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
来源：
Current Psychiatry Reports | 2003年 / 5卷 / 2期
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.
引用
收藏
页码：155 / 161
页数：6
相关论文
共 187 条
[1]  
Freedman R(1994)Schizophrenia and nicotinic receptors Harv Rev Psychiatry 2 179-192
[2]  
Adler LE(1997)Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus Proc Natl Acad Sci U S A 94 587-592
[3]  
Bickford P(2002)Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia Mol Psychiatry 6 293-301
[4]  
Freedman R(2002)Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia Proc Natl Acad Sci U S A 99 13675-13680
[5]  
Coon H(2001)Effect of COMT val 108/158 met genotype on frontal lobe function and risk for schizophrenia Proc Natl Acad Sci U S A 98 6917-6922
[6]  
Myles-Worsley M(20002)Genetic variation in the 6p22.3 gene DTNBP1, the human orthology of the mouse dysbindin gene is associated with schizophrenia Am J Hum Genet 7 337-348
[7]  
Mirnics K(1982)Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia Biol Psychiatry 17 639-654
[8]  
Middleton FA(1991)Replication and extension of P50 findings in schizophrenia Clin Electroencephalogr 22 40-45
[9]  
Stanwood GD(1992)Sensory gating deficits in schizophrenia: new results Am J Psychiatry 149 488-493
[10]  
Chumakov I(1997)Effects of P50 temporal variability on sensory gating in schizophrenia Psychiatry Res 70 71-81
12345678910