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Monoamine Mechanisms in Chronic Schizophrenia: Post-Mortem Neurochemical Findings

Published online by Cambridge University Press:  29 January 2018

T. J. Crow ,
H. F. Baker ,
A. J. Cross ,
M. H. Joseph ,
R. Lofthouse ,
A. Longden ,
F. Owen ,
G. J. Riley ,
V. Glover  and
W. S. Killpack
T. J. Crow
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ
H. F. Baker
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ
A. J. Cross
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ
M. H. Joseph
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ
R. Lofthouse
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ
A. Longden
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ
F. Owen
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ
G. J. Riley
Affiliation:
Division of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ
V. Glover
Affiliation:
Bernhard Baron Memorial Research Laboratories, Queen Charlotte's Maternity Hospital, London W6
W. S. Killpack
Affiliation:
King Edward's Memorial Hospital, Ealing, London W5
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Summary

Dopamine and its metabolites homovanillic acid and dihydroxyphenylacetic acid, noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid, and tryptophan and its metabolite kynurenine have been assayed in 9 schizophrenic and 10 control brains, together with the monoamine-related enzymes tyrosine hydroxylase monoamine oxidase, dopamine-β-hydroxylase, and catechol-o-methyltransferase. In schizophrenic brains dopamine, noradrenaline and serotonin were significantly increased in some areas of corpus striatum, but there were no significant changes in enzyme activity or monoamine metabolite concentrations in any of the brain areas examined. The findings are not consistent with theories that serotonin or noradrenaline stores are grossly depleted or noradrenaline neurones have degenerated, or that monoamine oxidase activity is abnormal, in schizophrenia, and provide no direct support for the hypothesis that dopamine neurones are overactive.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 134 , Issue 3 , March 1979 , pp. 249 - 256
Copyright
Copyright © Royal College of Psychiatrists, 1979 

