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Assessment of the hypothalamic–pituitary–adrenal axis activity: glucocorticoid receptor and mineralocorticoid receptor function in depression with early life stress – a systematic review

Published online by Cambridge University Press:  24 June 2014

Cristiane Von Werne Baes ,
Sandra M. de Carvalho Tofoli ,
Camila Maria S. Martins  and
Mario F. Juruena
Cristiane Von Werne Baes
Affiliation:
Department of Neuroscience and Behaviour, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brasil
Sandra M. de Carvalho Tofoli
Affiliation:
Department of Neuroscience and Behaviour, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brasil
Camila Maria S. Martins
Affiliation:
Department of Neuroscience and Behaviour, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brasil
Mario F. Juruena*
Affiliation:
Stress and Affective Disorders Programme, Department of Neurosciences and Behaviour, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brasil
*
Mario F. Juruena, Department of Neurosciences and Behaviour, Faculty of Medicine Ribeirao Preto, Saude Mental-USP, Av. Tenente Catao Roxo, 2650, Monte Alegre-Campus Universitario, University of Sao Paulo, Ribeirao Preto, Sao Paulo 14051-140, Brasil. Tel: +55 16 36307961; Fax: +55 16 36307961; E-mail: juruena@fmrp.usp.br
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Extract

Objective: The mechanisms involved in the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, especially in the functioning of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in depressed patients, are not well elucidated. The objective of this study was to conduct a systematic review of articles that assess the HPA axis activity from GR and MR in depressed patients and healthy controls with or without early life stress.

Methods: We conducted a systematic review of articles in PubMed, SCOPUS and SciELO published between 2000 and 2011, using the following search terms: child abuse, depression, HPA axis, dexamethasone, prednisolone, fludrocortisone and spironolactone. Thirty-four papers were selected for this review.

Results: Most studies identified in this review used the dexamethasone/corticotropin-releasing hormone test and dexamethasone suppression test. In these studies, hypercortisolaemia was associated with depression. We identified three studies with the Prednisolone suppression test, only one study with the use of fludrocortisone and one with spironolactone. This review found nine studies that evaluated the HPA axis in individuals with early life stress.

Conclusions: The majority of the studies assessed in this review show that early life stress leads to permanent changes in the HPA axis and may lead to development of depression in adults. The most consistent findings in the literature show increased activity of the HPA axis in depression associated with hypercortisolaemia and reduced inhibitory feedback. These findings suggest that this dysregulation of the HPA axis is partially attributable to an imbalance between GR and MR. Evidences have consistently showed that GR function is impaired in major depression, but few studies have assessed the activity of MR in depression and early life stress.

Keywords

affective disordercorticoidscortisolhypothalmo–pituitary–adrenal axisneuroendocrinologypituitary glandstress
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 24 , Issue 1 , February 2012 , pp. 4 - 15
Copyright
Copyright © Cambridge University Press 2011

