Is P50 suppression a measure of sensory gating in schizophrenia?

2014

Background: P50 amplitude changes in dual click conditioning-testing procedure might be a neurophysiological marker of deficient sensory gating in schizophrenia. However, the relationship between abnormalities in the neurophysiological and phenomenological dimensions of sensory gating in schizophrenia remains unclear. The aim of the present study was to determine if patients with low P50-suppression (below 50%) report more perceptual anomalies. Methods: Three groups were compared: twenty-nine schizophrenia patients with high P50-suppression (above 50% amplitude suppression), twenty-three schizophrenia patients with low P50-suppression (below 50%) and twenty-six healthy subjects. The Sensory Gating Inventory (SGI), a four-factor self-report questionnaire, was used to measure perceptual anomalies related to sensory gating. A comparison of demographic and clinical data was also carried out. Results: Patients with low P50-suppression presented: i) significantly higher scores on the SGI (for the overall SGI score and for each of the 4 factors) and ii) significantly larger P50 amplitude at the second click, than both patients with high P50-suppression and healthy subjects. There were no group differences in the most of demographic and clinical data. Discussion: The finding offers support for conceptual models wherein abnormal neurophysiologic responses to repetitive stimuli give rise to clinically relevant perceptions of being inundated and overwhelmed by external sensory stimuli. Further studies are needed to explore the contributions of clinical symptoms, medication and neuropsychological functions to the relationship between P50-suppression and the SGI, and the role of sensory "gating in" versus "gating out".

Schizophrenia Research, 2013

Impaired inhibition of P50 cerebral evoked response is one of the best validated endophenotypes in schizophrenia. There are controversial data on the relationship between P50 evoked potential deficit and measures of cognitive function in schizophrenia. A comprehensive clinical and neurocognitive assessment plus an evaluation of P50 sensory gating was performed in 160 schizophrenia patients and 64 controls. Neurocognitive scores from each cognitive domain were converted to demographically-adjusted T-scores (age, gender, and years of education) for all study participants. The relationship between P50 and neurocognitive variables was assessed via parametric and nonparametric correlations and categorical strategies: we compared neuropsychological test scores in patients and controls in the lowest P50 quartile vs. the highest. Controls had better performance than schizophrenia patients in all cognitive domains. Schizophrenia patients had significantly higher P50 ratios than controls, and no significant correlation was found between P50 gating measures and neuropsychological test scores in schizophrenia patients or healthy controls. Moreover, no differences in neurocognitive performance were found between subjects in the lowest P50 ratio quartile vs. the highest in healthy controls or patients with schizophrenia. We concluded that there is no evidence of an association between P50 ratio and cognitive measures in schizophrenia patients, and this seems to be also the case in healthy controls.

2006

A large percentage of patients with schizophrenia are characterized by an abnormality in P50 sensory gating. This abnormality has been shown to be genetically linked to the a-7 nicotinic receptor and is transiently reversed by acute nicotine administration. These observations have led to the development of pharmacological treatments designed to improve sensory gating. However, if normalization of P50 gating abnormalities is to guide drug development, then it becomes important to delineate the clinical correlates of enhanced P50 gating. We conducted a review of all available articles through March 2005 that have examined this issue. We found that, despite the prominent role that P50 abnormalities have played in our understanding of schizophrenia, there is a relative dearth of data examining P50 clinical correlates. There is evidence suggestive of an association between P50 and measures of attention, and multiple studies have failed to document a cross-sectional or longitudinal relationship between P50 and positive, negative, or other symptoms. These results suggest that considerably more work needs to be done to understand and validate the clinical significance of this impairment.

Psychiatry Research, 2008

Many studies have found that the P50 sensory gating ratio in a paired click task is smaller in normal control subjects than in patients with schizophrenia, indicating more effective sensory gating. However, a wide range of gating ratios has been reported in the literature for both groups. The purpose of this study was to compile these findings and to compare reported P50 gating ratios in controls and patients with schizophrenia. Current data collected from individual controls in eight studies from the University of California, Irvine (UCI), Indiana University (IU), and Yale University also are reported. The IU, UCI, and Yale data showed that approximately 40% of controls had P50 ratios within 1 S.D. below the mean of means for patients with schizophrenia. The meta-analysis rejected the null hypothesis that all studies showed no effect. The meta-analysis also showed that the differences were not the same across all studies. The mean ratios in 45 of the 46 group comparisons were smaller for controls than for patients, and the observed difference in means was significant for 35 of those studies. Reported gating ratios for controls from two laboratories whose findings were reported in the literature differed from all the other control groups. Variables affecting the gating ratio included band pass filter setting, rules regarding the inclusion of P30, sex, and age. Standards of P50 collection and measurement would help determine whether the gating ratio can be sufficiently reliable to be labeled an endophenotype, and suggestions are made toward this goal.

Personality and Individual Differences, 2015

Sensory gating is the ability to filter out irrelevant stimuli from the environment. Individuals with schizophrenia consistently demonstrate deficits in this ability leading to sensory overload and cognitive fragmentation. This dysfunction has also been found in schizotypy, which is defined as a manifestation of nonclinical symptoms qualitatively similar to those found in schizophrenia. In the present study, auditory sensory gating was assessed in healthy individuals by testing the attenuation of the P50 event-related potential. The degree of suppression was then correlated with schizotypy by using the O-LIFE questionnaire. Relative to the low-scoring individuals, P50 suppression was significantly reduced in those with high levels of schizotypy. Furthermore, the degree of deficit in P50 gating correlated with both cognitive disorganisation and impulsive nonconformity dimensions of schizotypy. These results suggest that schizotypal individuals may have early sensory gating deficits similar to schizophrenia patients, especially if they display a disorganised or impulsive profile. As they do not exhibit overt psychotic symptoms, it is likely that such deficits represent an underlying core cognitive dysfunction within the schizophrenia spectrum.

