Sensory gating deficits during the mid-latency phase of information processing in medicated schizophrenia patients

Sensory gating during preattentive phases of information processing has been extensively examined. Sensory gating processes that occur during subsequent phases of information processing have not been fully examined. The relationship between P50 sensory gating and schizophrenia symptoms remains underspecified and the clinical correlates of N100 and P200 gating are yet to be examined. Sensory gating indices derived from the mid-latency auditory evoked responses during preattentive (P50) and attentive (N100, P200) phases of information processing were collected from schizophrenia patients who were stable and mainly being treated with atypical antipsychotic medications (n=23) and age- and gender-matched healthy control subjects (n=23). Schizophrenia patients had demonstrable habituation or sensory gating difficulties throughout the mid-latency range of information processing. Moreover, we found no correlations between P50-derived sensory gating indices and the amplitude or latency of the more attention-related P300 evoked response. A number of N100 and P200 gating measures correlated with P300 variables. Finally, we found no correlations between sensory gating indices and schizophrenia symptoms clusters. These results suggest that sensory gating is a pervasive abnormality in schizophrenia patients that is not limited to the preattentive phase of information processing. Furthermore, the data suggest that N100 and P200 gating indices may influence subsequent information processing.     

A topographic event-related potential follow-up study on `prepulse inhibition' in first and second episode patients with schizophrenia

Dopamine agonists impair and antagonists normalize prepulse inhibition (PPI) of startle and gating of the P50 event-related potential (ERP), but the within-subject effect of treatment on impaired gating in schizophrenia has not been studied. We report the first results of a longitudinal study using PPI of ERPs as a measure of sensory gating in an auditory Go/NoGo discrimination. After admission and approximately 3 months later, at discharge, 15 patients with schizophrenia performed a discrimination between a 1.4 kHz target tone and an 0.8 kHz non-target tone with no prepulse, or with a prepulse at 100 ms or 500 ms before either tone. ERPs were recorded from 19 sites. Healthy subjects were studied twice, with 3 months between sessions. PPI of the P50 peak in the 100-ms condition was reduced in patients on admission. At discharge, decreased negative symptoms correlated with enhanced P50-PPI at frontocentral sites. After treatment increased N100-PPI at centrotemporal sites correlated with fewer positive symptoms. At frontal sites in the 100-ms condition, the initially small difference of non-target minus target P300 amplitudes increased as negative symptoms decreased. It is concluded that weak auditory prepulses interfere with early auditory stimulus processing (P50), channel selection (N100) and selective attention (P300). Gating of these stages of processing is impaired in psychotic patients and treatment tends to normalize gating in tandem with improvements of different types of symptoms.     

A topographic event-related potential follow-up study on 'prepulse inhibition' in first and second episode patients with schizophrenia.

Dopamine agonists impair and antagonists normalize prepulse inhibition (PPI) of startle and gating of the P50 event-related potential (ERP), but the within-subject effect of treatment on impaired gating in schizophrenia has not been studied. We report the first results of a longitudinal study using PPI of ERPs as a measure of sensory gating in an auditory Go/NoGo discrimination. After admission and approximately 3 months later, at discharge, 15 patients with schizophrenia performed a discrimination between a 1.4 kHz target tone and an 0.8 kHz non-target tone with no prepulse, or with a prepulse at 100 ms or 500 ms before either tone. ERPs were recorded from 19 sites. Healthy subjects were studied twice, with 3 months between sessions. PPI of the P50 peak in the 100-ms condition was reduced in patients on admission. At discharge, decreased negative symptoms correlated with enhanced P50-PPI at frontocentral sites. After treatment increased N100-PPI at centrotemporal sites correlated with fewer positive symptoms. At frontal sites in the 100-ms condition, the initially small difference of non-target minus target P300 amplitudes increased as negative symptoms decreased. It is concluded that weak auditory prepulses interfere with early auditory stimulus processing (P50), channel selection (N100) and selective attention (P300). Gating of these stages of processing is impaired in psychotic patients and treatment tends to normalize gating in tandem with improvements of different types of symptoms.     

