Association Of Polymorphisms In BDNF Gene With Antipsychotic-induced Weight Gain

Objective:Atypical antipsychotics,such as olanzapine,risperidone,are widely used in the clinical work,have become first-line drugs,greatly reducing extrapyramidal side effects,which are associated with the typical antipsychotics.The negative symptoms and cognitive impairment is improved obviously.However the atypical antipsychotics cause significant weight gain,which influences the patient's medication adherence,increased morbidity and mortality.Antipsychotic-induced weight gain has become a serious problem facing the current mental disorder treatment.AIWG is closely related to genetic factors,among them,BDNF play a role of a wide range in the nervous system,involved in cell survival and apoptosis,differentiation,growth.Growing evidences indicated that BDNF is closely related to mental illness and weight control.In addition,BDNF can promote synaptic plasticity and dopamine can interact and 5-HT neurons,prompt the antipsychotic drugs cause changes of brain function in patients with schizophrenia and the important role in the process of weight gain.The BDNF gene polymorphisms may lead to different brain circuits against antipsychotic reactions.Thus,we speculate that the candidate genes of genetic variation in help to explain change between individuals,observation of antipsychotic drug treatment response and induce weight gain.This experiment was to study the BDNF gene polymorphism,baseline glucose,lipid metabolism and biochemical indexes on the influence of the atypical antipsychotics cause weight gain.For schizophrenia patients treated with atypical psychotropic drugs after weight gain tendency forecast,provide basis for the establishment of individualized treatment plan for patients.Methods:In January 2014-January 2016 in Tianjin Anding hospital in hospitalized patients with schizophrenia,344 cases were collected.Into the set out standards of all patients received single atypical antipsychotics therapy intervention,dynamic observation of 12 weeks.By testing,included taking atypical antipsychotics(olanzapine,risperidone and quetiapine flat)the BDNF gene in patients with two loci(rs6265,rs11030104)genotype,and at baseline,2,4,6,8,12 weekend we record the patient's body weight,BMI,WHR to analyze relationship between the genetic variation and atypical antipsychotic-induced weight gain.And analysis of baseline of glucose,lipid metabolic factors: cholesterol(CHOL),triglyceride(TG),high-density lipoprotein(HDL),low density lipoprotein(LDL),fasting plasma glucose(FPG)forecast for weight gain,we used SPSS19.0 statistical software package for data analysis,changes in body weight,BMI,WHR,after taking this medicine biochemical index correlation with baseline using multiple regression analysis,and bivariate correlation analysis to the Spearman correlation analysis,changes in body weight,BMI,WHR,sex,drugs and genes,whether to start relationship with repeated measurement variance test,relations between the baseline and biochemical indexes of genes and variance analysis.All inspection level setting of alpha = 0.05.Results: 1.After treatment with single antipsychotic drug,compared with risperidone and quetiapine group,the weight of patients in olanzapine intervention group increased significantly(P ? 0.05);2.In female patients,BMI increased significantly higher than male(P ? 0.05);3.Weight gain is significantly higher than the first episode patients(P ? 0.05);4.The baseline weight is negatively related to the week 12 BMI increased obviously(rs =-12.164,P ? 0.05).In quetiapine group,FPG is significantly associated with an increased in BMI(rs = 2.737,P ? 2.737);5.Repeated measurement test show that rs6265 loci is associated with weight gain obviously,(P = 0.003,P ? 0.003);6.Rs11030104 loci is associated with weight gain obviously(P = 0.003,P ? 0.05).Conclusion: 1.The BDNF gene locus(rs6265,rs11030104)and two were significantly associated with an increased weight gain,WHR,2.Compared with risperidone and quetiapine group,olanzapine causes more weight gain.3.Women and first episode patients' weight gain is more obvious,4.In quetiapine group,fasting glucose were predicted for week 12 weight gain.