Hostname: page-component-7479d7b7d-c9gpj Total loading time: 0 Render date: 2024-07-12T04:52:09.690Z Has data issue: false hasContentIssue false

The use of cholecystokinin in schizophrenia: a review

Published online by Cambridge University Press:  09 July 2009

Stuart A. Montgomery*
Affiliation:
Department of Psychiatry, St Mary's Hospital Medical School, London
Mary C. D. Green
Affiliation:
Department of Psychiatry, St Mary's Hospital Medical School, London
*
1Address for correspondence: Dr S. A. Montgomery, Department of Psychiatry, St Mary's Hospital Medical School, Praed Street, London W2.

Synopsis

Cholecystokinin (CCK) is a peptide originally isolated from the gut. It has been investigated as a candidate treatment for schizophrenia on the assumption that the illness is associated with an imbalance between CCK and dopamine in the mesolimbic dopamine system. Many of the studies to assess the efficacy of CCK used open designs and are prone to observer bias and over-optimistic reporting. Most of the studies used CCK as an adjunct to standard neuroleptic treatment and are too small to be able to demonstrate extra efficacy above that of the active compound. Only three out of ten studies using CCK or placebo as an adjunct to neuroleptics reported limited efficacy. Of the 14 placebo-controlled reports only three were in drug-free patients. These were unfortunately too small, or too brief, to draw valid conclusions of efficacy. A summary of these data suggests that although 500 patients have received CCK, its efficacy in the treatment of schizophrenia has not been properly tested.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1988

