9230(00)00251-3. [DOI] [PubMed] [Google Scholar]
  39. Kay J. H., Altshuler L. L., Ventura J., Mintz J. Prevalence of axis II comorbidity in bipolar patients with and without alcohol use disorders. Ann Clin Psychiatry. 1999 Dec;11(4):187–195. doi: 10.1023/a:1022305327977. [DOI] [PubMed] [Google Scholar]
  40. Kessler R. C., McGonagle K. A., Zhao S., Nelson C. B., Hughes M., Eshleman S., Wittchen H. U., Kendler K. S. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994 Jan;51(1):8–19. doi: 10.1001/archpsyc.1994.03950010008002. [DOI] [PubMed] [Google Scholar]
  41. Kirschbaum C., Hellhammer D. H. Salivary cortisol in psychoneuroendocrine research: recent developments and applications. Psychoneuroendocrinology. 1994;19(4):313–333. doi: 10.1016/0306-4530(94)90013-2. [DOI] [PubMed] [Google Scholar]
  42. Kline M. D., Jaggers E. D. Mania onset while using dehydroepiandrosterone. Am J Psychiatry. 1999 Jun;156(6):971–971. doi: 10.1176/ajp.156.6.971. [DOI] [PubMed] [Google Scholar]
  43. Laaris N., Le Poul E., Laporte A. M., Hamon M., Lanfumey L. Differential effects of stress on presynaptic and postsynaptic 5-hydroxytryptamine-1A receptors in the rat brain: an in vitro electrophysiological study. Neuroscience. 1999;91(3):947–958. doi: 10.1016/s0306-4522(98)00674-5. [DOI] [PubMed] [Google Scholar]
  44. Ladd C. O., Owens M. J., Nemeroff C. B. Persistent changes in corticotropin-releasing factor neuronal systems induced by maternal deprivation. Endocrinology. 1996 Apr;137(4):1212–1218. doi: 10.1210/endo.137.4.8625891. [DOI] [PubMed] [Google Scholar]
  45. Lauer C. J., Schreiber W., Modell S., Holsboer F., Krieg J. C. The Munich vulnerability study on affective disorders: overview of the cross-sectional observations at index investigation. J Psychiatr Res. 1998 Nov-Dec;32(6):393–401. doi: 10.1016/s0022-3956(98)00026-0. [DOI] [PubMed] [Google Scholar]
  46. Liebsch G., Landgraf R., Engelmann M., Lörscher P., Holsboer F. Differential behavioural effects of chronic infusion of CRH 1 and CRH 2 receptor antisense oligonucleotides into the rat brain. J Psychiatr Res. 1999 Mar-Apr;33(2):153–163. doi: 10.1016/s0022-3956(98)80047-2. [DOI] [PubMed] [Google Scholar]
  47. Liebsch G., Wotjak C. T., Landgraf R., Engelmann M. Septal vasopressin modulates anxiety-related behaviour in rats. Neurosci Lett. 1996 Oct 18;217(2-3):101–104. [PubMed] [Google Scholar]
  48. Lupien S. J., McEwen B. S. The acute effects of corticosteroids on cognition: integration of animal and human model studies. Brain Res Brain Res Rev. 1997 Jun;24(1):1–27. doi: 10.1016/s0165-0173(97)00004-0. [DOI] [PubMed] [Google Scholar]
  49. Markowitz J. S., Carson W. H., Jackson C. W. Possible dihydroepiandrosterone-induced mania. Biol Psychiatry. 1999 Jan 15;45(2):241–242. doi: 10.1016/s0006-3223(98)00091-2. [DOI] [PubMed] [Google Scholar]
  50. McAllister-Williams R. H., Ferrier I. N., Young A. H. Mood and neuropsychological function in depression: the role of corticosteroids and serotonin. Psychol Med. 1998 May;28(3):573–584. doi: 10.1017/s0033291798006680. [DOI] [PubMed] [Google Scholar]
  51. McElroy S. L., Altshuler L. L., Suppes T., Keck P. E., Jr, Frye M. A., Denicoff K. D., Nolen W. A., Kupka R. W., Leverich G. S., Rochussen J. R. Axis I psychiatric comorbidity and its relationship to historical illness variables in 288 patients with bipolar disorder. Am J Psychiatry. 2001 Mar;158(3):420–426. doi: 10.1176/appi.ajp.158.3.420. [DOI] [PubMed] [Google Scholar]
