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Adrenocorticotropin hormone, β-endorphin and cortisol responses to oCRF in melancholic patients

Published online by Cambridge University Press:  09 July 2009

M. Maes*
Affiliation:
Department of Psychiatry, Department of Internal Medicine, and Department of Nuclear Medicine, University Hospital of Antwerp, Belgium
M. Claes
Affiliation:
Department of Psychiatry, Department of Internal Medicine, and Department of Nuclear Medicine, University Hospital of Antwerp, Belgium
M. Vandewoude
Affiliation:
Department of Psychiatry, Department of Internal Medicine, and Department of Nuclear Medicine, University Hospital of Antwerp, Belgium
C. Schotte
Affiliation:
Department of Psychiatry, Department of Internal Medicine, and Department of Nuclear Medicine, University Hospital of Antwerp, Belgium
M. Martin
Affiliation:
Department of Psychiatry, Department of Internal Medicine, and Department of Nuclear Medicine, University Hospital of Antwerp, Belgium
P. Blockx
Affiliation:
Department of Psychiatry, Department of Internal Medicine, and Department of Nuclear Medicine, University Hospital of Antwerp, Belgium
P. Cosyns
Affiliation:
Department of Psychiatry, Department of Internal Medicine, and Department of Nuclear Medicine, University Hospital of Antwerp, Belgium
*
1Address for correspondence: Dr M. Maes, Department of Psychiatry, University Hospital of Cleveland, 2040 Abington Road, Cleveland, Ohio 44106, USA.

Synopsis

Several authors have reported attenuated adrenocorticotropin hormone (ACTH) responses to corticotropin releasing factor (CRF) administration in melancholic patients as compared with healthy controls. In order to explore the integrity of the hypothalamic–pituitary–adrenal (HPA)-axis in melancholics, we examined the following parameters in 98 subjects: the ACTH; β-endorphin; and cortisol responses to ovine CRF (oCRF) (100 μg/i.v.); and the postdexamethasone cortisol values. We found significant lower CRF-induced ACTH responses in melancholic patients as opposed to healthy controls and minor depressives, while major depressives occupied an intermediate position. The psychopathological correlates of the blunted CRF-induced ACTH responses were feelings of worthlessness, self-reproach, or excessive guilt. The CRF-stimulated β-endorphin and cortisol response did not differ between the study samples. Higher baseline plasma cortisol was associated with attenuated CRF-induced ACTH responses, but these effects were not pertinent to melancholia. There were no relationships between the disordered oCRF test results, and postdexamethasone cortisol values, age, body size, sex and severity of illness. The diagnostic power of the oCRF and the dexamethasone suppression test for melancholia is enhanced when both test results are combined.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 1992

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References

American Psychiatric Association (1980). Diagnostic and Statistical Manual of Mental Disorders, 3rd edn.American Psychiatric Association: Washington, DC.Google Scholar
Amsterdam, J. D., Winokur, A., Abelman, E., Lucki, I. & Rickels, K. (1983). Cosyntropin (ACTH1–24) stimulation test in depressed patients and healthy subjects. American Journal of Psychiatry 140, 907909.Google Scholar
Amsterdam, J. D., Maislin, G., Abelman, E., Berwish, N. & Winokur, A. (1986). Adrenocortical responsiveness to the ACTH stimulation test in depressed patients and healthy volunteers. Journal of Affective Disorders 11, 265274.CrossRefGoogle Scholar
