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Hypothalamo-pituitary-adrenal axis abnormalities in depression: a review and a model

Published online by Cambridge University Press:  09 July 2009

Bruce G. Charlton  and
I. Nicol Ferrier
Bruce G. Charlton*
Affiliation:
Department of Physiological Sciences, University of Newcastle upon Tyne, and MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne
I. Nicol Ferrier
Affiliation:
Department of Physiological Sciences, University of Newcastle upon Tyne, and MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne
*
1Address for correspondence: Dr Bruce G. Charlton. Department of Physiological Sciences, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne NE2 4HH.
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Synopsis

A wide range of abnormalities of the hypothalamo-pituitary-adrenal (HPA) axis has been described in depression. This paper reviews recent advances in the understanding of this system, and draws them together to construct a model for the purposes of further research and discussion. It is proposed that there are two fundamental changes which both originate in the hypothalamus: an increased secretion of corticotropin-releasing hormone, and a neurally mediated adrenal hyper-responsivity to ACTH. The resulting changes in hormone regulation would be expected to produce all the characteristic HPA axis abnormalities commonly seen in depression. The model makes several predictions which could be tested by future experiment.

Type
Research Article
Information
Psychological Medicine , Volume 19 , Issue 2 , May 1989 , pp. 331 - 336
Copyright
Copyright © Cambridge University Press 1989

