P50 sensory gating deficits in schizotypy

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.

Biological Psychiatry, 2001

Background: P50 suppression is an electrophysiologic index of early sensory gating and has consistently been found deficient in schizophrenic patients. This gating deficit is thought to lead to sensory overload and cognitive fragmentation, and correspondingly many symptoms of the disorder. However, the link between P50 suppression deficits and symptomatology is yet to be established, and so this study was designed to determine whether such a relation is present within a nonclinical population. Methods: P50 suppression and schizotypy measures were obtained from 36 healthy volunteers, and correlation analyses determined whether measures of schizotypy were related to P50 suppression. Results: Consistent with the view that P50 gating deficits are related to schizophrenic symptoms, subjects with poorer P50 suppression reported more perceptual anomalies and magical ideation-an unreality syndrome-in contrast to other positive symptoms and to withdrawal. This study also found a trend to P50 suppression desensitization, and that whereas subjects low on "unreality" demonstrated desensitization to the second of the paired clicks, subjects high on "unreality" demonstrated sensitization. Conclusions: It is concluded that early sensory gating deficits, in the form of poor P50 suppression, are related to unreality aspects of schizotypy. This supports the view that poor P50 suppression in schizophrenia is related to symptomatology.

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.

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".

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.

Neuropsychiatric disease and treatment, 2014

Sensory gating disturbances in schizophrenia are often described as an inability to filter redundant sensory stimuli that typically manifest as inability to gate neuronal responses related to the P50 wave, characterizing a decreased ability of the brain to inhibit various responses to insignificant stimuli. It implicates various deficits of perceptual and attentional functions, and this inability to inhibit, or "gate", irrelevant sensory inputs leads to sensory and information overload that also may result in neuronal hyperexcitability related to disturbances of habituation mechanisms. These findings seem to be particularly important in the context of modern electrophysiological and neuroimaging data suggesting that the filtering deficits in schizophrenia are likely related to deficits in the integrity of connections between various brain areas. As a consequence, this brain disintegration produces disconnection of information, disrupted binding, and disintegration of consc...

The American journal of psychiatry, 2017

Although patients with schizophrenia exhibit impaired suppression of the P50 event-related brain potential in response to the second of two identical auditory stimuli during a paired-stimulus paradigm, uncertainty remains over whether this deficit in inhibitory gating of auditory sensory processes has relevance for patients' clinical symptoms or cognitive performance. The authors examined associations between P50 suppression deficits and several core features of schizophrenia to address this gap. P50 was recorded from 52 patients with schizophrenia and 41 healthy comparison subjects during a standard auditory paired-stimulus task. Clinical symptoms were assessed with the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. The MATRICS Consensus Cognitive Battery was utilized to measure cognitive performance in a subsample of 39 patients. Correlation and regression analyses were conducted to examine P50 suppression in relation to cl...

Psychiatry Research, 1997

The conditioning-testing S1-S2 P50 auditory evoked potential EP has been well-documented and accepted as an important tool for measuring sensory gating in schizophrenia research. However, the physiological mechanism of the phenomenon is not known. In this study a single-trial analysis was used to determine the influence of the latency variability of the responses in the formation of the averaged P50. Ten schizophrenic patients and 10 normal controls were tested in the dual-click EP paradigm. Using ensemble averaging analysis, we replicated the previous finding of a lower S1 P50 amplitude and higher S2rS1 ratio in schizophrenics compared with normal controls. The single-trial analysis revealed that patients had significantly higher trial-to-trial latency variability in S1 responses than normal subjects, while the S2 showed the same variability as in controls. Measured by the single-trial procedure, the arithmetic mean amplitudes of P50 responses to S1 and S2 were similar between normal and schizophrenic subjects. The same measure also eliminated the difference in averaged P50 amplitude between S1 and S2 for both groups. Temporal variability appears to be an important factor in the assessment of averaged EPs and thus contribute to the change of P50 amplitude observed in schizophrenia.

