Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics.
ABSTRACT Diminished gating of the P50 auditory evoked response to repeated stimuli is a psychophysiological feature of schizophrenia, that is also present in many relatives of patients. Animal models of auditory sensory gating indicate that nicotinic cholinergic neurotransmission is a critical neuronal substrate. The aim of this experiment was to determine if the deficit in sensory gating could be reversed by nicotine administration. Nonsmoking relatives of schizophrenics with abnormal sensory gating were selected as subjects for this initial double-blind trial, to avoid effects of psychotropic medications that might complicate trials in schizophrenic patients themselves. Nicotine-containing gum increased P50 sensory gating to near normal levels within 30 min of administration. The effect was transient; the gating of P50 returned to baseline levels within 1 hr. There was no change observed after placebo administration. In one of the subjects, the anticholinesterase inhibitor physostigmine similarly normalized P50 gating. The results are consistent with the hypothesis that nicotinic cholinergic neurotransmission may mediate a familial psychophysiological deficit in schizophrenia.
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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.
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ABSTRACT: The link between P50 suppression and psychometric schizotypy was previously reported in non-clinical English-speaking subjects; however, whether a similar relationship exists within a different ethnic sample is unknown. Furthermore, whether such a relationship can also be accounted for by such basic personality characteristics as extraversion or neuroticism has not yet been reported. In the present study, we investigated the correlations of P50 suppression with psychometric schizotypy, and with extraversion or neuroticism among non-clinical Japanese. Subjects were 34 healthy volunteers. The auditory P50 potential was obtained using a paired stimulus paradigm. Psychometric schizotypy was assessed using schizotypal personality questionnaire (SPQ). Extraversion and neuroticism were assessed using Maudsley personality inventory (MPI). P50 suppression correlated not only with total SPQ score, but also with extraversion and with neuroticism. However, the partial correlation analysis revealed a significant partial correlation of P50 suppression with SPQ when controlled for extraversion or neuroticism, and a non-significant partial correlation of P50 suppression with extraversion or neuroticism when controlled for SPQ. When subjects were divided into two subgroups according to the mean SPQ score, the degree of P50 suppression was lower in the high than in the low SPQ scorers. Our results indicate that P50 suppression is one of the neurobiological substrates underlying psychometric schizotypy, and that this relationship cannot be accounted for by measures of extraversion or neuroticism.International Journal of Psychophysiology 01/2004; DOI:10.1016/S0167-8760(03)00228-9 · 2.65 Impact Factor
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ABSTRACT: Although the attention-enhancing effects of nicotine have been behaviorally and neurophysiologically well-documented, its localized functional effects during selective attention are poorly understood. In this study, we examined the neuronal effects of nicotine during auditory selective attention in healthy human nonsmokers. We hypothesized to observe significant effects of nicotine in attention-associated brain areas, driven by nicotine-induced increases in activity as a function of increasing task demands. A single-blind, prospective, randomized crossover design was used to examine neuronal response associated with a go/no-go task after 7 mg nicotine or placebo patch administration in 20 individuals who underwent functional magnetic resonance imaging at 3T. The task design included two levels of difficulty (ordered vs. random stimuli) and two levels of auditory distraction (silence vs. noise). Significant treatment × difficulty × distraction interaction effects on neuronal response were observed in the hippocampus, ventral parietal cortex, and anterior cingulate. In contrast to our hypothesis, U and inverted U-shaped dependencies were observed between the effects of nicotine on response and task demands, depending on the brain area. These results suggest that nicotine may differentially affect neuronal response depending on task conditions. These results have important theoretical implications for understanding how cholinergic tone may influence the neurobiology of selective attention.Psychopharmacology 12/2014; DOI:10.1007/s00213-014-3832-7 · 3.99 Impact Factor