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References

Al-Dujail, E. A. S., Hope, J., Estivariz, F. E., Lowry, P J & Edwards, C R W. (1981). Circulating human pituitary progamma- melanotropin enhances the adrenal response to ACTH, Nature 291, 156–158 CrossRefGoogle Scholar
Amsterdam, J. D., Winokur, A., Abelman, E., Lucki, I & Rickel, K. (1983). Cosynotropin (ACTH 1–24) stimulation test in depressed patients and healthy subjects American Journal of Psychiatry 140, 907–909.Google Scholar
Amsterdam, J. D., Marinelli, D. L., Arger, P. & Winokur, A. (1987). Assessment of adrenal gland volume by computed tomography in depressed patients and healthy volunteers: a pilot study. Psychiatry Research 21. 189–197 CrossRefGoogle ScholarPubMed
Arana, G. W., Baldessarini, R. J. & Ornsteen, M. (1985). The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Archives of General Psychiatry 42, 1193–1204.CrossRefGoogle Scholar
Ball, R., Howlelt, T., Silverstone, T. & Rees, L. (1987). The interrelationship of beta-endorphin, ACTH and cortisol in depressive illness: a controlled study. Psychological Medicine 17, 31–37.CrossRefGoogle ScholarPubMed
Banki, C. M., Bisette, G., Arato, M., O'Connor, L. & Nemeroff, C. B. (1987) CSF corticotropin-releasing factor-like immunoreactivity in depression and schizophrenia American Journal of Psychiatry 144, 873–877.Google Scholar
Berieter, D. A., Plolsky, P. M. & Gann, D. S. (1982). Tooth pulp stimulation stimulates the adrenocorticotropin response to haemorrhage in cats. Endocrinology III, 907–909.Google Scholar
Bissette, G., Reynolds, G. P., Kilts, C. D., Widerlov, E. & Nemeroff, C. B. (1985). Corticotropin-releasing factor-like immunoreactivity in senile dementia of the Alzheimer type Journal of the American Medical Association 254, 3067–3069.CrossRefGoogle ScholarPubMed
Braddock, L. (1986). The dexamethasone suppression test: fact and artefact. British Journal of Psychiatry 148. 363–374.CrossRefGoogle ScholarPubMed
Brambilla, F., Genazzani, A. R., Facchinetti, F., Parrini, D., Petraglia, F., Sacchetti, E., Scarone, S., Gnastalla, A. & D'Antona, N. (1981). β-endorphin and β-lipotrophin plasma levels in chronic schizophrenia, primary affective disorders and secondary effective disorders. Psychoneuroendocrinology 6, 321–330.CrossRefGoogle Scholar
Butler, P. W. P. & Besser, G.M (1968). Pituitary-adrenal function in severe depressive illness. Lancet i, 1234–1236.CrossRefGoogle Scholar
Carroll, B. J. (1976). Limbic system-adrenal cortex regulation in depression and schizophrenia. Psychosomatic Medicine 38, 106–121.CrossRefGoogle Scholar
Carroll, B. J., Curtis, G. C. & Mendels, J (1976 a). Cerebrospinal fluid and plasma free cortisol concentrations in depression. Psychological Medicine 6, 235–244.CrossRefGoogle ScholarPubMed
Carroll, B. J., Curtis, G. C. & Mendels, J. (1976 b). Neuroendocrine regulation in depression: discrimination of depressed from nondepressed patients. Archives of General Psychiatry 33, 1051–1058.CrossRefGoogle ScholarPubMed
Carroll, B. J., Feinberg, M., Greden, F. J., Tarika, J., Albala, A. A., Haskett, R. F., James, N M, Kronfol, Z., Lohr. Steiner, M., Vigne, J. P. D & Young, E. (1981). A specific laboratory test for the diagnosis of melancholia Archives of General Psychiatry 38, 15–22.CrossRefGoogle Scholar
Charlton, B. G., Leake, A., Ferrier, I. N., Linton, E. A. & Lowry, P. J. (1986). Corticotropin-releasing factor in plasma of depressed patients and controls. Lancet i, 161–162.CrossRefGoogle Scholar
Charlton, B. G., Ferrier, I. N. & Perry, R. H. (1987 a). Distribution of corticotropin-releasing factor-like immunoreactivity in human brain. Neuropeptides 10, 329–334.CrossRefGoogle ScholarPubMed
Charlton, B. G., Leake, A., Wright, C., Griffiths, H. W. & Ferrier, I. N. (1987 b). A combined study of cortisol, ACTH and dexamethasone concentrations in major depression: multiple timepoint sampling. British Journal of Psychiatry 150, 791–796 CrossRefGoogle Scholar
Charlton, B. G., Cheetham, S.C., Horton, R.W, Katona, C. L. E., Crompton, M R & Ferrier, I. N. (1988 a). Corticotropin-releasing factor immunoreactivity in post-mortem brain from depressed suicides. Journal of Psychopharmacology 2, 13–18.CrossRefGoogle ScholarPubMed
Charton, B. G., Ferrier, I. N., Leake, A., Edwardson, J. A., Eccleston, D., Crowcombe, K., Jackson, S., McLean, C. & Lowry, P. J. (1988 b). A multiple timepoint study of N-terminal proopiomelanocortin in depression using a two-site recognition immunoradiometric assay. Clinical Endocrinology 28, 165–172.CrossRefGoogle Scholar
Cohen, M. R., Pickar, D., Extein, I, Gold, M S. & Sweeney, D. R. (1984). Plasma cortisol and B-endorphin immunoreactivity in nonmajor and major depression. American Journal of Psychiatry 141, 628–632.Google ScholarPubMed
Dallman, M. F., Engeland, W. C. & McBride, M. H. (1977). The neural regulation of compensatory adrenal growth. In ACTH and Related Peptides: Structure, Regulation and Action (ed. Krieger, D. T. and Ganong, W. F.), pp. 373–392. New York Academy of Sciences: New York.Google Scholar
Dorovini-Zis, K. & Zis, A. P. (1987) Increased adrenal weight in victims of violent suicide. American Journal of Psychiatry 144, 1214–1215.Google ScholarPubMed
