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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics. 145 Feb 87

Diminished neuronal response to repeated sensory input is a sensory-gating phenomenon that has been found to be deficient in schizophrenic patients. For example, schizophrenic patients fail to decrease the amplitude of the P50 wave of the auditory evoked potential to the second of paired click stimuli. In some studies, however, normal subjects have also failed to decrease their P50 responses. The aim of this study was to determine if accommodation to the recording situation over time would affect the gating of the P50 response. The gating of the P50 wave is measured as the ratio of the amplitude of the second response to the amplitude of the first. Three successive auditory evoked potentials were compiled, each from trains of 32 pairs of stimuli. Twelve normal subjects and 12 schizophrenic patients were studied. Unconjugated catecholamine metabolites were measured from venous samples drawn before and after the electrophysiological recording. Between the first and third trials, the normal subjects significantly increased their gating of P50. This increase in gating of P50 was related to decreased levels of the noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol. No similar phenomenon was observed in the schizophrenic patients, a number of whom had a further decrease in P50 gating over the three trials. Transient failure to observe gating of P50 in normal subjects may be related to increased state-dependent noradrenergic activity, which is known to disrupt sensory gating. This mechanism does not seem to account for the more persistent failure of sensory gating in schizophrenia.
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PMID:Auditory sensory gating and catecholamine metabolism in schizophrenic and normal subjects. 146 44

This paper describes an elementary deficit in sensory processing in people with schizophrenia. If paired sounds are presented to normal subjects, the response to the first sound, as measured by the P50 wave of the auditory-evoked potential, is much greater than the response to the second sound. The diminished response to the second sound is an example of a sensory gating mechanism that enables people to regulate their vigilance so that they can either detect all sounds in the environment or ignore most of them, in favor of narrowing the focus of their concentration. In schizophrenia, this mechanism is usually deficient; patients are in a state of hypervigilance and have diminished abilities to focus their attention. The deficiency appears to be genetically determined and to involve the brainstem control of sensory input to the hippocampus. Such sensory gating deficits may underlie more complex psychotic symptoms, such as hallucinations and delusions. Further studies of their neurobiology could lead to increased understanding of the pathophysiology of schizophrenia.
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PMID:Elementary neuronal dysfunctions in schizophrenia. 164 90

Because the clinical diagnosis of schizophrenia has not generally been an adequate phenotypic marker to detect the genes that convey risk for schizophrenia, efforts have been directed toward the identification of more elementary neuronal dysfunctions in schizophrenic patients and their families. Psychophysiological studies of sensory gating and selective attention suggest that defects in these brain functions are present in schizophrenic patients and some of their relatives. This study examines one of these defects in sensory gating, failure to suppress the P50 evoked response to repeated auditory stimuli. Six pedigrees, chosen because of the presence of large sibships containing several cases of schizophrenia, were studied. A mathematical model was developed to assess the familial association of the P50 defect with schizophrenia. The model preserves the quantitative nature of the data and is suitable for use in a sample with small numbers of pedigrees comprising many individuals. It is thus suitable for the evaluation of putative phenotypes in families to be studied by linkage analysis with polymorphic genetic markers. The results suggest that the P50 defect is familially associated with schizophrenia.
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PMID:Codistribution of a sensory gating deficit and schizophrenia in multi-affected families. 179 24

The auditory evoked component P50 has been reported as having an abnormal recovery cycle in patients with schizophrenia. Recent studies examining the effects of stimulus rate on the midlatency response (MLR) component P1, found P1 recovery cycles in normals similar to P50. This study examined the P1 recovery cycle in patients using a rate protocol and MLR recording procedures. MLRs were recorded from 13 controls and 13 patients with schizophrenia in response to binaurally presented clicks presented at three stimulus rates: 0.9/sec, 5.1/sec, and 9.9/sec. The P1 (50-70 msec latency) in patients did not decrease as much in amplitude as in controls at the 9.9/sec stimulus rate. This lack of recovery was correlated with clinical ratings of symptomatology. Since evidence from both the human and the cat model suggests that the P1 is generated in thalamus, these findings are consistent with reports of thalamic dysfunction in schizophrenia.
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PMID:Midlatency auditory evoked responses in schizophrenia. 193 93

In a paired click "conditioning (S1), Testing (S2)" paradigm the amplitudes of responses to (S1) as well as the degree of attenuation of S2 as compared to S1 (S2/S1) were studied in two schizophrenic groups. Thirteen undifferentiated/disorganized (US) and thirteen paranoid (PS) patients were compared to thirteen age and sex matched normal volunteers. The US patients had significantly lower (S1) response amplitudes (P less than 0.001), as well as degree of attenuation of the response to (S2) (P less than 0.001) than the other two groups. No significant differences were found between the PS and N groups. Our data replicates the prior finding of decreased attenuation of the amplitude of the P50 wave in a paired click paradigm in schizophrenia. In addition, we showed that this phenomenon is significant mainly in the disorganized/undifferentiated patients as compared to the paranoid schizophrenics.
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PMID:Replication and extension of P50 findings in schizophrenia. 199 11