Amsterdam, J. D., Maislin, G., Winokur, A., Berwish, N., Kling, M. & Gold, P. (1988). The oCRH stimulation test before and after clinical recovery from depression. Journal of Affective Disorders 14, 213222.CrossRefGoogle ScholarPubMed
Banki, C. M., Bissette, G., Arato, M., O'Connor, L. & Nemeroff, C. B. (1987). CSF corticotropin-releasing factor-like immuno-reactivity in depression and schizophrenia. American Journal of Psychiatry 144, 873877.Google Scholar
Calogero, A. E., Bernardini, R., Gold, P. W. & Chrousos, G. P. (1988). Regulation of rat hypothalamic corticotropin-releasing hormone secretion in vitro: potential clinical implications. Advances in Experimental and Medical Biology 245, 167181.CrossRefGoogle ScholarPubMed
Carroll, B. J. (1980). Clinical application of neuroendocrine research in depression. In Handbook of Biological Psychiatry, Part III. Brain Mechanisms and Abnormal Behavior-Genetics and Neuroendocrinology. (ed. van Praag, M. H., Lader, M. H., Rafaelsen, O. J. and Sachar, E. J.), pp. 179194. Marcel Dekker: New York.Google Scholar
Carroll, B. J., Curtis, G. C. & Mendels, J. (1976). Neuroendocrine regulation in depression; II: discrimination of depressed from nondepressed patients. Archives of General Psychiatry 33, 10511058.CrossRefGoogle ScholarPubMed
Carroll, B. J., Feinberg, M. & Greden, J. F. et al. (1981). A specific laboratory test for the diagnosis of melancholia: standardization, validation, and clinical utility. Archives of General Psychiatry 38, 1522.CrossRefGoogle ScholarPubMed
Coates, P. J., McNicol, A. M., Donaich, I. & Rees, L. H. (1988). Increased production of alpha-melanocyte-stimulating hormone in the pituitary gland of patients with untreated Addison's disease. Clinical Endocrinology 29, 421426.CrossRefGoogle ScholarPubMed
De-Souza, E. & Van Loon, G. R. (1984). Corticotropin releasing factor increases the adrenocortical responsiveness to adrenocorticotropin. Experientia 40, 10041006.CrossRefGoogle ScholarPubMed
Dillon, W. R. & Goldstein, M. (1984). Linear Structural Relations (Lisrel) in Multivariate Analyses: Methods and Applications, pp. 430489. John Wiley and Sons: New York.Google Scholar
Drouin, J., Charron, J., Gagner, J. P., Jeannotte, L., Nemer, M., Plante, R. K. & Wrange, O. (1987). Pro-opiomelanocortin gene: a model for negative regulation of transcription by glucocorticoids. Journal of Cell Biochemistry 35, 293304.CrossRefGoogle ScholarPubMed
Eberwine, J. H., Jonassen, J. A., Evinger, M. J. & Roberts, J. L. (1987). Complex transcriptional regulation by glucocorticoids and corticotropin-releasing hormone of proopiomelanocortin gene expression in rat pituitary cultures. DNA 6, 483492.CrossRefGoogle ScholarPubMed
Familari, M. & Funder, J. W. (1989). Isolated pituitary cells: glucocorticoids do not rapidly suppress ACTH secretion in response to CRF. American Journal of Physiology 256, 145151.Google Scholar
Fehm, H. L., Holl, R., Spath-Schwalbe, E., Born, J. & Voigt, K. H. (1988). Ability of corticotropin releasing hormone to stimulate cortisol secretion independent from pituitary adrenocorticotropin. Life Science 42, 679686.CrossRefGoogle ScholarPubMed
Feinberg, M. & Carroll, B. J. (1984) Biological ‘markers’ for endogenous depression: effects of age, severity of illness, weight loss and polarity. Archives of General Psychiatry 41, 10801085.CrossRefGoogle ScholarPubMed
Gold, P. W., Loriaux, D. L., Roy, A., Kling, M. A., Calabrese, J. R., Kellner, C. H., Nieman, L. K., Post, R. M., Pickar, D., Gallucci, W., Avgerinos, P., Paul, S., Oldfied, E. H., Cutler, G. B. Jr. & Chrousos, G. P. (1986). Responses to corticotropin-releasing hormone in the hypercortisolism of depression and Cushing's disease. New England Journal of Medicine 314, 13291335.CrossRefGoogle ScholarPubMed