Similarities in the disturbances in cortical information processing in alcoholism and aging: a pilot evoked potential study

OBJECTIVE: To examine the hypothesis that chronic alcohol use causes accelerated aging of the brain. METHODS: The auditory evoked potentials (EPs) were compared in three groups of 10 subjects each: (a) middle-aged individuals meeting DSM-IV criteria for alcohol dependence, (b) age- and gender-matched group of healthy individuals, and (c) an older (>65 years) group of gender-matched healthy individuals. Multiple levels of cortical information processing were examined using EPs. Early stages of information processing, related to sensory gating and stimulus classification (P50, N100/P200), were studied using a paired-click paradigm. Later stages of information processing associated with memory upgrading and identification of novel stimuli (P300) were studied using an oddball paradigm. RESULTS: The amplitude and latency of the P300 of the alcoholic patients and the older healthy subjects differed significantly from those of the younger healthy group. Both groups showed changes that have been reported in association with aging. A tendency towards decreased sensory gating in later stages of information processing was noted in the aged healthy individuals. CONCLUSIONS: These data suggest that alcohol dependence may accelerate the aging process. The tendency towards a sensory gating deficit during the attentive phase of information processing in older healthy subjects requires further investigation because it may be a marker for an increased proneness to developing psychotic symptoms in that group.     

Psychotic symptoms and paranoid ideation in a population-based sample of 95-year-olds.

OBJECTIVE: To examine the 1-year prevalence of psychotic symptoms and schizophrenia in nondemented 95-year-olds, and to examine the relation between psychotic symptoms and other psychiatric symptoms, sensory impairments, and cognitive functioning. PARTICIPANTS: The representative sample was 95-year-olds living in G?teborg, Sweden (N = 338). Individuals with dementia were excluded (N = 175), leaving 163 subjects for this study. DESIGN: This was a cross-sectional population study, including psychiatric and physical examinations, cognitive tests, and interviews with close informants. MEASUREMENTS: Diagnosis of schizophrenia, psychotic symptoms, paranoid ideation and dementia according to Diagnostic and Statistical Manual of Mental Disorders, Third Revision (DSM-III) were measured. Cognitive function was tested with the Mini-Mental State Exam. Other psychiatric symptoms were measured by the Comprehensive Psychopathological Rating Scale. RESULTS: The one-year prevalence of any psychotic symptom was 7.4% (95% confidence interval [CI] 3.8-12.5); including hallucinations 6.7% (95% CI 3.4-11.8) and delusions 0.6% (95% CI 0.0-3.4). Four (2.4%) individuals fulfilled DSM-III-R criteria for schizophrenia. Individuals with psychotic symptoms or paranoid ideation did not differ regarding cognitive functioning compared with individuals without these symptoms. Individuals with hallucinations and paranoid ideation had an increased frequency of previous paranoid personality traits compared with individuals without psychotic symptoms and paranoid ideation. No individuals with psychotic symptoms had a formal thought disorder, incoherence of speech, or flat affect. CONCLUSION: The authors found a high prevalence of psychotic symptoms, paranoid ideation, and schizophrenia in the very old. Most of the symptoms were elucidated by information from key informants, illustrating the importance of including relatives in the evaluation of elderly persons.     

Differential impact of heavy cannabis use on sensory gating in schizophrenic patients and otherwise healthy controls

Cannabis abuse may precipitate the onset of schizophrenia and a dysfunction of the endocannabinoid system may be involved in the pathology of schizophrenia. Nevertheless, only few studies have addressed the neurobiological consequences of cannabis abuse for the development and course of schizophrenia. We measured the long-term effect of chronic cannabis abuse on the inhibitory function of the brain by the auditory P50 sensory gating in schizophrenic (n=15) and otherwise healthy chronic cannabis abusers (i.e. cannabis controls; n=11) and compared it to that of schizophrenic patients (n=12) and healthy controls (n=18) without cannabis or other drug abuse. All study subjects had to be abstinent from cannabis for at least 28 days. The main finding of our study was a P50 sensory gating deficit in cannabis controls that was correlated with the number of years with daily consumption (r=0.81; p=0.003). In contrast, we found no differences in P50 sensory gating between schizophrenic cannabis-abusers and non-abusers or healthy controls and no correlation with the number of years with daily consumption in those groups. To our knowledge this is the first study comparing the influence of chronic cannabis abuse in schizophrenic and otherwise healthy abusers on the inhibitory function of the brain. Our data provide some evidence that chronic cannabis abuse may affect sensory cortical circuits even after prolonged abstinence and they point to a possible differential effect in schizophrenic and otherwise healthy users.     

首发和慢性精神分裂症急性期患者的感觉门控P50

目的探讨病程对精神分裂症感觉门控抑制缺陷的影响。方法对58名健康志愿者、38例首发精神分裂症急性期患者和36例慢性精神分裂症急性期患者进行感觉门控研究。应用听觉P50抑制评估感觉门控,实验模式为条件刺激（S1）-测试刺激（S2）模式。结果首发患者、慢性患者及对照组的S1波幅分别为（3.7±2.5）μV、（4.5±2.0）μV和（5.8±3.8）μV（F=5.P〈053,.01）,首发患者的S1波幅低于对照组（P〈0.01）;S2波幅分别为（2.8±1.1）μV、（3.5±1.5）μV和（2.1±1.4）μV（F=11.47,P〈0.01）,首发和慢性患者的S2波幅均高于对照组（P分别为0.02,小于0.01）,并且慢性患者的S2波幅高于首发患者（P=0.02）。P50抑制指标在三组之间差异均有统计学意义（P均小于0.01）,首发和慢性患者的S2/S1波幅比均大于对照组（P均小于0.01）,而S1-S2波幅差值和100（1-S2/S1）均低于对照组（P均小于0.01）,但首发患者和慢性患者之间P50抑制指标差异无统计学意义（P均大于0.05）。结论首发精神分裂症和慢性精神分裂症均存在明显的感觉门控P50抑制缺陷,病程对精神分裂症的感觉门控P50抑制缺陷无明显影响。     

N1 and P300 abnormalities in patients with schizophrenia, epilepsy, and epilepsy with schizophrenialike features.

BACKGROUND: The scalp-recorded N1 and P300 components of the event-related brain potential (ERP) are commonly reduced in patients with schizophrenia but not in patients with epilepsy. Epilepsy patients with interictal chronic schizophrenialike features (EPI-SZ) provide a comparison group for determining whether the ERP amplitude abnormalities seen in schizophrenic patients are associated with shared clinical features of EPI-SZ and schizophrenic patients or overlapping pathophysiologies, or are specific to a distinct schizophrenia etiology. METHODS: Patients with schizophrenia (n = 24) were compared with normal control subjects (n = 32) and patients with epilepsy syndromes on visual and auditory oddball ERP paradigms. Epilepsy patients included those with chronic interictal schizophrenialike features (n = 6) and those without (n = 16). RESULTS: Auditory P300 amplitude was reduced in both schizophrenic and EPI-SZ patients, whose positive or negative symptoms did not differ. In contrast, N1 amplitude was reduced only in schizophrenic patients. Delays in both N1 and P300 were associated with epilepsy patients and EPI-SZ but not schizophrenic patients. CONCLUSIONS: The schizophrenialike symptoms in epilepsy probably represent a phenocopy of schizophrenia with common clinical features and some common pathophysiologies but distinct etiologies. P300 amplitude appears to be sensitive to schizophrenialike features, regardless of whether they occur in the context of schizophrenia or epilepsy. N1 amplitude reduction appears to be specific to schizophrenia, suggesting its sensitivity to the distinct etiology of schizophrenia.     

Prospective study of adolescents with subsyndromal psychosis: characteristics and outcome

OBJECTIVE: The aim of this study was to examine the characteristics and outcome of adolescents with psychotic disorder not otherwise specified (PsyNOS) and brief psychotic disorder (BrPsy), two neglected subsyndromal diagnostic entities. METHODS: As part of an ongoing, naturalistic study investigating adolescents considered to be prodromal for schizophrenia, 29 youngsters (mean age, 16.2 +/- 2.7 years) with PsyNOS or BrPsy were identified as theoretically at highest risk for schizophrenia and followed for over 6 (mean, 22.8 +/- 19.4) months. RESULTS: Contrary to our expectations, only 7 of the 26 individuals (27.0%) with follow-up data developed schizophrenia or schizoaffective disorder, and only 2 subjects (7.7%) retained their diagnosis of BrPsy/PsyNOS. The most frequent other diagnoses at follow-up were mood disorders (34.6%), personality disorders (11.5%), and obsessive-compulsive disorder (7.7%). Regarding severity of outcome, 38.5% of the patients progressed to a syndromal psychotic disorder, 23.1% continued to have attenuated positive symptoms, and 38.4% improved to having attenuated negative symptoms only, or no positive or negative symptoms. BrPsy was associated with lower maximum levels of negative symptoms (p = 0.02) and higher likelihood of symptom remission (p = 0.02). CONCLUSIONS: This study indicates that psychotic symptoms not fulfilling criteria for schizophrenia or a psychotic mood disorder are unreliable predictors of a syndromal psychotic disorder outcome at 2 years. Long-term studies of PsyNOS and BrPsy are needed to clarify where these disorders fall in the developmental course of schizophrenia.     

