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Cerebrospinal fluid and plasma free cortisol concentrations in depression

Published online by Cambridge University Press:  09 July 2009

Bernard J. Carroll ,
George C. Curtis  and
J. Mendels
Bernard J. Carroll
Affiliation:
Department of Psychiatry and Mental Health Research Institute, University of Michigan, Ann Arbor, and the Department of Psychiatry, University of Pennsylvania, and Veterans Administration Hospital, Philadelphia
George C. Curtis
Affiliation:
Department of Psychiatry and Mental Health Research Institute, University of Michigan, Ann Arbor, and the Department of Psychiatry, University of Pennsylvania, and Veterans Administration Hospital, Philadelphia
J. Mendels
Affiliation:
Department of Psychiatry and Mental Health Research Institute, University of Michigan, Ann Arbor, and the Department of Psychiatry, University of Pennsylvania, and Veterans Administration Hospital, Philadelphia
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Synopsis

Cerebrospinal fluid (CSF) cortisol levels were examined in a total group of 65 patients. Those who were not depressed (ND), and those suffering from depressive neuroses (DN) had marginally elevated values. Patients with unipolar depression (UD) and bipolar depression (BD) had levels twice as high as the ND and DN patients. Psychotic UD and BD patients had the highest values, three to four times as high as the ND and DN subjects. A significant reduction of CSF cortisol levels was observed following treatment and recovery. Manic patients had moderately elevated CSF cortisol values. The CSF results were in good agreement with plasma total cortisol levels and with urinary free cortisol excretion. Age and sex effects were not responsible for the observed differences; similar results were found in patient subgroups studied in Australia and in the United States. Preliminary equilibrium dialysis data are presented for plasma and CSF cortisol binding. CSF cortisol was 20% bound and 80% free. Plasma free cortisol levels were in good agreement with CSF free cortisol values. Depressed patients have increased tissue and central nervous system (CNS) exposure to free, physiologically active glucocorticoids. The appearance of severe depressive symptoms which manifest a diurnal rhythm may be determined in part by excessive CNS exposure to glucocorticoids.

Type
Research Article
Information
Psychological Medicine , Volume 6 , Issue 2 , May 1976 , pp. 235 - 244
Copyright
Copyright © Cambridge University Press 1976

