The genetics of sensory gating deficits in schizophrenia.
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.
Freedman
Robert
R
Departments of Psychiatry and Pharmacology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, C-268-71, Denver, CO 80262, USA. robert.freedman@UCHSC.edu
Olincy
Ann
A
Ross
Randall G
RG
Waldo
Merilyne C
MC
Stevens
Karen E
KE
Adler
Lawrence E
LE
Leonard
Sherry
S
D001921:Brain / Q000503:physiopathology*; D006801:Humans; D009433:Neural Inhibition / Q000502:physiology; D010468:Perceptual Disorders / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics; D012559:Schizophrenia / Q000150:complications* / Q000503:physiopathology*; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005680:gamma-Aminobutyric Acid / Q000235:genetics
C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005680:gamma-Aminobutyric Acid