BDNF基因多态性与抗精神病药导致体重增加的关联研究
发布时间：2018-10-17 09:44
【摘要】：目的:非典型抗精神病药(atypical antipsychotics,AAPs),如奥氮平、利培酮,在临床工作中被广泛应用,已成为一线用药,大大减少了典型抗精神病药所伴有的锥体外系副作用,并对认知缺陷及阴性症状有较明显的改善。然而非典型抗精神病药(AAPs)引起部分服用者体重显著增加,影响了患者的服药依从性,增加了致残率和致死率。抗精神病药导致体重增加(antipsychotic-induced weight gain,AIWG)成为目前精神障碍治疗面临的一个严峻问题。AIWG与遗传因素密切相关。脑源神经营养因子(BDNF,brain derived neurotrophic factor)在神经系统中发挥了广泛作用,参与细胞存活、分化、生长和凋亡。越来越多的证据表明,BDNF与精神疾病和体重调控密切相关。此外,BDNF可促进突触可塑性,并与多巴胺能和5-HT的神经元相互作用,提示其在抗精神病药物引发的精神分裂症患者脑功能改变和体重增加过程中的重要作用。BDNF不同基因型可能导致大脑神经回路对抗精神病药的反应不同。因此,我们推测,研究这个候选基因的遗传变异可能有助于,观察抗精神病药物治疗方面的反应和诱导体重增加个体间的差别。本实验旨在研究BDNF基因多态性、基线糖、脂代谢等生化指标对非典型抗精神病药导致体重增加的影响。为精神分裂症患者接受非典型精神药物治疗后体重增加的倾向性进行预测,为患者个体化治疗方案的制定提供依据。方法:2014年1月-2016年1月在天津市安定医院的住院精神分裂症患者344例。接受单一非典型抗精神病药物治疗干预,动态观察12周。通过检测收录服用非典型抗精神病药物(奥氮平、利培酮、喹硫平)患者的BDNF基因2个位点(rs6265、rs11030104)的基因型,并记录基线、2周末、4周末、6周末、8周末、12周末患者的体重、体质指数(body mass index,BMI)、腰臀比(waist-to-hipratio,WHR),来分析基因变异与非典型抗精神病药导致体重增加之间的关系。使用SPSS19.0统计软件包进行数据分析,采用多元回归分析,采用Spearman相关分析进行双变量相关分析、重复测量方差检验、方差分析。所有检验水准设定为α=0.05。结果:1.经单一抗精神病药物治疗后,相比于利培酮组和喹硫平组,奥氮平干预组体重明显增加(P㩳0.05);2.女性BMI增加明显高于男性(P㩳0.05)。3.首发患者体重增加明显高于非首发患者(P㩳0.05),4.基线体重与第12周BMI增加明显负相关(rs=-12.164,P㩳0.05);在喹硫平组,FPG则与BMI增加明显相关(rs=-2.737,P㩳0.05)。5.重复测量检验显示,rs6265位点与体重增加明显相关,(P=0.003,P㩳0.05)6.rs11030104位点与体重增加明显相关(P=0.003,P㩳0.05)。结论:1.BDNF两基因位点(rs6265、rs11030104)不同基因型与体重增加、WHR增加均明显相关,2.相较于利培酮或者喹硫平,奥氮平造成的体重增加更为明显。3.女性、首发患者体重增加更为明显,4.喹硫平组空腹血糖则对第12周体重增加具有预测作用。
[Abstract]:Objective: atypical antipsychotics (atypical antipsychotics,AAPs), such as olanzapine and risperidone, have been widely used in clinical work and become first-line drugs, which greatly reduce the extrapyramidal side effects associated with typical antipsychotics. And the cognitive defects and negative symptoms were significantly improved. However, atypical antipsychotic (AAPs) caused significant weight gain in some users, which affected compliance and increased disability rate and fatality rate. Weight gain (antipsychotic-induced weight gain,AIWG) caused by antipsychotics has become a serious problem in the treatment of mental disorders. AIWG is closely related to genetic factors. Brain-derived neurotrophic factor (BDNF,brain derived neurotrophic factor) plays an important role in the nervous system and is involved in cell survival, differentiation, growth and apoptosis. There is growing evidence that BDNF is closely associated with mental illness and weight regulation. In addition, BDNF promotes synaptic plasticity and interacts with dopaminergic and 5-HT neurons. The results suggest that BDNF may play an important role in brain function change and weight gain in patients with schizophrenia induced by antipsychotic drugs. Different genotypes of BDNF may lead to different responses to antipsychotic drugs in the neurologic circuits of the brain. Therefore, we speculate that studying the genetic variation of this candidate gene may be helpful in observing the response to antipsychotic therapy and inducing individual differences in weight gain. The aim of this study was to investigate the effects of BDNF gene polymorphism, baseline glucose and lipid metabolism on weight gain induced by atypical antipsychotics. To predict the tendency of weight gain in schizophrenic patients after treatment with atypical psychotropic drugs, and to provide basis for the formulation of individualized treatment plan. Methods: from January 2014 to January 2016, 344 inpatients with schizophrenia were enrolled in Tianjin Anding Hospital. Patients were treated with atypical antipsychotics for 12 weeks. The genotypes of 2 loci (rs6265,rs11030104) of BDNF gene in patients with atypical antipsychotic drugs (olanzapine, risperidone, quinthiapine) were detected, and the body weight of patients at baseline, 2, 4, 6, 8, 12 weeks were recorded. Body mass index (body mass index,BMI), waist-to-hip ratio (waist-to-hipratio,WHR), to analyze the relationship between genetic variation and weight gain caused by atypical antipsychotics. SPSS19.0 statistical software package was used for data analysis, multivariate regression analysis, Spearman correlation analysis for bivariate correlation analysis, repeated measurement variance test, and variance analysis. All test levels are set to 伪 = 0.05. The result is 1: 1. After single antipsychotic treatment, compared with risperidone group and quinthiapine group, olanzapine intervention group significantly increased body weight (P0. 05); 2. The increase of BMI in females was significantly higher than that in males (P0. 05). The weight gain of first-episode patients was significantly higher than that of non-first-episode patients (P0. 05). Baseline body weight was negatively correlated with BMI increase at 12 weeks (rs=-12.164,P?0.05), and FPG was significantly correlated with BMI increase (rs=-2.737,P?0.05) in quetiapine group (5. 5%). Repeated measurements showed that rs6265 loci were significantly correlated with weight gain, and (P0. 003 P0. 05) 6.rs11030104 loci were significantly correlated with weight gain (P0. 003, P0. 05). Conclusion: different genotypes of 1.BDNF gene locus (rs6265,rs11030104) are significantly correlated with weight gain and WHR increase. Compared with risperidone or quinthiapine, olanzapine caused more significant weight gain. Female, the first patient weight gain was more significant, 4. 5%. Fasting blood glucose in quetiapine group had a predictive effect on body weight gain at week 12.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749