Sensory-gating deficit of the N100 mid-latency auditory evoked potential in medicated schizophrenia patients

The clinical and neuro-cognitive correlates of the P50 and N100 auditory evoked responses gating deficits in schizophrenia have thus far eluded identification. Based on our prior results, we hypothesized that, in addition to the P50, gating of the N100 is significantly decreased in schizophrenia and that this deficit correlates with the negative symptoms dimension of schizophrenia. Amplitudes and gating measures of the P50 and N100 were compared between stable out-patients (N = 45) (mainly on atypical antipsychotics) with chronic schizophrenia and age- and gender-matched healthy controls (N = 49) and the clinical correlates examined. All subjects underwent the paired-stimulus paradigm in 3 or 4 different days. Data from day one and the mean of all days (MOAD) were examined. P50 and N100 amplitudes and gating measures were correlated with PANSS and Wisconsin Card Sorting Test data. Utilizing day one data, no amplitude or gating measures were significantly different between the groups. Utilizing MOAD data, both P50 and N100 gating were significantly decreased in schizophrenia patients. The N100 gating deficit correlated with the negative-symptoms cluster and measures of frontal lobe dysfunction. The data suggest a correlation between N100 gating deficit and the negative-cognitive deficits dimensions of schizophrenia. Data also suggest that improving the signal to noise ratio (MOAD data) increases the sensitivity for detecting gating abnormalities and assessing their clinical correlates.     

Sensory gating deficits assessed by the P50 event-related potential in subjects with schizotypal personality disorder

OBJECTIVE: The schizophrenia spectrum includes individuals with schizophrenia, their relatives, and individuals with schizotypal personality disorder. Subjects in the schizophrenia spectrum have disorders of attention, cognition, and information processing. Attention and information processing can be assessed by testing suppression of the P50 event-related potential; the amplitude of the P50 wave is measured in response to each of two auditory clicks. In normal subjects, the P50 wave following the second click is suppressed, or "gated." Schizophrenic patients and their relatives show less suppression of the second P50 wave. Deficits in P50 suppression have high heritability and show linkage to the alpha-7 subunit of the nicotinic cholinergic receptor gene in families with schizophrenia, suggesting that deficits in P50 suppression are trait markers for gating abnormalities in schizophrenia spectrum subjects. Although schizotypal subjects have been shown to have deficits in sensorimotor gating as measured by prepulse inhibition, to the authors' knowledge P50 sensory gating in schizotypal personality disorder has yet to be reported. METHOD: P50 suppression in 26 subjects with schizotypal personality disorder and 23 normal subjects was assessed through auditory conditioning and testing. RESULTS: The subjects with schizotypal personality had significantly less P50 suppression than did the normal subjects. CONCLUSIONS: Subjects with schizotypal personality disorder may have trait-linked sensory gating deficits similar to those in patients with schizophrenia and their relatives. Because these subjects may manifest sensory gating deficits without overt psychotic symptoms, it is likely that these deficits represent a core cognitive dysfunction of the schizophrenia spectrum.     

Sensory gating in subjects at ultra high risk for developing a psychosis before and after a first psychotic episode

Objectives. To explore sensory gating deficits in subjects at Ultra High Risk (UHR) for psychosis before and after transition to a first psychotic episode. Methods. Sensory gating was assessed with the paired click paradigm in 61 UHR subjects, of whom 18 (30%) made a transition to psychosis (UHR + T) over a 3-year follow-up period and 28 matched healthy controls. Subjects were assessed at inclusion and again after approximately 18 months. P50, N100 (N1) and P200 (P2) sensory gating was established using the amplitude on the first (S1) and second (S2) click, the ratio- (S2/S1) and the difference score (S1-S2). Psychopathology was also assessed. Results. At baseline, UHR + T subjects presented smaller N1 difference scores compared to UHR + NT subjects and controls. The N1 difference score contributed modestly to the prediction of a first psychotic episode. Repeated measure analyses revealed smaller N1 and P2 S1 amplitudes, smaller P2 difference scores and larger P2 ratio's at follow-up compared to baseline in UHR + T subjects. Conclusion. The N1 difference score may be helpful in predicting a first psychosis. N1 and P2 sensory gating measures also showed alterations between the prodromal phase and the first psychosis, suggesting that these changes may relate to the onset of a frank psychotic episode.     