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

Albus, M., Ackenheil, M., Munch, U. & Naber, D. (1984). Ceruletide: a new drug for the treatment of schizophrenic patients? Archives of General Psychiatry 41, 258.Google Scholar
Albus, M., von Gellhorn, K., Munch, U., Naber, D. & Ackenheil, M. (1986). A double blind study with ceruletide in chronic schizophrenic patients: biochemical and clinical results. Psychiatry Research 19, 17.Google Scholar
Bech, P., Kastrup, M. & Rafaelsen, O. J. (1986). Mini-compendium of rating scales for states of anxiety, depression, mania, schizophrenia with corresponding DSM-III syndromes. Acta Pyschiatrica Scandinavica 326, 3237.Google ScholarPubMed
Bloom, D. M., Nair, M. D. & Schwartz, G. (1983). CCK-8 in the treatment of chronic schizophrenia. Psychopharmacology Bulletin 19, 361363.Google Scholar
Boza, R. A. & Retondo, D. J. (1985). Is cholecystokinin therapeutic in chronic schizophrenia? Journal of Clinical Psychiatry 46, 485486.Google ScholarPubMed
Chang, R. S. L., Lotti, V. J., Martin, G. E. & Chen, T. B. (1983). Increase in brain 125-I-Cholecystokinin (CCK) receptor binding following chronic haloperidol treatment, intracisternal 6-hydroxydopamine or ventral tegmental lesions. Life Science 32, 871878.Google Scholar
Crow, T. J. (1980). Molecular pathology of schizophrenia, more than one disease process? British Medical Journal 280, 6668.CrossRefGoogle ScholarPubMed
Dockray, G. J., Gregory, R. A., Hutchinson, J. B., Harris, J. L. & Runswick, M. J. (1977). Isolation, structure and biological activity of two cholecystokinin octapeptides from sheep brain. Nature 270, 359361.Google Scholar
Emson, P. C. & Sandberg, B. E. B. (1983). Cholecystokinin and Substance-P in the central nervous system. Annual Report of Medical Chemistry 18, 3139.Google Scholar
Farmery, S. M., Owen, F., Poulter, M. & Crow, T. J. (1985). Reduced high affinity cholecystokinin binding in hippocampus and frontal cortex of schizophrenic patients Life Science 36, 473477.Google Scholar
Ferrier, I. N., Roberts, G. W., Crow, T. J., Johnstone, E. C., Owens, D. G. C., Lee, Y. C., O'Shaughnessy, D., Adrian, T. E., Polak, J. M. & Bloom, S. R. (1983). Reduced cholecystokinin-like and somatostatin-like immunoreactivity in limbic lobe is associated with negative symptoms in schizophrenia. Life Science 33, 475482.Google Scholar
Frey, P. (1983). Cholecystokinin octapeptide levels in rat brain are changed after subchronic neuroleptic treatment. European Journal of Pharmacology 95, 8792.CrossRefGoogle ScholarPubMed
Fuxe, K., Andersson, K., Lacatelli, V., Agnati, L. F., Hokfelt, T., Skirboll, L. & Mutt, V. (1980). Cholecystokinin peptides produce masked reduction of dopamine turnover in discrete areas in the rat brain following intraventricular injection. European Journal of Pharmacology 67, 325331.Google Scholar
Gerner, R. H. & Yamada, T. (1982). Altered neuropeptide concentrations in cerebrospinal fluid of psychiatric patients. Brain Research 238, 298302.Google Scholar
Gerner, R. H., van Kammen, D. P. & Ninan, P. T. (1985). Cerebrospinal fluid cholecystokinin, bombesin and somatostatin in schizophrenia and normals. Progress in Neuro-Psychopharmacology and Biological Psychiatry 9, 7382.CrossRefGoogle ScholarPubMed
Govoni, S., Yang, H.-Y. T., Bosio, A., Pasinetti, G. & Costa, E. (1982). Possible interaction between cholecystokinin and dopamine. In Regulatory Peptides: From Molecular Biology to Function (ed. Costa, E. and Trabucchi, M.), pp. 437444. Raven Press: New York.Google Scholar
Hokfelt, T., Rehfeld, J. F., Skirboll, L., Ivenmark, B., Goldstein, M. & Markey, K. (1980 a). Evidence for co-existence of dopamine and CCK in mesolimbic neurons. Nature 285 476478.CrossRefGoogle Scholar
Hokfelt, T., Johannson, O., Ljungdahl, A., Lundberg, J. M. & Schultzberg, M. (1980 b). Peptidergic neurones. Nature 284, 515521.CrossRefGoogle ScholarPubMed