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References

1.Kendler, KS, Sheth, K, Gardner, CO, Prescott, CA.Childhood parental loss and risk for first-onset of major depression and alcohol dependence: the time-decay of risk and sex differences. Psychol Med 2002;32:1187–1194.CrossRefGoogle ScholarPubMed
2.Heim, C, Newport, DJ, Heit, S et al. Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA 2000;284:592–597.CrossRefGoogle ScholarPubMed
3.Fergusson, DM, Swain-Campbell, NR, Horwood, LJ.Does sexual violence contribute to elevated rates of anxiety and depression in females? Psychol Med 2002;32:991–996.Google Scholar
4.Cohen, P, Brown, J, Smailes, E.Child abuse and neglect and the development of mental disorders in the general population. Dev Psychopathol 2001;13:981–999.CrossRefGoogle ScholarPubMed
5.Post, RM.Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. Am J Psychiatry 1992;149:999–1010.Google Scholar
6.Shea, A, Walsh, C, Macmillan, H, Steiner, M.Child maltreatment and HPA axis dysregulation: relationship to major depressive disorder and post traumatic stress disorder in females. Psychoneuroendocrinology 2005;30:162–178.CrossRefGoogle ScholarPubMed
7.Mello, AAF, Mello, MF, Carpenter, LL, Price, LH.Update on stress and depression: the role of the hypothalamic-pituitary-adrenal (HPA) axis. Rev Bras Psiquiatr 2003;25:231–238.Google Scholar
8.Parker, KJ, Schatzberg, AF, Lyons, DM.Neuroendocrine aspects of hypercortisolism in major depression. Horm Behavr 2003;43:60–66.CrossRefGoogle ScholarPubMed
9.Juruena, MF, Cleare, AJ, Pariante, CM.The hypothalamic pituitary adrenal axis, glucocorticoid receptor function and relevance to depression. Rev Bras Psiquiatr 2004;26:189–201.CrossRefGoogle ScholarPubMed
10.Carroll, BJ, Cassidy, F, Naftolowitz, D et al. Pathophysiology of hypercortisolism in depression. Acta Psychiatr Scand 2007;115(Suppl. 433):90–103.CrossRefGoogle Scholar
11.Pariante, CM.The glucocorticoid receptor: part of the solution or part of the problem? J Psychopharmacol 2006;20:79–84.CrossRefGoogle ScholarPubMed
12.Pariante, CM, Miller, AH.Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment. Biol Psychiatry 2001;49:391–404.CrossRefGoogle Scholar
13.Herman, JP, Patel, PD, Akil, H, Watson, S.Localization and regulation of glucocorticoid and mineralocorticoid receptor messenger RNAs in the hippocampal formation of the rat. Mol Endocrinol 1989;3:1886–1894.CrossRefGoogle ScholarPubMed
14.Patel, PD, López, JF, Lyons, DM, Burke, S, Wallace, M, Schatzberg, AF.Glucocorticoid and mineralocorticoid receptor mRNA expression in squirrel monkey brain. J Psychiatr Res 2000;34:383–392.CrossRefGoogle ScholarPubMed
15.de Kloet, ER, Vreugdenhil, E, Oitzl, MS, Joels, M.Brain corticosteroid receptor balance in health and disease. Endocr Rev 1998;19:269–301.Google ScholarPubMed
16.Young, EA, Lopez, JF, Murphy-Weinberg, V, Watson, SJ, Akil, H.Normal pituitary response to metyrapone in the morning in depressed patients: implications for circadian regulation of CRH secretion. Biol Psychiatry 1997;41:1149–1155.Google Scholar
17.Carroll, BJ, Curtis, GC, Mendels, J.Neuroendocrine regulation in depression. II. Discrimination of depressed from nondepressed patients. Arch Gen Psychiatry 1976;33:1051–1058.Google Scholar
18.Arana, G, Baldessarini, R, Ornsteen, M.The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Arch Gen Psychiatry 1985;42:1192–1204.CrossRefGoogle ScholarPubMed
19.Ribeiro, SC, Tandon, R, Grunhaus, L, Greden, JF.The DST as a predictor of outcome in depression: a meta-analysis. Am J Psychiatry 1993;150:1618–1629.Google Scholar
20.Pariante, CM, Papadopoulos, AS, Poon, L et al. A novel prednisolone suppression test for the hypothalamic–pituitary–adrenal axis. Biol Psychiatry 2002;51:922–930.CrossRefGoogle ScholarPubMed
21.von Bardeleben, U, Holsboer, F.Effect of age on the cortisol response to human corticotropin-releasing hormone in depressed patients pretreated with dexamethasone. Biol Psychiatry 1991;29:1042–1050.CrossRefGoogle ScholarPubMed
22.Heuser, I, Yassouridis, A et al. The combined dexamethasone/CRH test: a refined laboratory test for psychiatric disorders. J Psychiatr Res 1994;28:341–356.CrossRefGoogle Scholar
23.Zobel, AW, Nickel, T, Sonntag, A, Uhr, M, Holsboer, F, Ising, M.Cortisol response in the combined dexamethasone/CRH test as predictor of relapse in patients with remitted depression. a prospective study. J Psychiatr Res 2001;35:83–94.CrossRefGoogle ScholarPubMed