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References

REFERENCES

Abelson, D., Baron, D. N. & Toakley, J. G. (1955). Studies of cerebrospinal fluid following oral administration of cortisone acetate or hydrocortisone. Journal of Endocrinology 12, 87–92.CrossRefGoogle ScholarPubMed
Allen, J. P., Kendall, J. W., McGilvra, R. & Vancura, C. (1974). Immunoreactive ACTH in cerebrospinal fluid. Journal of Clinical Endocrinology and Metabolism 38, 586–593.CrossRefGoogle ScholarPubMed
Anton-Tay, F. & Wurtman, R. J. (1969). Regional uptake of 3H-melatonin from blood or cerebrospinal fluid by rat brain. Nature 221, 474–475.CrossRefGoogle ScholarPubMed
Bassett, J. M. & Hinks, N. T. (1969). Micro-determination of corticosteroids in ovine peripheral plasma: effects of venepuncture, corticotrophin, insulin and glucose. Journal of Endocrinology 44, 387–403.CrossRefGoogle Scholar
Beardwell, G. C., Burke, C. W. & Cope, C. L. (1968). Urinary free Cortisol measured by competitive protein binding. Journal of Endocrinology 42, 79–89.CrossRefGoogle Scholar
Brooksbank, B. W. L., Brammall, M. A., Cunningham, A. E., Shaw, D. M. & Camps, F. E. (1972). Estimation of corticosteroids in human cerebral cortex after death by suicide, accident or disease. Psychological Medicine 2, 56–65.CrossRefGoogle ScholarPubMed
Brooksbank, B. W. L., Brammall, M. A. & Shaw, D. M. (1973). Estimation of Cortisol, cortisone and corticosterone in cerebral cortex, hypothalamus and other regions of the human brain after natural death and after death by suicide. Steroids and Lipids Research 4, 162–183.Google ScholarPubMed
Burke, C. W. (1969). Biologically active Cortisol in plasma of oestropen-treated and normal subjects. British Medical Journal ii, 798–800.CrossRefGoogle Scholar
Burke, C. W. & Roulet, F. (1970). Increased exposure of tissues to Cortisol in late pregnancy. British Medical Journal i, 657–659.CrossRefGoogle Scholar
Carpenter, W. T. Jr & Bunney, W. E. Jr. (1971). Adrenal cortical activity in depressive illness. American Journal of Psychiatry 128, 31–40.CrossRefGoogle ScholarPubMed
Carroll, B. J. (1972 a). Plasma Cortisol levels in depression. In Davies, B. et al. (eds.), Depressive Illness: Some Research Studies. Thomas: Springfield, Ill.Google Scholar
Carroll, B. J. (1972 b). Control of plasma Cortisol levels in depression: relation to integrity of psychological defenses. In Davies, B. et al. (eds.), Depressive Illness: Some Research Studies. Thomas: Springfield, Ill.Google Scholar
Carroll, B. J., Heath, B. & Jarrett, D. B. (1975). Corticosteroids in brain tissue. Endocrinology 97, 290–300.Google ScholarPubMed
Carroll, B. J. (1976 a). Psychoendocrine relationships in affective disorders. In Hill, O. W. (ed)., Modern Trends in Psychosomatic Medicine. Butterworth: London.Google Scholar
Carroll, B. J. (1976 b). Limbic system–adrenal cortex regulation in depression and schizophrenia. Psychosomatic Medicine (in press).CrossRefGoogle Scholar
Carroll, B. J., Curtis, G. C., Davies, B. M., Mendels, J. & Sugerman, A. A. (1976). Urinary free Cortisol excretion in depression. Psychological Medicine 6, 43–50.CrossRefGoogle ScholarPubMed
Carroll, B. J. & Mendels, J. (1976). Neuroendocrine regulation in affective disorders. In Sachar, E. J. (ed.), Hormones, Behaviour and Psychopathology. Raven Press: New York.Google Scholar
Coppen, A., Brooksbank, R., Noguera, R. & Wilson, D. (1971). Cortisol in the cerebrospinal fluid of patients suffering from affective disorders. Journal of Neurology, Neurosurgery and Psychiatry 34, 432–435.CrossRefGoogle ScholarPubMed
Daughaday, W. H. (1958). Binding of corticosteroids by plasma proteins. IV. The electrophoretic demonstration of corticosteroid binding globulin. Journal of Clinical Investigation 37, 519–523.CrossRefGoogle ScholarPubMed
