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Cholinergic mechanisms in schizophrenia: Current concepts

Abstract

Although the neurotransmitter dopamine plays a prominent role in the treatment of schizophrenia, the dopamine hypothesis fails to explain several aspects of the disorder. It is evident that the pathophysiology of schizophrenia involves other neurotransmitter systems as well. In this review, we discuss the increasing data implicating the cholinergic system in its pathogenesis. Cholinergic neurotransmission plays a crucial role in various central nervous system functions. The cholinergic system consists of two families of receptors, the muscarinic cholinergic and the nicotinic cholinergic, that use acetylcholine as a neurotransmitter. Data from clinical pharmacology, neuroimaging, and postmortem studies suggest an alteration of the muscarinic cholinergic system in schizophrenia. Muscarinic agonists are being evaluated as new treatment options with putative antipsychotic and cognition enhancing properties. Smoking is highly prevalent among schizophrenic subjects. Nicotine improves attention in schizophrenia. Nicotinic receptors, in particular the α7 nicotinic receptor, are candidates for the development of new medications to treat cognitive and perceptual deficits in schizophrenia. This review summarizes the evidence in support of a role for the muscarinic cholinergic system and the nicotinic cholinergic system in the pathophysiology of schizophrenia. As current treatments fail to sufficiently address all aspects of schizophrenia, promising new pharmacologic approaches that focus on the cholinergic system are currently under development.

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Raedler, T.J., Tandon, R. Cholinergic mechanisms in schizophrenia: Current concepts. Current Psychosis & Therapeutics Reports 4, 20–26 (2006). https://doi.org/10.1007/BF02629410

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Keywords

  • Nicotine
  • Schizophrenia
  • Clozapine
  • Muscarinic Receptor
  • Nicotinic Receptor