Study On The Relationship Between Oxidative Stress,mental Symptoms And Cognitive Function In Patients With First-episode Untreated Schizophrenia

Objective1.To observe the level of oxidative stress markers in baseline of first-episode untreated schizophrenic patients and to understand the oxidative stress status of schizophrenic patients.2.To explore the possible role and mechanism of oxidative stress in the pathogenesis of schizophrenia by analyzing the relationship between oxidative stress markers and mental symptoms in first-episode untreated schizophrenic patients.3.To analyze the relationship between oxidative stress markers and cognitive functions in first-episode untreated schizophrenic patients,and to explore the possible role and mechanism of oxidative stress in the occurrence of cognitive dysfunction in schizophrenia.4.By analyzing the relationship between the level of oxidative stress markers in patients with first-episode untreated schizophrenia and the improvement of cognitive function before and after treatment,and to explore the possible predictive role of oxidative stress in the improvement of cognitive function in patients with schizophrenia.Methods1.From December 2016 to October 2018,the first-episode untreated schizophrenic patients were recruited from the outpatient department and/or ward of the first affiliated Hospital of Zhengzhou University,at the same time students and healthy volunteers served as the healthy control group.All subjects including case group and healthy control group whose venous blood from the elbow were collected in the early morning of the second day after admission when they were fasting.The levels of liver and kidney function,blood glucose,blood lipid and oxidative stress markers such as superoxide dismutase（SOD）,glutathione（GSH）,homocysteine（HCY）,nitric oxide（NO）,folic acid（FA）and uric acid（UA）were measured.At the same time,the general clinical datas,including height,weight,waist circumference and so on,were collected on the day of admission.2.All patients who met the admission criterias obtained detailed medical history inquiry,physical and psychiatric examination on the day of admission and at the end of 12^th week of treatment.The severity of cognitive functions and mental symptoms were evaluated.The severity of mental symptoms in schizophrenic patients was evaluated by positive and negative symptom score（PANSS）,including positive symptom score,negative symptom score and general psychopathological symptom score.MATRICS cognitive function scale（MCCB）was used to evaluate cognitive functions.The Chinese version included 9 subtests:（1）Wired Test（TMT）;（2）symbol coding;（3）Hopkins word Learning Test（HVLT）;（4）Spatial breadth;（5）Labyrinth;（6）Visual Learning（BVMT）;（7）fluency Test;（8）emotional Management（MSCEIT）;（9）continuous operation-identical pairing（CTP-IP）.In order to ensure the consistency and effectiveness of the scale,the scale was completed by a professionally trained psychiatrist.The cognitive evaluation results were introduced into MCCB cognitive statistical software,and finally transformed into the corresponding seven domain scores for statistical analysis.3.Statistical analysis:The experimental datas were analyzed with SPSS 22.0statistical software.The results of K-S single sample test were normal distribution.If the results were subject to normal distribution,the results were expressed as mean±standard deviation（?x±s）.Independent sample T test was used to compare the parameters between the baseline period of the case group and the control group.If the normal distribution is not obeyed,the Mann-Whitney U test was used,and the results were expressed as the median.The counting datas were analyzed by chi-square test,and the results were expressed as the percentage of the number of cases[case（%）].The parameters of the case group before and after treatment were compared by paired sample T test.Pearson correlation analysis was used for correlation test in accordance with normal distribution,and Spearman correlation analysis was used if it did not conform to normal distribution.Multiple linear regression analysis was used to predict whether the level of oxidative stress markers in the baseline phase of the case group could predict the improvement of cognitive function.Statistical analysis showed that there was significant difference between the two sides（p<0.05）.Results1.A total of 125 cases were included in the screening period of the case group（A total of 117 cases were enrolled in the final baseline stage case group,and 80 cases were followed up for 12 weeks.）,and 100 cases were enrolled in the healthy control group.There was no significant difference in age,sex,education level,smoking history,height,weight,waist circumference,BMI,fasting blood glucose（FBG）,triglyceride（TG）,Total cholesterol（TCHO）,low density lipoprotein（LDL）,glutamic-pyruvic transaminase（ALT）,glutamic oxaloacetic transaminase（AST）,urea（UREA）and creatinine（CRE）between the case group and the control group（p>0.05）.2.The mean levels of UA,HCY and NO in baseline phase in the case group[（298.24±71.98）μmol/L,（20.35±14.88）μmol/L,（57.07±60.40）μmol/L]were higher than those in the control group[（277.55±75.34）μmol/L,（16.24±10.12）μmol/L,（34.05±38.97）μmol/L],and the difference was statistically significant（t=1.991,2.287,2.323,all p<0.05）.The mean levels of FA,GSH and SOD[（6.60±3.85）ng/ml,（22.17±9.20）μmol/L,（173.98±36.88）U/ml]were lower than those in the control group[（9.38±4.48）ng/ml,（31.04±12.77）μmol/L,（231.72±29.11）U/ml],and the difference was statistically significant（t=-4.725,-4.719,-7.599,all p<0.05）.3.The comparison of cognitive function between the baseline case group and the control group showed that the scores of the seven domains of cognitive functions,including information processing speed,attention and alertness,working memory,word learning,visual learning,reasoning and problem-solving,and social cognition[（29.73±11.74）,（29.66±11.68）,（37.25±9.61）,（34.81±9.01）,（34.36±8.59）,（36.94±11.98）,（31.72±9.09）]in the case group were significantly lower than those[（35.71±11.00）,（35.74±10.94）,（46.10±6.71）,（39.54±10.44）,（41.06±10.26）,（44.66±9.99）,（40.83±11.25）]in the healthy control group,the difference was statistically significant（all p<0.05）.4.Correlation analysis between baseline oxidative stress indexes such as GSH,SOD,NO,UA,HCY,FA and cognitive function as well as PANSS in the case group.The results showed that HCY was negatively correlated with word learning and visual learning（r=-0.207,r=-0.202,all p<0.05）,and was positively correlated with the total score of PANSS（r=0.204,p=0.041）.Folic acid was positively correlated with reasoning and problem solving（r=0.289,p=0.003）,and there was no significant correlation between the remaining oxidative stress indexes and the scores of cognitive functions in seven domains（all p>0.05）.GSH was negatively correlated with the general pathological score of mental symptoms（r=-0.220,p=0.027）.5.The changes of mental symptoms and cognitive functions in schizophrenic patients treated with risperidone at the end of 12th week showed that after risperidone treatment,the positive symptom score,negative symptom score,general pathological symptom score and PANSS total score of schizophrenic patients were significantly decreased（p<0.05）,at the same time the cognitive function areas such as attention and alertness,working memory,word learning and social cognition were improved（p<0.05）.6.After controlling for confounding factors such as age,sex,smoking and education,the results of multiple linear regression analysis showed that among the six baseline oxidative stress markers,only GSH was positively correlated with the improvement of attention and alertness（standardized coefficientβ=0.384,adjusted R²=0.151,p=0.003）.UA was positively correlated with the improvement of working memory（standardization coefficientβ=0.311,adjusted R²=0.080,p=0.036）.There was no correlation between other baseline oxidative stress markers and the improvement of cognitive function.Conclusions1.There was an imbalance between oxidation and antioxidation in the first untreated schizophrenia,in which the oxidation promoting system was activated and the compensatory ability of some antioxidants was enhanced.2.Homocysteine and glutathion are associated with the severity of schizophrenia.3.Folic acid and homocysteine are associated with cognitive impairment in schizophrenia.4.Glutathione and uric acid may be predictors of cognitive function improvement in schizophrenic patients.