David, G. F. X. & Kumar, T. C. A. (1974). Transfer of steroidal hormones from blood to the cerebrospinal fluid in the rhesus monkey. Neuroendocrinology 14, 114–120.CrossRefGoogle Scholar
de Moor, P., Heirwegh, K., Heremans, J. F. & Declerck-Raskin, M. (1962). Protein binding of corticoids studied by gel filtration. Journal of Clinical Investigation 41, 816–827.Google ScholarPubMed
Fazekas, I. Gy. & Fazekas, A. T. (1967). Die Corticosteroid-Fraktionen des menschlichen Gehirns. Endokrinologie 51, 183–210.Google Scholar
Ficher, M., Curtis, G. C., Ganjam, V. K., Joshlin, L. & Perry, S. (1973). Improved measurement of corticosteroids in plasma and urine by competitive protein-binding radioassay. Clinical Chemistry 19, 511–515.CrossRefGoogle ScholarPubMed
Gaddum, J. H. (1945). Log-normal distributions. Nature 156, 463–466.CrossRefGoogle Scholar
Haberfellner, H., Auer, B. & Gleispach, H. (1974). Preliminary studies in plasma and cerebrospinal fluid Cortisol in children with different diseases. Clinica Chimica Acta 54, 5–10.CrossRefGoogle ScholarPubMed
Hamanaka, Y., Manabe, H., Tanaka, H., Monden, Y., Uozumi, T. & Matsumoto, K. (1970). Effects of surgery on plasma levels of Cortisol, corticosterone and non-protein-bound cortisol. Acta Endocrinologica 64, 439–451.Google ScholarPubMed
Hansen, J. M. & Siersbaek-Neilsen, K. (1969). Cerebrospinal fluid thyroxine. Journal of Clinical Endocrinology and Metabolism 29, 1023–1026.CrossRefGoogle ScholarPubMed
Heath, D. F. (1967). Normal or log-normal: appropriate distributions. Nature 213, 1159–1160.CrossRefGoogle Scholar
Hsu, T. H. & Bledsoe, T. (1970). Measurement of urinary free corticoids by competitive protein binding radioassay in hypoadrenal states. Journal of Clinical Endocrinology and Metabolism 30, 443–448.CrossRefGoogle ScholarPubMed
Hunzicker, M. E. & Hazelwood, R. L. (1970). Chicken cerebrospinal fluid: insulin-like activity. Comparative Biochemistry and Physiology 36, 795–801.CrossRefGoogle Scholar
Jansen, J. A., Schou, J. & Singh, H. (1970). Cortisol release, distribution and metabolism in induced oestrogenic deficiency. Acta Endocrinologica 65, 125–132.Google ScholarPubMed
Kendall, J. W., Grimm, Y. & Shimshak, G. (1969). Relation of cerebrospinal fluid circulation to the ACTH-suppressing effects of corticosteroid implants in the rat brain. Endocrinology 85, 200–208.CrossRefGoogle Scholar
King, D. J. (1973). Plasma cortisol-binding capacity in mental illness. Psychological Medicine 3, 153–165.CrossRefGoogle ScholarPubMed
Knigge, K. M. & Scott, D. E. (1970). Structure and function of the median eminence. American Journal of Anatomy 129, 223–244.CrossRefGoogle ScholarPubMed
Kumar, T. C. A. & Thomas, G. H. (1968). Metabolites of 3H-oestradiol-17-β in the cerebrospinal fluid of the Rhesus monkey. Nature 219, 628–629.CrossRefGoogle ScholarPubMed
Linfoot, J. A., Garcia, J. F., Wei, W., Fink, R., Sarin, R., Born, J. L. & Lawrence, J. H. (1970). Human growth hormone levels in cerebrospinal fluid. Journal of Clinical Endocrinology and Metabolism 31, 230–232.CrossRefGoogle ScholarPubMed
Lurie, A. O. & Weiss, J. B. (1967). Progesterone in cerebrospinal fluid during human pregnancy. Nature 215, 1178.CrossRefGoogle ScholarPubMed
Mason, J. W. (1968). A review of psychoendocrine research on the pituitary-adrenal cortical system. Psychosomatic Medicine 30, 576–607.CrossRefGoogle ScholarPubMed
McClure, D. J. & Cleghorn, R. A. (1970). Hormone deficiency in depression. In Masserman, J. H. (ed.), Science and Psychoanalysis, vol. 17. Grune & Stratton: New York.Google Scholar
Meikle, A. W., Takiguchi, H., Mizutani, S., Tyler, F. H. & West, C. D. (1969). Urinary Cortisol excretion determined by competitive protein-binding radioassay: a test of adrenal cortical function. Journal of Laboratory and Clinical Medicine 74, 803–812.Google ScholarPubMed
