The genetics of sensory gating deficits in schizophrenia

被引:127
作者
Robert Freedman
Ann Olincy
Randall G. Ross
Merilyne C. Waldo
Karen E. Stevens
Lawrence E. Adler
Sherry Leonard
机构
[1] University of Colorado Health Sciences Center,Departments of Psychiatry and Pharmacology
关键词
Nicotine; Schizophrenia; Clozapine; Schizophrenia Patient; Nicotinic Receptor;
D O I
10.1007/s11920-003-0032-2
中图分类号
学科分类号
摘要
Sensory gating abnormalities are an early clinical symptom of schizophrenia, and are characterized by a decrease in the brain’s normal ability to inhibit the response to unimportant stimuli. Patients appear hypervigilant and have difficulty focusing their attention. A neurobiologic mechanism involved in these difficulties is nicotinic cholinergic modulation of inhibitory neuronal activity in the hippocampus. One measure of sensory gating abnormalities, diminished inhibition of the P50 evoked response to repeated auditory stimuli, has been linked to the chromosome 15q14 locus of the alpha-7-nicotinic receptor gene. This site is one of several that have shown evidence for linkage to schizophrenia, as well as to bipolar disorder, across several studies. Polymorphisms in the core promoter of the gene are associated with schizophrenia and also with diminished inhibition of the P50 response. These genetic data may identify a new pathophysiologic target for drug discovery.
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页码:155 / 161
页数:6
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