  52. McGuffin Peter, Rijsdijk Fruhling, Andrew Martin, Sham Pak, Katz Randy, Cardno Alastair. The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry. 2003 May;60(5):497–502. doi: 10.1001/archpsyc.60.5.497. [DOI] [PubMed] [Google Scholar]
  53. McQuade R., Young A. H. Future therapeutic targets in mood disorders: the glucocorticoid receptor. Br J Psychiatry. 2000 Nov;177:390–395. doi: 10.1192/bjp.177.5.390. [DOI] [PubMed] [Google Scholar]
  54. Modell S., Lauer C. J., Schreiber W., Huber J., Krieg J. C., Holsboer F. Hormonal response pattern in the combined DEX-CRH test is stable over time in subjects at high familial risk for affective disorders. Neuropsychopharmacology. 1998 Apr;18(4):253–262. doi: 10.1016/S0893-133X(97)00144-9. [DOI] [PubMed] [Google Scholar]
  55. Nemeroff C. B. The role of corticotropin-releasing factor in the pathogenesis of major depression. Pharmacopsychiatry. 1988 Mar;21(2):76–82. doi: 10.1055/s-2007-1014652. [DOI] [PubMed] [Google Scholar]
  56. Nemeroff C. B., Widerlöv E., Bissette G., Walléus H., Karlsson I., Eklund K., Kilts C. D., Loosen P. T., Vale W. Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science. 1984 Dec 14;226(4680):1342–1344. doi: 10.1126/science.6334362. [DOI] [PubMed] [Google Scholar]
  57. Nieman L. K., Chrousos G. P., Kellner C., Spitz I. M., Nisula B. C., Cutler G. B., Merriam G. R., Bardin C. W., Loriaux D. L. Successful treatment of Cushing's syndrome with the glucocorticoid antagonist RU 486. J Clin Endocrinol Metab. 1985 Sep;61(3):536–540. doi: 10.1210/jcem-61-3-536. [DOI] [PubMed] [Google Scholar]
  58. Pariante C. M., Miller A. H. Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment. Biol Psychiatry. 2001 Mar 1;49(5):391–404. doi: 10.1016/s0006-3223(00)01088-x. [DOI] [PubMed] [Google Scholar]
  59. Plotsky P. M., Meaney M. J. Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. Brain Res Mol Brain Res. 1993 May;18(3):195–200. doi: 10.1016/0169-328x(93)90189-v. [DOI] [PubMed] [Google Scholar]
  60. Purba J. S., Hoogendijk W. J., Hofman M. A., Swaab D. F. Increased number of vasopressin- and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression. Arch Gen Psychiatry. 1996 Feb;53(2):137–143. doi: 10.1001/archpsyc.1996.01830020055007. [DOI] [PubMed] [Google Scholar]
  61. Raadsheer F. C., Hoogendijk W. J., Stam F. C., Tilders F. J., Swaab D. F. Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology. 1994 Oct;60(4):436–444. doi: 10.1159/000126778. [DOI] [PubMed] [Google Scholar]
  62. Rush A. J., Giles D. E., Schlesser M. A., Orsulak P. J., Parker C. R., Jr, Weissenburger J. E., Crowley G. T., Khatami M., Vasavada N. The dexamethasone suppression test in patients with mood disorders. J Clin Psychiatry. 1996 Oct;57(10):470–484. doi: 10.4088/jcp.v57n1006. [DOI] [PubMed] [Google Scholar]
  63. Rybakowski J. K., Twardowska K. The dexamethasone/corticotropin-releasing hormone test in depression in bipolar and unipolar affective illness. J Psychiatr Res. 1999 Sep-Oct;33(5):363–370. doi: 10.1016/s0022-3956(99)00014-x. [DOI] [PubMed] [Google Scholar]
  64. Sachar E. J. Twenty-four-hour cortisol secretory patterns in depressed and manic patients. Prog Brain Res. 1975;42:81–91. doi: 10.1016/S0079-6123(08)63647-X. [DOI] [PubMed] [Google Scholar]
  65. Sapolsky R. M., Krey L. C., McEwen B. S. The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev. 1986 Aug;7(3):284–301. doi: 10.1210/edrv-7-3-284. [DOI] [PubMed] [Google Scholar]