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References

Angrist, B., Lee, H. K. & Gershon, S. (1974) The antagonism of amphetamine-induced symptomatology by a neuroleptic. American Journal of Psychiatry, 131, 817–19.CrossRefGoogle ScholarPubMed
Belmaker, R. H., Ebbesen, K., Ebstein, R. & Rimon, R. (1976) Platelet monoamine oxidase in schizophrenia and manic-depressive illnesses. British Journal of Psychiatry, 129, 227–32.CrossRefGoogle Scholar
Bird, E. D., Spokes, E., Barnes, J., Mackay, A. V. P., Iversen, L. L. & Shepherd, M. (1977) Increased brain dopamine and reduced glutamic acid decarboxylase and choline acetyl transferase activity in schizophrenia and related psychoses. Lancet, ii, 1157–9.Google Scholar
Bowers, M. B. (1974) Central dopamine turnover in schizophrenic syndromes. Archives of General Psychiatry, 31, 50–4.CrossRefGoogle ScholarPubMed
Carpenter, W. T., Murphy, D. L. & Wyatt, R. J. (1975) Platelet monoamine oxidase activity in acute schizophrenia. American Journal of Psychiatry, 132, 438–41.Google Scholar
Cicero, T. J., Sharpe, L. G., Robins, E. & Grote, S. S. (1972) Regional distribution of tyrosine hydroxylase in rat brain. Journal of Neurochemistry, 19, 2241–3.Google Scholar
Clement-Cormier, Y. C., Kebabian, J. W., Petzold, G. L. & Greengard, P. (1974) Dopamine-sensitive adenylate cyclase in mammalian brain: a possible site of action of antipsychotic drugs. Proceedings of the National Academy of Sciences, U.S.A., 71, 1113–7.CrossRefGoogle Scholar
Connell, P. H. (1958) Amphetamine Psychosis. Maudsley Monograph. No. 5. London: Chapman and Hall.Google Scholar
Coyle, J. T. & Henry, D. (1973) Catecholamines in foetal and newborn rat brain. Journal of Neurochemistry, 21, 61–7.Google Scholar
Crow, T. J. & Johnstone, E. C. (1977) Stereochemical specificity in the antipsychotic effects of flupenthixol in man. British Journal of Pharmacology, 59, 466P.Google ScholarPubMed
Crow, T. J. & Mitchell, W. S. (1975) Subjective age in chronic schizophrenia: evidence for a subgroup of patients with defective learning capacity? British Journal of Psychiatry, 126, 360–3.CrossRefGoogle ScholarPubMed
Crow, T. J., Spear, P. J. & Arbuthnott, G. W. (1972) Intracranial self-stimulation with electrodes in the region of the locus coeruleus. Brain Research, 36, 275–87.CrossRefGoogle ScholarPubMed
Curzon, G., Joseph, M. H. & Knott, P. J. (1972) Effects of immobilisation and food deprivation on rat brain tryptophan metabolism. Journal of Neurochemistry, 19, 1967–74.Google Scholar
De Armond, S. J., Fusco, H. M. & Dewey, M. M. (1974) Structure of Human Brain. London: Oxford University Press.Google Scholar
Domino, E. F. & Khanna, S. S. (1976) Decreased blood platelet MAO activity in unmedicated chronic schizophrenic patients. American Journal of Psychiatry, 133, 323–6.Google ScholarPubMed
Domino, E. F., Krause, R. R. & Bowers, J. (1973) Various enzymes involved with putative neurotransmitters. Archives of General Psychiatry, 29, 195–201.CrossRefGoogle ScholarPubMed
Feighner, J. P., Robins, E., Guze, S. B., Woodruff, R. A., Winokur, G. & Munoz, R. (1972) Diagnostic criteria for use in psychiatric research. Archives of General Psychiatry, 26, 57–63.Google Scholar
Friedman, E., Shopsin, B., Sathananthan, G. & Gershon, S. (1974) Blood platelet monoamine oxidase activity in psychiatric patients. American Journal of Psychiatry, 131, 1392–4.CrossRefGoogle ScholarPubMed
Gaddum, J. H. (1954) Drugs antagonistic to 5-hydroxytryptamine. pp 75–77, In: Ciba Foundation Symposium on Hypertension, (ed. Wolstenholme, G. W.). Boston: Little Brown.Google Scholar
Gunne, L. M., Ängård, E. & Jönsson, L. E. (1972) Clinical trials with amphetamine blocking drugs. Psychiatria, Neurologia, Neurochirurgia. (Amsterdam), 75, 225–6.Google Scholar
Johnston, J. P. (1968) Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochemical Pharmacology, 17, 1285–97.Google Scholar
Johnstone, E. C., Crow, T. J., Frith, C. D., Husband, J. & Kreel, L. (1976) Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet, ii, 924–6.Google Scholar
Johnstone, E. C., Crow, T. J., Frith, C. D., Carney, M. W. P. & Price, J. S. (1978a) The mechanism of the antipsychotic effect in the treatment of acute schizophrenia. Lancet, i, 848–51.Google Scholar
Johnstone, E. C., Crow, T. J., Frith, C. D., Stevens, M., Kreel, L. & Husband, J. (1978b) The dementia of dementia praecox. Acta Psychiatrica Scandinavica, 57, 305–24.Google Scholar
Joseph, M. H. & Baker, H. F. (1976) The determination of 5-hydroxytryptophan and its metabolites in plasma following administration to man. Clinica Chimica Acta, 72, 125–31.CrossRefGoogle ScholarPubMed
Joseph, M. H., Baker, H. F. & Lawson, A. M. (1978) Positive identification of kynurenine in rat and human brain. Biochemical Society Transactions, 6, 123–6.Google Scholar
Lerner, P., Hartman, P., Ames, M. M. & Lovenberg, W. (1977) The role of reductants in the tyrosine hydroxylase reaction. Archives of Biochemistry and Biophysics, 182, 164–70.Google Scholar
McCaman, R. E. (1965) Microdetermination of catechol-O-methyltransferase in brain. Life Sciences, 4, 2353–9.Google Scholar
Matthysse, S. (1973) Antipsychotic drug actions, a clue to the neuropathology of schizophrenia? Federation Proceedings, 32, 200–5.Google Scholar
Meltzer, H. & Stahl, S. M. (1974) Platelet monoamine oxidase activity and substrate preferences in schizophrenic patients. Research Communications in Chemical Pathology and Pharmacology, 7, 419–31.Google Scholar
