Hostname: page-component-cd9895bd7-gxg78 Total loading time: 0 Render date: 2024-12-23T00:50:26.213Z Has data issue: false hasContentIssue false
  • English
  • Français

Neuroendocrine changes in acute schizophrenia as a function of clinical state and neuroleptic medication

Published online by Cambridge University Press:  09 July 2009

P. Mary Cotes ,
T. J. Crow ,
Eve C. Johnstone ,
W. Bartlett  and
Rachel C. Bourne
P. Mary Cotes*
Affiliation:
Division of Psychiatry and Division of Clinical Chemistry, Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex
T. J. Crow
Affiliation:
Division of Psychiatry and Division of Clinical Chemistry, Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex
Eve C. Johnstone
Affiliation:
Division of Psychiatry and Division of Clinical Chemistry, Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex
W. Bartlett
Affiliation:
Division of Psychiatry and Division of Clinical Chemistry, Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex
Rachel C. Bourne
Affiliation:
Division of Psychiatry and Division of Clinical Chemistry, Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex
*
1Address for correspondence: Dr P. Mary Cotes, Division of Clinical Chemistry, Clinical Research Centre, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ.
Get access Rights & Permissions [Opens in a new window]

Synopsis

Changes in levels of prolactin, growth hormone, luteinizing hormone, and follicle stimulating hormone in serum, and testosterone in plasma, have been studied in 38 patients with acute schizophrenic illnesses in a 4-week double-blind comparison of the 2 isomers of flupenthixol and placebo. Only prolactin showed changes which could be related either to changes in clinical state or to the effects of medication. Prolactin levels increased during treatment with the therapeutically active α-isomer of flupenthixol but were unchanged with the inactive β-isomer and placebo. Although there was a significant relationship between prolactin level and antipsychotic effect in patients on α-flupenthixol, in the individual case prolactin level was not a strong predictor of therapeutic response; and in patients on inactive medication changes in prolactin level could not be related to symptom change. There was a time lag of at least 2 weeks between the increase in prolactin secretion in patients on α-flupenthixol and the therapeutic effect attributable to medication. This delay suggests that if the antipsychotic effect is dependent upon dopamine receptor blockade it is not a direct consequence of this action. Perhaps dopamine receptor blockade permits other, and slower, changes to take place and it is these changes, rather than dopamine receptor blockade itself, which are reflected in clinical improvement.

Type
Research Article
Information
Psychological Medicine , Volume 8 , Issue 4 , November 1978 , pp. 657 - 665
Copyright
Copyright © Cambridge University Press 1978

