Article

Normalization of auditory physiology by cigarette smoking in schizophrenic patients

Department of Psychiatry, Denver VA Medical Center, CO.
American Journal of Psychiatry (Impact Factor: 13.56). 01/1994; 150(12):1856-61. DOI: 10.1176/ajp.150.12.1856
Source: PubMed

ABSTRACT Because many schizophrenic patients are heavy smokers, it has been suggested that nicotine normalizes some neuronal deficit involved in their illness. Schizophrenic subjects have various difficulties with maintenance of attention and selective processing of sensory information. One defect in sensory gating in schizophrenia has been characterized by recording auditory evoked potentials. Most normal subjects have a decrease in the evoked response to the second of two closely paired stimuli, whereas most schizophrenic subjects do not. The aim of this study was to determine whether smoking normalizes this deficit in auditory sensory gating in schizophrenia.
Changes in auditory sensory gating in response to smoking cigarettes were studied in 10 smokers without psychiatric illness and 10 schizophrenic smokers. Both groups were asked to abstain from smoking from 11:00 p.m. until 8:00 a.m. the next morning, when their auditory evoked responses to pairs of clicks were recorded. The ability to gate sensory information is reflected in a decrease in the P50 wave amplitude in response to the second of the two stimuli. After baseline recordings, the subjects smoked as much as they wished, and then two postsmoking recordings were performed.
The schizophrenic patients had a marked but brief improvement in P50 auditory gating immediately after smoking, whereas P50 gating for the normal smokers was slightly impaired.
This study suggests that cigarette smoking can transiently normalize the impairment of auditory sensory gating in schizophrenic patients.

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    • "Experimental participants attended two morning appointments (approximately one week apart), one after abstaining from nicotine from at least 11 pm (e.g. Adler et al.1993; 'abstinent'), the other in the context of usual smoking behaviour ('smoking'). The order of cognitive assessment was randomly allocated from one of six testing orders, generated using a Latin square design. "
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    ABSTRACT: Smoking prevalence in schizophrenia is significantly elevated relative to other clinical and to non-clinical groups. The cognitive self-medication hypothesis attributes this to the beneficial effects of nicotine on illness-related cognitive deficits. Significant effects of nicotine have been observed on visual spatial working memory (VSWM), sustained attention (Continuous Performance Test — Identical Pairs; CPT-IP) and prepulse inhibition (PPI). It remains unclear whether these neurophysiological and neurocognitive effects of nicotine influence self-reported smoking motivation.
    01/2015; 32(1). DOI:10.1016/j.scog.2014.12.001
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    • "There is a high prevalence of cigarette smoking among patients with schizophrenia (92–95). This may reflect an effort by schizophrenia patients to “self-medicate” clinical symptoms and a number of neurocognitive impairments including deficits in attention and memory (19) and deficient sensory gating (96). Thus, there is significant interest in developing nicotinic acetylcholine receptor (nAChR) agonists to target the neurocognitive symptoms of schizophrenia. "
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    ABSTRACT: Background: N-methyl-D-aspartate (NMDA) receptor hypofunction has been implicated in the pathophysiology of schizophrenia and its associated neurocognitive impairments. The high rate of cigarette smoking in schizophrenia raises questions about how nicotine modulates putative NMDA receptor hypofunction in the illness. Accordingly, we examined the modulatory effects of brain nicotinic acetylcholine receptor (nAChR) stimulation on NMDA receptor hypofunction by examining the interactive effects of nicotine, a nAChR agonist, and ketamine, a noncompetitive NMDA receptor antagonist, on behavioral and neurophysiological measures in healthy human volunteers.Methods: From an initial sample of 17 subjects (age range 18 - 55 years), 8 subjects successfully completed 4 test sessions, each separated by at least 3 days, during which they received ketamine or placebo and two injections of nicotine or placebo in a double-blind, counterbalanced manner. Schizophrenia-like effects (PANSS), perceptual alterations (CADSS), subjective effects (VAS) and auditory event-related brain potentials (mismatch negativity, P300) were assessed during each test session.Results: Consistent with existing studies, ketamine induced transient schizophrenia-like behavioral effects. P300 was reduced and delayed by ketamine regardless of whether it was elicited by a target or novel stimulus, while nicotine only reduced the amplitude of P3a. Nicotine did not rescue P300 from the effects of ketamine; the interactions of ketamine and nicotine were not significant. While nicotine significantly reduced MMN amplitude, ketamine did not. Conclusion: Nicotine failed to modulate ketamine-induced schizophrenia-like effects in this preliminary study. Interestingly, ketamine reduced P3b amplitude and nicotine reduced P3a amplitude, suggesting independent roles of NMDA receptor and nAChR in the generation of P3b and P3a, respectively.
    Frontiers in Psychiatry 01/2014; 5:3. DOI:10.3389/fpsyt.2014.00003
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    • "SNPs were selected from GWAS of nicotine dependence [Bousman et al., 2012], based on prior evidence that P50 sensory gating ERP is specifically related to nicotine use and nicotinic receptor function [Adler et al., 1993; Quednow et al., 2012]. In addition, four SNPs at the GLS1 locus were selected based on our prior finding of a significant association with brain measures of the glutamine/glutamate ratio using magnetic resonance spectroscopy [Ongur et al., 2011]. "
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    ABSTRACT: Genome-wide association studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) as disease associated variants for schizophrenia (SCZ), bipolar disorder (BPD), or both. Although these results are statistically robust, the functional effects of these variants and their role in the pathophysiology of SCZ or BPD remain unclear. Dissecting the effects of risk genes on distinct domains of brain function can provide important biological insights into the mechanisms by which these genes may confer illness risk. This study used quantitative event related potentials to characterize the neurophysiological effects of well-documented GWAS-derived SCZ/BPD susceptibility variants in order to map gene effects onto important domains of brain function. We genotyped 199 patients with DSM-IV diagnoses of SCZ or BPD and 74 healthy control subjects for 19 risk SNPs derived from previous GWAS findings and tested their association with five neurophysiologic traits (P3 amplitude, P3 latency, N1 amplitude, P2 amplitude, and P50 sensory gating responses) known to be abnormal in psychosis. The TCF4 SNP rs17512836 risk allele showed a significant association with reduced auditory P3 amplitude (P = 0.00016) after correction for multiple testing. The same allele was also associated with delayed P3 latency (P = 0.005). Our results suggest that a SCZ risk variant in TCF4 is associated with neurophysiologic traits thought to index attention and working memory abnormalities in psychotic disorders. These findings suggest a mechanism by which TCF4 may contribute to the neurobiological basis of psychotic illness. © 2013 Wiley Periodicals, Inc.
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