Gold, P. W., Kling, M. A., Khan, I., Calabrese, J. R., Kalogeras, K., Post, R. M., Avgerinos, P. C., Loriaux, D. L. & Chrousos, G. P. (1987). Corticotropin releasing hormone: relevance to normal physiology and to the pathophysiology and differential diagnosis of hypercortisolism and adrenal insufficiency. In Hypothalamic Dysfunction in Neuropsychiatric Disorders (ed. Nerozzi, D., Goodwin, F. K. and Costa, E.), pp. 183200. Raven Press: New York.Google Scholar
Gold, P. W., Kling, M. A., Demitrack, M. A., Whitfield, H., Kalogeras, K., Loriaux, D. L. & Chrousos, G. P. (1988 a). Clinical studies with corticotropin releasing hormone: implications for hypothalamic–pituitary–adrenal dysfunction in depression and related disorders. In Current Topics in Neuroendocrinology: Neuroendocrinology of Mood (ed. Ganten, D. and Pfaff, D.), pp. 5578. Springer-Verlag: New York.CrossRefGoogle Scholar
Gold, P. W., Whitfield, H. J., Kling, M. A., Demitrack, M. A., Brandt, H. A. & Chrousos, G. P. (1988 b). The relevance of corticotropin releasing hormone to normal physiology and to pathophysiologic alterations in hypothalamic–pituitary–adrenal–function. In The Hypothalamic–Pituitary–Adrenal–Axis: Physiology Pathophysiology, and Psychiatric Implications (ed. Schatzberg, A. F. and Nemeroff, C. B.), pp. 101114. Raven Press: New York.Google Scholar
Grossman, A. B., Howlett, T. A., Perry, L., Coy, D. H., Savage, M. O., Lavender, P., Rees, L. H. & Besser, G. M. (1988). CRF in the differential diagnosis of Cushing's syndrome: a comparison with the dexamethasone suppression test. Clinical Endocrinology Oxford 29, 167178.CrossRefGoogle ScholarPubMed
Ham, J. & Smyth, D. G. (1986). Chronic stimulation of anterior pituitary cell cultures with CRF leads to the secretion of lipotropin. Neuroendocrinology 44, 433438.CrossRefGoogle Scholar
Hamilton, M. (1960). A rating scale for depression. Journal of Neurological and Neurosurgical Psychiatry 23, 5661.CrossRefGoogle ScholarPubMed
Henville, K. L., Hinson, J. P., Vinson, G. P. & Laird, S. M. (1989). Actions of desacetyl-alpha-melanocyte-stimulating hormone on human adrenocortical cells. Journal of Endocrinology 121, 579583.CrossRefGoogle ScholarPubMed
Hermus, A. R., Pieters, G. F., Pesman, G. J., Smals, A. G., Benraad, T. J. & Kloppenberg, P. W. (1986 a). Responsivity of adrenocorticotropin to corticotropin-releasing hormone and lack of suppressibility by dexamethasone are related phenomena in Cushing's disease. Journal of Clinical Endocrinology and Metabolism 62, 634639.CrossRefGoogle ScholarPubMed
Hermus, A. R., Pieters, G. F., Pesman, G. J., Smals, A. G., Benraad, T. J. & Kloppenberg, P. W. (1986 b). The corticotropin-releasing-hormone test versus the high-dose dexamethasone test in the differential diagnosis of Cushing's syndrome. Lancet ii, 540544.CrossRefGoogle Scholar
Holsboer, F., Doerr, H. G., Gerken, A., Muller, O. A. & Sippell, W. G. (1984 a). Cortisol, 11-deoxycortisol, and ACTH concentrations after dexamethasone in depressed patients and healthy volunteers. Psychiatry Research 17, 1523.CrossRefGoogle Scholar
Holsboer, F., Muller, O. A., Doerr, H. G., Sippell, W. G., Stalla, G. K., Gerken, A., Steiger, A., Boll, E. & Benkert, O. (1984 b). ACTH and multisteroid responses to corticotropin-releasing factor in depressive illness: relationship to multisteroid responses after ACTH stimulation and dexamethasone suppression. Psychoneuroendocrinology 9, 147160.CrossRefGoogle ScholarPubMed
