Control Study Of P50 Sensory Gating In Patients With Schizophrenia And Its Systematic Review

PART ONE:CONTROL STUDY OF SENSORY GATING P50 IN PATIENTS WITH SCHIZOPHRENIAObject:Studies have shown that schizophrenic patients have P50 sensory gating dysfunction. However, the influence in variety of antipsychotics on sensory gating is still unknown. There have no control study which aims at effects on P50 of clozapine, chlorpromazine and sodium valproate in China. Therefore, we intend to verify that P50 sensory gating in patients with schizophrenia. And we want to observe the changes of P50 in patients before and after treatment and explore the differences among these drugs.Methods:A total of 56 patients with schizophrenia and 22 normal controls were enrolled from January 2008 to December 2009. All patients met Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria for schizophrenia. This is an exploratory study. We compared the sensory gating P50 differences between the schizophrenia group and the control group by the case-control study, and compared the difference between before and after treatment through the anterior-posterior self-control study, and compared the difference among different medicine through the randomized controlled study. Fifty six patients were divided into four sub-groups according to random sequence numbers generated by SAS software, chlorpromazine (CPZ) group (n=15), CPZ+valproate (VPA) group (n=15), clozapine (CLZ) group (n=14) and CLZ + VPA group (n=12). The follow-up was eight weeks,13 patients dropout. Conditions (S1)-Test (S2) stimulus paradigm was used to detect the P50 auditory evoked potential in subjects. The P50 measurement indicators are S1 and S2 potential amplitude (μV) and latency (ms). P50 ratio and P50 difference were defined as the ratio of the P50 amplitudes for S2 and S1 (S2/S1; ratio) and difference between the P50 amplitudes (S2-S1; difference), respectively. The efficacy and safety were estimated by positive and negative symptom scale (PANSS), clinical global impression severity of illness (CGI-SI) and the treatment emergent symptom scale (TESS), respectively. This is a single-blind study; the investigator who measured the indicators was blinded.Results:There have no statistically significant differences in age, gender, smoking and educational level between schizophrenia group and control group (P>0.05). There have no statistically significant differences in the demographic data among four sub-groups except the gender (P=0.049). S1 amplitude and P50 difference were lower in the baseline of schizophrenia group than the control group (P=0.034 and P=0.032, respective). Schizophrenia patients had significant higherP50 ratio than control groups (P=0.004). Three were no difference in S2 amplitude and S1 and S2 latency. The area under ROC curve of P50 ratio was0.743. The sensitivity and specificity were 80.4% and 50.0% respectively when used 50 as a cut-off point. There had no relationship between the P50 ratio and PANSS total score or duration of illness in schizophrenia patients. The P50 ratio showed decreased (P=0.005) in schizophrenia patients after 8 weeks treatment used antipsychotics by generalized estimating equation (GEE). But there was no significant difference between patients whether used sodium valproate or not (P=0.719). It showed statistical difference between patients treated with clozapine and chlorpromazine (P=0.045). Repeated measures analysis of variance (ANOVA) showed that there have no statistically significant differences in the changes of PANSS total score, positive symptom scale (SAPS), negative symptom scale (SANS), the general psychopathology scale (GPS), CGI-SI scale scores among the schizophrenia patients in the four sub-groups. Safety analysis showed that extrapyramidal side effects (EPS) were higher in chlorpromazine group than other groups.Conclusion:Schizophrenia patients had sensory gating dysfunction and the P50 ratio was a reliable indicator could reflect sensory gating. There was no relationship between sensory gating and severity of clinical symptoms or the duration of illness in the schizophrenia patients. The sensory gating function may be partly improvement in patients treated by antipsychotic. However, the patients P50 suppression defection can not be completely reversed. The effects of clozapine on the improvement in sensory gating are superior to chlorpromazine. It is not clear whether sodium valproate could improve sensory gating. The efficacy was of equivalent among the four sub-groups. Chlorpromazine showed more EPS than that of clozapine. PART TWO:A SYSTEMATIC REVIEW OF SENSORY GATING P50 STUDIES IN SCHIZOPHRENIC PATIENTSObjective:It is not clear that whether the P50 sensory gating dysfunction can be reversed by antipsychotics and its characteristics of schizophrenia patients. We didn't find Meta-analysis in electrical physiology of schizophrenia in China. Thus we made a systematic review of P50 sensory gating studies in schizophrenia patients and the change of P50 ratio between before and after treatment.Methods:Standard search strategy according to the Cochrane Review Group was performed by two review authors. Searches were made in PubMed, EMBase, and Web of knowledge, PsycINFO, Cochrane Library, CNKI, Wanfang, VIP and CBMDisc databases from 1982 to January 2010. Search the relevant references and the recent relevant journals by hand retrieve. STROBE(strengthening the reporting of observational studies in epidemiology, STROBE)were used to assess the methodological quality of the studies. The data were independently extracted and input and cross-checking by two reviewers. RevMan 5.0.23 software was used to make Meta analysis.Results:Seventy one literatures were reviewed and 7 studies met the included criteria were included to make Meta analysis. Random effects meta-analysis showed that S1 amplitude was lower in the schizophrenia group than in the normal control group (P=0.02), and S2 amplitude was significant higher in schizophrenia group than the normal control group (P=0.001).There were no statistical significance between schizophrenia group and the normal control group in S1 and S2 latency (P=0.34 and P=0.19 respectively).P50 Ratio in schizophrenia group was significantly higher than the normal control group, the difference was statistically significant [Z=11.46, P<0.00001, combined SMD=44.18,95% CI (36.62,51.74)]. However the P50 difference shows no significant different (P= 0.14). Fixed effects analysis showed that the P50 Ratio difference was not statistically significant in patients with schizophrenia between before and after treatment (P=0.46). Conclusion:These results suggest that schizophrenia patients had sensory gating dysfunction. P50 Ratio is a stable and reliable indicator which could reflect the sensory gating function. Antipsychotics may partly enhanced P50 sensory gating in schizophrenia patients, but the medicine can not completely reverse the defect of P50 suppression function. The results show that there have heterogeneity and publication bias between these reports. Future research with larger sample sizes is needed and standard P50 method and blinded measurement should be established to provide reliability data and high-quality evidence.