  66. Sassi R. B., Nicoletti M., Brambilla P., Harenski K., Mallinger A. G., Frank E., Kupfer D. J., Keshavan M. S., Soares J. C. Decreased pituitary volume in patients with bipolar disorder. Biol Psychiatry. 2001 Aug 15;50(4):271–280. doi: 10.1016/s0006-3223(01)01086-1. [DOI] [PubMed] [Google Scholar]
  67. Schatzberg A. F., Rothschild A. J., Langlais P. J., Bird E. D., Cole J. O. A corticosteroid/dopamine hypothesis for psychotic depression and related states. J Psychiatr Res. 1985;19(1):57–64. doi: 10.1016/0022-3956(85)90068-8. [DOI] [PubMed] [Google Scholar]
  68. Schmider J., Lammers C. H., Gotthardt U., Dettling M., Holsboer F., Heuser I. J. Combined dexamethasone/corticotropin-releasing hormone test in acute and remitted manic patients, in acute depression, and in normal controls: I. Biol Psychiatry. 1995 Dec 15;38(12):797–802. doi: 10.1016/0006-3223(95)00064-X. [DOI] [PubMed] [Google Scholar]
  69. Scott L. V., Dinan T. G. Vasopressin and the regulation of hypothalamic-pituitary-adrenal axis function: implications for the pathophysiology of depression. Life Sci. 1998;62(22):1985–1998. doi: 10.1016/s0024-3205(98)00027-7. [DOI] [PubMed] [Google Scholar]
  70. Solomon D. A., Keller M. B., Leon A. C., Mueller T. I., Shea M. T., Warshaw M., Maser J. D., Coryell W., Endicott J. Recovery from major depression. A 10-year prospective follow-up across multiple episodes. Arch Gen Psychiatry. 1997 Nov;54(11):1001–1006. doi: 10.1001/archpsyc.1997.01830230033005. [DOI] [PubMed] [Google Scholar]
  71. Timpl P., Spanagel R., Sillaber I., Kresse A., Reul J. M., Stalla G. K., Blanquet V., Steckler T., Holsboer F., Wurst W. Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1. Nat Genet. 1998 Jun;19(2):162–166. doi: 10.1038/520. [DOI] [PubMed] [Google Scholar]
  72. Vale W., Rivier C., Brown M. R., Spiess J., Koob G., Swanson L., Bilezikjian L., Bloom F., Rivier J. Chemical and biological characterization of corticotropin releasing factor. Recent Prog Horm Res. 1983;39:245–270. doi: 10.1016/b978-0-12-571139-5.50010-0. [DOI] [PubMed] [Google Scholar]
  73. Valentino R. J., Foote S. L., Page M. E. The locus coeruleus as a site for integrating corticotropin-releasing factor and noradrenergic mediation of stress responses. Ann N Y Acad Sci. 1993 Oct 29;697:173–188. doi: 10.1111/j.1749-6632.1993.tb49931.x. [DOI] [PubMed] [Google Scholar]
  74. Vieta E., Gasto C., Martinez de Osaba M. J., Nieto E., Canto T. J., Otero A., Vallejo J. Prediction of depressive relapse in remitted bipolar patients using corticotrophin-releasing hormone challenge test. Acta Psychiatr Scand. 1997 Mar;95(3):205–211. doi: 10.1111/j.1600-0447.1997.tb09621.x. [DOI] [PubMed] [Google Scholar]
  75. Vieta E., Martínez-De-Osaba M. J., Colom F., Martínez-Arán A., Benabarre A., Gastó C. Enhanced corticotropin response to corticotropin-releasing hormone as a predictor of mania in euthymic bipolar patients. Psychol Med. 1999 Jul;29(4):971–978. doi: 10.1017/s0033291799008727. [DOI] [PubMed] [Google Scholar]
  76. Webster M. J., Knable M. B., O'Grady J., Orthmann J., Weickert C. S. Regional specificity of brain glucocorticoid receptor mRNA alterations in subjects with schizophrenia and mood disorders. Mol Psychiatry. 2002;7(9):985-94, 924. doi: 10.1038/sj.mp.4001139. [DOI] [PubMed] [Google Scholar]
  77. Wehr T. A., Goodwin F. K. Do antidepressants cause mania? Psychopharmacol Bull. 1987;23(1):61–65. [PubMed] [Google Scholar]