24.Grossmann, C, Scholz, T, Rochel, M et al. Transactivation via the human glucocorticoid and mineralocorticoid receptor by therapeutically used steroids in CV-1 cells: a comparison of their glucocorticoid and mineralocorticoid properties. Eur J Endocrinol 2004;151:397–406.CrossRefGoogle Scholar
25.Ballard, PL, Carter, JP, Graham, BS, Baxter, JD.A radioreceptor assay for evaluation of the plasma glucocorticoid activity of natural and synthetic steroids in man. J Clin Endocrinol Metab 1975;41:290–304.CrossRefGoogle ScholarPubMed
26.Heuser, I, Deuschle, M, Weber, B, Stalla, GK, Holsboer, F.Increased activity of the hypothalamus-pituitary-adrenal system after treatment with the mineralocorticoid receptor antagonist spironolactone. Psychoneuroendocrinology 2000;25:513–518.Google Scholar
27.Holsboer, F.The rationale for corticotropin-releasing hormone receptor (CRH-R) antagonists to treat depression and anxiety. J Psychiatr Res 1999;33:181–214.CrossRefGoogle ScholarPubMed
28.Otte, C, Hinkelmann, K, Moritz, S, Yassouridis, A, Jahn, H, Wiedemann, K, Kellner, M.Modulation of the mineralocorticoid receptor as add-on treatment in depression: a randomized, double-blind, placebo-controlled proof-of-concept study. J Psychiatr Res 2010;44:339–346.CrossRefGoogle ScholarPubMed
29.Carpenter, LL, Ross, NS, Tyrka, AR, Anderson, GM, Kelly, M, Price, LH.Dex/CRH test cortisol response in outpatients with major depression and matched healthy controls. Psychoneuroendocrinology 2009;34:1208–1213.Google Scholar
30.Heim, C, Mletzko, T, Purselle, D, Musselman, DL, Nemeroff, CB.The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma. Biol Psychiatry 2008;63:398–405.Google Scholar
31.Kunugi, H, Ida, I, Owashi, T et al. 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. Neuropsychopharmacology 2006;31:212–220.CrossRefGoogle ScholarPubMed
32.Gervasoni, N, Bertschy, G, Osiek, C et al. Cortisol responses to combined dexamethasone/CRH test in outpatients with a major depressive episode. J Psychiatr Res 2004;38:553–557.Google Scholar
33.Pfennig, A, Kunzel, HE, Kern, N et al. Hypothalamus-pituitary-adrenal system regulation and suicidal behavior in depression. Biol Psychiatry 2005;57:336–342.Google Scholar
34.Kunugi, H, Urushibara, T, Nanko, S.Combined DEX/CRH test among Japanese patients with major depression. J Psychiatr Res 2004;38:123–128.Google Scholar
35.Van Den Eede, F, Van den Bossche, B, Hulstijn, W, Sabbe, BG, Cosyns, P, Claes, SJ.Combined dexamethasone/CRF test in remitted outpatients with recurrent major depressive disorder. J Affect Disord 2006;93:259–263.Google Scholar
36.Owashi, T, Otsubo, T, Oshima, A, Nakagome, K, Higuchi, T, Kamijima, K.Longitudinal neuroendocrine changes assessed by dexamethasone/CRH and growth hormone releasing hormone tests in psychotic depression. Psychoneuroendocrinology 2008;33:152–161.CrossRefGoogle ScholarPubMed
37.Oshima, A, Yamashita, S, Owashi, T et al. The differential ACTH responses to combined dexamethasone/CRH administration in major depressive and dysthymic disorders. J Psychiatr Res 2000;34:325–328.Google Scholar
38.Duval, F, Mokrani, MC, Correa, H et al. Lack of effect of HPA axis hyperactivity on hormonal responses to d-fenfluramine in major depressed patients: implications for pathogenesis of suicidal behaviour. Psychoneuroendocrinology 2001;26:521–537.Google Scholar
39.Nunes, SOV, Reiche, EMV, Morimoto, HK et al. Immune and hormonal activity in adults suffering from depression. Braz J Med Biol Res 2002;35:581–587.CrossRefGoogle ScholarPubMed
40.Galard, R, Catalán, R, Castellanos, JM, Gallart, JM.Plasma corticotropin-releasing factor in depressed patients before and after the dexamethasone suppression test. Biol Psychiatry 2002;51:463–468.CrossRefGoogle ScholarPubMed
41.Vreeburg, SA, Hoogendijk, WJ, van Pelt, J et al. Major depressive disorder and hypothalamic-pituitary-adrenal axis activity: results from a large cohort study. Arch Gen Psychiatry 2009;66:617–626.CrossRefGoogle ScholarPubMed
42.Pitchot, W, Scantamburlo, G, Pinto, E, Hansenne, M, Reggers, J, Ansseau, M, Legros, JJ.Vasopressin-neurophysin and DST in major depression: relationship with suicidal behavior. J Psychiatr Res 2008;42:684–688.CrossRefGoogle ScholarPubMed
43.Jokinen, J, Nordström, P.HPA axis hyperactivity and attempted suicide in young adult mood disorder inpatients. J Affect Disord 2009;116:117–120.Google Scholar
44.Fountoulakis, KN, Iacovides, A, Fotiou, F et al. Neurobiological and psychological correlates of suicidal attempts and thoughts of death in patients with major depression. Neuropsychobiology 2004;49:42–52.Google Scholar
