Clinical Study In The Treatment Of Tic Disorder And Regulation Mechanism On Neurotransmitters Of Thalamus Of Qufeng Zhidong Decoction

Objective:1.To evaluate the clinical efficacy of Qufeng Zhidong Decoction in the treatment of tic disorder(TD),as to provide a scientific basis for the clinical standardized treatment according to the international guidelines.2.The level of monoamines and amino acid neurotransmitters in the thalamus of rats were measured by UPLC-3QMS to reveal the pathogenesis of TD and the mechanism of Qufeng Zhidong Decoction.Methods:1.In a randomized,parallel,controlled,double-blind and double-simulated designed study,300 children with moderate and severe TD were divided into three groups:Chinese medicine(CM)group(Qufeng Zhidong Decoction),Chinese and western medicine(CWM)group(Qufeng Zhidong Decoction and Risperidone)and western medicine(WM)group(Risperidone).The patients were followed up at 2 weeks,4 weeks,8 weeks,12 weeks and 24 weeks after treatment.The total effective rate of Yale score and TCM syndrome score,the reduction rate of Yale score,the time when the drug takes effect,the change of effective rate at different time points and the individual score of Yale scale were evaluated at the end of the study,and the safety was evaluated as well.2.The TD rat model was established by intraperitoneal of IDPN.40 SD rats were randomly divided into control group,model group,CM group,WM group and CWM group.The behavioral scores were recorded every week and the levels of the neurotransmitters including DA,5-HT,Glu,GABA,Asp,Gly in the thalamus were measured by UPLC-3QMS after 3 weeks.Results:Clinical study: 1.After 24 weeks of treatment,the total effective rate of YGTSS score was 88.8% in the CM group,82.2% in the WM group,and 96.5% in the CWM group.There was a significant difference among the three groups(P=0.009)by the Chi-square test.Logistic regression showed that group was the main influencing factor.The total effective rate of TCM syndrome score was 89.88% in the CM group,86.67% in the WM group,and 86.67% in the CWM group.There was no significant difference among the three groups.There were significant differences in the reduction rate of the YGTSS score among the three groups before and after treatment(P < 0.001).There was no significant difference among the three groups at all five follow-up points(P > 0.05,0.427,0.739,0.339,0.596,0.275).2.There was no significant difference in the total effective rate of YGTSS score between 8 weeks and 24 weeks of treatment in the CM and the WM group(P > 0.05),and there was no significant difference between 12 weeks and 24 weeks(P > 0.05)in the CWM group.After 8 weeks of treatment,there was no significant difference between the two groups(P > 0.05).And there was no significant difference among the three groups after 8 weeks of treatment(P > 0.629).3.There were significant differences(P<0.001)in 10 dimensions of the YGTSS score of the three groups before and after treatment,and the improvement was positively correlated with the time of treatment.4.During the fifth follow-up,the incidence of side effects was2.27% in the CM group,10.47% in the WM group,and 0.007% in the CWM group.There was a significant difference among the three groups(P=0.0017).After dividing the chi-square,there were significant differences between the CM group,CWM group with the WM group(P=0.0031,P=0.0264).At the 4th and 5th follow-up,there was no significant difference in diagnostic and safety indexes among the three groups(P >0.05).Animal study:1.After 3 weeks of intervention,there were significant differences in open field test score,stereotyped motor score,and autonomous motor score between the model group and the control group(P<0.01).Compared with the model group,there were significant differences in the open field test score and autonomous motor score in the CM group,the WM group,and the CWM group after 2 weeks(open field test: 0.029,0.012,0.008),and there were significant differences in the stereotyped motor score in the CM group,the WM group and the CWM group after 3 weeks(P<0.05).2.Compared with the control group,the levels of DA,Glu,and Asp in the thalamus of the model group were significantly increased(P=0.00,P=0.00,P=0.00),while the levels of 5-HT and GABA were significantly decreased(P=0.00,P=0.00).3.Compared with the model group,the levels of DA,Glu and Asp in CM group,WM group and CWM group decreased significantly(DA:P=0.00,P=0.00,P=0.00;Glu:P=0.00,P=0.00,P=0.00;Asp:P=0.00,P=0.001,P=0.00),while the levels of 5-HT and GABA increased significantly(5-HT:P=0.01,P=0.03,P=0.001;GABA:P=0.00,P=0.00,P=0.00).4.Compared with the WM group,the levels of DA,Glu,and Asp in the CWM group decreased significantly(DA: P=0.002;Glu: P=0.005;Asp: P=0.000),while the level of GABA increased significantly(P=0.044).Conclusion:1.In the treatment of moderate and severe TD,all three medications are safe and effective and can improve TCM clinical syndromes,of which the combined application has the best clinical effect.2.Risperidone alone has a high incidence of side effects,which can be significantly reduced by Qufeng Zhidong Decoction.3.All three medications can significantly improve the behavior of TD rat model,in which combined application is the most effective.4.All three medications could significantly down-regulate the level of DA,Glu and Asp and up-regulate the level of 5-HT and GABA and regulate the unbalanced monoamine and amino acid neurotransmitters in the thalamus of TD rats.The combined application is better than risperidone alone in down-regulation effect on excitatory neurotransmitters.5.The pathogenesis of TD is related to the imbalance of monoamine and amino acid neurotransmitters in the thalamus.6.It is recommended that Qufeng Zhidong Decoction should be the first choice and the combined application should be selected if necessary in the treatment of TD,while risperidone alone is not recommended.And it is recommended to treat with Qufeng Zhidong Decoction if children with TD are taking risperidone alone.