Sensorimotor Gating Study In Schizophrenia And Psychotic Major Depression Patients

OBJECTIVE：The purpose of this study is explore the characteristic of sensorimotor gating functionof schizophrenia in acute stage and post-treatment and psychotic major depression patientsin acute stage through measure the level of prepulse inhibition (PPI). In the mean time, thecorrelation between PPI and psychosis symptom was analyzed, in order to providingexperiment evidences for PPI as an objective index to evaluate the recognition dysfunctionof patients.METHODS：All experiments in this study are clinical trials and we have3parts:（1）Sensorimotor gating study of schizophrenia after12weeks of olanzapinetreatment;（2）Sensorimotor gating compares between new admission schizophrenia whodid/did not take antipsychotic in at least1month before admission;（3）Sensorimotorgating study of psychotic major depression patients.In part1, we compared the PPI index and clinical symptom (PANSS scale) before and after12weeks olanzapine treatment, and compare those with healthy control, toobserve the improvement of PPI index and clinical symptom after drug treatment, and toanalyze the connection between the two aspects. There were two groups in this part:①Acute stage schizophrenia patient group（n=36）, PPI index and clinical symptom were tobe measure before and after olanzapine treatment.②Healthy control who come fromclerk of hospital and mate of patient（n=31）. There were no significant differencebetween healthy control and schizophrenia in age and gender. Human startle reflexsoftware and a physiological data acquisitions system were used for data acqursition.Each trial consisted of three blocks. In the first blocks, the startle response to pulsealone was recorded eight times (sound pressure:110dB, duration:40ms) to measureacoustis startle repsponse. In the second block, the startle session consisted of40trials,with five conditions: a110dB white noise burst of40ms (pulse alone) and the same burstpreceded30,60,120or240ms earlier by a prepulse of40ms of86dB; these conditionswere presented in a pseudorandomized order. In the first and third blocks, the startleresponse to pulse alone was recorded eight times to measure startle habituation.Theinter-trial interval averaged15s (range12í18s) and each session lasted forapproximately16min.In part2, we separated newly admission schizophrenia patients to2groups on thebasis of whether they take atypical antipsychotic within at least last1month beforeadmission, to observe the PPI impairment in acute stage of schizophrenia and to anynalzeif medication can influence sersorimotor gating directly when symptome can not becontrolled. There were3groups in this study:①schizophrenia who have take atypicalantipsychotic within at least last1month before admission (n=20）；②schizophrenia whodid not take atypical antipsychotic within at least last1month，but relapsed patients (n=26）;③healthy control as part1. PPI trial is as part1.In part3, we compared the PPI difference of psychotic major depression, non-psychotic major depression, schizophrenia and healthy control. And analyze therelationship between symptom (including depression symptom and psychotic sympotom)and sensorimotor gatiog. There were4groups in this part:①psychotic major depressiongroup（n=18）；②non-psychotic major depression group（n=33）；③schizophrenia group（n=50）；④healthy control as part1. All patients are in acute stage, PPI test were conducted within24hours of administion. PPI trial is as part1.Indexes observed in this study is including acurstic startle response, habituation, PPI,acurstic startle response latency, clinical symptom severity (PANSS, HAM-D) and therelationship between those aspects.RESULTS：In part1, we found that after12weeks of olanzapine treatment, acute stageschizophrenia symptomatic relief (PANSS scale reduced), PPI increased, but still lowerthan healthy control. PANSS positive and negative scale is negtively correlation with PPI.1. PPI index: there was significent difference between schizophrenia and healthy controlbefore medication at30ms,60ms and120mscondition (Mann-Whitney U=350, P=0.01；U=359, P=0.012；U=373, P=0.02), but there was no statistic difference at240ms; there was significent difference between schizophrenia and healthy controlafter medication in120ms (Mann-Whitney U=352, P=0.01), but30ms,60ms and240ms; before and after medication, there was significent difference at60ms(Mann-Whitney U=437, P=0.017) and120ms (Mann-Whitney U=456.5, P=0.03),but30ms and240ms.2. Correlation between PPI and PANSS scale：there was significantly negative correlationbetween PANSS and30ms positive scale PPI before medication（P=0.047）,120msPPI and PANSS negative scale（P=0.030）. But there was no statistic correlationbetween acoustic startle response, habituation and PANSS scale. After12weeksolanzapine medication, there was significantly negative correlation between PANSSpositive scale and60ms PPI（P=0.019）, habituation and PANSS positive scale（P=0.017）, acoustic startle response and PANSS totle scale（P=0.037）.3. Acoustic startle response and habituation: there was no significant difference betweenhealthy control and schizophrenia before and after medication in acoustic startleresponse and habituation index.In part2, we found that the PPI of both two group of acute stage schizophrenia werelower than healthy control, but no difference between two schizophrenia groups. PPI andPANSS positive, negative, general pathology and total scale were negtively correlated inschizophrenia. Acoustic startle latency of healthy control group was shorter than twoschizophrenia groups. But there was no significant difference between three groups inacoustic startle response and habituation： 1. PPI index: the PPI level of schizophrenia who did not take antipsychotic within at leastlast1month (no medicated group) was low than healthy control at30ms(Mann-Whitney U=233, P=0.01) and120ms conditions (Mann-Whitney U=267, P=0.03), but not at60ms和240ms conditions。