Role of the cholinergic system in the pathology and treatment of schizophrenia

Schizophrenia is a devastating psychiatric disorder; the diagnosis probably encompasses a number of illnesses with similar clinical presentations, complicating both treatment and studies into the pathology of the disorder. The development of antipsychotic medications revolutionized treatment for the disorder. However, there are still symptom domains that are relatively untouched by the drugs currently available; these are the cognitive deficits and the negative symptoms. Basic research strongly supports a role of acetylcholine in cognitive processes, making it a primary target for drugs designed to improve this most impairing symptom. In addition, the fact that acetylcholine can modulate dopamine release makes the cholinergic system a target for novel antipsychotic drugs, ideally without the side-effect profiles that contribute to patient noncompliance seen with current antipsychotic drugs. Thus far, the results of clinical trials with cholinomimetics have been equivocal; where beneficial effects are seen they are, by and large, modest rather than compelling. These trials and studies investigating the role of both nicotinic and muscarinic receptors in the pathology of the disorder, published during the last 5 years, are reviewed to ascertain whether there is a role for the cholinergic system in the treatment of schizophrenia.