title: Smoking and schizophrenia: abnormal nicotinic receptor expression.
abstract: 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 are decreased in postmortem brain of schizophrenics compared to control subjects. 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 receptor (alpha-bungarotoxin and methyllycaconitine) induce a loss of gating in rodents. 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 in both the brain and in peripheral blood cells of normal subjects, but is missing 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.
authors.affiliation: Department of Psychiatry, University of Colorado Health Sciences Center, Denver, CO 80262, USA. sherry.leonard@uchsc.edu
authors.forename: S
authors.initials: S
authors.lastname: Leonard
authors.forename: C
authors.initials: C
authors.lastname: Breese
authors.forename: C
authors.initials: C
authors.lastname: Adams
authors.forename: K
authors.initials: K
authors.lastname: Benhammou
authors.forename: J
authors.initials: J
authors.lastname: Gault
authors.forename: K
authors.initials: K
authors.lastname: Stevens
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: L
authors.initials: L
authors.lastname: Adler
authors.forename: A
authors.initials: A
authors.lastname: Olincy
authors.forename: R
authors.initials: R
authors.lastname: Ross
authors.forename: R
authors.initials: R
authors.lastname: Freedman
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D009538:Nicotine / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D012907:Smoking / Q000235:genetics* / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine