| Objective:The obesity,dyslipidemia and abnormal glucose metabolisms induced by antipical antiphychotic drugs(AAPD)are a serious problem in the mental disorders treatment.We performed a 8-week clinical follow-up study in schizophrenia patients,tracked body weight,glucose and lipid parameters after single AAPD intervention,these parameters were recorded and compared among different AAPD groups.We analyzed the associations between obesity,dyslipidemia,abnormal glucose metabolisms caused by AAPDs and gene MC4 R,SH2B1,SBK1.Methods:Three hundred patients meeting the entry criteria were recruited and received a single AAPD intervention for eight weeks according to their conditions.One hundred fifty three patients received olanzapine(OLA)treatment,while one hundred forty seven patients took risperidone(RIS).All patients were measured for body weight,fasting plasma glucose(FPG),triglyceride(TG),T Cholesterol(TC),high density lipoprotein(HDL),low density lipoprotein(LDL)data at baseline and at the end of 8th week.The polymorphisms of MC4 R,SH2B1,SBK1 gene were determined with PCR-RFLP technique in all inpatients.All data were analyzed by SPSS17.0 software,data before and after treatment were used by paired T test,while data between groups were used by independent sample T test,the frequencies of different genotypes and alleles of SNPs were calculated by Hardy-Weinberg and Chi-square test and Fisher exact probability test.The creteria level is α=0.05.Results:1.After 8 weeks of treatment with atypical antiphychotic drugs,body weights of patients in every group increased significantly(P=0.000).Compared to Risperidone treatment group,the Olanzapine group patients gained more weight after 8 weeks of treatment.(P=0.001).2.After 8-week treatment,there was a difference in every group’ s weight gain rate mass(%),Olanzapine group data mainly concentrated in the 7%-14% range,while Risperidone group in the 0%-7% range,Both Male and Female patients group were in the 7%-14% range;First episode and Non-first episode patients group were mainly concentrated in the 7%-14% range.3.In total patients group,TG,TC,HDL,and LDL were significantly changed after 8weeks atypical antipsychotics treatment(P=0.000).In each subgroup analysis,lipid metabolism indices of the Olanzapine group,Non-first episode patientsl group,Male group and Female group significantly changed after 8 weeks,and the difference was statistically significant(P=0.000).Compared to Rrisperidone group,the TG levels in the olanzapine group increased more after 8 weeks(P=0.047).4.In all patients,FPG level was significantly decreased after 8 weeks atypical antipsychotics treatment(P=0.000).In the subgroup analysis,FPG in both Risperidone group and the Female group was significantly lower than baseline database(P=0.047,0.018).5.After 8-week treatment,in MC4 R gene rs8087522,patients who carried with A allele(GA+AA)gained more WGR than Non-carried A allele(GG)patients(P=0.018,OR=1.80),meanwhile,the A allete frequency was higher in the WGR≥7% group(P=0.018,OR=1.80);Besides,patients with the A allele(GA+AA)in MC4 R gene rs8087522 gained more TG change(P=0.009);Another finding is patients who carried with T allele in MC4 R gene rs571312 had a significantly lower decline in HDL after treatment(P = 0.035).6.After 8 weeks of treatment,patients with GG genotype in SBK1 gene rs2650492 had more WGR changes than patients with GA/AA genotype carriers(P=0.030),and G allele frequency in the WGR≥7% group was higher than the WGR<7% group(P=0.016,OR=0.36).7.After 8 weeks of treatment,patients with GG genotype in SH2B1 gene rs3888190 had more WGR changes(P=0.030),and G allele frequency in the WGR≥7% group was higher than the WGR<7% group(P=0.038,OR=0.52).Conclusions:1.Atypical antiphychotic drugs could induce weight gain,dyslipidemia and abnormal glucose metabolisms.The WGR and TG changes were more significant in patients receiving olanzapine.2.After 8-week treatment,weight change rate were different in each groups.Olanzapine group data mainly concentrated in the 7%-14% range,Risperidone group in the0%-7% range.3.The genetic factors of AIWG may be different from simple obesity,associations cannot be found in some well-known gene snps,such as SH2B1 rs2650492,MC4 R rs571312;In our research,MC4 R,SBK1,SH2B1 genes may be related to Antipsychotic-induced weight gain in Chinese Han patients with schizophrenia.4.The MC4 R gene rs8087522、rs571312 may be related to TG、HDL changes after taking antipsychotic drugs in Han Chinese schizophrenia patients. |
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