【摘要】：目的:非典型抗精神病藥(atypical antipsychotics,AAPs),如奧氮平、利培酮,在臨床工作中被廣泛應用,已成為一線用藥,大大減少了典型抗精神病藥所伴有的錐體外系副作用,并對認知缺陷及陰性癥狀有較明顯的改善。然而非典型抗精神病藥(AAPs)引起部分服用者體重顯著增加,影響了患者的服藥依從性,增加了致殘率和致死率。抗精神病藥導致體重增加(antipsychotic-induced weight gain,AIWG)成為目前精神障礙治療面臨的一個嚴峻問題。AIWG與遺傳因素密切相關。腦源神經營養(yǎng)因子(BDNF,brain derived neurotrophic factor)在神經系統(tǒng)中發(fā)揮了廣泛作用,參與細胞存活、分化、生長和凋亡。越來越多的證據(jù)表明,BDNF與精神疾病和體重調控密切相關。此外,BDNF可促進突觸可塑性,并與多巴胺能和5-HT的神經元相互作用,提示其在抗精神病藥物引發(fā)的精神分裂癥患者腦功能改變和體重增加過程中的重要作用。BDNF不同基因型可能導致大腦神經回路對抗精神病藥的反應不同。因此,我們推測,研究這個候選基因的遺傳變異可能有助于,觀察抗精神病藥物治療方面的反應和誘導體重增加個體間的差別。本實驗旨在研究BDNF基因多態(tài)性、基線糖、脂代謝等生化指標對非典型抗精神病藥導致體重增加的影響。為精神分裂癥患者接受非典型精神藥物治療后體重增加的傾向性進行預測,為患者個體化治療方案的制定提供依據(jù)。方法:2014年1月-2016年1月在天津市安定醫(yī)院的住院精神分裂癥患者344例。接受單一非典型抗精神病藥物治療干預,動態(tài)觀察12周。通過檢測收錄服用非典型抗精神病藥物(奧氮平、利培酮、喹硫平)患者的BDNF基因2個位點(rs6265、rs11030104)的基因型,并記錄基線、2周末、4周末、6周末、8周末、12周末患者的體重、體質指數(shù)(body mass index,BMI)、腰臀比(waist-to-hipratio,WHR),來分析基因變異與非典型抗精神病藥導致體重增加之間的關系。使用SPSS19.0統(tǒng)計軟件包進行數(shù)據(jù)分析,采用多元回歸分析,采用Spearman相關分析進行雙變量相關分析、重復測量方差檢驗、方差分析。所有檢驗水準設定為α=0.05。結果:1.經單一抗精神病藥物治療后,相比于利培酮組和喹硫平組,奧氮平干預組體重明顯增加(P㩳0.05);2.女性BMI增加明顯高于男性(P㩳0.05)。3.首發(fā)患者體重增加明顯高于非首發(fā)患者(P㩳0.05),4.基線體重與第12周BMI增加明顯負相關(rs=-12.164,P㩳0.05);在喹硫平組,FPG則與BMI增加明顯相關(rs=-2.737,P㩳0.05)。5.重復測量檢驗顯示,rs6265位點與體重增加明顯相關,(P=0.003,P㩳0.05)6.rs11030104位點與體重增加明顯相關(P=0.003,P㩳0.05)。結論:1.BDNF兩基因位點(rs6265、rs11030104)不同基因型與體重增加、WHR增加均明顯相關,2.相較于利培酮或者喹硫平,奧氮平造成的體重增加更為明顯。3.女性、首發(fā)患者體重增加更為明顯,4.喹硫平組空腹血糖則對第12周體重增加具有預測作用。
[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 偽 = 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.
【學位授予單位】：天津醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R749

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