Miller, R. J., Horn, A. S. & Iversen, L. L. (1974) The action of neuroleptic drugs on dopamine-stimulated adenosine cyclic 3′, 5′-monophosphate production in rat neostriatum and limbic forebrain. Molecular Pharmacology, 10, 759–66.Google Scholar
Murphy, D. L. & Wyatt, R. J. (1972) Reduced MAO activity in blood platelets from schizophrenic patients. Nature, 238, 226.CrossRefGoogle ScholarPubMed
O'Keefe, R., Sharman, D. F. & Vogt, M. (1970) Effect of drugs used in psychoses on cerebral dopamine metabolism. British Journal of Pharmacology, 38, 287–304.Google Scholar
Owen, F., Bourne, R. C., Crow, T. J., Johnstone, E. C., Bailey, A. R. & Hershon, H. I. (1976) Platelet monoamine oxidase in schizophrenia: an investigation in drug-free chronic hospitalized patients. Archives of General Psychiatry, 33, 1370–3.Google Scholar
Owen, F., Cross, A. J., Crow, T. J., Longden, A., Poulter, M. & Riley, G. J. (1978) Increased dopamine receptor sensitivity in schizophrenia. Lancet, ii, 223–6.Google Scholar
Post, R. M., Fink, E., Carpenter, W. T. & Goodwin, F. K. (1975) Cerebrospinal fluid amine metabolites in acute schizophrenia. Archives of General Psychiatry, 32, 1013–69.Google Scholar
Randrup, A. & Munkvad, I. (1972) Evidence indicating an association between schizophrenia and dopaminergic hyperactivity in the brain. Orthomolecular Psychiatry, 1, 2–7.Google Scholar
Robinson, D. S., Lovenberg, W., Keiser, H. & Sjoerdsma, A. (1968) Effect of drugs on human blood platelet and plasma amine oxidase activity in vitro and in vivo. Biochemical Pharmacology, 17, 109–19.Google Scholar
Schildkraut, J. J., Herzog, J. M., Orsulak, P. J., Edelman, S. E., Shein, H. M. & Frazier, S. H. (1976) Reduced platelet monoamine oxidase activity in a subgroup of schizophrenic patients. American Journal of Psychiatry, 133, 438–40.Google Scholar
Schwartz, M., Aikens, A. M. & Wyatt, R. J. (1974) Monoamine oxidase activity in brains from schizophrenics and mentally normal individuals. Psychopharmacologia, 38, 319–28.CrossRefGoogle ScholarPubMed
Shaskan, E. G. & Becker, R. E. (1975) Platelet monoamine oxidase in schizophrenics. Nature, 253, 659–60.Google Scholar
Snyder, S. H. (1973) Amphetamine psychosis: a model of schizophrenia mediated by catecholamines. American Journal of Psychiatry, 120, 61–7.Google Scholar
Stein, L. & Wise, C. D. (1971) Possible etiology of schizophrenia: progressive damage to the noradrenergic reward system by 6-hydroxydopamine. Science, 171, 1032–6.CrossRefGoogle Scholar
Stevens, J. R. (1973) An anatomy of schizophrenia. Archives of General Psychiatry, 29, 177–89.CrossRefGoogle ScholarPubMed
Sullivan, J., Stanfield, C. N. & Dackis, C. (1977) Platelet MAO activity in schizophrenia and other psychiatric illnesses. American Journal of Psychiatry, 134, 1098–102.Google Scholar
Utena, H., Kanamura, H., Suda, S., Nakamura, R., Machiyama, Y. & Takahashi, R. (1968) Studies on the regional distribution of monoamine oxidase activity in the brains of schizophrenic patients. Proceedings of the Japan Academy, 44, 1078–83.CrossRefGoogle Scholar
Vogel, W. H., Orfei, V. & Century, B. (1969) Activities of enzymes involved in the formation and destruction of biogenic amines in various areas of human brain. Journal of Pharmacology and Experimental Therapeutics, 165, 195–203.Google ScholarPubMed
Watson, E., Travis, B. & Wilk, S. (1974) Simultaneous determination of 3,4-dihydroxyphenylacetic acid and homovanillic acid in milligram amounts of rat striatal tissue by gas-liquid chromatography. Life Sciences, 15, 2167–78.Google Scholar
White, H. L., McLead, M. N. & Davidson, J. R. T. (1976) Platelet monoamine oxidase in schizophrenia. American Journal of Psychiatry, 133, 1191–3.Google Scholar
Wing, J. K., Cooper, J. E. & Sartorius, N. (1974) Measurement and Classification of Psychiatric Symptoms. Cambridge University Press.Google Scholar
Winokur, G., Morrison, J. R., Clancy, J. & Crowe, R. (1974) Iowa 500: the clinical and genetic distinction of hebephrenic and paranoid schizophrenia. Journal of Nervous and Mental Disease, 159, 12–19.Google Scholar
Wise, C. D. (1976) A sensitive assay for dopamine-β-hydroxylase. Journal of Neurochemistry, 27, 883–8.Google Scholar
Wise, C. D. & Stein, L. (1975) Dopamine-β-hydroxylase activity in brains of chronic schizophrenic patients. Science, 187, 370A.CrossRefGoogle Scholar
Wise, C. D., Baden, M. M. & Stein, L. (1974) Postmortem measurement of enzymes in human brain: evidence of a central noradrenergic deficit in schizophrenia. Journal of Psychiatric Research, 11, 185–98.Google Scholar
Woolley, D. W. & Shaw, E. (1954) A biochemical and pharmacological suggestion about certain mental disorders. Proceedings of the National Academy of Sciences, U.S.A., 40, 228–31.CrossRefGoogle ScholarPubMed
Wyatt, R. J., Murphy, D. L., Belmaker, R., Cohen, S., Donelly, C. H. & Pollin, W. (1973) Reduced monoamine oxidase activity in platelets: a possible genetic marker for vulnerability to schizophrenia. Science, 179, 916–18.Google Scholar
Wyatt, R. J., Schwartz, M. A., Erdelyi, E. & Barchas, J. P. (1975) Dopamine-β-hydroxylase activity in brains of chronic schizophrenic patients. Science, 187, 368–9.Google Scholar
Youdim, M. B. H. (1974) Heterogeneity of rat brain mitochondrial monoamine oxidase. Advances in Biochemical Psychopharmacology, 11, 59–63.Google Scholar
Zeller, E. A., Boshes, B., Davis, J. H. & Thorner, M. (1975) Molecular aberration in platelet monoamine oxidase in schizophrenia. Lancet, i, 1385.CrossRefGoogle Scholar
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