The Diagnostic Value Of P300 In Schizophrenia

Background:The P300 event related potentials (ERP) is a positive going wave 300ms after the external stimulation. It was used to reflect cognitive function of the brain such as attention and memory in human beings. P300 changes were found in dementia, depression and schizophrenia patients in psychiatric diseases. Previous studies found P300 latency could be used as a diagnostic index for dementia patients, with acceptable sensitivity and specificity. Schizophrenia patients often show cognitive impairs and changes of P300 amplitude and latency. However, Diagnostic efficiency of P300 in schizophrenia were affected by two factors:①Single diagnostic index, such as P300 amplitude and latency, only produced poor positive rate of schizophrenia, which may caused by some confounding factor: medication, duration of illness, gender, and age….②Although combined use of p300 and other indexes in schizophrenia diagnosis may improve the positive rate, greater complexity also appears.Studying of first episode schizophrenia (FES) and stratification of gender and age may reduce the effects of confounding factors above, and improve the diagnostic efficiency of the P300. No such study was seen yet.Objectives:To review the evidence for the difference of P300 amplitude and latency between FES and normal control (NC), and to explore whether P300 amplitude and latency in FES differ from those in NC, and to investigate the affecting factors. On this basis, to define the value of P300 amplitude and latency in diagnosis of schizophrenia, and to explore the changes of diagnostic efficiency of certain values in receiver operating characteristic curve (ROC) of p300 amplitudes and latencies after gender and age stratification made.Methods:Literatures (published between 1990 to 2010) about P300 changes in FES, were searched in Pubmed, Medline, Cochrane Library, Chinese BioMedical Literature Database on disc (CBMdisc), and Chinese scientific Periodical database (VIP database). And a manual search was performed using reference lists of identified papers and all reviews articles. Data were extracted after quality assessment of the literature was done by two reviewers. A Meta analysis was conducted to examine the differences of P300 amplitude and latency between FES and NC. Factors influencing the effect size of P300 amplitude and latency were explored by Meta-regression and subgroup analyses. After that, the best cutoff point of P300 amplitude and latency for diagnosis of schizophrenia was calculated in ROC analysis. They were also calculated in different gender and age group, and Youden's indexes and the distance was compared in these two situations.Results:17 studies were eligible for inclusion, including 4 Chinese articles and 13 English articles. Meta analysis shows:①P300 amplitudes were decreased in FES than in NC with the standard mean difference (SMD) of -0.83[95% CI -1.02--0.65], and obvious heterogeneity between individual studies was found (p=0.003, I2=55%). Meta-regression reveals that the heterogeneity comes from reaction pattern(β=0.410), difference between targets and nontargets(β=-0.671) and research place(β=0.460). Subgroup analysis demonstrate that no or less heterogeneity were found in studies with smaller sample (n<80), patients unmedicated, subjects counting targets, conducted in non-Asian area, and with a target probability less than 0.2, While more heterogeneity were found in studies with larger sample (n≥80), patients medicated, subjects pressing keys, conducted in Asian area, with a target probability≥0.2.②Prolonged P300 latencies were found in FES than in NC with the SMD of 0.48 [95% CI 0.14-0.81], and obvious heterogeneity between individual studies was found (p<0.001, I2=86%). Meta-regression revealed that the main heterogeneity come from the difference between targets and nontargets. Subgroup analysis demonstrate that prolonged P300 latencies were only existed in studies with larger sample (n≥80), patients unmedicated, subjects counting targets, conducted in non-Asian area, and with a bigger difference between targets and nontargets, While no statistical significance was found on P300 latencies in studies with smaller sample (n<80), patients medicated, subjects pressing keys, conducted in Asian area, and with a smaller difference between targets and nontargets.In ROC analysis, the area under ROC curve for P300 amplitude predicting schizophrenia was 0.746 (p<0.001), while P300 latency showed poor power in predicting schizophrenia (p=0.373). Best cutoff points of P300 amplitude was 5.097μV, with a sensitivity of 80.14% and a specificity of 63.74%. After gender and age stratification was made, the Youden's index were enhanced in all 5 subgroups (from 1.8% to 14.88%). And the sensitivities of corresponding cutoff were enhaned obviously in subgroups of male (25.01%),≦25 years (22.22%) and﹥40years (28.80%) patients.Conclusions:FES showed small P300 amplitudes and prolonger P300 latencies, compared with NC. The qualities of domestic research remain to improve. P300 amplitude has certain values in schizophrenia diagnosis. Gender and age stratification can enhance the diagnostic efficiency of ROC curve in diagnosis of schizophrenia in group with higher incidence.