Smoking and schizophrenia: abnormal nicotinic receptor expression

Biological and genetic evidence suggests a role for the neuronal nicotinic receptors in the neuropathophysiology of schizophrenia. Nicotine normalizes an auditory evoked potential deficit seen in subjects who suffer from the disease. Nicotinic receptors with both high and low affinity for nicotine a re decreased in postmortem brain of schizophrenics compared to control subj ects. The chromosomal locus of the human alpha-7 gene (15q14) is linked to the gating deficit with a lod of 5.3, and antagonists of the alpha-7 recept or (alpha-bungarotoxin and methyllycaconitine) induce a loss of gating in r odents. We have cloned the human alpha-7 gene and found it to be partially duplicated proximal to the full-length gene. The duplication is expressed i n both the brain and in peripheral blood cells of normal subjects, but is m issing in some schizophrenic subjects. The results of these studies suggest the presence of abnormal expression and function of the neuronal nicotinic receptor gene family in schizophrenia. (C) 2000 Elsevier Science B.V. All rights reserved.