the n400 component of event - related potentials ( erp ) has recently drawn widespread attention at home and abroad . its clinical value is that , not only is it most frequently used to assess diseases associated with linguistic disorder in the department of neurology and psychiatry , but also , to effectively improve patients linguistic disorder has become an important candidate target of the research and development on the new generation of anti - psychotic drugs . this research enrolled patients with first - episode schizophrenia ( fes ) , who had never taken any antipsychotic drugs before , and carried out a 1-year follow - up on them . this way , we could eliminate the cross - effect among different antipsychotic drugs and draw some conclusions on n400 changes in fes patients and its clinical value . the patient group included a total of 58 patients of the han nationality , who were out - patients and in - patients with fes in shanghai mental health center affiliated to school of medicine , shanghai jiaotong university from january 2009 to february 2014 . the criteria of enrollment were : ( 1 ) the schizophrenic patients had no history of antipsychotic treatment and visited shanghai mental health center for the first time in their life , ( 2 ) the symptoms fitted the diagnostic criteria of schizophrenia in the chinese classification of mental disorders-3 and the diagnostic and statistical manual of mental disorders - iv , ( 3 ) mother language : chinese , fluent in spoken and written mandarin , ( 4 ) they had no organic mental health disorders , psychotic diseases other than schizophrenia , or history of substance dependence . age : 1951 years , mean age : 29.5  7.3 years , and average education years : 16.3  2.9 years . disease course : 0.62.5 years ( beginning from the moment when the patients relatives firstly found them strange until their enrollment into the group ) , median : 1.6 years . their positive and negative syndrome scale ( panss ) total score at the moment of enrollment was 104.3  11.7 . the normal controls ( ncs ) consisted of the volunteers from shanghai mental health center affiliated to school of medicine of shanghai jiaotong university , shanghai jiaotong university school of medicine and the communities nearby from january 2009 to february 2014 . the criteria of enrollment were : ( 1 ) no physical diseases were found during the physical examination , ( 2 ) the complete blood count , biochemical routine , and chest radiograph showed no abnormality , ( 3 ) the candidates received psychiatric interviews to insure that they had never had any mental disorder before and were then in good mental health , ( 4 ) the candidate 's second - degree and third - generation relatives had no history of psychosis , ( 5 ) mother language : chinese , fluent in spoken and written mandarin , education level : college degree and above . age : 1950 , mean age : 29.6  6.6 , and average education years : 16.7  2.2 years . there was no significant difference in sex , age , nationality , or education level between the two groups ( p > 0.05 ) . the patients or their guardians have all been informed and signed on the informed consent forms . the last word of each sentence is the target word , which classifies the sentence into one of the two groups , matching ( congruent ) or mismatching ( incongruent ) . when the logical and semantic relationship between the target word and the main body of the sentence is highly expected , the sentence is congruent . for example ,  in the coffee , i put sugar  is congruent . otherwise , if the expected probability of this relationship is zero , the sentence is incongruent . for example ,  in the coffee , i put a dog  is incongruent . all the words in the stimuli are high - frequency chinese words , whose frequency of use is higher than 30 times per 10,000 . presentation of the stimuli we referred to the chinese sentence tests of zhou et al . and the eyes of the subjects kept parallel with the words , with a distance of 1 m to the screen . below is the verbal instruction : some chinese sentences will present on the screen in front of you . at the end of the countdown , judge carefully whether the word that lastly appears in the sentence is semantically correct until the screen turns black . after the test ends , your number of correct and incorrect answers will be shown ( if the sentence is incongruent , the subject clicks on  no ;  if it is congruent , the subject clicks on  yes  ) . the guangzhou runjie wj-1 erp instruments were used in the test . in accordance with the international 1020 system , the electrodes at fp1 , fp2 , fz , f3 , f4 , cz , c3 , c4 , pz , p3 , p4 , o1 , o2 , f7 , f8 , t3 , t4 , t5 , t6 , fp locations were grounding electrodes . the electrodes at a1 , a2 locations ( at two ears ) were reference electrodes . the electrode resistance was < 5 k. the wave filtering was between 0.53 and 60 hz . the waves whose amplitude were bigger than 75 v due to eye movements or other factors were eliminated . the collected data were kept on the hard disk of the computer for further use . the therapeutic effect was evaluated with the panss before treatment , 6 months after treatment , and 15 months after treatment . the primary evaluation index is the reduction rate of panss total score at the end of 6 months after treatment . it is calculated as below : reduction rate = ( panss total score before treatment  panss total score after treatment)/panss total score before treatment  100% . the maximal n400 latencies and amplitudes at fz , cz , and pz were detected for each congruent or incongruent erp . all data were automatically detected , calculated , and presented by the digital cursor of this instrument . the data were processed with spss version 11.0 ( spss incorporated , chicago , usa ) . the f test analyzed changes in the fes group between before and after treatment . the correlation between n400 components of the fes group and panss scores was calculated with spearman correlation analysis . the patient group included a total of 58 patients of the han nationality , who were out - patients and in - patients with fes in shanghai mental health center affiliated to school of medicine , shanghai jiaotong university from january 2009 to february 2014 . the criteria of enrollment were : ( 1 ) the schizophrenic patients had no history of antipsychotic treatment and visited shanghai mental health center for the first time in their life , ( 2 ) the symptoms fitted the diagnostic criteria of schizophrenia in the chinese classification of mental disorders-3 and the diagnostic and statistical manual of mental disorders - iv , ( 3 ) mother language : chinese , fluent in spoken and written mandarin , ( 4 ) they had no organic mental health disorders , psychotic diseases other than schizophrenia , or history of substance dependence . age : 1951 years , mean age : 29.5  7.3 years , and average education years : 16.3  2.9 years . disease course : 0.62.5 years ( beginning from the moment when the patients relatives firstly found them strange until their enrollment into the group ) , median : 1.6 years . their positive and negative syndrome scale ( panss ) total score at the moment of enrollment was 104.3  11.7 . the normal controls ( ncs ) consisted of the volunteers from shanghai mental health center affiliated to school of medicine of shanghai jiaotong university , shanghai jiaotong university school of medicine and the communities nearby from january 2009 to february 2014 . the criteria of enrollment were : ( 1 ) no physical diseases were found during the physical examination , ( 2 ) the complete blood count , biochemical routine , and chest radiograph showed no abnormality , ( 3 ) the candidates received psychiatric interviews to insure that they had never had any mental disorder before and were then in good mental health , ( 4 ) the candidate 's second - degree and third - generation relatives had no history of psychosis , ( 5 ) mother language : chinese , fluent in spoken and written mandarin , education level : college degree and above . age : 1950 , mean age : 29.6  6.6 , and average education years : 16.7  2.2 years . there was no significant difference in sex , age , nationality , or education level between the two groups ( p > 0.05 ) . the patients or their guardians have all been informed and signed on the informed consent forms . the last word of each sentence is the target word , which classifies the sentence into one of the two groups , matching ( congruent ) or mismatching ( incongruent ) . when the logical and semantic relationship between the target word and the main body of the sentence is highly expected , the sentence is congruent . for example ,  in the coffee , i put sugar  is congruent . otherwise , if the expected probability of this relationship is zero , the sentence is incongruent . for example ,  in the coffee , i put a dog  is incongruent . all the words in the stimuli are high - frequency chinese words , whose frequency of use is higher than 30 times per 10,000 . presentation of the stimuli we referred to the chinese sentence tests of zhou et al . and the eyes of the subjects kept parallel with the words , with a distance of 1 m to the screen . below is the verbal instruction : some chinese sentences will present on the screen in front