Grant: Project Grant

Acetylcholine is a natural chemical in the brain that carries signals between brain neurons. It is released by one set of neurons, called cholinergic neurons, and attaches to muscarinic and nicotinic 'receptors' on other sets of neurons. This is known as the cholinergic system. There are several types of nicotinic and muscarinic receptors (e.g. M1, M2, M3, M4, and M5). Changes in acetycholine levels and a reduction in the number of muscarinic receptors are thought to contribute to the symptoms of schizophrenia. Many medications, including common over-the-counter medications like diphenhydramine (aka Benadryl), act on muscarinic receptors. They can produce symptoms similar to that of schizophrenia when taken at toxic doses, such as confusion and hallucinations. However, little research has focused on the role of muscarinic receptors in schizophrenia. The M2 receptor is thought to control the release of acetylcholine in the striatum, a part of the brain directly related to the symptoms of schizophrenia. M2 is the first muscarinic receptor that can be studied independent of the others using the brain imaging technique PET (Positron Emission Tomography). With the discovery of a compound the binds preferentially to M2 receptors, it is now possible to measure their amount and location within the brain. The current study therefore seeks to quantify the amount of M2 receptors in patients with schizophrenia. To do this we will: (1) compare 20 patients with good response to antipsychotic treatment with 20 healthy controls matched for age, sex, and smoking status, and (2) determine the statistical relationship between the symptoms of schizophrenia and the quantity of M2 receptors. The results of this study may lead to a new diagnostic marker for schizophrenia, increase our understanding of the pathophysiology of the disease, and provide a new target for treatment.