Michael, R. P. & Gibbons, J. L. (1963). Interrelationships between the endocrine system and neuropsychiatry. In International Review of Neurobiology, vol. 5. Academic Press: New York.Google Scholar
Mills, I. H., Schedl, H. P., Chen, P. S. & Bartter, F. C. (1960). The effect of estrogen administration on the metabolism and protein binding of Cortisol. Journal of Clinical Endocrinology and Metabolism 20, 515–528.CrossRefGoogle Scholar
Murphy, B. E. P. (1967). Some studies of the protein-binding of steroids and their application to the routine micro and ultramicro measurements of various steroids in body fluids by competitive protein-binding radioassay. Journal of Clinical Endocrinology and Metabolism 27, 973–990.CrossRefGoogle Scholar
Murphy, B. E. P., Cosgrove, J. B., McIlquham, M. C. & Pattee, C. J. (1967). Adrenal corticoid levels in human cerebrospinal fluid. Canadian Medical Association Journal 97, 13–17.Google ScholarPubMed
Murphy, B. E. P. (1968). Clinical evaluation of urinary Cortisol determinations by competitive protein-binding radioassay. Journal of Clinical Endocrinology and Metabolism 28, 343–348.CrossRefGoogle Scholar
Murray, D. (1967). Cortisol binding to plasma proteins in man in health, stress and at death. Journal of Endocrinology 39, 571–591.CrossRefGoogle ScholarPubMed
Oliver, C., Charvet, J. P., Codaccioni, J. L., Vague, J. & Porter, J. C. (1974). TRH in human CSF. Lancet i, 873.CrossRefGoogle Scholar
Persky, H., Smith, K. D. & Basu, G. K. (1971). Effect of corticosterone and hydrocortisone on some indicators of anxiety. Journal of Clinical Endocrinology and Metabolism 33, 467–473.CrossRefGoogle ScholarPubMed
Rubin, R. & Mandell, A. (1966). Adrenal cortical activity in pathological emotional states: a review. American Journal of Psychiatry 123, 387–400.CrossRefGoogle ScholarPubMed
Ruf, K. & Steiner, F. A. (1967). Steroid-sensitive single neurons in rat hypothalamus and midbrain: identification by microelectrophoresis. Science 156, 667–669.CrossRefGoogle ScholarPubMed
Sachar, E. J. (1967 a). Corticosteroids in depressive illness. I. A re-evaluation of control issues and of the literature. Archives of General Psychiatry 17, 544–553.CrossRefGoogle Scholar
Sachar, E. J. (1967 b). Corticosteroids in depressive illness. II A longitudinal psychoendocrine study. Archives of General Psychiatry 17, 554–567.CrossRefGoogle Scholar
Sachar, E. J., Hellman, L., Fukushima, D. K. & Gallagher, T. F. (1970). Cortisol production in depressive illness: a clinical and biochemical clarification. Archives of General Psychiatry 23, 289–298.CrossRefGoogle ScholarPubMed
Sachar, E. J., Hellman, L., Roffwarg, H., Halpern, F., Fukushima, D. & Gallagher, T. (1973). Disrupted 24 hour patterns of Cortisol secretion in psychotic depression. Archives of General Psychiatry 28, 19–24.CrossRefGoogle ScholarPubMed
Slaunwhite, W. R. & Sandberg, A. A. (1959). Transcortin: a corticosteroid-binding protein of plasma. Journal of Clinical Investigation 38, 384–391.CrossRefGoogle ScholarPubMed
Slaunwhite, W. R., Lockie, G. N., Back, N. & Sandberg, A. A. (1962). Inactivity in vivo of transccrtin-bound Cortisol. Science 135, 1062–1063.CrossRefGoogle ScholarPubMed
Uete, T., Nishimura, S., Ohya, H., Shimomura, T. & Tatebayashi, Y. (1970). Corticosteroid levels in blood and cerebrospinal fluid in various diseases. Journal of Clinical Endocrinology and Metabolism 30, 208–214.CrossRefGoogle ScholarPubMed
Vorherr, H., Bradbury, M. W. B., Hoghoughi, H. & Klee-man, C. R. (1968). Antidiuretic hormone in cerebrospinal fluid during endogenous and exogenous changes in its blood level. Endocrinology 83, 246–250.CrossRefGoogle ScholarPubMed
Walker, M. D., Henkin, R. I., Harlan, A. B. & Casper, A. G. T. (1971). Distribution of tritiated Cortisol in blood, brain, CSF and other tissues of the cat. Endocrinology 88, 224–232.CrossRefGoogle Scholar