Evidence for a role of nicotinic acetylcholine receptors in schizophrenia.

Schizophrenia is a debilitating, complex and costly illness affecting roughly 1% of the world's inhabitants. The excessive degree of cigarette smoking exhibited by schizophrenic patients suggests that they might be self-medicating to ameliorate certain aspects of the characteristic positive, negative and cognitive symptoms associated with the disease. Morphological examinations found alterations in nicotinic receptors in postmortem tissue from schizophrenic individuals compared to controls, especially in the a7 and a4b2 subtypes. These data were consistent with molecular biology studies which demonstrated associations between polymorphisms in gene coding for these receptors and schizophrenia. In studies of nicotinic receptor stimulation in schizophrenia patients, improvement in sensory inhibition and cognitive deficits were observed following treatment, though the effects were transient. These results have spurred the development of new pharmaceuticals specifically designed to modulate nicotinic receptor function. The initial results from clinical trials of these new drugs appear promising, potentially opening new avenues of treatment for this devastating disease.