of you . at the end of the countdown , the test will set off . during the test judge carefully whether the word that lastly appears in the sentence is semantically correct until the screen turns black . after the test ends , your number of correct and incorrect answers will be shown ( if the sentence is incongruent , the subject clicks on  no ;  if it is congruent , the subject clicks on  yes  ) . the guangzhou runjie wj-1 erp instruments were used in the test . in accordance with the international 1020 system , the electrodes at fp1 , fp2 , fz , f3 , f4 , cz , c3 , c4 , pz , p3 , p4 , o1 , o2 , f7 , f8 , t3 , t4 , t5 , t6 , fp locations were grounding electrodes . the electrodes at a1 , a2 locations ( at two ears ) were reference electrodes . the electrode resistance was < 5 k. the wave filtering was between 0.53 and 60 hz . the waves whose amplitude were bigger than 75 v due to eye movements or other factors were eliminated . the collected data were kept on the hard disk of the computer for further use . all the patients were medicated only with risperidone ( xian - janssen pharmaceutical ltd . , the therapeutic effect was evaluated with the panss before treatment , 6 months after treatment , and 15 months after treatment . the primary evaluation index is the reduction rate of panss total score at the end of 6 months after treatment . it is calculated as below : reduction rate = ( panss total score before treatment  panss total score after treatment)/panss total score before treatment  100% . the maximal n400 latencies and amplitudes at fz , cz , and pz were detected for each congruent or incongruent erp . all data were automatically detected , calculated , and presented by the digital cursor of this instrument . the data were processed with spss version 11.0 ( spss incorporated , chicago , usa ) . the f test analyzed changes in the fes group between before and after treatment . the correlation between n400 components of the fes group and panss scores was calculated with spearman correlation analysis . compared with ncs , n400 latencies in the patient group at the 5 locations were significantly prolonged before treatment . in both congruent and incongruent situations , the changes in n400 latency in the patient group were alike at fz , pz , c3 , and c4 locations [ table 1 ] . comparison of n400 latency and amplitude in congruent and incongruent situations , 62 ncs and 58 fes ( mean  sd ) sd : standard deviation ; nc : normal control ; fes : first episode schizophrenia . compared with ncs , n400 amplitudes in the patient group at the 5 locations the changes in n400 amplitude in the patient group were alike at fz , pz , c3 , and c4 locations . positive scores , negative scores , and general psychopathology scores , and total scores were significantly decreased at 6 and 15 months after treatment [ table 2 ] . panss scores of schizophrenia patients at baseline , 6 months , and 15 months compared with before treatment : * p<0.05 , p<0.01 . compared with 6 months after treatment : p<0.05 . panss : positive and negative syndrome scale ; ps : positive scores of panss ; ns : negative scores of panss ; gps : general psychopathology scores of panss ; ts : total scores of panss . at cz location , the prolongation of n400 latency was negatively correlated with panss positive symptoms score ( 0.463 , p = 0.032 ) , and the decrease of n400 amplitude was negatively correlated with panss positive symptoms score ( 0.431 , p = 0.008 ) and panss total score ( 0.382 , p = 0.023 ) . among the 58 fes patients , we carried out follow - up on 52 of them 6 months after treatment , and on 45 of them 15 months after treatment . the loss to follow - up was due to the fact that some patients lived outside shanghai or had moved away . as shown in table 2 , 6 months after the risperidone treatment , the 58 fes patients psychotic symptoms did not significantly alleviate , and there was no significant difference in n400 latency or amplitude between then and before treatment . however , 15 months after the treatment , their psychotic symptoms began to alleviate ( panss total score 29.5  3.3 , reducing rate > 50% ) , and n400 began to improve : n400 latency moved forward and n400 amplitude increased . there was a significant difference in n400 latency and amplitude ( p < 0.05 ) [ table 3 ] . a comparison of n400 components in congruent and incongruent situations , fes , before and after treatment ( cz ) ( mean  sd ) compared with before treatment : * p<0.05 , p<0.01 . compared with 6 months after treatment : p<0.05 , p<0.01 . compared with ncs , n400 latencies in the patient group at the 5 locations were significantly prolonged