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Andén, N. E. (1972). Dopamine turnover in the corpus striatum and the limbic system after treatment with neuroleptic and anti-acetylcholine drugs. Journal of Pharmacy and Pharmacology 24, 905–906.Google Scholar
Beumont, P. J. V., Gelder, M. G., Friesen, H. G., Harris, G. W., MacKinnon, P. C. B., Mandelbrote, B. M. & Wiles, D. H. (1974). The effects of phenothiazines on endocrine function. British Journal of Psychiatry 124, 413–419.Google Scholar
Bowers, M. B. & Rozitis, A. (1974). Regional differences in homovanillic acid concentrations after acute and chronic administration of antipsychotic drugs. Journal of Pharmacy and Pharmacology 26, 743–745.CrossRefGoogle ScholarPubMed
Brambilla, F., Guerrini, A., Guastalla, A., Rovere, C. & Riggi, F. (1975). Neuroendocrine effects of haloperidol therapy in chronic schizophrenia. Psychopharmacologia 44, 17–22.CrossRefGoogle ScholarPubMed
Brambilla, F., Guastalla, A., Guerrini, A., Rovere, C., Legnoni, G., Sarno, M. & Riggi, F. (1976 a). Prolactin secretion in chronic schizophrenia. Acta Psychiatrica Scandinavica 54, 275–286.CrossRefGoogle ScholarPubMed
Brambilla, F., Rovere, C., Guastalla, A., Guerrini, A. & Riggi, F. (1976 b). Gonadotrophin response to synthetic gonadotrophin hormone-releasing hormone (GnRH) in chronic schizophrenia. Acta Psychiatrica Scandinavica 54, 131–145.CrossRefGoogle ScholarPubMed
Clemens, J. A., Smalstig, E. B. & Sawyer, B. D. (1974). Antipsychotic drugs stimulate prolactin release. Psychopharmacologia 40, 123–127.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 (USA) 71, 1113–1117.CrossRefGoogle Scholar
Cotes, P. M. (1973). Research Standard A for human prolactin (in ampoules coded 71/222). In Human Prolactin (ed. Pasteels, J. L. and Robyn, C.), pp. 97–101. Excerpta Medica: Amsterdam.Google Scholar
Crow, T. J., Deakin, J. F. W. & Longden, A. (1977 a). The nucleus accumbens–possible site of antipsychotic action of neuroleptic drugs? Psychological Medicine 7, 213–221.CrossRefGoogle ScholarPubMed
Crow, T. J., Frith, C. D. & Johnstone, E. C. (1977 b). The clinical effects of the isomers of flupenthixol–the consequences of dopamine receptor blockade in acute schizophrenia. British Journal of Clinical Pharmacology 4, 648P.CrossRefGoogle ScholarPubMed
Enna, S. J., Bennett, J. P., Burt, D. R., Creese, I. & Snyder, S. H. (1976). Stereospecificity of interaction of neuroleptic drugs with neurotransmitters and correlation with clinical potency. Nature 263, 338–347.CrossRefGoogle ScholarPubMed
Fuxe, K. & Hökfelt, T. (1967). The influence of central catecholamine neurones on the hormone secretion from the anterior and posterior pituitary. In Neurosecretion (ed. Stutinsky, F.), pp. 166–177. Fourth International Symposium on Neurosecretion.Google Scholar
Fuxe, K., Hökfelt, T. & Nilsson, O. (1969). Factors involved in the control of the activity of tubero-infundibular dopamine neurons during pregnancy and lactation. Neuroendocrinology 5, 257–270.CrossRefGoogle ScholarPubMed
Fuxe, K., Löfström, A., Agnati, L. F., Everitt, B. J., Hökfelt, T., Jonsson, G. & Wiesel, F. A. (1975). On the role of central catecholamine and 5-hydroxytryptamine neurons in neuroendocrine regulation. In Anatomical Neuroendocrinology (ed. Sumpf, W. E. and Grant, L. D.), pp. 420–432. Karger: Basel.Google Scholar
Healy, M. J. R. (1972). Statistical analysis of radioimmunoassay data. Biochemical Journal 130, 207–210.CrossRefGoogle Scholar
Johnstone, E. C., Crow, T. J. & Mashiter, K. (1977). Anterior pituitary hormone secretion in chronic schizophrenia–an approach to neurohumoural mechanisms. Psychological Medicine, 7, 223–228.CrossRefGoogle ScholarPubMed
Johnstone, E. C., Crow, T. J., Frith, C. D., Carney, M. W. P. & Price, J. S. (1978). Mechanism of the antipsychotic effect in the treatment of acute schizophrenia. Lancet i, 848–851.CrossRefGoogle Scholar
Klein, D. F. & Davis, J. M. (1969). Diagnosis and Drug Treatment of Psychiatric Disorders. Williams and Wilkins: Baltimore.Google Scholar
