Hostname: page-component-5447f9dfdb-6cxwp Total loading time: 0 Render date: 2025-07-30T01:54:09.572Z Has data issue: false hasContentIssue false
  • English
  • Français

Cholinergic aspects of schizophrenia

Published online by Cambridge University Press:  06 August 2018

Rajiv Tandon
Rajiv Tandon*
Affiliation:
Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109-0120, USA
Get access Rights & Permissions [Opens in a new window]

Abstract

While increased dopamine activity is central to our current understanding of the pathophysiology of schizophrenia, dysregulation of a single neurotransmitter is unlikely to explain the disorder adequately. It is argued here that the muscarinic aspects of schizophrenia should be reassessed for a number of reasons. These include current evidence that cholinergic modulation affects both positive and negative symptoms, and neuroendocrine and polysomnographic data that suggest an increased muscarinic cholinergic activity in schizophrenia. In addition, the interactions between the dopaminergic and cholinergic systems are becoming better understood and appear to occur especially in regions that are thought to be relevant in schizophrenia. The fact that the highest affinity of clozapine, with its unique therapeutic profile, is to the muscarinic receptor encourages further evaluation. Finally, the use of anticholinergic agents to treat extrapyramidal side-effects and the fact that many antipsychotic agents have intrinsic anticholinergic activity suggest that the role of the cholinergic system in schizophrenia needs to be more clearly delineated.

Information

Type
Research Article
Information
The British Journal of Psychiatry , Volume 174 , Issue S37: Focus on schizophrenia , February 1999 , pp. 7 - 11
Copyright
Copyright © The Royal College of Psychiatrists, 1999 

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.)