Schizophrenia Research: Cognition, 2015

The P50 is an early component of auditory evoked potentials and a measure of sensory gating deficits. This evoked potential component is thought to be an important endophenotype candidate for schizophrenia. Recent research suggests that instead of the P50 ratio, S1 and S2 amplitudes should be evaluated for sensory gating. However, no studies have focused on the relationship between cognitive dysfunction and P50 sensory gating deficits using S1 and S2 amplitudes. The purpose of the present study was to investigate the association between the P50 ratio (S2/S1), S1 and S2 amplitudes, and neuropsychological cognitive domains using stepwise multiple linear regression analyses. Results demonstrated a significant relationship between executive functioning and the P50 ratio and between sustained attention and S2 amplitude, respectively. Our findings suggest that the P50 ratio and S2 amplitude reflect distinct neurophysiological substrates associated with different cognitive functions.

Schizophrenia Research, 2020

Introduction: Inhibitory sensory gating of the P50 cerebral evoked potential to paired auditory stimuli (S1, S2) is a widely used paradigm for the study of schizophrenia and related conditions. Its use to measure genetic, treatment, and developmental effects requires a metric with more stable properties than the simple ratio of the paired responses. Methods: This study assessed the ratio P50 S2 μV/P50 S1 μV and P50 S2 μV co-varied for P50 S1 μV in all 27 independent published studies that compared schizophrenia patients with healthy controls from 2000-2019. The largest study from each research group was selected. The Colorado research group's studies were excluded to eliminate bias from the first report of the phenomenon. Results: Across the 27 studies encompassing 1179 schizophrenia patients and 1091 health controls, both P50 S2 μV co-varied for P50 S1 μV and P50 S2 μV/P50 S1 μV significantly separated the patients from the controls (both P < 0.0001). Effect size for P50 S2 μV co-varied for P50 S1 μV is d' = 1.23. The normal distribution of P50 S2 μV co-varied for P50 S1 μV detected influences of maternal inflammation and effects on behavior in a recent developmental study, an emerging use for the P50 inhibitory gating measure. P50 S2 μV/P50 S1 μV was not normally distributed. Results from two multi-site NIMH genetics collaborations also support the use of P50 S2 μV as a biomarker. Conclusion: Both methods detect an abnormality of cerebral inhibition in schizophrenia with high significance across multiple independent laboratories. The normal distribution of P50 S2 μV co-varied for P50 S1 μV makes it more suitable for studies of genetic, treatment, and other influences on the development and expression of inhibitory deficits in schizophrenia. Contributors: R. Freedman designed the study and wrote the first draft of the paper. Both authors reviewed all the papers and independently extracted the data. Both authors were responsible for critical revision of the manuscript and have accepted the final version. The Consortium on the Genetics of Schizophrenia provided its data for analysis. Data Sharing: All data are contained within the Tables of the article and its Supplement.

Biological Psychiatry, 2008

Background: Abnormal sensory gating in schizophrenia has frequently been reported; however, only limited data on unmedicated patients and patients at risk to develop a psychosis have, as yet, been available.

Acta Psychiatrica Scandinavica, 2008

Objective: P50 gating in schizophrenia has contributed much to our understanding of the pathophysiology of the illness. We examined euthymic bipolar patients to determine if they also have a P50 gating deficit.Method: P50 gating was measured in 81 euthymic bipolar patients (50 with a lifetime history of psychotic symptoms), 92 stable schizophrenic patients, and 67 control subjects.Results: P50 gating was significantly lower in control subjects than in bipolar patients with a lifetime history of psychosis (P = 0.001) and schizophrenic patients (P = 0.0001). In all patient groups, the percentage of patients with P50 gating was higher than in the control group (χ2 = 30.596; P < 0.0001). There was no statistically significant correlation between P50 gating and other clinical variables.Conclusion: Our data suggest that P50 gating deficit is a neurobiological marker that is present in stable schizophrenic patients and euthymic bipolar patients.

Psychiatry Research, 1996

Schizophrenic patients reportedly have a deficit in the control of sensitivity to auditory stimuli as shown by the P50 auditory evoked potential wave in a conditioning-testing paradigm that measures suppression of response to a repeated stimulus. Although this finding has been replicated by several US laboratories, one European group has not found differences between schizophrenic patients and normal control subjects. In the present study, investigators in the Schizophrenia Research Center at the Prince of Wales Hospital in Sydney, Australia, selected 22 normal control subjects, 11 acutely ill schizophrenic inpatients, and 11 clinically stable schizophrenic outpatients. Both schizophrenic groups were treated with similar doses of classical neuroleptic medications. Evoked potentials were recorded by an investigator from the US laboratory that initially reported the difference; five averages, each the response to 32 stimulus pairs, were recorded from each subject. The normal control subjects demonstrated significantly more suppression of the P50 response to the repeated stimuli than the schizophrenic groups, as previously reported. There were no significant changes in the suppression measure over the five trials. The suppression of the P50 wave by schizophrenic outpatients was somewhat greater than that by schizophrenic inpatients, but both schizophrenic groups had decreased suppression, compared with the normal subjects. The mean P.50 suppression for five averages was successfully used in a logistic regression to classify subjects as normal or schizophrenic. This method was more accurate than attempts to classify subjects with only one average. The mean amplitude of the initial conditioning response did not differ between groups. Schizophrenic patients had slightly shorter mean latencies. There was no direct relationship of P50 suppression to measures of clinical psychopathology.