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Clinical and Magnetic Resonance Imaging Correlates of Hypothalamic–Pituitary–Adrenal Axis Function in Depression and Alzheimer's Disease

Published online by Cambridge University Press:  02 January 2018

John T. O'Brien*
Affiliation:
Newcastle General Hospital
David Ames
Affiliation:
Department of Psychiatry, Royal Melbourne Hospital
Isaac Schweitzer
Affiliation:
Department of Psychiatry, Royal Melbourne Hospital
Peter Colman
Affiliation:
Department of Diabetes and Endocrinology, Royal Melbourne Hospital
Patricia Desmond
Affiliation:
Department of Radiology, University of Melbourne, Royal Melbourne Hospital, Victoria 3050 Australia
Brian Tress
Affiliation:
Department of Radiology, University of Melbourne, Royal Melbourne Hospital, Victoria 3050 Australia
*
Dr John T. O'Brien, Brighton Clinic, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE. Fax: 0191 272 0816

Abstract

Background

An age-related dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis is well recognised in animals, but still remains controversial in humans. There is increasing interest that raised corticosteroid levels, due to activation of the HPA axis, may cause both depressive symptoms and cognitive impairments. Steroid effects on cognition may be via the hippocampus, a major site of corticosteroid action and an important structure involved in learning and memory.

Method

To investigate this further, we examined the relationship between the dexamethasone suppression test, cognitive function, depressive symptoms and hippocampal atrophy on magnetic resonance imaging (MRI) in 32 normal controls, 49 subjects with NINCDS/ADRDA Alzheimer's disease and 51 patients with DSM–III–R Major Depression.

Results

Controlling for differences in dexamethasone concentrations, post-dexamethasone cortisol levels were related to advancing age in controls and depressed subjects. However, among subjects with Alzheimer's disease, post-dexamethasone cortisol levels were independently associated with both minor depressive symptoms and hippocampal atrophy on MRI.

Conclusion

An association between advancing age and increased HPA axis dysregulation is supported for controls and depressed subjects. In Alzheimer's disease, HPA axis changes were associated with depressive symptoms and hippocampal atrophy. Longitudinal studies are now needed to determine the causal direction of these associations.

Type
Papers
Copyright
Copyright © 1996 The Royal College of Psychiatrists 

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Footnotes

This paper is based on a dissertation submitted by Dr John O'Brien which was awarded the 1995 Research Prize and Bronze Medal by the Royal College of Psychiatrists.

