癫痫患者事件相关电位P300及影响因素研究

目的探讨癫痫患者事件相关电位P300的特点及影响因素。方法选择经临床及脑电图确诊的癫痫患者53例和21例与其年龄、性别、文化程度相匹配的健康正常人为研究对象,进行事件相关电位P300测定,并使用Pearson相关分析对其可能的影响因素进行分析。结果癫痫患者和对照组P3波潜伏期分别为(361.32±26.76)ms与(311.27±18.43)ms,P3波波幅分别为(3.38±1.52)μV与(6.79±1.93)μV,差异均有统计学意义(P0.01)。相关分析显示,癫痫患者P3波潜伏期与病程、发作频率及每次发作持续时间呈正相关(P均0.05),与起病年龄呈负相关(P0.01);P3波的波幅与病程、发作频率、每次发作持续时间呈负相关(P均0.05),与起病年龄呈正相关(P0.01);而与患者的年龄、受教育年限、服用抗癫痫药物的种类无明显相关性。结论癫痫患者存在事件相关电位P300异常,其变化特点与癫痫患者的起病年龄、病程、发作频率及每次发作持续时间相关。     

P300 amplitude as a possible correlate of frontal degeneration in schizophrenia

The existence of neurodegeneration is a debated issue in schizophrenia research. The P300 component of event-related electrical potentials (ERP) has been related to the different degree of damage to gray and white matter. This study explores the possible relationship between P300 amplitude and/or latency and the existence of degenerative processes in schizophrenia, by assessing its correlation with volume of sulcal CSF and duration of illness, as transversal indicators of neurodegeneration. Nineteen patients (14 males, 5 females) and 13 controls (6 males, 7 females) were studied with MRI and electrophysiological records (P300). The possible influence of sex and age at the time of the exploration was statistically controlled in both groups. The results show a significant negative correlation between P300 amplitude and prefrontal CSF volume in the patient group. A lower though still significant correlation was also found between P300 amplitude and duration of illness, whereas no correlation was found in the control group. These results support the hypothesis that P300 amplitude may be interpreted as a marker of neurodegeneration in schizophrenia.     

P300 reduction and prolongation with illness duration in schizophrenia.

BACKGROUND: The P300 component of the auditory event-related potential (ERP) is both reduced in amplitude and delayed in schizophrenia. P300 is prolonged and, less consistently, reduced with normal aging. Additional latency delays are observed in neurodegenerative disorders. We asked whether P300 is reduced and delayed with longer illness duration in schizophrenia, consistent with a neurodegenerative process. METHODS: P300 amplitude and latency were recorded to infrequent auditory target stimuli from 35 men with schizophrenia (DSM-III-R) and 26 control men. Effects of current age, age of onset, and duration of illness on P300 were assessed using regression analysis. RESULTS: P300 amplitude showed no age-related decrease in either group; however, among schizophrenic participants, P300 amplitude correlated positively with onset age and negatively with illness duration. P300 latency correlated positively with age in schizophrenic participants and also tended to increase with age in controls. Slopes of the latency-age relationships were significantly greater in schizophrenic participants than in control participants. Latency also correlated positively with illness duration but showed no relationship to onset age. CONCLUSIONS: P300 amplitude and latency are reduced and delayed with longer illness duration in schizophrenia, consistent with a progressive pathophysiological process. Reduced P300 amplitude may also be a marker of an early onset variant of schizophrenia.     

Alteration of event related potentials in siblings discordant for schizophrenia

This study was aimed at confirming that auditory event related potential (ERP) abnormalities are indicators of vulnerability to schizophrenia. Auditory ERP performances were assessed at Fz, Cz, and Pz, with an oddball paradigm, in 21 clinically stable patients with schizophrenia, 21 of their healthy biological full siblings and 21 control subjects. The evoked response did not differ between the three groups on N200 waves. Compared to controls, patients with schizophrenia exhibited reduced amplitudes of N100 and P300, and prolonged latency of P300, while their siblings showed prolonged latency of P200 and P300. Among the patients with schizophrenia, ERP abnormalities did not correlate with age, clinical state, duration of illness or antipsychotic treatments. Although other conditions also accounted for alterations of the same type, ERP abnormalities may represent a neurobiological marker of the genetic vulnerability to schizophrenia, independent of phenotypic expression.     