Article purchase

Temporarily unavailable

References

Andreasen, N. C. & Olsen, S. (1982) Negative vs positive schizophrenia: definition and validation. Archives of General Psychiatry, 39, 789–794.Google Scholar
Angrist, B., Rotrosen, J. & Gershon, S. (1980) Differential effects of amphetamine and neuroleptics on negative versus positive symptoms in schizophrenia. Psychopharmacology, 72, 17–19.Google Scholar
Bolden, C., Cusack, B. & Richelson, E. (1991) Clozapine is a potent and selective muscarinic antagonist at the five cloned human muscarinic acetylcholine receptors expressed in the CHO-KI cells. European Journal of Pharmacology, 1921, 205–206.Google Scholar
Bolden, C., Cusack, B. & Richelson, E. (1992) Antagonism by antimuscarinic and neuroleptic compounds at the cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. Journal of Pharmacology and Experimental Therapeutics, 260, 379–389.Google Scholar
Buchsbaum, M. S. (1990) The frontal lobes, basal ganglia, and temporal lobes as sites for schizophrenia. Schizophrenia Bulletin, 16, 379–389.CrossRefGoogle ScholarPubMed
Carlsson, A. (1974) Antipsychotic drugs and catecholamine synapses. Journal of Psychiatric Research, 11, 57–64.Google Scholar
Carpenter, W. T., Jr, Heinrichs, D. W. & Wagman, A. M. I. (1988) Deficit and nondeficit forms of schizophrenia: the concept. American Journal of Psychiatry, 145, 578–583.Google Scholar
Chouinard, G., Annable, L., Mercier, P., et al (1987) Long-term effects of L-dopa and procyclidine on neuroleptic-induced extrapyramidal and schizophrenic symptoms. Psychopharmacology Bulletin, 23, 221–226.Google Scholar
Cohen, L. H., Thale, T. & Tissenbaum, M. J. (1944) Acetylcholine treatment of schizophrenia. Archives of Neurology and Psychiatry, 51, 171–175.Google Scholar
Crow, T.J. (1980) Molecular pathology of schizophrenia: more than one disease process? British Medical Journal, 280, 1–9 Google Scholar
Fayen, M., Goldman, M. B., Moulthrop, M. A., et al (1988) Differential memory function with dopaminergic versus anticholinergic treatment of drug-induced extrapyramidal symptoms. American Journal of Psychiatry, 145, 483–486.Google Scholar
Fisch, R. Z. (1987) Trihexyphenidyl abuse: therapeutic implications for negative symptoms of schizophrenia. Acta Psychiatrica Scandinavica, 75, 91–94.Google Scholar
Friedhoff, A. J. & Alpert, M. (1973) A dopaminergic-cholinergic mechanism in production of psychotic symptoms. Biological Psychiatry, 6, 165–169.Google ScholarPubMed
Goff, D. C., Amico, E., Dreyfuss, D., et al (1994) A placebo-controlled trial of trihexyphenidyl in unmedicated patients with schizophrenia. American Journal of Psychiatry, 151, 429–431.Google ScholarPubMed
Hinze-Selch, D., Mullington, J., Orth, A., et al (1997) Effects of clozapine on sleep: a longitudinal study. Biological Psychiatry, 42, 260–266.Google Scholar
Janowsky, D. S., El-Yousef, M. K., Davis, J. M., et al (1973) Antagonist effects of physostigmine and methylphenidate in man. American Journal of Psychiatry, 130, 1370–1376.Google Scholar
Jibson, M. D. & Tandon, R. (1996) A summary of new research findings on the new antipsychotic drugs. Essential Psychopharmacology, 1, 27–37.Google Scholar
Johnstone, E. C., Crow, T. J., Ferrier, I. N., et al (1983) Adverse effects of anticholinergic medication on positive schizophrenic symptoms. Psychological Medicine, 13, 513–527.Google Scholar
Kane, J. M., Honigfeld, G., Singer, J., et al (1988) Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine. Archives of General Psychiatry, 45, 789–796.Google Scholar
Meltzer, H. Y., Chai, B. L., Thompson, P. A., et al (1994) Effect of scopolamine on the efflux of dopamine and its metabolites after clozapine, haloperidol, or thioridazine. Journal of Pharmacology and Experimental Therapeutics, 268, 1452–1461.Google Scholar
Meltzer, H. Y., & Stahl, S. M. (1976) The dopamine hypothesis of schizophrenia: a review. Schizophrenia Bulletin, 2, 19–76.Google Scholar
Richelson, E. (1984) Neuroleptic affinities for human brain receptors and their use in predicting adverse effects. Journal of Clinical Psychiatry, 45, 331–336.Google ScholarPubMed
Riemann, D., Gann, H., Fleckenstein, P., et al (1994) Effect of RS 86 on REM latency in schizophrenia. Psychiatry Research, 38, 89–92.Google Scholar
Rivest, R. & Marsden, C. A. (1991) Muscarinic antagonists attenuate the increase in accumbens and striatum dopamine metabolism produced by clozapine but not by haloperidol. British Journal of Pharmacology, 104, 234–238.CrossRefGoogle Scholar
Singh, M. M., Kay, S. R. & Opler, L. A. (1987) Anticholinergic-neuroleptic antagonism in terms of positive and negative symptoms of schizophrenia: implications for psychobiological subtyping. Psychological Medicine, 17, 39–48.CrossRefGoogle ScholarPubMed
Tandon, R. (1997) Effects of atypical antipsychotics on polysomnographic measures in schizophrenia. Bibliotheca Psychiatrica, 167, 219–222.Google Scholar
Tandon, R., Greden, J. F. & Silk, K. R. (1988) Treatment of negative schizophrenic symptoms with trihexyphenidyl. Journal of Clinical Psychopharmacology, 8, 212–215.Google Scholar
Tandon, R. & Greden, J. F. (1989) Cholinergic hyperactivity and negative schizophrenic symptoms: a model of dopaminergic/cholinergic interactions in schizophrenia. Archives of General Psychiatry, 46, 745–753.CrossRefGoogle Scholar
Tandon, R., Goldman, R.,Goodson, J., et al (1990a) Mutability and relationship between positive and negative symptoms during neuroleptic treatment in schizophrenia. Biological Psychiatry, 27, 1323–1326.Google Scholar
Tandon, R., Mann, N., Eisner, W., et al (1990b) Effect of anticholinergic medication on positive and negative symptoms in medication-free schizophrenic patients. Psychiatry Research, 31, 235–241.Google Scholar
Tandon, R., Greden, J. F., Goodson, J., et al (1991a) Muscarinic hyperactivity in schizophrenia: relationship to positive and negative symptoms. Schizophrenia Research, 4, 23–30.Google Scholar
Tandon, R., Mazzara, C., DeQuardo, J., et al (1991b) Dexamethasone suppression test in schizophrenia: relationship to symptomatology, ventricular enlargement, and outcome. Biological Psychiatry, 29, 953–964.CrossRefGoogle ScholarPubMed
Tandon, R., DeQuardo, J. R., Goodson, J., et al (1992a) Effect of anticholinergics on positive and negative symptoms in schizophrenia. Psychopharmacology Bulletin, 28, 297–302.Google Scholar
Tandon, R., Shipley, J. E., Taylor, S., et al (1992b) Electroencephalographic sleep abnormalities in schizophrenia: relationship to positive/negative symptoms and prior neuroleptic treatment. Archives of General Psychiatry, 49, 185–194.Google Scholar
Tandon, R. & Kane, J. M. (1993) Neuropharmacologic basis for clozapine's unique profile. Archives of General Psychiatry, 50, 157–159.Google Scholar
Tandon, R., Goldman, R., DeQuardo, J. R., et al (1993a) Covariance of positive and negative symptoms during clozapine treatment in schizophrenia. Journal of Psychiatric Research, 27, 341–347.CrossRefGoogle Scholar
Tandon, R., Ribeiro, S. C. M., DeQuardo, J. R., et al (1993b) Covariance of positive and negative symptoms during neuroleptic treatment in schizophrenia: a replication. Biological Psychiatry, 34, 495–497.Google Scholar
Tandon, R., Jibson, M., Taylor, S. F., et al (1995) The pathophysiology of positive and negative symptoms in schizophrenia. In Contemporary Issues in the Treatment of Schizophrenia (eds C. Shriqui & H. A. Nasrallah), pp. 190–224. Washington, DC: American Psychiatric Press.Google Scholar
Tandon, R., Lewis, C., Taylor, S. F., et al (1996) Relationship between DST nonsuppression and shortened REM latency in schizophrenia. Biological Psychiatry, 40, 660–663.Google Scholar
Tandon, R., DeQuardo, J. R., & Taylor, S. F. (1999) Neurobiology of schizophrenia. In Textbook of Psychopharmacology (ed. Ananth, J.). New Delhi: Jaypee Brothers (in press).Google Scholar
Yeoman, O. (1995) Role of tegmental cholinergic neurons in dopaminergic activation, antimuscarinic psychosis and schizophrenia. Neuropsychopharmacology, 12, 3–16.CrossRefGoogle Scholar
Zeng, X. P., Le, F. & Richelsen, E. (1997) Muscarinic M4 receptor activation by some atypical antipsychotic drugs. European Journal of Pharmacology, 321, 349–354.Google Scholar
Zorn, S. H., Jones, S. B., Ward, K. M., et al (1994) Clozapine is a potent and selective muscarinic M4 receptor agonist. European Journal of Pharmacology, 269, RI–R2.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.