DRD3 and DAT1 genes in schizophrenia: an association study

OBJECTIVE: To investigate the role of the dopamine receptor 3 (DRD3) and transporter 1 (DAT1) genes in schizophrenia or in modulating its phenotype. METHODS: a Ser9Gly polymorphism in codon 9 of the DRD3 and a VNTR polymorphism in the DAT1genes were examined in two groups of schizophrenic patients, one of excellent neuroleptic responders (N=42) and one of nonresponders (N=64). A group of healthy volunteers screened for major psychiatric disorders was also included (N=89). In addition, age at onset of psychotic symptoms, attention performance and family loading for schizophrenia spectrum disorders were compared between patients with different genotypes in the DRD3 and DAT1 genes. RESULTS: No significant differences in the allelic distribution of the DRD3 and DAT1 polymorphisms were detected between schizophrenic patients and controls. A trend toward an excess of DRD3 genotype Gly/Gly was observed in neuroleptic nonresponder schizophrenic patients compared to controls (chi(2)=3. 30, df=1, p=0.07). No significant differences in age at onset of psychotic symptoms, attention task performance or family loading for schizophrenia spectrum disorders were observed between groups with different DRD3 and DAT1 genotypes. CONCLUSION: These results do not support the role of either of these genes in increasing susceptibility to schizophrenia or in modulating its phenotype in the studied population.     

Lack of relationship of auditory gating defects to negative symptoms in schizophrenia

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.     

Evidence of a cohort effect for age at onset of schizophrenia

OBJECTIVE: The authors address whether a possible age-at-onset cohort effect may have introduced a bias into anticipation studies of schizophrenia. METHOD: A retrospective review of the medical records of all admissions for psychotic disorders (N=877) was conducted. All subjects with a confirmed DSM-IV diagnosis of schizophrenia and age-at-onset data were included (N=419). For analyses, subjects were placed into one of three successive birth cohorts: 1905-1944 (N=96), 1945-1964 (N=200), and 1965-1984 (N=123). RESULTS: The mean age at first appearance of psychotic symptoms and, similarly, the mean age at first hospitalization significantly decreased over time in successive birth cohorts (25.3, 23.3, and 20.4 years, respectively, for age at first appearance of psychotic symptoms). CONCLUSIONS: This potential birth cohort effect for age at onset of schizophrenia needs to be incorporated into genetic models.     

Increased p50 gating but intact prepulse inhibition in borderline personality disorder

The authors explore sensory gating deficits in borderline personality disorder patients, such as those described in schizophrenia, in patients with borderline personality disorder. Gating of the P50, N100, and P200 auditory evoked potentials and prepulse inhibition of the startle response (PPI) were measured in borderline patients and a group of healthy comparison subjects. Borderline patients did not show lower sensory gating, but showed higher P50, N100, and P200 gating than comparison subjects. This was mainly due to the increased response after the first stimulus. There were no group differences in PPI. Unlike in other major psychiatric disorders, such as schizophrenia, sensory (motor) gating is intact in borderline personality disorder. The higher early preattentive and mid-latency evoked potentials suggest a higher response tendency in borderline personality disorder, but this needs further replication.     

Neuropsychological function in subjects with psychotic and affective disorders. Relationship to diagnostic category and duration of illness.

OBJECTIVE: To explore the links between neuropsychological performance, diagnostic category and duration of illness in subjects with psychotic and affective disorders. METHODS: Memory and executive abilities were tested in consecutively admitted patients with schizophrenia (N = 20), other non-schizophrenic psychotic disorders (N = 29), bipolar disorder (N = 33) and major depression (N = 19). RESULTS: Subjects with schizophrenia had poorer global memory performances than subjects with major depression, and poorer delayed verbal memory abilities than those from the other three diagnostic groups. Executive abilities explored by the Stroop test and the Wisconsin Card Sorting Test did not differ between diagnostic groups. Neuropsychological performances were not influenced by previous duration of illness. CONCLUSION: Memory deficits are the most discriminatory cognitive features between subjects with schizophrenia and those with other psychotic or mood disorders. The fact that cognitive deficits are static whatever the diagnostic group indirectly suggests that they may have a neurodevelopmental origin in subjects with schizophrenia, but perhaps also in subjects with other psychotic and mood disorders.     

