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PMID: 9012828 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 2 ·1997-01-21 ·Pages 587-92

Freedman R, Coon H, Myles-Worsley M, Orr-Urtreger A, Olincy A, Davis A, Polymeropoulos M, Holik J, Hopkins J, Hoff M, Rosenthal J, Waldo MC, Reimherr F, Wender P, Yaw J, Young DA, Breese CR, Adams C, Patterson D, Adler LE, Kruglyak L, Leonard S, Byerley W

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.

MeSH Terms
Auditory Perception/physiology Chromosomes, Artificial, Yeast Chromosomes, Human, Pair 15 Evoked Potentials Female Genes Genetic Linkage Genetic Markers Humans Male Pedigree Receptors, Nicotinic/genetics Schizophrenia/genetics
Chemicals
Genetic Markers Receptors, Nicotinic
Authors & Affiliations
23 authors, click to expand affiliations / ORCID
Freedman R
Department of Psychiatry, University of Colorado School of Medicine, Denver, USA.
Coon H
Myles-Worsley M
Orr-Urtreger A
Olincy A
Davis A
Polymeropoulos M
Holik J
Hopkins J
Hoff M
Rosenthal J
Waldo M C
Reimherr F
Wender P
Yaw J
Young D A
Breese C R
Adams C
Patterson D
Adler L E
Kruglyak L
Leonard S
Byerley W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.2.587
Published
1997-01-21
Pages
587-92
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC19557
Subset
IM
Grants
NCRR NIH HHS · P41 RR003655 · United States
NIDA NIH HHS · R01 DA009457 · United States
NIMH NIH HHS · MH01089 · United States
NIMH NIH HHS · MH44212 · United States
NIMH NIH HHS · MH10168-F32 · United States
NCRR NIH HHS · M01 RR000064 · United States
NIA NIH HHS · T32 AG000029 · United States
External Links
PubMed source DOI: 10.1073/pnas.94.2.587 PMC Full Text View journal details
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