Kolakowska, T., Wiles, D. H., Gelder, M. G. & McNeilly, A. S. (1976). Clinical significance of plasma chlorpromazine levels. Psychopharmacology 49, 101–107.Google Scholar
Krawiecka, M., Goldberg, D. & Vaughan, M. (1977). A standardized psychiatric assessment for rating chronic psychotic patients. Acta Psychiatrica Scandinavica 55, 299–308.Google Scholar
Lal, S., Martin, J. B., de la Vega, C. D. & Friesen, H. G. (1975). Comparison of the effect of apomorphine and Ldopa on serum growth hormone levels in normal men. Clinical Endocrinology 4, 277–285.CrossRefGoogle ScholarPubMed
Langer, G., Sachar, E. J., Gruen, P. H. & Halpern, F. S. (1977). Human prolactin responses to neuroleptic drugs correlate with antischizophrenic potency. Nature 266, 639–640.CrossRefGoogle ScholarPubMed
Meltzer, H. Y. & Fang, V. S. (1976). The effect of neuroleptics on serum prolactin schizophrenic patients. Archives of General Psychiatry 33, 279–286.CrossRefGoogle ScholarPubMed
Meltzer, H. Y., Sachar, E. J. & Frantz, A. G. (1974). Serum prolactin levels in unmedicated schizophrenic patients. Archives of General Psychiatry 31, 564–569.Google Scholar
Meltzer, H. Y., Goode, D. J. & Fang, V. S. (1977 a). Effect of chlorpromozine on plasma prolactin and chlorpromazine levels. Psychopharmacology Bulletin 13, 59–60.Google ScholarPubMed
Meltzer, H. Y., Paul, S. M. & Fang, V. S. (1977 b). Effect of flupenthixol and butaclamol isomers on prolactin secretion in rats. Psychopharmacology 51, 181–183.CrossRefGoogle ScholarPubMed
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 neostriatum and limbic forebrain. Molecular Pharmacology, 10, 759–766.Google Scholar
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
Post, R. M. & Goodwin, F. K. (1975). Time-dependent effects of phenothiazines on dopamine turnover in psychiatric patients. Science 190 488–489.CrossRefGoogle ScholarPubMed
van Praag, H. M. (1977). The significance of dopamine for the mode of action of neuroleptics and the pathogenesis of schizophrenia. British Journal of Psychiatry 130, 463–474.Google Scholar
Pratt, J. J., Wiegman, T., Lappohn, R. E. & Woldring, M. G. (1975). Estimation of plasma testosterone without extraction and chromatography. Clinical Chimica Acta 59, 337–346.CrossRefGoogle ScholarPubMed
Randrup, A. & Munkvad, I. (1972). Evidence indicating an association between schizophrenia and dopaminergic hyperactivity in the brain. Orthomolecular Psychiatry 1, 2–7.Google Scholar
de Rivera, J. L., Lal, S., Ettigi, P., Hontela, S., Muller, H. F. & Friesen, H. G. (1976). Effect of acute and chronic therapy on serum prolactin levels in men and women of different age groups. Clinical Endocrinology 5, 273–282.Google Scholar
Scatton, B., Glowinski, J. & Julou, L. (1976). Dopamine metabolism in the mesolimbic and mesocortical dopaminergic systems after single or repeated administrations of neuroleptics. Brain Research 109, 184–189.CrossRefGoogle ScholarPubMed
Schimmelbusch, W. H., Mueller, P. S. & Sheps, J. (1971). The positive correlation between insulin resistance and duration of hospitalisation in untreated schizophrenia. British Journal of Psychiatry 118, 429–436.CrossRefGoogle ScholarPubMed
Stein, L. & Wise, C. D. (1971). Possible etiology of schizophrenia: progressive damage to the noradrenergic reward system by 6-hydroxydopamine. Science 171, 1032–1036.Google Scholar
Vigneri, R., Pezzino, V., Squatrito, S., Calandra, A. & Maricchiolo, M. (1974). Sleep-associated growth hormone (GH) release in schizophrenia. Neuroendrocrinology 14, 356–361.CrossRefGoogle ScholarPubMed
Wilson, R. G., Hamilton, J. R., Boyd, W. D., Forrest, A. P. M., Cole, E. N., Boyns, A. R. & Griffiths, K. (1975). The effect of long-term phenothiazine therapy on plasma prolactin. British Journal of Psychiatry 127, 71–74.CrossRefGoogle Scholar
Wing, J. K., Cooper, J. E. & Sartorius, N. (1974). Measurement and Classification of Psychiatric Symptoms. Cambridge University Press: London.Google Scholar