| Background:Schizophrenia is a kind of chronic major psychiatric disorder.At present,the treatment of schizophrenia mainly relied on antipsychotics in clinical practice,particularly,the atypical antipsychotics(the second generation antipsychotics,SGA).Risperidone is used commonly in clinical,and there is obvious individual variability on efficacy of risperidone and risperidone may induce EPS.The acute EPS is not only associated with reduced compliance,but also a risk factor for tardive dyskinesia.The mechanisms influencing individual differences in risperidone efficacy and acute EPS remain unclear.At present,the relevant researches focused on single gene polymorphism,for example,dopamine 2 receptor(DRD2)or Serotonin receptor or 5-hydroxytryptamine receptor 2(5-HTR2A).However,risperidone antagonizes DRD2(dopamine 2 receptor)and 5-HTR2A(Serotonin receptor or 5-hydroxytryptamine receptor 2A)to improve the symptoms of schizophrenia.Therefore,considering the association between one kind of gene polymorphisms-DRD2 or 5-HTR2A and the efficacy of risperidone may ignore significant associations which can only be identified using a combination of multiple genomic loci.In addition,there are few studies on acute EPS and 5-HTR2A gene polymorphisms.Aim:To investigate whether the interaction between DRD2 and 5-HTR2A gene polymorphism affects the efficacy of risperidone in the treatment of schizophrenia and whether the interaction between DRD2 and 5-HTR2A gene polymorphism affects the occurrence of acute EPS induced by risperidone.Method:In the study of efficacy of risperidone,we included 105 schizophrenic inpatients,and applying PANSS to assess the inpatients’psychiatric symptoms,then calculated scores reduction rate,according to the reduction rate at 4 weeks,the patients were classified as good responders and poor responders.In the study of EPS induced by risperidone,we included 102 subjects,and applying the Treatment Emergent symptom scale(TESS)to evaluate extrapyramidal symptoms,if there is one’s severity score≥2of four items(acute dystonia,tremor,akathisia,torsion dystonia)in the TESS,the patients were regarded as the existence of acute extrapyramidal symptoms.In addition,we would collect 2ml of blood to genotype for DRD2(939C>T,-241A>GTaq1A)and 5-HTR2A(102T>C,IVS2G>A)by the improved multiplex ligase detection reaction(i MLDR).All of the subjects accepted a sole antipsychotic-risperidone to treat,everyone did not receive any physical or psychological treatment,and beside the first week,the dose was4-6mg/d within 4 weeks.Method of statistics:If continuous variables were normally distributed,we would use t test or analysis of variance to analysis.If the distribution is non-normal,the Mann-Whitney U test would be used.Categorical variables were analysed byχ~2 test or binary logistics regression analysis.GMDR analysis was used to analysed the effect of gene polymorphism interaction on risperidone efficacy,and logistics regression analysis was used to verify the results of GMDR.Results:The results of studies on the efficacy of risperidone in the treatment of schizophrenia are as follows:Student’s test showed that the course of disease impacted the efficacy of risperidone(P=0.003).χ~2 test showed that gene polymorphisms of DRD2 Taq1A(P=0.040)and DRD2 939C>T(P=0.036)affected the efficacy of risperidone;Logistics regression showed that course of diease and DRD2939C>T had statistical significance on the effect of risperidone in the treatment of acute schizophrenia(P=0.003,OR=0.934,95CI%:0.892-0.978;P=0.028,OR=2.952,95CI%:1.126-7.739,respectively).GMDR and logistics regression both showed that interaction between DRD2 939C>T and 5-HTR2A 102T>C effected the efficacy of risperidone(GMDR:P=0.0107,CV=10/10,testing ACC=0.6684,logistics:P=0.023,95%CI:0.348—0.924).And the course of disease impacted the efficacy of risperidone(P=0.004,95%CI:0.893—0.979).The results of risperidone induced acute EPS were as follows:χ~2 test showed that gene polymorphisms of 5-HTRA2 IVS2G>A(P=0.022)affected the acute extrapyramidal symptoms induced by risperidone;logistics regression analysis showed that the gene polymorphisms of DRD2 Taq1A (P=0.044,OR=2.720,95%CI:1.030—7.188),5-HTR2A IVS2G>A(P=0.013,OR=2.944,95%CI:1.260—6.880)affected the acute extrapyramidal symptoms induced by risperidone.GMDR and logistics regression both showed that interaction among DRD2-241A>G vs Taq1A vs IVS2G>A effected the acute EPS induced by risperidone (GMDR:P=0.0107,CV=9/10,testing ACC=0.637;logistics regession:P=0.013,95%CI:0.044—0.694)Conclusion:The course of disease had an influence on the efficacy of risperidone in the treatment of acute schizophrenia,and the combination of 5-HTR2A(102C)and DRD2(939T)alleles has a better efficacy.Patients with the DRD2 Taq1A-A and 5-HTR2A IVS2A alleles were more likely to develop acute EPS.In the case of mutational genotype of IVS2G G>A,the patients with Taq1A-G and-241G at the same time were less likely to develop acute EPS.When IVS2G G>A and-241G without mutational genotype,Taq1A-A carriers were more likely to develop acute EPS. |