Holsboer, F., von Bardeleben, U., Heuser, I. & Steiger, A. (1988). Human corticotropin-releasing hormone challenge tests in depression. In The Hypothalamic–Pituitary–Adrenal–Axis: Physiology, Pathophysiology, and Psychiatric Implications (ed. Schatzberg, A. F. and Nemeroff, C. B.), pp. 79100. Raven Press: New York.Google Scholar
Jackson, R. V., DeCherney, G. S., DeBold, C. R., Sheldon, W. R., Alexander, A. N., Rivier, J., Vale, W. & Orth, D. N. (1984). Synthetic ovine corticotropin-releasing hormone: simultaneous release of proopiolipomelanocortin peptides in man. Journal of Clinical Endocrinology and Metabolism 58, 740743.CrossRefGoogle ScholarPubMed
Jingami, H., Matsukura, S., Numa, S. & Tmura, H. (1985). Effects of adrenalectomy and dexamethasone administration on the level of pre-pro-corticotropin-releasing factor messenger ribonucleic acid (mRNA) in the hypothalamus and adrenocorticotropin/β-lipotropin precursor mRNA in the pituitary in rats. Endocrinology 117, 13141320.CrossRefGoogle ScholarPubMed
Lesch, K.-P., Laux, G., Schulte, H. M., Pfuller, H. & Beckmann, H. (1988). Corticotropin and cortisol response to human CRH as a probe for HPA system integrity in major depressive disorder. Psychiatry Research 24, 2534.CrossRefGoogle ScholarPubMed
Liposits, Z., Uht, R. M., Harrison, R. W., Gibbs, F. P., Paull, W. K. & Bohn, M. C. (1987). Ultrastructural localization of glucocorticoid receptor (GR) in hypothalamic paraventricular neurons synthesizing corticotropin releasing factor (CRF). Histochemistry 87, 407412.CrossRefGoogle ScholarPubMed
Lowy, M. T., Gormley, G. J., Reder, A. T., Hospelhorn, V. D., Antel, J. P. & Meltzer, H. Y. (1987). Glucocorticoid receptor function in depression. In Hormones and Depression (ed. Halbreich, U.). Raven Press: New York.Google Scholar
McLoughlin, L., Tomlin, S., Grossman, A., Lytras, N., Schally, A. V., Coy, D., Besser, G. M. & Rees, L. H. (1984). CRH-41 stimulates the release of β-lipotrophin and β-endorphin in normal human subjects. Neuroendocrinology 38, 282284.CrossRefGoogle Scholar
Maes, M., De Ruyter, M., Hobin, P. & Suy, E. (1986). The dexamethasone suppression test, the Hamilton depression rating scale and the DSM-III depressive categories. Journal of Affective Disorders 10, 207214.CrossRefGoogle ScholarPubMed
Maes, M., De Ruyter, M. & Suy, E. (1989). Use of the dexamethasone suppression test in an inpatient setting: a replication and new findings. Psychoneuroendocrinology 14, 231240.CrossRefGoogle Scholar
Maes, M., Cosyns, P., Maes, L., D'Hondt, P. & Schotte, C. (1990 a). Clinical subtypes of unipolar depression, part I: a validation of the vital and non-vital clusters. Psychiatry Research 34, 2941.CrossRefGoogle Scholar
Maes, M., Jacobs, M.-P., Suy, E., Leclercq, C., Christiaens, F. & Raus, J. (1990 b). An augmented escape of β-endorphins to suppression by dexamethasone in severely depressed patients. Journal of Affective Disorders 18, 149156.CrossRefGoogle ScholarPubMed
Maes, M., Minner, B. & Suy, E. (1990 c). Prediction of the DST results in depression by means of free urinary cortisol, availability of desamethasone, age and diagnostic classification. Biological Psychiatry 28, 349357.CrossRefGoogle Scholar
Maes, M., Vandewoude, M., Schotte, C., Maes, L., Martin, M. & Blockx, P. (1990 d). A revised interpretation of the postdexamethasone ACTH and cortisol values in unipolar depressed females. Psychiatry Research 34, 107126.CrossRefGoogle ScholarPubMed
Maes, M., Vandervorst, C., Suy, E., Minner, B. & Raus, J. (1990 e). A multivariate study on the simultaneous urinary free cortisol, plasma cortisol, adrenocorticotropic hormone and β-endorphin escape from suppression by dexamethasone in depressed patients. Acta Psychiatrica Scandinavica 83, 480491.CrossRefGoogle Scholar