Neuropsychological dysfunction in antipsychotic-naive first-episode unipolar psychotic depression

OBJECTIVE: The profile of neuropsychological impairment associated with unipolar psychotic depression remains unclear. The authors used a neuropsychological test battery to characterize the neuropsychiatric profile of patients with unipolar psychotic depression, relative to that of patients with nonpsychotic unipolar depression, patients with schizophrenia, and healthy comparison subjects. METHOD: Study subjects included antipsychotic-naive patients with a first episode of psychotic unipolar depression (N=20), antipsychotic-naive and unmedicated patients with nonpsychotic unipolar depression (N=14), antipsychotic-naive patients with first-episode schizophrenia (N=86), and healthy volunteers (N=81). Groups were matched on age, sex, race, education, parental socioeconomic status, and estimated premorbid intelligence. Psychotic patients were followed clinically for 2 years to confirm diagnosis. All participants completed a standard neuropsychological battery, including tests of general intelligence, executive function, attention, verbal memory, motor skills, and visual-spatial perception. RESULTS: Patients with psychotic depression had a pattern of neuropsychological dysfunction that was similar to but less severe than that of patients with schizophrenia. In contrast, patients with nonpsychotic unipolar depression had a neuropsychological profile that was similar to that of healthy individuals but that included mild dysfunction on tests of attention. Neuropsychological test performance was generally independent of acute clinical symptoms, but some pairwise group differences were attenuated by covariation for symptom severity. CONCLUSIONS: The similar neuropsychological profiles for schizophrenia and psychotic depression suggest that these psychotic disorders may have common pathophysiological features. The dramatic differences in performance between the patients with psychotic depression and those with nonpsychotic depression point to a marked distinction in neurocognitive function associated with the expression of psychosis in depressed patients.     

Sensory gating deficit in a subtype of chronic schizophrenic patients

The dual click P50 paradigm has been established as a neurophysiological method to detect gating mechanisms. Studies of schizophrenic patients have shown that an insufficient reduction of the P50 amplitude after the second relative to the first stimulus indicates a deficient sensory gating mechanism. The aim of this study was to compare the P50 responses in the dual click paradigm of healthy volunteers to those of patients with different psychotic disorders, especially with regard to psychopathology and nosology according to ICD-10 and DSM-IV and to the classification system of Leonhard. A total of 34 patients and 12 healthy volunteers were investigated electrophysiologically while they performed the P50 dual click experiment. Patients with prominent negative symptoms and without perceptual abnormalities and patients with a hebephrenic subtype of schizophrenia showed less suppression in the dual click P50 paradigm than did healthy controls. Patients with brief/acute and transient psychotic disorders or cycloid psychoses did not differ from healthy volunteers with regard to suppression in the dual click P50 paradigm. No striking influence of gender, age, duration of disease and present medication was found. The findings confirm the lack of sensory gating measured by the dual click P50 paradigms in some but not all patients with schizophrenia. Both subtype of schizophrenia and current form of psychopathology appear to be related to the presence or absence of abnormal sensory gating.     

Reduction of auditory event-related P300 amplitude in subjects with at-risk mental state for schizophrenia

Neurophysiological methods allow the examination of cognitive-cortical functioning in patients with schizophrenia in its prodromal states. As revealed by previous studies, event-related potential components such as auditory evoked P300 associated with cognitive processes, such as attention and orientation, are known to be reduced in amplitude in acute and chronic as well as in medicated and unmedicated patients. It is, however, unclear whether a P300 amplitude reduction occurs before the schizophrenic psychosis is fully manifested. We studied patients in the prodromal phase of the schizophrenic disorder (i.e. subjects with an at-risk mental state showing attenuated psychotic symptoms or brief limited intermittent symptoms) as well as first-episode patients and chronic patients with schizophrenia and compared these groups to healthy subjects. The event-related P300 was recorded during an auditory oddball paradigm. Groups differed significantly from each other in the P300 amplitude at Pz (F(3/149)=2.532, p=0.02). Post-hoc tests revealed significantly lower P300 amplitudes of non-medicated prodromal (p=.03), first-episode (p=.01) and chronic patients (p=.001) compared to the healthy controls. The study revealed that there are neurophysiological changes as the reduction in P300 amplitudes begins early in schizophrenia at the prodromal phase, i.e. before a manifestation of full-blown psychosis, and that these changes seem to have a progressive course from prodromal to chronic state of schizophrenia as assumed in this cross-sectional study.