Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients suffering from schizophrenia are known to show an increased prevalence of nicotine addiction. The aim of this paper is to elucidate the relationship between schizophrenia and (chronic) use of nicotine. Nicotine seems to improve cognitive functions critically affected in schizophrenia, in particular sustained attention, focused attention, working memory, short-term memory, and recognition memory. Furthermore, several studies using evoked potentials (P50 paradigm) and prepulse inhibition of the acoustic startle reflex suggest that deficient preattentive information processing, a core feature of schizophrenia illness, is improved following treatment with nicotine. Smoking can also improve extrapyramidal secondary effects of antipsychotic medication and it induces cytochrome P4501A2, an enzyme system involved in the metabolism of several antipsychotics. There is substantial evidence that nicotine could be used by patients with schizophrenia as a "self-medication" to improve deficits in attention, cognition, and information processing and to reduce side effects of antipsychotic medication. Possible pharmacotherapeutic approaches for the regulation of abnormal neurotransmission at nicotinic acetylcholine receptors are discussed.
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PMID:[Why do schizophrenic patients smoke?]. 1544 20

Suppression of the P50 component of the evoked potential is an electrophysiological index of sensory gating that is blunted in schizophrenia spectrum disorders. Although P50 suppression is thought to be related to symptomatology, this is yet to be shown. The failure to demonstrate this relation has led some to argue that P50 suppression and symptomatology are not related. However, a possible confound has recently been corroborated [i.e., chronic smoking is related to superior P50 suppression [Crawford et al., Neuroscience Letters 317 (2002) 151]], and a relation has been found in questionnaire-defined individuals with indications of schizotypy [i.e., psychometric schizotypy is related to poor P50 suppression [Croft et al., Biological Psychiatry 50 (2001) 441]]. The present study attempted to replicate and extend both studies by examining P50 suppression, smoking histories, psychometric schizotypy and NEO Five-Factor Inventory (NEO-V) scores in 37 healthy participants. Replicating Crawford et al., P50 suppression was better in the heavier smokers. Providing a partial replication of Croft et al., P50 suppression was inversely related to schizotypy scores in participants who smoked little or not at all; however, P50 suppression was positively related to schizotypy in heavier smokers. Covarying for age and NEO-V scale scores had little effect on these relations. The findings provide evidence of important confounds that would limit our ability to detect P50 suppression/symptom relations in schizophrenia.
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PMID:Suppression of P50 evoked potential component, schizotypal beliefs and smoking. 1545 Sep 14

Schizophrenic patients are thought to have an impaired ability to process sensory information. This deficit leads to disrupted auditory gating measured electrophysiologically as a reduced suppression of the second of paired auditoryevoked responses (P50) and is proposed to be associated with decreased function and/or expression of the homomeric alpha7 nicotinic acetylcholine receptor (nAChR). Here, we provide evidence that N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-282987), a novel selective agonist of the alpha7 nAChR, evoked whole-cell currents from cultured rat hippocampal neurons that were sensitive to the selective alpha7 nAChR antagonist methyllycaconitine (MLA) and enhanced GABAergic synaptic activity when applied to hippocampal slices. Amphetamine-induced sensory gating deficit, determined by auditory-evoked potentials in hippocampal CA3 region, was restored by systemic administration of PNU-282987 in chloral hydrate-anesthetized rats. Auditory gating of rat reticular thalamic neurons was also disrupted by amphetamine; however, PNU-282987 normalized gating deficit only in a subset of tested neurons (6 of 11). Furthermore, PNU-282987 improved the inherent hippocampal gating deficit occurring in a subpopulation of anesthetized rats, and enhanced amphetamine-induced hippocampal oscillation. We propose that the alpha7 nAChR agonist PNU-282987, via modulating/enhancing hippocampal GABAergic neurotransmission, improves auditory gating and enhances hippocampal oscillatory activity. These results provide further support for the concept that drugs that selectively activate alpha7 nAChRs may offer a novel, potential pharmacotherapy in treatment of schizophrenia.
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PMID:The selective alpha7 nicotinic acetylcholine receptor agonist PNU-282987 [N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride] enhances GABAergic synaptic activity in brain slices and restores auditory gating deficits in anesthetized rats. 1552 1