the PPI level of schizophrenia who didtake atypical antipsychotic within at least last1month (medicated group) was lowthan healthy control at30ms (Mann-Whitney U=195, P=0.03) and60ms(Mann-Whitney U=209, P=0.05) and120ms (Mann-Whitney U=182, P=0.01)conditions, but not at240ms conditions. There was no significant differencebetween no medicated group and medicated group in PPI level in30ms(U=234, P=0.57),60ms (U=251, P=0.84),120ms (U=229, P=0.49) and240ms (U=233, P=0.55) conditions.2. Relationship between PPI index and PANSS, age, gender：in no medicated group,there was negative correlation between30ms PPI and PANSS positive scale,120msPPI and PANSS negative and total scale（P=0.024；P=0.029；P=0.044）. inmedicated group, there was negative correlation between120ms PPI and PANSSpositive, negative, general pathology and total scale（P=0.038；P=0.037；P=0.005；P=0.007）. In no medicated group, there was negative correlation onset ageand60ms condition PPI（P=0.040）In medicated group, there was negativecorrelation between age and acoustic startle response and30ms condition（P=0.026，P=0.007）, onset age and60ms condition PPI（P=0.046）. But we did notfind any statistic correlation between acoustic startle response or habituation andPANSS scale.3. Acoustic startle latency：Acoustic startle latency of healthy control group was shortthan two schizophrenia groups in60ms PPI（P=0.012）.In part3, we found the PPI of psychotic major depression and schizophrenia is lowerthan healthy control, but there was no difference between schizophrenia and psychoticmajor depression and between non-psychotic major depression and healthy control. ThePPI level of non-psychotic major depression is statisicly higher than psychotic majordepression and schizophrenia groups. PPI and PANSS positive, negative, generalpathology and total scale were negtively correlated, but no correlation between PPI andHAM-D. 1． PPI index: the PPI level of schizophrenia and non-psychotic major depression disorderwere significant difference at60ms (U=605.00，Z=-2.047，P=0.041) and120mscondition(U=571.00，Z=-2.363，P=0.018). Compare to control, schizophreniagroup lower PPI in total4PPI condition (30ms condition: U=551.00，Z=-2.177，P=0.030;60ms condition: U=493.00，Z=-2.740，P=0.006；120ms condition: U=419.00，Z=-3.459，P=0.001；240ms condition: U=418.00，Z=-3.469，P=0.001).But schizophrenia group did not differ significantly from psychotic major depressiondisorder group. psychotic major depression disorder and non-psychotic majordepression disorder differed at60ms condition PPI (U=190.00，Z=-2.109，P=0.035). But there was no significant deviation between control and non-psychoticmajor depression group (30ms,60ms,120ms and240ms). Differ fromnon-psychotic major depression, psychotic major depression have lower PPI thancontrol at60ms (U=159.00, Z=-2.489, P=0.013) and240ms （U=155.00, Z=-2.572, P=0.010) condition, but not at30ms and120ms condition.2. Relationship between PPI index and PANSS and HAM-D scale: in psychotic majordepression group, there was negative correlation between habituation and PANSSpositive scale（P=0.002）, PANSS negative and120ms and60ms PPI（P=0.001;P=0.005; P=0.002）, PANSS total scale and120mscondition PPI（P=0.039）. Inschizophrenia group, there was negative correlation between PANSS positive scaleand60ms,120ms condition PPI（P=0.002, P=0.034）, PANSS negative scale and240ms condition PP（IP=0.036）, PANSS general pathology scale and30ms、60mscondition PPI（P=0.011； P=0.026）, PANSS total scale and30ms、60mscondition PPI（P=0.029；P=0.000）. But we did not find any relationship betweenHAM-D and PPI in two depression groups.3. Acoustic startle response and habituation: there was no significant difference within4groups in habituation index. But there are difference in acoustic startle response:psychotic major depression group and psychotic major depression group lower thancontrol (F=6.106， P=0.016; F=11.74，P=0.001).CONCLUTIONS：This study systematicly explored the relationship between psychotic symptom andPPI. Furthermore, we investigate the PPI charactristic of schizophrenia who relapsed within atypical antipsychotic therapy and psychotic major depression patients.Though3parts of experiments, we found:①After12weeks of olanzapine therapy,the psychotic sympotom of schizophrenia improved significantly, and sensorimotorgationg also restored, but still lower than healthy control.②The PPI level ofschizophrenia who did not take antipsychotic within at least last1month (no medicatedgroup) displays obvious symptom and have lower sersorimotor gating function. Similarly,the PPI level of schizophrenia who did take atipical antipsychotic within at least last1month but relapsed (medicated group), due to medication can not control symptom, havesimilar sersorimotor gating function with no medicated group.③Psychotic majordepression have similar sersorimotor gating charactristic with schizophrenia patients. Butnon-psychotic major depression patients have similar sersorimotor gating with healthycontrol. These results indicate whether schizophrenia or psychotic major depression havesimilar sersorimotor gating charactristic because of psychotic symptom.This study expounded the PPI demage of schizophrenia did not be easily directinfuenced by antipsychotic and the PPI improve effect of antipsychotic is connected withpsychotic symptom improvement. Similar level of psychotic major depression patients andschizophrenia further indicate the close relationship between PPI and psychotic symptom.Our study provided experiment evidences for PPI as an objective index to evaluate therecognition dysfunction, psychotic symptom severity and drug effect of patients.