The differences between schizophrenic patients with positive and negative symptoms have been the subject of extensive investigations. Psychophysiologists have proposed that there are elementary auditory sensory processing deficits in schizophrenia, but their prevalence in particular positive or negative subtypes has not been described. Our previous studies have shown that schizophrenics have impaired auditory sensory gating relative to normal controls, as demonstrated by the P50 auditory evoked potential conditioning-testing paradigm. In this paradigm, schizophrenics fail to show the normally expected diminished response to the second or 'test' stimulus. In the present study we assessed the possible relationship of this defect to negative symptoms in 20 schizophrenic patients treated with neuroleptics. Nine patients met the Andreasen criteria for predominantly 'negative schizophrenia'. 12 normal controls with no family history of schizophrenia were also studied electrophysiologically. Negative schizophrenics showed greater impairment than patients without such symptoms on the Trails B test of organic impairment, but there were no differences between groups on electrophysiological measurements of auditory sensory gating. Both schizophrenic groups showed impaired P50 auditory gating compared to normal controls. Both groups of schizophrenics also had a significantly diminished amplitude of the N100 waveform in the conditioning response, compared to normal controls. Auditory sensory processing defects in schizophrenia appear to be independent of negative symptoms.
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PMID:Lack of relationship of auditory gating defects to negative symptoms in schizophrenia. 227 77

Acutely ill psychiatric inpatients were examined for a deficit in sensory gating, measured as failure to suppress the P50 wave of the auditory-evoked response to the second of paired stimuli. Previously, we had found that in mania, this sensory gating deficit is correlated with increased plasma-free levels of the noradrenergic metabolite 3-methoxy, 4-hydroxyphenylglycol (pMHPG), whereas in schizophrenia, there is no correlation with catecholamine metabolism. To assess the generalizability of these findings, we examined inpatients with a broader range of diagnoses, including those with multiple DSM III-R Axis I, II, and III diagnoses. The patients were grouped into three diagnostic spectra for analysis: schizophrenic, manic, and depressive. In the schizophrenic patients, there was no relationship between pMHPG or other catecholamine metabolites and the sensory gating deficit. In manic patients, however, a positive correlation between pMHPG level and the sensory gating deficit was again observed. This relationship did not extend to the depressive patients, who uniquely showed sensory gating deficits that correlated negatively with the severity of their illness. The data suggest that sensory gating deficits are common to these three diagnostic spectra, but the deficits in each group have different relationships to catecholamine metabolism and symptom severity that may reflect differences in the underlying neuronal pathophysiology of these illnesses.
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PMID:Sensory gating deficits in psychiatric inpatients: relation to catecholamine metabolites in different diagnostic groups. 231 Aug 7

In a series of investigations, suppression of the auditory-evoked P50 potential to the second of two paired clicks presented 500 msec apart has been shown to be absent in schizophrenic patients, whereas normals suppress their second response to less than 20% of the first response. The phenomenon has been discussed as a possible trait marker for schizophrenia. The present study with 19 schizophrenics and 23 healthy control subjects was intended as an extended replication of the phenomenon using different stimulus parameters and a slightly different method of measuring P50 amplitudes. Replication was unsuccessful, revealing only weak suppression scores in normal subjects not significantly superior to schizophrenics. Retest sessions yielded generally stronger P50 suppression suggesting that the stability of the measure over time is questionable. The methodological changes are discussed as possible sources of this failure to replicate. It is concluded that the conditions under which P50-suppression occurs should be better clarified in order to facilitate replication.
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PMID:Sensory gating in normals and schizophrenics: a failure to find strong P50 suppression in normals. 228 2

The sensory disturbance in schizophrenia is often described as an inability to filter out extraneous noise from meaningful sensory inputs. The neurobiological basis of this inability to filter has been examined using auditory evoked potentials, which are computerized averages of the brain's electrical response to sound. The sounds are presented in pairs to test the ability of the brain to inhibit, or gate, its response to a repeated stimulus. Schizophrenic patients lack the ability to gate the neuronal response shown by a particular wave, the P50 wave. The measurement of this deficit in human subjects and the exploration of its neurobiology in animals has produced evidence about several issues in the pathophysiology of schizophrenia: (1) the role of dopamine in improvement of sensory function in schizophrenic patients treated with neuroleptic drugs, (2) the interaction between familial or genetic deficits in sensory functioning in schizophrenic patients and possible abnormalities in dopamine metabolism, and (3) a mechanism by which noradrenergic hyperactivity in mania and other psychiatric illnesses might mimic some pathophysiological deficits in schizophrenia.
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PMID:Neurobiological studies of sensory gating in schizophrenia. 289 74


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