before treatment . in both congruent and incongruent situations , the changes in n400 latency in the patient group were alike at fz , pz , c3 , and c4 locations [ table 1 ] . comparison of n400 latency and amplitude in congruent and incongruent situations , 62 ncs and 58 fes ( mean  sd ) sd : standard deviation ; nc : normal control ; fes : first episode schizophrenia . compared with ncs , n400 amplitudes in the patient group at the 5 locations the changes in n400 amplitude in the patient group were alike at fz , pz , c3 , and c4 locations . positive scores , negative scores , and general psychopathology scores , and total scores were significantly decreased at 6 and 15 months after treatment [ table 2 ] . panss scores of schizophrenia patients at baseline , 6 months , and 15 months compared with before treatment : * p<0.05 , p<0.01 . compared with 6 months after treatment : p<0.05 . panss : positive and negative syndrome scale ; ps : positive scores of panss ; ns : negative scores of panss ; gps : general psychopathology scores of panss ; ts : total scores of panss . at cz location , the prolongation of n400 latency was negatively correlated with panss positive symptoms score ( 0.463 , p = 0.032 ) , and the decrease of n400 amplitude was negatively correlated with panss positive symptoms score ( 0.431 , p = 0.008 ) and panss total score ( 0.382 , p = 0.023 ) . among the 58 fes patients , we carried out follow - up on 52 of them 6 months after treatment , and on 45 of them 15 months after treatment . the loss to follow - up was due to the fact that some patients lived outside shanghai or had moved away . as shown in table 2 , 6 months after the risperidone treatment , the 58 fes patients psychotic symptoms did not significantly alleviate , and there was no significant difference in n400 latency or amplitude between then and before treatment . however , 15 months after the treatment , their psychotic symptoms began to alleviate ( panss total score 29.5  3.3 , reducing rate > 50% ) , and n400 began to improve : n400 latency moved forward and n400 amplitude increased . there was a significant difference in n400 latency and amplitude ( p < 0.05 ) [ table 3 ] . a comparison of n400 components in congruent and incongruent situations , fes , before and after treatment ( cz ) ( mean  sd ) compared with before treatment : * p<0.05 , p<0.01 . compared with 6 months after treatment : p<0.05 , p<0.01 . as an endogenous component of erp , n400 reflects the linguistic and cognitive process of the brain and has increasingly received widespread attention . ever since the 1990 's when koyama et al . firstly reported n400 changes in schizophrenic patients , quite an amount of repeated research has found decreased n400 amplitude and prolonged n400 latency in schizophrenic patients . currently , sentence stimuli are most frequently used in n400 tests . the operational paradigm of this study accords with the recording standards and publication criteria of erp proposed by the society for psychophysiological research . this study selected the fes patients , who had never taken anti - psychotic drugs and whose disease course was < 2 years , so that the cross - effect of multiple factors on the cerebral function , such as anti - psychotic drugs , nondrug treatments ( e.g. , electro - convulsive therapy ) , and long - term disease course , could be eliminated and the dynamic progression of the disease could be observed . in this study , the data collected on n400 show that : ( 1 ) latency  compared with ncs , n400 latencies in the patient group at the 5 locations were significantly prolonged before treatment . in both congruent and incongruent situations , the changes in n400 latency in the patient group were alike at fz , pz , c3 , and c4 locations . ( 2 ) amplitude  compared with ncs , n400 amplitudes in the patient group at the 5 locations were significantly decreased before treatment . in both congruent and incongruent situations , the changes in n400 amplitude in the patient group were alike at fz , pz , c3 , and c4 locations . the results of this study are the same as that of grillon et al . the decreased n400 amplitude means that schizophrenic patients can not make correct semantic expectations face to irrelevant semantic stimuli , which suggests that the patients impaired semantic information process function could lead to the worsening of speed and accuracy in making semantic expectations . the prolonged n400 latency means that the information process of stimuli in schizophrenic patients is slowed down or easy to interrupt . andrews reported that the positive symptoms score of thought and attention disorder was