Abstract
As suggested by several studies, abnormal sensory gating measured by the P50 paradigm could be an endophenotype predisposing to schizophrenia. In a previous work, we have shown a significant association between the presence of at least one −2 bp deletion located within exon 6 of the CHRNA7-like gene and the P50 abnormality in the general population. A recent study involved polymorphisms located in the core promoter region of the CHRNA7 gene as risk factors for the P50 inhibitory deficit. Screening for promoter variants in a large population of schizophrenic patients (n=111) and control subjects (85), for whom auditory-evoked potentials had been recorded did not allow us to replicate these results. By contrast, we showed a significant association between the −194 C allele and a T/C ratio <0.45, thus demonstrating a protective effect of this variant for the sensory gating deficit. Such conflicting results can be reconciled if we consider that the −194 C polymorphism has no causative effect, but is in linkage disequilibrium with other causal variations for the P50 sensory gating deficit, and that different alleles are in disequilibrium in different populations.
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References
Freedman R, Adler LE, Leonard S . Alternative phenotypes for the complex genetics of schizophrenia. Biol Psychiatry 1999; 45: 551–558.
Leonard S, Adams C, Breese CR, Adler LE, Bickford P, Byerley W et al. Nicotinic receptor function in schizophrenia. Schizophrenia Bull 1996; 22: 431–444.
Freedman R, Coon H, Myles-Worsley M, Orr-Urtreger A, Olincy A, Davis A et al. Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci USA 1997; 94: 587–592.
Gault J, Robinson M, Berger R, Drebing C, Logel J, Hopkins J et al. Genomic organization and partial duplication of the human alpha 7 neuronal nicotinic acetylcholine receptor gene (CHRNA7). Genomics 1998; 52: 173–185.
Raux G, Bonnet-Brilhault F, Louchart S, Houy E, Gantier R, Levillain D et al. The −2 bp deletion in exon 6 of the alpha 7-like nicotinic receptor subunit gene is a risk factor for the P50 sensory gating deficit. Mol Psychiatry 2002; 7: 1006–1011.
Leonard S, Gault J, Hopkins J, Logel J, Vianzon R, Short M et al. Association of the promoter variants in the α7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia. Arch Gen Psychiatry 2002; 59: 1085–1096.
Kathman N, Engel R . Sensory gating in normals and schizophrenics: a failure to find strong P50 suppression in normals. Biol Psychiatry 1990; 27: 1216–1226.
Bramon E, Stagias K, Croft RJ, McDonald C, Muray RM . The P50 waveform is normal in people with schizophrenia and their relatives. Schizophrenia Res 2002; 53: 214.
American Psychiatry Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn revised American Psychiatric Press: Washington, DC, 1994.
Fyer AJ, Endicott J, Manuzza S, Klein DF . Schedule for affective disorders and schizophrenia—lifetime version modified for the study of anxiety disorders. In: Anxiety Disorders Clinic. Psychiatric Institute Press: New York State, NY, 1985.
Louchart-de la Chapelle S, Levillain D, Ménard JF, Van Der Elst A, Allio G, Haouzir S et al. P50 inhibitory gating deficit is correlated with the negative symptomatology of schizophrenia. Psychiatry Res 2003, (in press).
Freedman R, Adler A, Waldo M . Gating of the auditory evoked potential in children and adults. Psychophysiology 1987; 24: 223–227.
Nagamoto HT, Adler LE, Waldo M, Griffith J, Freedman R . Gating of auditory response in schizophrenics and normal controls. Effects of recording site and stimulation interval on the P50 wave. Schizophrenia Res 1991; 4: 31–40.
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This study was supported by a grant from Pfizer.
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Houy, E., Raux, G., Thibaut, F. et al. The promoter −194 C polymorphism of the nicotinic alpha 7 receptor gene has a protective effect against the P50 sensory gating deficit. Mol Psychiatry 9, 320–322 (2004). https://doi.org/10.1038/sj.mp.4001443
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DOI: https://doi.org/10.1038/sj.mp.4001443
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