Journal Article

Nicotinic Receptor Function in Schizophrenia

Sherry Leonard, Catherine Adams, Charles R. Breese, Lawrence E. Adler, Paula Bickford, William Byerley, Hilary Coon, Jay M. Griffith, Christine Miller, Marina Myles-Worsley, Herbert T. Nagamoto, Yvonne Rollins, Karen E. Stevens, Merilyne Waldo and Robert Freedman

in Schizophrenia Bulletin

Published on behalf of Maryland Psychiatric Research Center

Volume 22, issue 3, pages 431-446
Published in print January 1996 | ISSN: 0586-7614
e-ISSN: 1745-1701 | DOI: http://dx.doi.org/10.1093/schbul/22.3.431
Nicotinic Receptor Function in Schizophrenia

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Schizophrenia can be partially characterized by deficits in sensory processing. Biochemical, molecular, and genetic studies of one such endophenotype, the P50 auditory-evoked potential gating deficit, suggest that one of the neuronal nicotinic receptors, the α7 nicotinic receptor, may function in an inhibitory neuronal pathway involved in this phenotype. The P50 deficit is normalized in nongating subjects by nicotine. Although most schizophrenia patients are heavy smokers, the effects of nicotine may be transient, as α7 receptors are known to desensitize rapidly. In an animal model of the P50 gating deficit, antagonists of the α7 nicotinic receptor block normal gating of the second of paired auditory stimuli. Regional localization of receptor expression includes areas known to function in sensory filtering. An inhibitory mechanism, in the hippocampus, may involve nicotinic stimulation of γ-aminobutyric acid (GABA)ergic interneurons, resulting in decreased response to repetitive stimuli. Expression of the α7 receptor is decreased in hippocampal brain tissue, dissected postmortem, from schizophrenia subjects. The P50 deficit is inherited in schizophrenia pedigrees, but it is not sufficient for disease development and thus represents a predisposition factor. Linkage analysis between the P50 deficit in multiplex schizophrenia pedigrees and deoxyribonucleic acid (DNA) markers throughout the genome yielded positive lod scores to DNA markers mapping to a region of chromosome 15 containing the α7 nicotinic receptor gene. Elucidation of possible interactions of the P50 with other factors, known to be important in the etiology of the disease, is important in determining an overall pathobiology of schizophrenia.

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Subjects: Child and Adolescent Psychiatry

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