negatively correlated with the average n400 amplitude in a time - window of 300500 ms . until now , it is unclear if n400 reduction relates to real - world functioning and recovery . this study found that the prolongation of n400 latency and decrease of n400 amplitude were negatively correlated with panss total score and positive symptoms score . this suggests that n400 latency and amplitude change with the progression of the disease , and thus reflect the seriousness of schizophrenia . is n400 a trait marker , a state marker , or a mix of the two in schizophrenia ? the follow - up in this study plays an important role in verifying the nature of this marker . the follow - up in this study shows that there was a significant difference in n400 changes between patients with notable psychotic symptoms and patients whose symptoms have alleviated . the follow - up included n400 aberration data from before treatment until the disappearance or alleviation of symptoms . as the disease ameliorates , n400 gradually turns normal . therefore , the aberration of n400 is a state marker that indicates the onset and seriousness of the disease , and the impairment of n400 might be one of the important pathogenetic factors of schizophrenia . currently , there is a lack of biological markers to facilitate the clinical diagnosis of psychotic diseases . n400 has been used as a candidate electroencephalologic marker in a series of research on schizophrenia . currently , in europe and north - america , n400 has been used in the aceologic and pharmacological research on neuropsychiatric drugs . in our study , we found that during the early stage of treatment , the antipsychotic drug did not have a great influence on n400 . in other words , n400 in schizophrenic patients is relatively stable at the beginning of the medical treatment , and thus , clinical examinations on n400 are feasible after a short period of medical treatment . since all of the schizophrenic patients in this study only took risperidone , further follow - up needs to be carried out on patients who take other antipsychotic drugs in order to see if the same conclusion could be reached . first , as only risperidone was used in the treatment of schizophrenia , the results may not suit to other situations . second , the materials used in this study are chinese sentences , which may also cause some bias when inferring the results to phonetic materials . n400 therefore , it can be used as a cognitive electrical potential with clinical value to assess multiple diseases associated with linguistic disorder . during the recent years , the combination of n400 and the neuroimaging technique has opened up a whole new field for the research on n400 as well as on language . in addition , if the research on n400 could combine the knowledge of genetics , molecular biology , psychopharmacology , and psychotic symptoms , it will help to fully understand this potential biological marker of n400 and the mechanism of cerebral dysfunction in schizophrenia .
background : the n400 component of event - related potentials ( erp ) has recently drawn widespread attention at home and abroad . 
 this study was to explore the relationship between n400 changes and risperidone treatment and rehabilitation in first - episode schizophrenia ( fes).methods : erp component n400 was recorded by guangzhou runjie wj-1 erp instruments , in 58 fes before and 6 months , 15 months after risperidone treatment , and in 62 normal controls . 
 the patients syndromes were assessed by positive and negative syndrome scale ( panss ) . and the stimuli are chinese sentences with matching ( congruent ) or mismatching ( incongruent ) ending words.results:n400 latencies were prolonged , and amplitudes were decreased in cz , pz , fz , c3 , c4 , in fes compared with in nc , before treatment . 
 the prolonged n400 latencies and decreased amplitudes were negatively correlated with the patients positive scale and total scale of panss . 
 there are significant differences of n400 amplitudes and latencies in 6 months and 15 months follow - up after treatment . before treatment , 
 6 months and 15 months after treatment , n400 latencies are 446  35 ms , 440  37 ms , 414  31 ms ( f = 9.72 , p < 0.01 ) in incongruent situation ; n400 amplitudes are 5.2  4.6 v , 5.7  4.8 v , 7.3  5.0 v ( f = 2.06 , p > 0.05 ) in congruent situation , and 8.5  5.9 v , 10.1  5.0 v , 11.9  7.0 v ( f = 3.697 , p < 0.05 ) in incongruent situation.conclusions:n400 could be used to predict the effects of treatment of schizophrenia to some degree 
 . the linguistic and cognitive impairment in schizophrenia can be improved by antipsychotic drugs .