  78. Weissman M. M., Bland R. C., Canino G. J., Faravelli C., Greenwald S., Hwu H. G., Joyce P. R., Karam E. G., Lee C. K., Lellouch J. Cross-national epidemiology of major depression and bipolar disorder. JAMA. 1996 Jul 24;276(4):293–299. [PubMed] [Google Scholar]
  79. Whalley L. J., Christie J. E., Blackwood D. H., Bennie J., Dick H., Blackburn I. M., Fink G. Disturbed endocrine function in the psychoses. I: Disordered homeostasis or disease process? Br J Psychiatry. 1989 Oct;155:455–461. doi: 10.1192/bjp.155.4.455. [DOI] [PubMed] [Google Scholar]
  80. White-Gbadebo D., Hamm R. J. Chronic corticosterone treatment potentiates deficits following traumatic brain injury in rats: implications for aging. J Neurotrauma. 1993 Fall;10(3):297–306. doi: 10.1089/neu.1993.10.297. [DOI] [PubMed] [Google Scholar]
  81. Wolkowitz O. M., Reus V. I., Keebler A., Nelson N., Friedland M., Brizendine L., Roberts E. Double-blind treatment of major depression with dehydroepiandrosterone. Am J Psychiatry. 1999 Apr;156(4):646–649. doi: 10.1176/ajp.156.4.646. [DOI] [PubMed] [Google Scholar]
  82. Wolkowitz O. M., Reus V. I., Roberts E., Manfredi F., Chan T., Raum W. J., Ormiston S., Johnson R., Canick J., Brizendine L. Dehydroepiandrosterone (DHEA) treatment of depression. Biol Psychiatry. 1997 Feb 1;41(3):311–318. doi: 10.1016/s0006-3223(96)00043-1. [DOI] [PubMed] [Google Scholar]
  83. Young A. H., Sahakian B. J., Robbins T. W., Cowen P. J. The effects of chronic administration of hydrocortisone on cognitive function in normal male volunteers. Psychopharmacology (Berl) 1999 Aug;145(3):260–266. doi: 10.1007/s002130051057. [DOI] [PubMed] [Google Scholar]
  84. Young A. H., Sharpley A. L., Campling G. M., Hockney R. A., Cowen P. J. Effects of hydrocortisone on brain 5-HT function and sleep. J Affect Disord. 1994 Oct;32(2):139–146. doi: 10.1016/0165-0327(94)90072-8. [DOI] [PubMed] [Google Scholar]
  85. Young Allan H., Gallagher Peter, Porter Richard J. Elevation of the cortisol-dehydroepiandrosterone ratio in drug-free depressed patients. Am J Psychiatry. 2002 Jul;159(7):1237–1239. doi: 10.1176/appi.ajp.159.7.1237. [DOI] [PubMed] [Google Scholar]
  86. Young E. A., Carlson N. E., Brown M. B. Twenty-four-hour ACTH and cortisol pulsatility in depressed women. Neuropsychopharmacology. 2001 Aug;25(2):267–276. doi: 10.1016/S0893-133X(00)00236-0. [DOI] [PubMed] [Google Scholar]
  87. Zarate C. A., Jr, Tohen M., Land M., Cavanagh S. Functional impairment and cognition in bipolar disorder. Psychiatr Q. 2000 Winter;71(4):309–329. doi: 10.1023/a:1004632206684. [DOI] [PubMed] [Google Scholar]
  88. Zobel A. W., Nickel T., Künzel H. E., Ackl N., Sonntag A., Ising M., Holsboer F. Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: the first 20 patients treated. J Psychiatr Res. 2000 May-Jun;34(3):171–181. doi: 10.1016/s0022-3956(00)00016-9. [DOI] [PubMed] [Google Scholar]
  89. de Kloet E. R., Oitzl M. S., Joëls M. Functional implications of brain corticosteroid receptor diversity. Cell Mol Neurobiol. 1993 Aug;13(4):433–455. doi: 10.1007/BF00711582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. van der Lely A. J., Foeken K., van der Mast R. C., Lamberts S. W. Rapid reversal of acute psychosis in the Cushing syndrome with the cortisol-receptor antagonist mifepristone (RU 486). Ann Intern Med. 1991 Jan 15;114(2):143–144. doi: 10.7326/0003-4819-114-2-143. [DOI] [PubMed] [Google Scholar]

Articles from Indian Journal of Psychiatry are provided here courtesy of Wolters Kluwer -- Medknow Publications

RESOURCES