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Noradrenergic Overactivity in Chronic Schizophrenia: Evidence Based on Cerebrospinal Fluid Noradrenaline and Cyclic Nucleotide Concentrations

Published online by Cambridge University Press:  29 January 2018

U. C. R. Gomes
Affiliation:
Department of Chemical Pathology, University of Stellenbosch, P.O. Box 63, Tygerberg, 7505, South Africa
B. C. Shanley
Affiliation:
Department of Chemical Pathology, University of Stellenbosch, P.O. Box 63, Tygerberg, 7505, South Africa
L. Potgieter
Affiliation:
Department of Psychiatry, University of Stellenbosch, P.O. Box 63, Tygerberg, 7505, South Africa
J. T. Roux
Affiliation:
Department of Psychiatry, University of Stellenbosch, P.O. Box 63, Tygerberg, 7505, South Africa

Summary

Concentrations of noradrenaline (NA), homovanillic acid, 5-hydroxyindoleacetic acid and cyclic nucleotides were determined in lumbar cerebrospinal fluid (CSF) from acute and chronic schizophrenics and various groups of psychiatric and non-psychiatric control subjects. Statistically significant increases in NA and cyclic adenosine monophosphate were found in CSF from chronic schizophrenics compared to all other groups. These results were shown by statistical analyses to be unrelated to medication. They may be interpreted as evidence for noradrenergic overactivity as a possible primary abnormality in chronic schizophrenia.