Oxidative mechanisms in schizophrenia and their relationship with illness subtype and symptom profile

Aim:  The aim of the present study was to investigate the differences in the antioxidant–oxidant balance (AO-OB) between schizophrenic patients and healthy individuals and to explore the relationship of AO-OB with illness subtypes and symptom profiles.
Methods:  After a 15-day drug-free period, schizophrenia patients ( n  = 50) in a clinical sample, and age- and sex-matched healthy subjects ( n  = 49) were enrolled. Total antioxidant potentials (TAOP) and total peroxide levels (TPEROX) of all participants were measured and the oxidative stress index (OSI) was calculated. The assessment included structured measurements, including the Positive and Negative Syndrome Scale (PANSS), and the Brief Psychiatric Rating Scale (BPRS).
Results:  TAOP had a significant positive correlation with age at onset of schizophrenia ( P  = 0.013), a negative correlation with the PANSS negative subscale scores ( P  = 0.008), a negative correlation with the PANSS total scores ( P  < 0.001), and a significant negative correlation with BPRS scores ( P  = 0.001). OSI had a significant negative correlation with age at onset ( P  = 0.046) and a significant positive correlation with PANSS negative subscale ( P  = 0.015). A multiple regression model indicated a significant linear combination of age, gender, duration of illness, subtype of schizophrenia, and PANSS scores, in which only the subtype of schizophrenia made a statistically significant contribution to predicting mean OSI ( F [5,35] = 2.44, P  = 0.04).
Conclusion:  Several parameters in the pathogenesis of schizophrenia, such as age of onset, level of negative symptoms, and subtype of illness, but not the presence of the illness itself, are associated with the level of oxidative stress.     

Auditory P300 in patients with bipolar disorder and their unaffected relatives

Objectives: There is evidence that genetic susceptibility may be shared between bipolar disorder (BD) and schizophrenia, but electrophysiological phenotypes which have been extensively used in studies of genetic susceptibility for schizophrenia remain far less explored in bipolar illness. This study assesses whether auditory P300 latency delays and amplitude reductions, which have been demonstrated in patients with schizophrenia and their unaffected first‐degree relatives, are associated with familial liability to psychotic bipolar illness. Methods: The P300 auditory evoked potential was obtained using an oddball task from 37 participants with BD who had a history of psychotic symptoms, 38 of their unaffected first‐degree relatives and 42 healthy unrelated comparison subjects. Patients and relatives came from families multiply affected with BD or another functional psychotic disorder. P300 amplitude and latency at midline sites were compared between the groups, using linear regression analyses and robust variance estimators for clustered data, including age and gender as covariates. Results: Bipolar disorder patients with a history of psychosis and their unaffected relatives showed significantly delayed P300 latency at Pz compared to controls. The groups did not differ in P300 amplitude. Conclusions: P300 latency delays are associated with both psychotic BD and familial liability for this illness. Sample size limited our ability to test for multimodal distribution of P300 measures among relatives, which might be expected if only a subgroup inherits any deficits. In future it will be of interest to directly compare groups of families with psychotic and non‐psychotic forms of BD to explore further the role of psychotic symptoms with regard to P300 measures in the disorder. Our results indicate that delayed P300 latency is a promising candidate endophenotype for psychotic BD, as well as schizophrenia, and may reflect the impact of shared susceptibility genes for both types of psychosis.     

Increased rate of P300 latency prolongation with age in drug-naive and first episode schizophrenia.

OBJECTIVE: Previous studies have found an increased rate of P300 latency prolongation with age in medicated chronic patients with schizophrenia, suggesting a pathological neurodegenerative process. In this study, we investigated whether this abnormality was identified in drug-naive and first episode patients with schizophrenia. METHODS: P300 from auditory stimuli was recorded from 20 drug naive and first episode male patients with schizophrenia and compared with 23 age and handedness matched healthy male controls. The relationship of P300 latency and P300 amplitude to age in each group was evaluated using polynomial regression analyses. RESULTS: Reduction of P300 amplitude was significant in drug-naive and first episode schizophrenia patients. P300 amplitude negatively correlated with age in schizophrenia patients but not in controls. Although the prolongation of P300 latency with age was observed in both groups, the regression slope for P300 latency with age was significantly steeper in patients with schizophrenia than in normal controls. Significant overall curvilinear correlations with age were also found for P300 latency and amplitude in patients with schizophrenia, and for P300 latency in normal controls. CONCLUSIONS: The greater increase in P300 latency and reduction in P300 amplitude with age may be a primary neuropathological effect of schizophrenia. SIGNIFICANCE: This study suggests that neurodegenerative processes are involved in the etiology of schizophrenia.     