Hommer, D. W., Pickar, D. Roy, A., Ninan, P., Boronow, J. & Paul, S. M. (1984). The effects of ceruletide in schizophrenia. Archives of General Psychiatry 41, 617619.CrossRefGoogle ScholarPubMed
Hommer, D. W., Pickar, D., Crawley, J. N., Weingartner, H. & Paul, S. M. (1985). The effects of cholecystokinin-like peptides in schizophrenics and normal subjects. Annals New York Academy of Science 448, 542551.Google Scholar
Innis, R. B., Correa, F. M., Uhl, G. R., Schneider, B. & Snyder, S H. (1979). Cholecystokinin octapeptide-like immunoactivity: histochemical localisation in rat brain. Proceedings of the National Academy of Science (USA) 76, 521525.Google Scholar
Itoh, H., Tanoue, J., Yagi, G., Tateyama, M., Kamisada, M., Fujii, Y., Takamiya, M. & Nakajima, S. (1982). Clinical study on the psychotropic effects of Caerulein – an open clinical trial in chronic schizophrenic patients. Keio Journal of Medicine 31, 7195.CrossRefGoogle ScholarPubMed
Itoh, H., Shimazono, Y., Kawakita, Y., Kudo, Y., Satoh, Y. & Takahashi, R. (1986). Clinical evaluation of ceruletide in schizophrenia: a multi-institutional cooperative double-blind controlled study. Psychopharmacology Bulletin 22, 123128.Google ScholarPubMed
Kleinman, J. E., Govoni, S., Memo, M., Hanbauer, I. & Wyatt, R. J. (1982). Cholecystokinin and Calmodulin in schizophrenic brains, 37th Annual Meeting of the Society of Biological Psychiatry,12–16 May,Toronto. Abstract 98, p. 129.Google Scholar
Koulischer, G., Moroder, L. & Deschodt-Lanceman, M. (1982). Degradation of Cholecystokinin Octopeptide, related fragments and analogs by human and rat plasma in vitro. Regulatory Peptides 4, 127139.Google Scholar
Krieger, D. T. & Martin, J. B. (1981). Brain peptides. New England Journal of Medicine 304, 876885.CrossRefGoogle ScholarPubMed
Kudo, Y. (1983). The effect of ceruletide on chronic schizophrenia. Abstracts of the VIIth World Congress of Psychiatry,11–16 July,Vienna, Abstract K.14.Google Scholar
Lotstra, F., Verbanck, P., Mendlewicz, J. & Vanderhaeghen, J. J. (1984). No evidence of antipsychotic effect of caerulein in schizophrenic patients free of neuroleptics: a double blind crossover study. Biological Psychiatry 19, 877882.Google Scholar
Mattes, J. A., Hom, W., Rochford, J. M. & Orlosky, M. (1985). Ceruletide for Schizophrenia: a double blind study. Biological Psychiatry 20, 533538.Google Scholar
Montgomery, S., Taylor, P. & Montgomery, D. (1978). Development of a schizophrenia scale sensitive to change. Neuropharmacology 17, 10611062.CrossRefGoogle ScholarPubMed
Moroji, T., Watanabe, N., Aoki, N. & Itoh, S. (1982). Antipsychotic effects of caerulein, a decapeptide chemically related to cholecystokinin octapeptide on schizophrenia. International Pharmacopsychiatry 17, 255273.Google Scholar
Moroji, T., Itoh, K. & Itoh, K. (1985). Antipsychotic effects of ceruletide in chronic schizophrenia. Annals New York Academy of Science 448, 518533.CrossRefGoogle ScholarPubMed
Mutt, V. & Jorpes, J. E. (1968). Structure of porcine cholecystokinin–pancreozymin. 1. Clearage with thrombin and trypsin. European Journal of Biochemistry 6, 156162.CrossRefGoogle Scholar
Nakamura, G., Nobuyama, M. & Kudo, Y. (1984). Antipsychotic effect of ceruletide as a sole agent. 14th C.I.N.P. Conference.Florence, Italy. Abstract F-5.Google Scholar
Nair, N. P. V., Bloom, D. M., Debonnel, G., Schwartz, G. & Mosticyan, S. (1984). Cholecystokinin octapeptide in chronic schizophrenia: a double blind placebo-controlled study. Progress in Neuropsychopharmacology and Biological Psychiatry 8, 711714.CrossRefGoogle ScholarPubMed
Nair, N. P. V., Bloom, D. M. & Nesteros, J. N. (1982). Cholecystokinin appears to have antipsychotic properties. Programme of Neuropsychopharmacology and Biological Psychiatry 6, 509512.Google Scholar
Nair, N. P. V., Bloom, D. M. Nesteros, J. N. & Schwartz, G. (1983). Therapeutic efficacy of cholecystokinin in neuroleptic-resistant schizophrenic subjects. Psychopharmacological Bulletin 19, 134136.Google Scholar