References

American Psychiatric Association Task Force (1987) The dexamethasone suppression test: an overview of its current status in psychiatry. American Journal of Psychiatry, 144, 12531262.CrossRefGoogle Scholar
Axelson, D. A., Doraiswamy, P. M., McDonald, W. M., et al (1993) Hypercortisolaemia and hippocampal changes in depression. Psychiatry Research, 47, 163173.CrossRefGoogle Scholar
Caine, E. D., Yerevanian, B. I. & Bamford, K. A. (1984) Cognitive function and the dexamethasone suppression test in depression. American Journal of Psychiatry, 141, 116118.Google ScholarPubMed
Carroll, B. J., Feinberg, M., Greden, J. F., et al (1981) A specific laboratory test for the diagnosis of melancholia. Archives of General Psychiatry, 38, 1522.Google Scholar
Checkley, S. (1992) Neuroendocrine mechanisms and the precipitation of depression by life events. British Journal of Psychiatry, 160 (Suppl. 15), 717.Google Scholar
Cicchetti, D. V. (1976) Assessing inter-rater reliability for rating scales: resolving some basic issues. British Journal of Psychiatry, 129, 452456.CrossRefGoogle ScholarPubMed
De Leon, M. J., McRae, T., Tsai, J. R., et al (1988) Abnormal cortisol response in Alzheimer's disease linked to hippocampal atrophy. Lancet, ii, 391392.Google Scholar
Dinan, T. G. (1994) Glucorticoids and the genesis of depressive illness. British Journal of Psychiatry, 164, 365371.Google Scholar
Ferrier, I. N., Pascual, J., Charlton, B. G., et al (1988) Cortisol, ACTH, and dexamethasone concentrations in a psychogeriatric population. Biological Psychiatry, 23, 252260.Google Scholar
Hamilton, M. (1967) Development of a rating scale for primary depressive illness. British Journal of Social A Clinical Psychology, 6, 278296.CrossRefGoogle ScholarPubMed
Hunt, G. E., O'Sullivan, B. T., Johnson, G. F., et al (1991) Effect of high plasma dexamethasone levels on DST sensitivity: dose-response study in depressed patients and controls. Psychiatric Research, 36, 209222.Google Scholar
Jacobson, L. & Sapolsky, R. (1991) The role of the hippocampus in feedback regulation of the hypothalamic–pituitary–adreno-cortical axis. Endocrine Reviews, 12, 118134.Google Scholar
Katona, C. L. E. & Aldridge, C. R. (1985) The dexamethasone suppression test and depressive signs in dementia. Journal of Affective Disorders, 8, 8389.CrossRefGoogle ScholarPubMed
Keitner, G. I., Ryan, C. E., Kohn, R., et al (1992) Age and the dexamethasone suppression test: results from a broad unselected patient population. Psychiatry Research, 44, 920.Google Scholar
McAllister, T. W. & Hays, L. R. (1987) TRH test, DST, and response to desipramine in primary degenerative dementia. Biological Psychiatry, 22, 189193.Google Scholar
McKeith, I. (1984) Clinical use of the DST in a psychogeriatric population. British Journal of Psychiatry, 145, 389393.CrossRefGoogle Scholar
McKhann, G., Drachman, D., Folstein, M., et al (1984) Clinical diagnosis of Alzheimer's Disease: report of the NINCDS-ADRDA work group under the auspices of the Dept of Health and Human Task Force in Alzheimer's Disease. Neurology, 34, 939944.Google Scholar
Maguire, K. P., Tuckwell, V. M., Schweitzer, I., et al (1990) Dexamethasone kinetics in depressed patients before and after clinical response. Psychoneuroendocrinology, 15, 113123.Google Scholar
Molchan, S. E., Hill, J., Mellow, A. M., et al (1990) The dexamethasone suppression test in Alzheimer's disease and Major depression: relationship to dementia severity, depression and CSF monoamines. International Psychogeriatrics, 2, 99122.Google Scholar
Montgomery, S. A. & Åsberg, M. (1979) A new depression scale designed to be sensitive to change. British Journal of Psychiatry, 134, 382389.CrossRefGoogle ScholarPubMed
Nieuwenhuys, R., Voogd, J. & Van Huijzen, C. (1988) The Human Central Nervous System, 3rd edn. Berlin: Springer-Verlag.CrossRefGoogle Scholar
O'Brien, J. T., Ames, D. & Schweitzer, I. (1993) HPA axis function in depression and dementia: a review. International Journal of Geriatric Psychiatry, 8, 887898.CrossRefGoogle Scholar
O'Brien, J. T., Schweitzer, I., Ames, D., et al (1994) Cortisol suppression by dexamethasone in the healthy elderly: effects of age, dexamethasone levels and cognitive function. Biological Psychiatry, 36, 389394.CrossRefGoogle ScholarPubMed
Parker, G., Hazdi-Pavlovic, D., Wilhelm, K., et al (1994) Defining melancholia: properties of a refined sign-based measure. British Journal of Psychiatry, 164, 316326.CrossRefGoogle ScholarPubMed
Poland, R. E., Rubin, R. T., Lesser, I. M., et al (1987) Neuroendocrine aspects of primary endogenous depression II. Serum dexamethasone concentrations and HPA cortical activity as determinants of the dexamethasone suppression test response. Archives of General Psychiatry, 44, 790795.Google Scholar
Roth, M., Tym, E., Mountjoy, C., et al (1986) CAMDEX: a standardised instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. British Journal of Psychiatry, 149, 698709.Google Scholar
Rubinow, D. R., Post, R. M., Savard, R., et al (1984) Cortisol hypersecretion and cognitive impairment in depression. Archives of General Psychiatry, 41, 279283.CrossRefGoogle ScholarPubMed
Sapolsky, R. M., Krey, L. C. & McEwen, B. (1986) The neuroendocrinology of stress and aging: The glucocorticoid cascade hypothesis. Endocrine Reviews, 7, 284301.Google Scholar
Siegel, B., Gurevich, D. & Oxenkrug, G. F. (1989) Cognitive impairment and cortisol resistance to dexamethasone suppression in elderly depression. Biological Psychiatry, 25, 229234.Google Scholar
Starkman, M. N., Gebarski, S. S., Berent, S., et al (1992) Hippocampal formation volume, memory dysfunction and cortisol levels in patients with Cushing's syndrome. Biological Psychiatry, 32, 756765.CrossRefGoogle ScholarPubMed
Tiller, J. W. G., Maguire, K. P., Schweitzer, I., et al (1988) The dexamethasone suppression test a study in a normal population. Psychoneuroendocrinology, 13, 377384.Google Scholar
Weiner, M. F., Vobach, S., Svetlik, D., et al (1993) Cortisol secretion and Alzheimer's disease progression – A preliminary report Biological Psychiatry, 34, 158163.CrossRefGoogle ScholarPubMed
Zubenko, G. S. & Moossy, J. (1988) Major depression in primary dementia. Archives of Neurology, 45, 11821186.CrossRefGoogle ScholarPubMed
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