Effect of age and global function score on schizophrenic p300 characteristics

The relationship between function level and P300 has long been ignored and awaits clarification. Further, previous Western studies have discussed the trait/state markers of schizophrenic P300; this has not been assessed for an analogous Chinese population. P300 was recorded and compared in 153 schizophrenic patients and 101 normal controls. Reduced and delayed P300 was demonstrated for the schizophrenic group. Regression analysis was performed to determine the factors contributing to P300 amplitude and latency variation. Global Assessment of Functioning score and age had a significant influence on P300 latency prolongation. Amplitude decrement was not affected by age, duration of illness, education, psychotic status, antipsychotic dosage, or function level. Our results were grossly concordant with analogous Western reports and provided evidence that function level is an important variable contributing to P300 latency change in Chinese schizophrenics. Besides, the effect of gender on P300 amplitude was noted in normal population.     

Long-term olanzapine treatment and p300 parameters in schizophrenia

The well-known amplitude reduction of the P300 appears to be unaffected by the treatment with classical antipsychotics in schizophrenia, whereas the effects of atypical neuroleptics on this event-related potential are less understood. The study of these changes could help in deciding whether the P300 amplitude reduction in schizophrenia is a trait or state marker of that illness and in better describing the effect of atypical antipsychotics on altered cognitive functions. We present a prospective longitudinal study of P300 amplitude and latency before and after 6 months' treatment with olanzapine in 11 patients with schizophrenia. A healthy control group (n = 30) was also studied. Overall, no significant changes, either in amplitude or in latency as measured at Pz and Fz electrodes, were found when comparing the pre- and postolanzapine conditions, despite the overall improvement in positive and negative symptoms. Nevertheless a direct specific association was observed between a P300 amplitude increase with olanzapine and the improvement in negative symptoms. These data would suggest that P300 amplitude reduction in schizophrenia may be relatively independent from clinical state and treatment, thus constituting a trait marker of schizophrenia. Our data also suggest that, in addition to this, some further changes in P300 amplitude might depend on the clinical state of the patients.     

ERPs changes during neuroleptic treatment in schizophrenia--a vulnerability marker in schizophrenia]

P300 amplitude reduction and P300 latency prolongation are consistent findings in schizophrenia, but it is unclear if these abnormalities were the effect of current or past neuroleptic treatment or were present at the onset of illness. We previously recorded ERPs in drug free schizophrenic patients (45 neuroleptic-naive and 56 previously treated with neuroleptics). In that study, P300 amplitude reduction was observed in both the neuroleptic-naive and the previously treated patients. However, both N200 and P300 latencies were prolonged only in the previously treated schizophrenic patients. In this study, we investigated ERPs in 60 drug free schizophrenic patients before and after neuroleptic treatment was begun. According to DSM-IV, schizophrenia subtype classification, 26 cases were paranoid type, 14 were disorganized, 2 catatonic and 18 undifferentiated. Twenty six of the patients were neuroleptic-naive and 34 had been previously treated. Sixty gender- and age-matched healthy controls were also investigated. ERPs were recorded during an auditory oddball task. The scalp EEGs were recorded from AgAgCl electrodes at 16 sites according to the international 10-20 system. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). Before treatment, all schizophrenic patients displayed larger N200 amplitudes than the controls; however, increases in N200 amplitudes were not observed after neuroleptic treatment was begun. Both N200 and P300 latencies in the patients before treatment were prolonged only in those previously treated. Neuroleptic-naive patients demonstrated prolongation of both N200 and P300 latencies only after treatment. P300 amplitudes in patients were increased by neuroleptic treatment; but patients had smaller P300 amplitudes than the controls even after treatment. The change in P300 amplitudes (Pz) and the change in total BPRS scores by neuroleptic treatment were positively correlated in the patients whose duration of illness was six months or less (mean: 2.4 months). However, no correlation was observed for patients whose duration of illness was over six months (mean: 49.7 months). There were no significant differences in ERPs changes among subtypes. These results suggested that the P300 amplitude should be considered a vulnerability marker in schizophrenia and that both N200 and P300 latencies might be markers for neuroleptic exposure.     

Visual event-related potential changes at two different tasks in nondemented Parkinson's disease.

A visual oddball paradigm and an S1-S2 paradigm were employed to evoke event-related potentials (ERPs) in 38 nondemented Parkinson's disease (PD) patients and 24 healthy elderly subjects. Delayed N200 and reduced P300 amplitude in the whole PD sample were only found in the S1-S2 paradigm. Delayed N200 and reaction time in PD with short duration of illness were found only after the S1-S2 paradigm, which might be an early sign of cognitive changes in PD. This is the first study to apply an S1-S2 paradigm for a visual P300 test in PD and proved the value of this paradigm for detecting minor cognitive abnormalities. ERP changes were correlated with clinical features. Reduced P300 amplitude for the S1-S2 paradigm was significantly correlated with WAIS-R scores and gait disturbance. The correlation between P300 amplitude and clinical scores has rarely been discussed before. P300 latency during the oddball paradigm in PD was influenced by age at test, age at onset, and duration of illness. This may explain why P300 results in nondemented PD have varied among previous authors.     