Martin, J. B. & Reichlin, S. (1987). Regulation of adrenocorticotrophic hormone (ACTH) secretion and its disorders. In Clinical Neuroendocrinology (ed. Martin, J. B. and Reichlin, S.), pp. 159231. G. A. Davis Company: Philadelphia.Google Scholar
Mossman, D. & Somoza, E. (1989). Assessing improvements in the dexamethasone suppression test using receiver operating characteristic analysis. Biological Psychiatry 25, 159173.CrossRefGoogle Scholar
Muller, O. A., Dorr, H. G., Hagen, B., Stalla, G. K. & v. Werder, K. (1982). Corticotropin releasing factor (CRF)-stimulation test in normal controls and patients with disturbances of the hypo-thalamic pituitary–adrenal–axis. Klinische Wochenschrift 60, 14851491.CrossRefGoogle Scholar
Muller, O. A., Hartwimmer, J., Hauer, A., Kaliebe, T., Schopohl, J., Stalla, G. K. & von Werder, K. (1986). Corticotropin-releasing factor (CRF): stimulation in normal controls and in patients with Cushing's syndrome. Psychoneuroendocrinology 11, 4960.CrossRefGoogle ScholarPubMed
Nemeroff, C. B., Widerlow, E., Bissette, G., Walleus, H., Karlsson, I., Eklund, K., Kiets, C. D., Loosen, P. T. & Vale, W. (1984). Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 266, 13421344.CrossRefGoogle Scholar
Nerozzi, D., Bersani, G., Melia, E., Magnani, A., Antonozzi, I. & Frajese, G. (1988). Corticotropin-releasing factor and adrenal function in major depression. Journal of Endocrinology Investigation 11, 697701.CrossRefGoogle ScholarPubMed
Nieman, L. K., Chrousos, G. P., Oldfield, E. H., Avgerinos, P. C., Cutler, G. B. & Loriaux, D. L. (1986). The ovine corticotropin-releasing hormone stimulation test and the dexamethasone suppression test in the differential diagnosis of Cushing's syndrome. Annals of Internal Medicine 105, 862867.CrossRefGoogle ScholarPubMed
Oelkers, W., Boelke, T. & Bahr, V. (1988). Dose-response relationships between plasma adrenocorticotropin (ACTH), cortisol, aldosterone, and 18-hydroxycorticosterone after injection of ACTH-(1–39) or human corticotropin-releasing hormone in man. Journal of Clinical Endocrinology and Metabolism 66, 181186.CrossRefGoogle ScholarPubMed
Ohashi, M., Fujio, N., Kato, K., Nawata, H. & Ibayashi, H. (1986). Aging is without effect on the pituitary-adrenal axis in men. Gerontology 32, 335339.CrossRefGoogle ScholarPubMed
Orth, D. N., Jackson, R. V., DeCherney, G. S., DeBold, C. R., Alexander, A. N., Island, D. P., Rivier, J. (1983). Effect of synthetic ovine corticotropin-releasing factor: dose response of plasma adrenocorticotropin and cortisol. Journal of Clinical Investigation 71, 587595.CrossRefGoogle ScholarPubMed
Owens, M. J. & Nemeroff, C. B. (1988). The neurobiology of corticotropin-releasing factor: implications for affective disorders. In The Hypothalamic–Pituitary–Adrenal-Axis: Physiology, Pathophysiology, and Psychiatric Implications (ed. Schatzberg, A. F. and Nemeroff, C. B.), pp. 136. Raven Press: New York.Google Scholar
Pavlov, E. P., Harman, S. M., Chrousos, G. P., Loriaux, D. L. & Blackman, M. R. (1986). Responses of plasma adrenocorticotropin, cortisol, and dehydroepiandrosterone to ovine corticotropin-releasing hormone in healthy aging man. Journal of Clinical Endocrinology and Metabolism 62, 767772.CrossRefGoogle Scholar
Reisine, T. & Affotter, H. U. (1987). Hormone receptor regulated proopiomelanocortin gene expression. Biochemical Pharmacology 36, 191195.CrossRefGoogle ScholarPubMed
Rivier, C., Brownstein, M., Spiess, J., Rivier, J. & Vale, W. (1982). In vivo corticotropin-releasing factor-induced secretion of adrenocorticotropin, β-endorphin, and corticosterone. Endocrinology 110, 272278.CrossRefGoogle ScholarPubMed