The paper presents a review of recent data on research and clinical significance of gating of the P50 component of the auditory evoked potentials (AEP). Information filters are a necessary element for the proper functioning of the brain. It appears as though they have an important role in the information-transfer mechanisms. Neurophysiologically, they appear hypothetically in the sensory gating of the P50 component of the AEP. Schizophrenic patients and their first degree relatives do not have proper sensory gating of the P50 AEP. This suggests that there is a common biological base for these disorders. Some clinical aspects of the schizophrenic psychoses can be linked to this disordered gating. There are also notes which show the contrary. Currently we do not know whether the improper sensory gating of the P50 AEP is a trait endophenotypically linked to schizophrenia, or only something that partially explains the pathophysiology of the illness--especially since the described phenomena may be evoked in healthy persons.
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PMID:[P50 sensory gating disorders of auditory evoked potentials (AEP) in persons with schizophrenia]. 1552 30

The human alpha7 neuronal nicotinic receptor subunit gene has been considered as a candidate gene for P50 sensory gating deficit in schizophrenic patients. Because P50 sensory gating deficit is a common neurophysiological dysfunction in patients with schizophrenia and schizophrenia spectrum disorders, it is conceivable to hypothesize that the human alpha7 neuronal nicotinic receptor subunit gene might be a susceptible gene for schizophrenia. Researchers have reported that mutations in the protein-coding sequences of the human alpha7 neuronal nicotinic receptor subunit gene are very rare. Therefore, we searched for mutations at the promoter region of the human alpha7 neuronal nicotinic receptor subunit gene and performed a genetic association study in 249 unrelated Han Chinese schizophrenic patients and 273 non-psychotic subjects from Taiwan. Two molecular variants were identified and designated g.-213G>A and g.-324A>G, respectively. The g.-213G>A variant was found to obliterate a putative NF-1 transcription factor binding site using computer analysis. One out of 249 patients was detected to be a heterozygote for this variant, but none of 273 control subjects was. The g.-324A>G variant was also very rare in both patients and control subjects, only one heterozygote of this variant was identified in 249 patients and 273 control subjects, respectively. Hence, in this study, we did not find mutations in the human alpha7 neuronal nicotinic receptor subunit gene that are associated with schizophrenia in our population.
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PMID:Identification of molecular variants at the promoter region of the human alpha 7 neuronal nicotinic acetylcholine receptor subunit gene but lack of association with schizophrenia. 1553 Oct 77

Impaired auditory sensory gating is considered characteristic of schizophrenia and a marker of the information processing deficit inherent to that disorder. Predominance of negative symptoms also reflects the degree of deficit in schizophrenia and is associated with poorer pre-morbid functioning, lower IQ, and poorer outcomes. However, a consistent relationship between auditory sensory gating and negative symptoms in schizophrenia has yet to be demonstrated. The absence of such a finding is surprising, since both impaired auditory gating and negative symptoms have been linked with impaired fronto-temporal cortical function. The present study measured auditory gating using the P50 event related potential (ERP) in a paired-click paradigm and capitalized on the relative localization advantage of magnetoencephalography (MEG) to assess auditory sensory gating in terms of the event related field (ERF) M50 source dipoles on bilateral superior temporal gyrus (STG). The primary hypothesis was that there would be a positive correlation between lateralized M50 auditory sensory gating measures and negative symptoms in patients with schizophrenia. A standard paired-click paradigm was used during simultaneous EEG and MEG data collection to determine S2/S1 sensory gating ratios in a group of 20 patients for both neuroimaging techniques. Participants were administered the Schedule for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptom Scale (PANSS), and the Calgary Depression Scale for Schizophrenia. Consistent with previous reports, there was no relationship between ERP P50 sensory gating and negative symptoms. However, right (not left) hemisphere ERF M50 sensory gating ratio was significantly and positively correlated with negative symptoms. This finding is compatible with information processing theories of negative symptoms and with more recent findings of fronto-temporal abnormality in patients with predominantly negative symptoms.
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PMID:M50 sensory gating predicts negative symptoms in schizophrenia. 1565 76