White matter anisotropy related to electrophysiology of first episode schizophrenia during NoGo inhibition

Patients with schizophrenia have reduced execution functions and white matter alterations indicating cerebral disconnectivity. Here we investigated the relationship between white matter integrity and event related potentials (ERP) during a continuous performance test (CPT). Anisotropy values were correlated with the brain electrical P300 microstate duration and P300 latency associated to the NoGo- and the Go-stimuli of the CPT in 11 patients with first episode schizophrenia and 11 matched healthy controls. Both groups showed significant positive correlations of the NoGo-microstate duration with the white matter signal in the superior frontal region, the optic radiation, the posterior cingulate, and the inferolateral fascicle. In addition, patients with first episode schizophrenia had significant correlations with the right radiation and the left genu of the corpus callosum, bilateral geniculate, and the left middle and the superior temporal regions. We interpreted these findings as a sign of functional correlates of extended circuits for the active inhibition of a motor response in the visual CPT as compared to controls.     

Dorsolateral prefrontal cortex contribution to abnormalities of the P300 component of the event-related potential in schizophrenia

Abnormalities of the P300 component of the event-related potential are a common finding in schizophrenia. It seems possible that the dysfunction in the dorsolateral prefrontal (DLPF) region that has been reported in schizophrenia contributes to this finding. To explore this possibility, we calculated the relationship between, on the one hand, P300 latency and amplitude and, on the other hand, the degree of DLPF atrophy (as measured by magnetic resonance imaging) and metabolic activity during an attentional task (as measured by positron emission tomography). Seventeen schizophrenia patients with a brief duration of illness and minimal exposition to treatment and 25 healthy controls were studied. Patients exhibited significantly lower metabolic activity in the DLPF region, but they did not show cortical atrophy. P300 amplitude was also significantly reduced in the schizophrenia patients compared with the controls. Right DLPF region metabolic activity correlated significantly with P300 amplitude. This pattern remained after partialling out the influence of activity in the hippocampus, superior temporal gyrus and parietal lobe. It is therefore suggested that the prefrontal cortex could be implicated in the P300 amplitude reduction in schizophrenia.     

P300 deficits are present in young first-episode patients with schizophrenia and not in their healthy young siblings

ObjectiveTo evaluated P300 (P3b) abnormalities in young first episode patients with schizophrenia and their healthy young siblings.MethodsAn auditory oddball paradigm was used to assess P300 in 53 patients, 27 unaffected siblings and 28 healthy controls. Amplitude and latency of the three midline sites (Fz, Cz, and Pz) were compared between patients, siblings, and controls by a mixed-effects regression model.ResultsP300 amplitude was significantly reduced in patients with schizophrenia but not in healthy siblings, when compared to healthy controls. P300 latency did not significantly differ between the three groups.ConclusionsP300 amplitude but not latency was found to be affected in young patients with recent onset schizophrenia. However, P300 amplitude and latency were found not to be affected in healthy unaffected young siblings and, therefore, did not qualify as an endophenotype for schizophrenia.SignificanceThe failure to find the P300 (P3b) abnormality in healthy siblings of patients with schizophrenia is an important finding and should be added to P300 literature.     

不同性别精神分裂症患者视觉、听觉诱发电位事件相关电位P300相关性研究

目的 探讨不同性别精神分裂症患者视觉、听觉诱发电位，事件相关电位P300异常的意义。方法 对129例不同性别的精神分裂症患者的视觉诱发电位（PS-VEP）、听觉诱发电位（AEP）、事件相关电位P300与同性别正常人比较。结果 男性和女性精神分裂症患者Cz点AEPP3、P300P3波潜伏期均延迟，女性PS-VEPP3波亦延迟；男性患者组AEPP2、N2波潜伏期延迟，与对照组比较差异均有统计学意义。结论 男性精神分裂患者有2项诱发电位P3波潜伏期延迟，女性3项诱发电位P3波潜伏期均延迟，结合临床对精神分裂症诊断有一定的意义。     

Age-related changes of auditory event-related potential (P300) in children

Auditory event-related potentials (ERPs) were recorded from 53 neurologically normal children of 5 to 15 years of age, and 8 healthy adults. To clarify the developmental changes and to obtain a normative value in childhood, the latency and amplitude of ERPs (N100, P200, N200, and P300) were examined. ERPs were elicited with the auditory oddball paradigm. P300 components were detected in all subjects. A strong positive correlation was demonstrated between latencies of two trials, and a small latency difference between trials was interpreted as being clinically unimportant. A significant negative correlation was observed between P300 latency and age during childhood (latency (msec) = -9.81 X (Age) + 459: r = 0.75, p less than 0.01). A mild negative correlation was also observed between N100, P200 and N200 latency and age. P300-topography of amplitude showed various patterns in young childhood, but in adolescence a maximum point was Pz in almost all subjects. These findings suggest that auditory ERPs can be easily measured in childhood and are useful for objective evaluation of the cognitive function.     