Feibel, J., Kelly, M, Lee, L & Woolf, P. (1983). Loss of adrenocortical suppression after acute brain injury Journal of Clinical Endocrinology and Metabolism 57, 1245–1250.CrossRefGoogle ScholarPubMed
Ferrier, I. N., Pascual, J Charlton, B.G, Wright, C, Leake, A., Griffiths, H. W., Fairbairn, A. F. & Edwardson, J. A. (1988). Cortisol, ACTH and dexamethasone concentrations in a psychogeriatric population. Biological Psychiatry 23, 252–260.Google Scholar
Gann, D. S. (1979). Cortisol secretion after haemorrhage. Nephron 23, 119–124.CrossRefGoogle Scholar
Gillies, G & Grossman, A. (1985). The CRFs and their control: chemistry, physiology and clinical implications. Clinics and Endocrinology and Metabolism 14, 821–843.CrossRefGoogle ScholarPubMed
Gold, P. W., Crousos, G. P., Kellner, C, Post, R., Roy, A., Augerinos, P., Schulte, H., Oldfield, E. & Lynn Loriaux, D. (1984) Psychiatric implications of basic and clinical studies with corticotropin- releasing factor. American Journal of Psychiatry 141, 619–627.Google ScholarPubMed
Hall, R., Anderson, J., Smart, G A. & Besser, M. (1981). Fundamentals of Clinical Endocrinology Pitman: Glasgow.Google Scholar
Hodgkinson, S C, Allolio, B., Landon, J. & Lowry, P. J. (1984). Development of a non-extracted two-site immunoradiometric assay for corticotropin utilising extreme amino and carboxy terminally directed antibodies. Biochemistry Journal 218, 703–711.CrossRefGoogle Scholar
Holsboer, F., Gerken, A., Von Bradelbeau, U., Grimm, W., Beyer, H., Muller, O. A. & Stalla, G. K. (1986). Human corticotropinreleasing hormone in depression correlation with thyrotropin secretion following thyrotropin-releasing hormone. Biological Psychiatry 21, 601–611.CrossRefGoogle Scholar
Jaeckle, R S., Kathol, R. G., Lopez, J.F, Meller, W. H. & Krummel, S. J. (1987) Enhanced adrenal sensitivity to exogenous cosynotropin (ACTH 1–24) stimulation in major depression. Archives of General Psychiatry 44, 233–240.CrossRefGoogle ScholarPubMed
Kalin, N. H., Weiler, S J & Sheldon, S. E. (1982). Plasma ACTH and cortisol concentration before and after dexamethasone. Psychiatry Research 7, 87–92.CrossRefGoogle Scholar
Krieger, D. T. (1979 a). Rhythms in CRF, ACTH and corticosteroids. In Comprehensive Endocrinology Endocrine Rhythms (ed. Krieger, D. T.), pp 123–142. Raven Press: New York.Google Scholar
Krieger, D. T. (1979 b). Plasma ACTH and corticosteroids. In Endocrinology, (ed. Degroot, L. J.), pp. 1139–1156. Grune and Stratton: New York.Google Scholar
Lightman, S. L. & Young, W S. III, (1988). Corticotrophin-releasing factor, vasopressin and pro-opiomelanocortin mRNA responses to stress and opiates in the rat. Journal of Physiology 403, 511–523.CrossRefGoogle ScholarPubMed
Linkowski, P., Mendlewicz, J., Leclerq, R., Brasseur, M., Mubain, P., Golstein, J., Copinschi, G. & Cauter, E. V. (1985) The 24 hour profile of adrenocorticotropin and cortisol on major depressive illness. Journal of Clinical Endocrinology and Metabolism 61, 429–438.CrossRefGoogle ScholarPubMed
Lowry, P.J (1984). Pro-opiocortin: the multiple adrenal hormone precursor. Bioscience Reports 4, 467–482.CrossRefGoogle ScholarPubMed
Lowry, P.J, Silas, L., Maclean, C., Linton, E. A. & Estivariz, F.E (1983) Pro-gamma-melanocyte stimulating hormone cleavage in adrenal gland undergoing compensatory growth. Nature 306, 70–73.CrossRefGoogle Scholar
Matthews, J, Akil, H., Greden, J. & Watson, S. (1982). Plasma measures of β-endorphin-like immunoreactivity in depressives and other psychiatric subjects. Life Sciences 31, 1867–1870.CrossRefGoogle Scholar
Nemeroff, C. B., Widerlov, E., Bisette, G., Wallens, H., Karlsson, I., Eklund, K., Kilts, C D., Lossen, P T & Vale, W. W. (1984). Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 226, 1342–1344.CrossRefGoogle ScholarPubMed
Nemeroff, C. B., Owens, M. J., Bisette, G., Andorn, A. C. & Stanley, M (1988). Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims. Archives of General Psychiatry 45, 577–579.CrossRefGoogle ScholarPubMed
Pedersen, R.C, Brownie, A. C. & Ling, N. (1980). Pro-adrenocorticotropin endorphin-derived peptides. Science 208, 1044–1045.CrossRefGoogle ScholarPubMed
Reus, V. I., Marshall, J. & Dallman, M (1983). Regulation of ACTH and cortisol in depression. Peptides 4, 786–788.CrossRefGoogle ScholarPubMed
Roy, A., Gold, P. W., Pickard, D., Wolkouritz, O. M., Chrousos, G. & Paul, S. M. (1986). Pre- and post- dexamethasone ACTH levels in depressed patients and normal controls. Journal of Affective Disorders 10, 95–99.CrossRefGoogle ScholarPubMed
Rubin, R. T. (1985). The prospects for clinical psychoneuroendocrinology: has the curtain been drawn across the neuroendocrine window? Psychological Medicine 15, 451–454.CrossRefGoogle ScholarPubMed
Sachar, E. J., Hellman, M. D., Roffwarg, H. P., Halpern, F. S., Fukushima, D. H. & Gallagher, T F (1973). Disrupted 24-hour patterns of cortisol secretion in psychotic depression. Archives of General Psychiatry 28, 19–24.CrossRefGoogle ScholarPubMed
Schoneshofer, M., Feuner, A. & Molnar, I. (1981). Heterogeneity of corticotrophin-immunoreactive compounds in human body fluids. Clinical Chemistry 27, 1875–1877 CrossRefGoogle ScholarPubMed
Yerevanian, B. G. & Wolf, P. D. (1983). Plasma ACTH levels in primary depression. Psychiatry Research 9, 45–51.CrossRefGoogle ScholarPubMed