title: Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus.
abstract: Inheritance of a defect in a neuronal mechanism that regulates response to auditory stimuli was studied in nine families with multiple cases of schizophrenia. The defect, a decrease in the normal inhibition of the P50 auditory-evoked response to the second of paired stimuli, is associated with attentional disturbances in schizophrenia. Decreased P50 inhibition occurs not only in most schizophrenics, but also in many of their nonschizophrenic relatives, in a distribution consistent with inherited vulnerability for the illness. Neurobiological investigations in both humans and animal models indicated that decreased function of the alpha 7-nicotinic cholinergic receptor could underlie the physiological defect. In the present study, a genome-wide linkage analysis, assuming autosomal dominant transmission, showed that the defect is linked [maximum logarithm of the odds (lod) score = 5.3 with zero recombination] to a dinucleotide polymorphism at chromosome 15q13-14, the site of the alpha 7-nicotinic receptor. Despite many schizophrenics' extremely heavy nicotine use, nicotinic receptors were not previously thought to be involved in schizophrenia. The linkage data thus provide unique new evidence that the alpha 7-nicotinic receptor gene may be responsible for the inheritance of a pathophysiological aspect of the illness.
authors.affiliation: Department of Psychiatry, University of Colorado School of Medicine, Denver, USA.
authors.forename: R
authors.initials: R
authors.lastname: Freedman
authors.forename: H
authors.initials: H
authors.lastname: Coon
authors.forename: M
authors.initials: M
authors.lastname: Myles-Worsley
authors.forename: A
authors.initials: A
authors.lastname: Orr-Urtreger
authors.forename: A
authors.initials: A
authors.lastname: Olincy
authors.forename: A
authors.initials: A
authors.lastname: Davis
authors.forename: M
authors.initials: M
authors.lastname: Polymeropoulos
authors.forename: J
authors.initials: J
authors.lastname: Holik
authors.forename: J
authors.initials: J
authors.lastname: Hopkins
authors.forename: M
authors.initials: M
authors.lastname: Hoff
authors.forename: J
authors.initials: J
authors.lastname: Rosenthal
authors.forename: M C
authors.initials: MC
authors.lastname: Waldo
authors.forename: F
authors.initials: F
authors.lastname: Reimherr
authors.forename: P
authors.initials: P
authors.lastname: Wender
authors.forename: J
authors.initials: J
authors.lastname: Yaw
authors.forename: D A
authors.initials: DA
authors.lastname: Young
authors.forename: C R
authors.initials: CR
authors.lastname: Breese
authors.forename: C
authors.initials: C
authors.lastname: Adams
authors.forename: D
authors.initials: D
authors.lastname: Patterson
authors.forename: L E
authors.initials: LE
authors.lastname: Adler
authors.forename: L
authors.initials: L
authors.lastname: Kruglyak
authors.forename: S
authors.initials: S
authors.lastname: Leonard
authors.forename: W
authors.initials: W
authors.lastname: Byerley
mesh_terms: D001307:Auditory Perception / Q000502:physiology*; D018244:Chromosomes, Artificial, Yeast; D002884:Chromosomes, Human, Pair 15; D005071:Evoked Potentials; D005260:Female; D005796:Genes; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008297:Male; D010375:Pedigree; D011978:Receptors, Nicotinic / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D011978:Receptors, Nicotinic