Auditory P300 latency prolongation with age in schizophrenia: gender and subcomponent effects

Previous studies showing prolongation of auditory P300b latency with increasing age provided support for post-onset progressive change in schizophrenia. We sought to extend the findings by evaluating the effects of gender and the subcomponents (P3b versus P3a) in schizophrenia (N=108) and controls (N=70). P3b latency significantly correlated with age in schizophrenia (Spearman's rho=0.214, P=0.026) and in male patients with schizophrenia (rho=0.260, P=0.049) whereas, it did not reach significance in female patients with schizophrenia (rho=0.174, P=0.23). P3a latency showed no correlation. Our findings may provide evidence for progressive change in the brain function in schizophrenia, and this change may be slower in female than male patients. P3b may serve as a more sensitive index for cognitive decline than P3a.     

Meta-analysis of the P300 and P50 waveforms in schizophrenia

Objective: To determine whether patients with schizophrenia have abnormalities in the P300 and P50 waves and to quantify the magnitude of any differences from controls. Method: We conducted a systematic search for articles published between January 1994 and August 2003 that reported P50 or P300 measures in schizophrenic patients and controls. Metaregression analyses were performed using a random effects model. The pooled standardised effect size (PSES) was calculated as the difference between the means of the two groups divided by the common standard deviation. Results: We identified 46 studies suitable for analysis of P300 measures, including 1443 patients and 1251 controls. There were 20 P50 studies including 421 patients and 401 controls. The PSES for the P300 amplitude was 0.85 (95% CI: 0.65 to 1.05; p<0.001), and for the P300 latency was −0.57 (95% CI: −0.75 to −0.38; p<0.001). The PSES of the P50 ratio was −1.56 (95% CI: −2.05 to −1.06; p<0.001). There were no significant differences between patients and controls in P50 latency. Across-study variations in filters, task difficulty, antipsychotic medication and duration of illness did not influence the PSES significantly. Conclusions: This meta-analysis confirms the existence of ERP deficits in schizophrenia. The magnitude of these deficits is similar to the most robust findings reported in neuroimaging and neuropsychology in schizophrenia.     

多发性硬化患者认知改变与事件相关电位研究

目的研究多发性硬化(MS)患者认知功能障碍的发生情况,及其与事件相关电位(ERPs)的相关关系。方法对70例MS患者进行韦氏智力量表测查及ERPs检查。结果韦氏智力量表测试发现MS组全量表智商(FIQ)不正常者(<90分)的比率为40%(28/70),与正常组比较差异显著(P<0.01)。MS组N2、P300潜伏期明显延长,与对照组比较差异具有显著性(P<0.05)。脑或脑脊髓型及进展型MS患者P300潜伏期明显延长,P300波幅降低。病程与P300潜伏期呈显著正相关。言语量表智商(VIQ)、FIQ与P300潜伏期呈负相关,与P300波幅呈正相关;操作量表智商(PIQ)与P300波幅呈正相关。结论MS患者存在有认知障碍。ERPs检查对MS认知障碍的判断有一定参考意义。     

Correlations between P300 components and regional cerebral blood flows.

To evaluate the diagnostic importance of event-related potential P300, the correlation between P300 and regional cerebral blood flow (rCBF) was investigated in various brain regions in patients with multiple cerebral infarction (16 cases), chronic alcoholism (11 cases) and Alzheimer's disease (5 cases) and in seven healthy people. Cognitive function was also evaluated by mini-mental state examination. P300 latency and rCBF was measured by recording of evoked potentials using an oddball paradigm and stable xenon computed tomographic scanning, respectively. A significant (P<0.05) negative correlation between P300 and rCBF was observed in the thalamus in patients with multiple cerebral infarction and chronic alcoholism. In addition, a significant (P<0.01) negative correlation between P300 latency and the mini-mental state examination score and positive correlation between rCBF in the thalamus and the mini-mental state examination score were observed. These findings suggest that P300 latency is associated with rCBF in the thalamus and cognitive function.