本文编号：2276273
[Abstract]:Objective: atypical antipsychotics (atypical antipsychotics,AAPs), such as olanzapine and risperidone, have been widely used in clinical work and become first-line drugs, which greatly reduce the extrapyramidal side effects associated with typical antipsychotics. And the cognitive defects and negative symptoms were significantly improved. However, atypical antipsychotic (AAPs) caused significant weight gain in some users, which affected compliance and increased disability rate and fatality rate. Weight gain (antipsychotic-induced weight gain,AIWG) caused by antipsychotics has become a serious problem in the treatment of mental disorders. AIWG is closely related to genetic factors. Brain-derived neurotrophic factor (BDNF,brain derived neurotrophic factor) plays an important role in the nervous system and is involved in cell survival, differentiation, growth and apoptosis. There is growing evidence that BDNF is closely associated with mental illness and weight regulation. In addition, BDNF promotes synaptic plasticity and interacts with dopaminergic and 5-HT neurons. The results suggest that BDNF may play an important role in brain function change and weight gain in patients with schizophrenia induced by antipsychotic drugs. Different genotypes of BDNF may lead to different responses to antipsychotic drugs in the neurologic circuits of the brain. Therefore, we speculate that studying the genetic variation of this candidate gene may be helpful in observing the response to antipsychotic therapy and inducing individual differences in weight gain. The aim of this study was to investigate the effects of BDNF gene polymorphism, baseline glucose and lipid metabolism on weight gain induced by atypical antipsychotics. To predict the tendency of weight gain in schizophrenic patients after treatment with atypical psychotropic drugs, and to provide basis for the formulation of individualized treatment plan. Methods: from January 2014 to January 2016, 344 inpatients with schizophrenia were enrolled in Tianjin Anding Hospital. Patients were treated with atypical antipsychotics for 12 weeks. The genotypes of 2 loci (rs6265,rs11030104) of BDNF gene in patients with atypical antipsychotic drugs (olanzapine, risperidone, quinthiapine) were detected, and the body weight of patients at baseline, 2, 4, 6, 8, 12 weeks were recorded. Body mass index (body mass index,BMI), waist-to-hip ratio (waist-to-hipratio,WHR), to analyze the relationship between genetic variation and weight gain caused by atypical antipsychotics. SPSS19.0 statistical software package was used for data analysis, multivariate regression analysis, Spearman correlation analysis for bivariate correlation analysis, repeated measurement variance test, and variance analysis. All test levels are set to 伪 = 0.05. The result is 1: 1. After single antipsychotic treatment, compared with risperidone group and quinthiapine group, olanzapine intervention group significantly increased body weight (P0. 05); 2. The increase of BMI in females was significantly higher than that in males (P0. 05). The weight gain of first-episode patients was significantly higher than that of non-first-episode patients (P0. 05). Baseline body weight was negatively correlated with BMI increase at 12 weeks (rs=-12.164,P?0.05), and FPG was significantly correlated with BMI increase (rs=-2.737,P?0.05) in quetiapine group (5. 5%). Repeated measurements showed that rs6265 loci were significantly correlated with weight gain, and (P0. 003 P0. 05) 6.rs11030104 loci were significantly correlated with weight gain (P0. 003, P0. 05). Conclusion: different genotypes of 1.BDNF gene locus (rs6265,rs11030104) are significantly correlated with weight gain and WHR increase. Compared with risperidone or quinthiapine, olanzapine caused more significant weight gain. Female, the first patient weight gain was more significant, 4. 5%. Fasting blood glucose in quetiapine group had a predictive effect on body weight gain at week 12.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749
【参考文献】
相关期刊论文 前1条
1 刘星毅;农国才;;几种不同缺失值填充方法的比较[J];南宁师范高等专科学校学报;2007年03期
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