The promoter −194 C polymorphism of the nicotinic alpha 7 receptor gene has a protective effect against the P50 sensory gating deficit
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.
Full-textDOI: · Available from: Florence Thibaut, Apr 03, 2014
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- "Patients with schizophrenia usually show defi cits in both paradigms: PPI (e.g., Aggernaes et al. 2010; Braff et al. 1978), P50 suppression: (e.g., Adler et al. 1982; Boutros et al. 1991; Oranje et al. 2013). There is some evidence indicating that gating defi cits can be ameliorated by among others, nicotine (Adler et al. 1993; Raux et al. 2002; Houy et al, 2004) and α 2a-noradrenergic agonists (Oranje and Glenth ø j 2013, 2014). P50 suppression and PPI defi cits are considered as interesting endophenotypes in schizophrenia. "
ABSTRACT: The neurophysiological components that have been proposed as biomarkers or as endophenotypes for schizophrenia can be measured through electroencephalography (EEG) and magnetoencephalography (MEG), transcranial magnetic stimulation (TMS), polysomnography (PSG), registration of event-related potentials (ERPs), assessment of smooth pursuit eye movements (SPEM) and antisaccade paradigms. Most of them demonstrate deficits in schizophrenia, show at least moderate stability over time and do not depend on clinical status, which means that they fulfil the criteria as valid endophenotypes for genetic studies. Deficits in cortical inhibition and plasticity measured using non-invasive brain stimulation techniques seem promising markers of outcome and prognosis. However the utility of these markers as biomarkers for predicting conversion to psychosis, response to treatments, or for tracking disease progression needs to be further studied.The World Journal of Biological Psychiatry 08/2015; 16(5):280-90. DOI:10.3109/15622975.2015.1050061 · 4.18 Impact Factor
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- "Schizophrenic patients are usually heavy smokers (Dickerson et al., 2013) and smoking is often considered a type of selfmedication which is very much in accordance with deficits in the cholinergic system (Moran et al., 2012). In schizophrenia, the gene for the alpha 7 receptor subunit was found to be related to deficits in sensory gating (Raux et al., 2002; Houy et al., 2004; Martin et al., 2007). In addition, visual acuity was found to be low in CHRNA7 knockout mice (Origlia et al., 2012). "
ABSTRACT: The obvious symptoms of schizophrenia are of cognitive and psychopathological nature. However, schizophrenia affects also visual processing which becomes particularly evident when stimuli are presented for short durations and are followed by a masking stimulus. Visual deficits are of great interest because they might be related to the genetic variations underlying the disease (endophenotype concept). Visual masking deficits are usually attributed to specific dysfunctions of the visual system such as a hypo- or hyper-active magnocellular system. Here, we propose that visual deficits are a manifestation of a general deficit related to the enhancement of weak neural signals as occurring in all other sorts of information processing. We summarize previous findings with the shine-through masking paradigm where a shortly presented vernier target is followed by a masking grating. The mask deteriorates visual processing of schizophrenic patients by almost an order of magnitude compared to healthy controls. We propose that these deficits are caused by dysfunctions of attention and the cholinergic system leading to weak neural activity corresponding to the vernier. High density electrophysiological recordings (EEG) show that indeed neural activity is strongly reduced in schizophrenic patients which we attribute to the lack of vernier enhancement. When only the masking grating is presented, EEG responses are roughly comparable between patients and control. Our hypothesis is supported by findings relating visual masking to genetic deviants of the nicotinic α7 receptor (CHRNA7).Frontiers in Psychology 05/2013; 4:254. DOI:10.3389/fpsyg.2013.00254 · 2.80 Impact Factor
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- "In a case–control study, Stephens et al. (2009) detected that rs3087454 ()1831C > A) was significantly associated with schizophrenia . Houy et al. (2004) found that )194G > C in the core promoter region of CHRNA7 was associated with P50 sensory gate deficit. Hong et al. (2004) reported that a )2 bp deletion polymorphism in the duplicated CHRNA7 gene might play a role in the pathogenesis of bipolar disorders patients. "
ABSTRACT: Alpha 7 nicotinic acetylcholine receptor, a kind of ligand-gated ion channel mainly expressed in macrophages, plays a crucial role in improving survival in sepsis via suppressing proinflammatory cytokines. The predisposition of genomic polymorphisms within alpha 7 nicotinic acetylcholine receptor gene (CHRNA7) to sepsis has not been investigated. The current association study was performed to analyse six common genetic variations within 5'-upstream region of CHRNA7 gene in 229 patients with severe sepsis and 267 controls. Neither allelic frequencies nor genotype distributions were significantly different between patients and controls, as well as between surviving and nonsurviving patients. The frequencies of estimated haplotypes were also comparable between above defined groups. The present study suggests that genomic polymorphisms in the 5'-upstream region of CHRNA7 gene may not be a major risk factor for severe sepsis in Chinese Han population.International Journal of Immunogenetics 10/2010; 37(5):361-5. DOI:10.1111/j.1744-313X.2010.00933.x · 1.25 Impact Factor