45.Fountoulakis, KN, Gonda, X, Rihmer, Z, Fokas, C, Iacovides, A.Revisiting the dexamethasone suppression test in unipolar major depression: an exploratory study. Ann Gen Psychiatry 2008;7:22.Google Scholar
46.Gaudiano, BA, Epstein-Lubow, G, Miller, IW.Does the dexamethasone suppression test reliably discriminate between psychotic and nonpsychotic major depression?: an exploratory analysis of potential confounds. J Nerv Ment Dis 2009;197:395–400.CrossRefGoogle ScholarPubMed
47.Contreras, F, Menchon, JM, Urretavizcaya, M, Navarro, MA, Vallejo, J, Parker, G.Hormonal differences between psychotic and non-psychotic melancholic depression. J Affect Disord 2007;100:65–73.CrossRefGoogle ScholarPubMed
48.Stewart, JW, Quitkin, FM, McGrath, PJ, Klein, DF.Defining the boundaries of atypical depression: evidence from the HPA axis supports course of illness distinctions. J Affect Disord 2005;86:161–167.CrossRefGoogle ScholarPubMed
49.Levitan, RD, Vaccarino, FJ, Brown, GM, Kennedy, SH.Low-dose dexamethasone challenge in women with atypical major depression: pilot study. J Psychiatry Neurosci 2002;27:47–51.Google ScholarPubMed
50.Stetler, C, Miller, GE.Depression and hypothalamic-pituitary-adrenal activation: a quantitative summary of four decades of research. Psychosomatic Medicine 2011;73:114–126.CrossRefGoogle ScholarPubMed
51.Watson, S, Gallagher, P, Del-Estal, D, Hearn, A, Ferrier, IN, Young, AH.Hypothalamic-pituitary-adrenal axis function in patients with chronic depression. Psychol Med 2002;32:1021–1028.CrossRefGoogle ScholarPubMed
52.Watson, S, Gallagher, P, Smith, MS, Ferrier, IN, Young, AH.The dex/CRH test–is it better than the DST? Psychoneuroendocrinology 2006;31:889–894.CrossRefGoogle Scholar
53.Paslakis, G, Krumma, B, Gilles, M, Schweiger, U, Heuser, I, Inga Richter, I, Deuschle, M.Discrimination between patients with melancholic depression and healthy controls: Comparison between 24-h cortisol profiles, the DST and the Dex/CRH test. Psychoneuroendocrinology 2011;36:691–698.Google Scholar
54.Juruena, MF, Pariante, CM, Papadoulos, AS, Poon, L, Lightman, S, Cleare, AJ.Prednisolone suppression test in depression: prospective study of the role of HPA axis dysfunction in treatment resistance. Br J Psychiatry 2009;194:342–349.Google Scholar
55.Juruena, MF, Cleare, AJ, Papadopoulos, AS, Poon, L, Ligtman, S, Pariante, CM.The prednisolone suppression test in depression: dose-response and changes with antidepressant treatment. Psychoneuroendocrinology 2010;35:1485–1491.Google Scholar
56.Juruena, MF, Cleare, AJ, Papadopoulos, AS, Poon, L, Lightman, S, Pariante, CM.Different responses to dexamethasone and prednisolone in the same depressed patients. Psychopharmacology 2006;189:225–235.Google Scholar
57.Buckley, TM, Mullen, BC, Schatzberg, AF.The acute effects of a mineralocorticoid receptor (MR) agonist on nocturnal hypothalamic-adrenal-pituitary (HPA) axis activity in healthy controls. Psychoneuroendocrinology 2007;32:859–864.CrossRefGoogle ScholarPubMed
58.Young, EA, Lopez, JF, Murphy-Weinberg, V, Watson, SJ, Akil, H.Mineralocorticoid receptor function in major depression. Arch Gen Psychiatry 2003;60:24–28.Google Scholar
59.Carpenter, LL, Tyrka, AR, Ross, NS, Khoury, L, Anderson, GM, Price, LH.Effect of childhood emotional abuse and age on cortisol responsivity in adulthood. Biol Psychiatry 2009;66:69–75.Google Scholar
60.Klaassens, ER, van Noorden, MS, Giltay, EJ, van Pelt, J, van Veen, T, Zitman, FG.Effects of childhood trauma on HPA-axis reactivity in women free of lifetime psychopathology. Prog Neuropsychopharmacology Biol Psychiatry 2009;33:889–894.CrossRefGoogle ScholarPubMed
61.Newport, DJ, Heim, C, Bonsall, R, Miller, AH, Nemeroff, CB.Pituitary-adrenal responses to standard and low-dose dexamethasone suppression tests in adult survivors of child abuse. Biol Psychiatry 2004;55:10–20.CrossRefGoogle ScholarPubMed
62.Tyrka, AR, Wier, L, Price, LH, Ross, N, Anderson, GM, Wilkinson, CW, Carpenter, LL.Childhood parental loss and adult hypothalamic-pituitary-adrenal function. Biol Psychiatry 2008;63:1147–1154.Google Scholar
63.Spencer, RL, Kim, PJ, Kalman, BA, Cole, MA.Evidence for mineralocorticoid receptor facilitation of glucocorticoid receptor-dependent regulation of hypothalamic-pituitary-adrenal axis activity. Endocrinology 1998;139:2718–2726.CrossRefGoogle ScholarPubMed
64.Mello, AF, Juruena, MF, Pariante, CM et al. Depressão e estresse: existe um endofenótipo? Rev Bras Psiquiatr 2007;29(Suppl. I):13–18.Google Scholar