Roy, A., Pickar, D., Paul, S., Doran, A., Chrousos, G. P. & Gold, P. W. (1987). CSF corticotropin-releasing hormone in depressed patients and normal subjects. American Journal of Psychiatry 144, 641645.Google Scholar
Rupprecht, R., Lesch, K. P., Muller, U., Beck, G., Beckmann, H. & Schulte, H. M. (1989). Blunted adrenocorticotropin but normal β-endorphin release after human corticotropin-releasing hormone administration in depression. Journal of Clinical Endocrinology and Metabolism 69, 600603.CrossRefGoogle ScholarPubMed
Sapolsky, R. M. & McEwen, B. S. (1988). Why dexamethasone resistance? Two possible Neuroendocrine Mechanisms. In The Hypothalamic–Pituitary–Adrenal Axis (ed. Schatzberg, A. F. and Nemeroff, C. B.), pp. 155169. Raven Press: New York.Google Scholar
Sato, S. M. & Mains, R. E. (1986). Regulation of adrenocorticotropin-endorphin-related peptide secretion in neonatal rat pituitary cultures. Endocrinology 119, 793801.CrossRefGoogle ScholarPubMed
Schopohl, J., Hauer, A., Kaliebe, T., Stalla, G. K., von Werder, K. & Muller, O. A. (1986). Repetitive and continuous administration of human corticotropin releasing factor to human subjects. Acta Endocrinologica Copenhagen 112, 157165.Google ScholarPubMed
Schurmeyer, T. H., Schulte, H. M., Avgerinos, P. C., Tomai, T. P., Loriaux, D. L., Gold, P. W. & Chrousos, G. P. (1987). Pharmacology of ovine and human CRH. Hormone Metabolism Research, Supplementum 16, 2430.Google Scholar
Spitzer, R. L., Williams, J. B. W. & Gibbon, M. (1985). Structured Clinical Interview for DSM-III Patient Version. Biometrics Research Department: New York.Google Scholar
Stalla, G. K., Hartwimmer, J., Schopohl, J., von Werder, K. & Muller, O. A. (1986 a). Intravenous application of ovine and human corticotropin releasing factor (CRF): ACTH, cortisol and CRF levels. Neuroendocrinology 42, 15.CrossRefGoogle ScholarPubMed
Stalla, G. K., Stalla, J., Schopohl, J., von Werder, K. & Muller, O. A. (1986 b). Corticotropin-releasing factor in humans. 1. CRF stimulation in normals and CRF radioimmunoassay. Hormone Research 24, 229245.CrossRefGoogle Scholar
Stangl, D., Pfohl, B., Zimmerman, M., Coryell, W. & Corenthal, C. (1986). The relationship between age and post-dexamethasone cortisol: test of three hypotheses. Journal of Affective Disorders 11, 185197.CrossRefGoogle ScholarPubMed
Stokes, P. E., Stoll, P. M., Koslow, S. H., Maas, J. W., Davis, J. M., Swann, A. C. & Robins, E. (1984). Pretreatment DST and Hypothalamic–pituitary–adrenocortical function in depressed patients and comparison groups. Archives of General Psychiatry 41, 257267.CrossRefGoogle ScholarPubMed
Tsukada, T., Nakai, Y., Koh, T., Tsujii, S. & Imura, H. (1983). Plasma adrenocorticotropin and cortisol responses to intravenous injection of corticotropin-releasing factor in the morning and evening. Journal of Clinical Endocrinology and Metabolism 57, 869871.CrossRefGoogle ScholarPubMed
Vale, W., Spiess, J., Rivier, C. & Rivier, J. (1981). Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and β-endorphins. Science 213, 13941397.CrossRefGoogle Scholar
Vale, W., Vaughan, J., Smith, M., Yamamoto, G., Rivier, J. & Rivier, C. (1983). Effects of synthetic ovine corticotropin-releasing factor, glucocorticoids, catecholamines, neurohypophysial peptides, and other substances on cultured corticotropic cells. Endocrinology 113, 11211131.CrossRefGoogle ScholarPubMed
Young, E. A., Lewis, J. & Akil, H. (1986). The preferential release of β-endorphin from the anterior pituitary lobe by corticotropin releasing factor (CRF). Peptides 7, 603607.CrossRefGoogle ScholarPubMed