Schizophrenia, Sensory Gating, and Nicotinic Receptors

Abstract

A series of human and animal investigations has suggested that altered expression and function of the alpha7-nicotinic cholinergic receptor may be responsible for the auditory sensory gating deficit characterized in schizophrenia patients and their relatives as diminished suppression of an auditory-evoked response (P50) to repeated stimuli. This finding, in conjunction with evidence for familial transmission of this sensory gating deficit, suggests a pathogenic role of the gene for the alpha7-nicotinic receptor in schizophrenia. This article considers the possible effects of this dysfunction in a broader context. Not only is this dysfunction consistent with difficulties in sensory gating, but it might also predispose patients to problems with learning efficiency and accuracy. Such learning problems could underlie schizophrenia patients' delusional thinking, hallucinations, and social dysfunction. In addition, heavy smoking in many schizophrenia patients is consistent with the high concentration of nicotine necessary to activate the receptor and with the receptor's extremely rapid desensitization. Finally, the receptor's possible role in cell growth and differentiation should be considered in connection with developmental deficits and other cellular abnormalities in schizophrenia.

The translationally relevant mouse model of the 15q13.3 microdeletion syndrome reveals deficits in neuronal spike firing matching clinical neurophysiological biomarkers seen in schizophrenia

“…This study further provides deeper understanding and confidence in the face validity of this model, because decreased AEP amplitudes have repeatedly been reported in patients with schizophrenia (Adler et al . 1998, de Wilde et al . 2007, Light et al .…”

α7 Nicotinic Receptor Agonists: Potential Therapeutic Drugs for Treatment of Cognitive Impairments in Schizophrenia and Alzheimer’s Disease

“…Moreover, an association has been demonstrated between the homozygous 113 bp allele on the D15S1360 polymorphism of the CNRNA7 gene and smoking risk in schizophrenia [63]. Taken together, these results suggest that the CHRNA7 gene is likely susceptible to the deficits of P50 sensory gating in schizophrenia [10, 23, 44, 49, 50, 53, 58, 63-67]. Interestingly, a 2 bp deletion in exon 6 of CHRFAM7A, which disrupts the hybrid gene for the CHRNA7 gene, was associated with episodic memory performance in schizophrenia, suggesting that the CHRFAM7A/CHRNA7 locus plays a role in modulating episodic memory function [68].…”

Overview of the pharmacogenomics of cigarette smoking

“…144 Nicotine can transiently reduce deficit of the P50-auditory evoked-potential, a physiological indicator of the illness. 145 In schizophrenics, a polymorphism in intron 2 of CHRNA7 was associated with smoking status. 146 Interestingly, the region near CHRNA7 on chromosome 15q13.1 has been associated with habitual smoking in a genome-wide linkage scan (Table 1).…”