Nair, N. P. V., Bloom, D., Lal, S., Debonnel, G., Schwartz, G. & Mosticyan, S. (1985 a). Clinical and neuroendocrine studies with cholecystokinin peptides. Annals New York Academy of Science 448, 535541.Google Scholar
Nair, N. P. V., Lal, S. & Bloom, D. M. (1985 b). Cholecystokinin peptides, dopamine and schizophrenia – a review. Progress in Neuro-Psychopharmacology and Biological Psychiatry 9, 515524.CrossRefGoogle ScholarPubMed
Perry, R. H., Dockray, G. J., Dimaline, R., Perry, E. K., Blessed, G. & Tomlinson, B. E. (1981). Neuropeptides in Alzheimer's disease, depression and schizophrenia Journal of Neurological Science 51 465472.Google Scholar
Peselow, E., Angrist, B., Sudilovsky, A., Corwin, J., Siekierski, J., Trent, F. & Rotrosen, J. (1987). Double blind controlled trials of cholecystokinin octapeptide in neuroleptic-refractory schizophrenia. Psychopharmacology 91 8084.Google Scholar
Piazza, E., Brambilla, M., Cattaneo, M. T. & Martin, A. (1981). Analgesic activity of ceruletide in cancer patients. In International Symposium on Brain Gut Axis: The New Frontier (ed. Basso, N., Le Zoche, E., Speronza, V. and Walsh, J. H.), abstract p. 146. Florence.Google Scholar
Pinget, M., Straus, E. & Yalow, R. S. (1979). Release of cholecystokinin peptides from a synaptosome-enriched fraction of rat cerebral cortex. Life Science 25, 339342.Google Scholar
Pugh, C. R., Steinert, J. & Priest, R. G. (1983). Propranolol in schizophrenia: a double blind, placebo-controlled trial of propranolol as an adjunct to neuroleptic medication. British Journal of Psychiatry 143, 151155.Google Scholar
Rehfeld, J. F., Golterman, N., Larsson, L. I., Emson, P. M. & Lee, C. M. (1979). Gastrin and cholecystokinin in central and periphery neurons. Federation Proceedings 38 23252329.Google Scholar
Straus, E., Muller, J. E., Choi, H. S., Paronetto, F. & Yalow, R. S. (1978). Immunohistochemical localization in rabbit brain of a peptide resembling the COOH-terminal octapeptides of cholecystokinin. Proceedings of the National Academy of Science (USA) 74, 30333034.Google Scholar
Tamminga, C. A., Lewitt, P. & Chase, T. N. (1985). Cholecystokinin and neurotensin gradients in human cerebrospinal fluid. Archives of Neurology 42, 354355.CrossRefGoogle Scholar
Tamminga, C. A., Littman, R. L., Alphs, L. D., Chase, T. N., Tuaker, G. K. & Wagman, A. M. (1986). Neuronal cholecystokinin and schizophrenia: pathogenic and therapeutic studies. Psychopharmacology 88, 387391.CrossRefGoogle ScholarPubMed
Verbanck, P. M. P., Lotstra, F., Giles, C., Linkowski, P., Mendlewicz, J. & Vanderhaeghen, J. J. (1984). Reduced cholecystokinin immunoreactivity in the cerebrospinal fluid of patients with psychiatric disorder. Life Science 34, 6772.Google Scholar
Verhoeven, W. M. A., Westenberg, H. G. M. & Van Ree, J. M. (1986). A comparative study on the antipsychotic properties of desenkephalin – endorphin and ceruletide in schizophrenic patients. Acta Psychiatrica Scandinavica 73, 372382.Google Scholar
Van Ree, J. M., Gaffori, O. & De Wied, D. (1983). In rats the behavioural profile of CCK-8 related peptides resembles that of antipsychotic agents. European Journal of Pharmacology 93, 6378.Google Scholar
Van Ree, J. M., Verhoeven, W. M. A., Brouvers, G. J. & De Wied, D. (1984). Ceruletide resembles antipsychotics in rats and schizophrenics. Neuropsychobiology 12, 48.Google Scholar
Yamagani, S. Hirayama, E., Mori, K. & Kawakita, Y. (1986). Dose effect relationship of ceruletide in the treatment of neuroleptic-resistant schizophrenia. Current Therapeutic Research 39, 10441053.Google Scholar
Zetler, G. (1983). Neuroleptic-like effects of ceruletide and cholecystokinin octapeptide: interactions with apomorphine, nethylphenidate and picrotoxin. European Journal of Pharmacology 94, 261270.Google Scholar