Schizophrenia Research, 2010

The interrelationship between the ability to inhibit incoming redundant input (gating out) and the ability of the brain to respond when the stimulus changes (gating in), has not been extensively examined. We administered a battery of auditory evoked potential tests to a group of chronic, medicated schizophrenia patients (N=12) and a group of healthy subjects (N=12) in order to examine relationships between "gating out" measures (suppression with repetition of the P50, N100, and P200 evoked responses), and the mismatch negativity (MMN) and the P300 event related potentials as measures of "gating in". Gating ratios for N100 and P200 in a visual attention paired-click task differed significantly between groups. Mismatch negativity and P300 potential amplitudes were also significantly reduced in the patient group. When including all subjects (N=24) a negative correlation was found between the P50 gating and the amplitude of the MMN. In healthy subjects this correlation was significantly stronger compared to schizophrenia patients. While no significant correlation was noted between the amplitudes of the P300 and any gating measures when all 24 subjects were included, a significant negative correlation was seen between the P200 gating and the P300 amplitudes in schizophrenia patients; an opposite trend was noted in healthy subjects. Finally, a positive correlation was seen between the P300 and MMN (to abstract deviance) amplitudes in healthy subjects, but the opposite was found in patients. These results suggest that further study of these interrelationships could inform the understanding of information processing abnormalities in schizophrenia.

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.

PLoS ONE, 2013

Objectives: Endophenotypes in schizophrenia research is a contemporary approach to studying this heterogeneous mental illness, and several candidate neurophysiological markers (e.g. P50 sensory gating) and neuropsychological tests (e.g. Continuous Performance Test (CPT) and Wisconsin Card Sorting Test (WCST)) have been proposed. However, the clinical utility of a single marker appears to be limited. In the present study, we aimed to construct a diagnostic model incorporating P50 sensory gating with other neuropsychological tests in order to improve the clinical utility. Methods: We recruited clinically stable outpatients meeting DSM-IV criteria of schizophrenia and age-and gender-matched healthy controls. Participants underwent P50 sensory gating experimental sessions and batteries of neuropsychological tests, including CPT, WCST and Wechsler Adult Intelligence Scale Third Edition (WAIS-III). Results: A total of 106 schizophrenia patients and 74 healthy controls were enrolled. Compared with healthy controls, the patient group had significantly a larger S2 amplitude, and thus poorer P50 gating ratio (gating ratio = S2/S1). In addition, schizophrenia patients had a poorer performance on neuropsychological tests. We then developed a diagnostic model by using multivariable logistic regression analysis to differentiate patients from healthy controls. The final model included the following covariates: abnormal P50 gating (defined as P50 gating ratio .0.4), three subscales derived from the WAIS-III (Arithmetic, Block Design, and Performance IQ), sensitivity index from CPT and smoking status. This model had an adequate accuracy (concordant percentage = 90.4%; c-statistic = 0.904; Hosmer-Lemeshow Goodness-of-Fit Test, p = 0.64.0.05). Conclusion: To the best of our knowledge, this is the largest study to date using P50 sensory gating in subjects of Chinese ethnicity and the first to use P50 sensory gating along with other neuropsychological tests to develop a diagnostic model for schizophrenia. Further research to validate the predictive accuracy of this model by applying it on other samples is warranted.

Clinical Neurophysiology, 2016

Psychiatry Research, 2004

Originally, the hypothesis of a sensory gating defect in schizophrenia evolved from studies of somatosensory evoked potentials (SEP), although the idea has primarily been pursued in the auditory modality. Gating is the relative attenuation of amplitude following the second stimulus in a stimulus pair. Recently, SEP P50 gating was seen when recording the SEP P50 in a paradigm similar to the one used for auditory P50 gating. Hypothetically, abnormality of somatosensory information processing could be related to anhedonia, which is considered a core feature of schizophrenia. Twelve unmedicated, male, schizophrenia spectrum patients (seven schizophrenic and five schizotypal personality disorder patients) and 14 age-matched healthy men participated in recordings of pair-wise presented auditory and median nerve stimuli. The patients had smaller amplitudes of the SEP P50 at the first stimulus, but no gating defect. The reduced amplitude was particularly evident in subjects with high scores on the Revised Social Anhedonia Scale. Early somatosensory information processing seems abnormal in schizophrenia spectrum patients. This could be in agreement with the theory of loss of the benefit of regularity in schizophrenia, while the results are in-conclusive regarding sensory gating theory. ᮊ

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.

Schizophrenia …

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 ...