Individuals with schizophrenia are known to exhibit diminished auditory gating, as manifested by prepulse inhibition of the startle response and suppression of the P50 evoked potential. Those observations indicate that schizophrenics have deficits of inhibitory auditory processing. The precedence effect is a phenomenon in which inhibitory processing in the auditory system aids the localization of sound sources and segregation of speech in complex auditory environments. We tested the hypothesis that schizophrenic subjects would exhibit deficits in psychophysical tests of the precedence effect. The performance of 12 male medicated schizophrenic subjects was compared with that of 12 male comparison subjects. Schizophrenics and comparison subjects clearly demonstrated all three aspects of the precedence effect that were evaluated: echo suppression, buildup of echo suppression, and breakdown of echo suppression. In none of these aspects did the performance of schizophrenic subjects differ significantly from that of the comparison subjects. These findings suggest that abnormalities of auditory spatial processing and speech segregation are unlikely to contribute to the clinical pathology of schizophrenia.
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PMID:Auditory gating in schizophrenia: a pilot study of the precedence effect. 1565 78

Recent developments in neuroscience, especially in neuropsychology and neuroimaging, have shed light on cognitive dysfunction in schizophrenia. Cognitive dysfunction may be the underlying basis of schizophrenic symptoms and also the vulnerability marker such as an endophenotype used in genetic studies. Among various cognitive functions, attention is currently focused on "social cognition" as a new realm of research which it may determine the social and occupational abilities of patients with schizophrenia. Recent studies indicate that the second-generation antipsychotics may improve some aspects of cognitive dysfunction in schizophrenia. This urges us to reveal whether such drugs also improve the long-term prognosis as well as quality of life of the patients. Although cognitive function has usually been evaluated by neuropsychological tests, it is advisable to employ electroencephalogram especially event-related potential, which has high time resolution, in combination with neuroimaging with high spatial resolution. In this paper, studies with event-related potentials including P50, MMN, Nd, NA, P300, and N400 are reviewed and we propose a pathophysiological model of schizophrenia from the viewpoint of information processing. The model consists of a controlled processing system (e. g., perceptual organization, and semantic integration) and regulatory system which is mainly automatic processing and enables the controlled processing to be efficient. We postulate that both systems will be primarily affected in schizophrenia and that disruptions in the regulatory system from any cause will impose. further burden on the controlled system and lead to psychosis. Finally, comprehensive and sophisticated assessment of these systems will be required in schizophrenia research.
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PMID:[Cognitive dysfunction and electroencephalogram in schizophrenia]. 1592 Sep 43

Physiological deficits in inhibition of the P50 auditory evoked potential in schizophrenia have been related to diminished expression of alpha7 nicotinic acetylcholine receptors. Diminished P50 inhibition is correlated with neuropsychological deficits in attention, one of the principal neurocognitive disturbances in schizophrenia. Nicotine administration improves P50 inhibition, presumably by achieving additional activation of these diminished receptors, but its toxicity and marked tachyphylaxis make it an ineffective therapeutic. Nicotine also has weak positive effects on several neurocognitive deficits in schizophrenia, which raises the possibility that the alpha7 nicotinic receptor is a clinically relevant therapeutic target that should be addressed by less toxic agents. Tropisetron, a drug already approved for clinical use outside the United States as an anti-emetic, is a partial agonist at alpha7 nicotinic receptors and an antagonist at 5-HT(3) receptors. As an initial proof-of-principle study, we determined that a single administration of tropisetron significantly improves P50 inhibition in schizophrenia. These data are consistent with biological activity at a pathophysiological mechanism in schizophrenia and support further trials of this drug as a possible therapeutic for neurocognitive deficits in schizophrenia.
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PMID:Tropisetron improves deficits in auditory P50 suppression in schizophrenia. 1592 99

Auditory P50/M50 paired-click studies have established an association between schizophrenia and impaired sensory gating in the auditory modality. However, the presumed cross-modal generality of the gating deficit has received little study. The present study examined gating in area 3b of primary somatosensory cortex to evaluate patients' somatosensory gating at this first stage of cortical processing. One hundred twenty-two channels of magnetoencephalography (MEG) data were collected from 27 subjects with chronic schizophrenia and 21 controls during a somatosensory paired-pulse paradigm with a 75- or 500-ms interstimulus interval. M20 somatosensory responses were localized using magnetic source imaging, and a gating ratio was calculated. In a subset of these subjects, MEG was also done for the standard auditory paradigm to assess M50 gating. Patients showed abnormal auditory M50 gating but normal somatosensory M20 gating. Results argue against a cross-modal gating deficit in primary somatosensory cortex.
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PMID:Cross-modal generality of the gating deficit. 1594 86


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