Type
Research Article
Copyright
Copyright © Royal College of Psychiatrists, 1980 

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References

Bennett, J. P., Enna, S. J., Bylund, D. B., Gillin, J. C., Wyatt, R. J. & Snyder, S. H. (1979) Neurotransmitter receptors in frontal cortex of schizophrenics. Archives of General Psychiatry, 36, 927–34.CrossRefGoogle ScholarPubMed
Biederman, J., Rimon, R., Ebstein, R., Belmaker, R. H. & Davidson, J. T. (1977) Cyclic AMP in CSF of patients with schizophrenia. British Journal of Psychiatry, 130, 64–7.CrossRefGoogle ScholarPubMed
Blumberg, J. B., Vetulani, J., Stawarz, R. J. & Sulser, F. (1976) The noradrenergic cyclic AMP-generating system in the limbic forebrain: pharmacological characterization in vitro and possible role of limbic noradrenergic mechanisms in the mode of action of antipsychotics. European Journal of Pharmacology, 37, 357–66.Google Scholar
Bowers, M. B. (1974) Central dopamine turnover in schizophrenia syndromes. Archives of General Psychiatry, 31, 50–4.Google Scholar
Carlsson, A. (1977) Does dopamine play a role in schizophrenia? Psychological Medicine, 7, 583–97.Google Scholar
Coyle, J. T. & Henry, D. (1973) Catecholamines in fetal and newborn rat brain. Journal of Neurochemistry, 21, 61–7.Google Scholar
Dahlstrom, A. & Fuxe, K. (1965) Evidence for the existence of monoamine neurons in the central nervous system. II. Experimentally induced changes in the intraneuronal amine levels of bulbospinal neurons systems. Acta Physiologica Scandinavica, 64 Supp., 136.Google Scholar
De Champlain, J., Farley, L., Cousineau, D. & Van Amerigen, M. R. (1976) Circulating catecholamine levels in human and experimental hypertension. Circulation Research, 38, 109–14.CrossRefGoogle ScholarPubMed
Dunn, O. J. (1964) Multiple comparisons using rank sums. Technometrics, 6, 241–52.Google Scholar
Farley, I. J., Price, K. S. McCullough, E., Deck, J. H. N., Hordynski, W. & Hornykiewicz, O. (1978) Norepinephrine in chronic paranoid schizophrenia: above-normal levels in limbic forebrain. Science, 200, 456–8.Google Scholar
Farley, I. J. & Hornykiewicz, O. (1977) Noradrenaline distribution in subcortical areas of the human brain. Brain Research, 126, 5362.CrossRefGoogle ScholarPubMed
Friedhoff, A. J. & Alpert, M. (1978) Receptor sensitivity modification as a potential treatment. In Psychopharmacology: a generation of progress (eds. M. A. Lipton, A. Di Mascio and K. F. Killan). New York: Raven Press.Google Scholar
Garattini, S., Pujol, J. F. & Samanin, R. (1978) Interactions between putative neurotransmitters (eds.). New York: Raven Press.Google Scholar
Goodwin, F. K., Webster, M. H. & Post, R. M. (1978) Cerebrospinal fluid amine metabolites in affective illness and schizophrenia: clinical and pharmacological studies. In Biochemistry of Mental Disorders—New Vistas (eds. E. Usdin and A. J. Mandell). New York: Marcel Dekker Inc.Google Scholar
Korf, J., Roos, B. E. & Werdinius, B. (1971) Fluprometric determination of homovanillic acid in tissues using anion exchange separation and mixed solvent elution. Acta Chimica Scandinavica, 25, 333–5.Google Scholar
Korf, J. & Valkenburg-Sikkema, T. (1969) Fluorometric determination of 5-hydroxyindoleacetic acid in human urine and cerebrospinal fluid. Clinica Chimica Acta, 26, 201306.CrossRefGoogle Scholar
Lake, C. R., Sternberg, D. E., Van Kammen, D. P., Ballenger, J. C., Ziegler, M. G., Post, R. M., Kopin, I. J. & Bunney, W. E. (1980) Schizophrenia: elevated cerebrospinal fluid norepinephrine. Science, 207, 331–3.CrossRefGoogle ScholarPubMed
Lee, T., Seeman, P., Tourtellotte, W. W., Farley, I. J. & Hornykiewicz, O. (1978) Binding of 3H-neuroleptics and 3H-apomorphine in schizophrenic brains. Nature, 274, 897900.CrossRefGoogle ScholarPubMed
Matthyse, S. W. & Kety, S. S. (1975) Catecholamines and Schizophrenia (eds.). Oxford: Pergamon Press.Google Scholar
Peuler, J. D. & Johnson, G. A. (1977) Simultaneous single isotope radioenzymatic assay of plasma norepinephrine, epinephrine and dopamine. Life Sciences, 21, 625–36.CrossRefGoogle ScholarPubMed
Post, R. M., Fink, E., Carpenter, W. T. & Goodwin, F. K. (1975) Cerebrospinal fluid amine metabolites in acute schizophrenia. Archives of General Psychiatry, 32, 1063–9.Google Scholar
Post, R. M., Lake, C. R., Jimerson, D. C., Bunney, W. E., Wood, J. H., Ziegler, M. G. & Goodwin, F. K. (1978) Cerebrospinal fluid norepinephrine in affective illness. American Journal of Psychiatry, 135, 907–12.Google Scholar
Richter, D. (1976) The impact of biochemistry on the problem of schizophrenia. In Schizophrenia Today (eds. D. Kemali, G. Bartholini and D. Richter). Oxford: Pergamon Press.Google Scholar
Smith, C. C., Tallman, J. F., Post, R. M., Van Kammen, D. P., Jimerson, D. C. & Brown, G. L. (1976) An examination of baseline and drug-induced levels of cyclic nucleotides in the cerebrospinal fluid of control and psychiatric patients. Life Sciences, 19, 131–6.CrossRefGoogle ScholarPubMed
Smythies, J. R. (1975) The biochemical basis of schizophrenia. In New Perspectives in Schizophrenia (eds. A. Forrest and J. Affleck). Edinburgh: Churchill Livingstone.Google Scholar
Tsang, D., Lal, S., Sourkes, T. L., Form, R. M. & Arnoff, A. (1976) Studies on cyclic AMP in different compartments of cerebrospinal fluid. Journal of Neurology, Neurosurgery and Psychiatry, 39, 1186–90.Google Scholar
Wyatt, R. J., Termini, B. A. & David, J. (1976) Biochemical and sleep studies of schizophrenia: a review of the literature 1960–1970. In Foundations of Biochemical Psychiatry (eds. D. S. Segal, J. Yager and J. L. Sullivan). Boston: Butterworths.Google Scholar
Ziegler, M. G., Lake, C. R., Wood, J. H., Brooks, B. R. & Ebert, M. H. (1977) Relationship between norepinephrine in blood and cerebrospinal fluid in the presence of a blood-cerebrospinal fluid barrier for norepinephrine. Journal of Neurochemistry, 28, 677–9.Google ScholarPubMed
Zohar, J., Biederman, J., Rimon, R., Ebstein, R. & Belmaker, R. H. (1978) Clinical correlates of CSF cyclic nucleotides in schizophrenia. American Journal of Psychiatry, 135, 253–5.Google Scholar
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