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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 簡國龍 | |
| dc.contributor.author | Ching-Jow Hiseh | en |
| dc.contributor.author | 謝青宙 | zh_TW |
| dc.date.accessioned | 2021-06-08T04:44:19Z | - |
| dc.date.copyright | 2009-09-16 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-08-04 | |
| dc.identifier.citation | American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity, 2004. Consensus statement: Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 27 (2), 596–601.
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Psychiatry 168 (6), 702-708. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/23147 | - |
| dc.description.abstract | 背景與目標：遲發性運動異常 (Tardive dyskinesia, TD)，是抗精神病藥物副作用中較嚴重的一種。TD的病理機轉目前並未完全了解，有研究指出與血清素基因有關。本研究目的為探討血清素第2A型接受體T102C 基因多型性、血清素運送基因多型性與血清素第2C型接受體Cys23Ser基因多型性與慢性精神分裂症患者之TD有無相關。
方法：本研究屬於遺傳的相關性研究。評估於台灣具代表性的兩家精神科專科醫院之慢性住院精神分裂症病患，再以有無TD現象分為TD組 (n=32)與non-TD組 (n=135)，並有正常對照組 (n=91)參與，所有參加者皆為台灣漢族人。實驗室方面將抽血得到之白血球所抽出的DNA進行聚合鏈反應，以瞭解各基因多型性在TD組與non-TD組的分布是否有差異。並以logistic regression 調整相關變項，及根據年齡與性別做次族群的分析。 結果：於血清素第2A型接受體基因，TD組相較於non-TD組有較少的CC及CT基因型 (P=0.022)；C allele frequency於TD組為29.7%，於non-TD組為45.6%，兩組的allele分布亦已達統計上顯著差異 (P=0.021)。經logistic regression調整變項後，TD的有無僅與血清素第2A型接受體基因多型性有統計上的相關，特別是在顯性模式 (OR=0.26, 95%CI=0.10-0.71, P=0.008) 與加成性模式 (OR=0.40, 95% CI=0.19-0.86, P=0.019)。於血清素運送基因多型性與血清素第2C型接受體基因多型性則與TD沒有相關。於次族群分析，年齡大於等於50 歲 (OR=0.28, 95% CI=0.10-0.84, P=0.022) 及男性病患 (OR=0.033, 95% CI=0.003-0.37, P=0.006)，其血清素2A接受體基因多型性與TD相關。 結論：本研究發現血清素第2A型接受體T102C基因多型性，會影響台灣漢族慢性精神分裂症患者的TD發生。 | zh_TW |
| dc.description.abstract | Background and Objective: Tardive dyskinesia (TD) is a serious side effect of antipsychotics. Although the pathogenesis of TD is still not fully understood, studies
have reported TD is associated with serotonin genes. This study is aimed at exploring the association between the serotonin gene polymorphisms (HTR2A T102C, 5-HTTLPR, HTR2C Cys23Ser) and chronic schizophrenic patients with or without TD. Methods: Genetic association study with case control design was performed to analyze the allele and genotype frequencies of schizophrenia patients with TD (n=32), patients without TD (n=135), and normal control participants (n=91). All participants are Ethnic Han Taiwanese. Genotyping of HTR2A T102C polymorphism, 5-HTTLPR polymorphism and HTR2C Cys23Ser polymorphism were performed by polymerase chain reaction-based restriction analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed by multivariate logistic regression analysis. Subgroup analysis was performed according to age and gender. Results: The C allele frequency of HTR2A is 29.7% in TD group and 45.6% in non-TD group (P=0.021). Patients carrying C allele were likely to be protected from TD (OR=0.26, 95% CI=0.10-0.71, P=0.008 for dominant mode; OR=0.40, 95% CI=0.19-0.86, P=0.019 for additive mode). However, no association between 5-HTTLPR and HTR2C polymorphisms and TD was found. HTR2A T102C was associated with TD in subgroup of older than 50 years (OR=0.28, 95% CI=0.10-0.84, P=0.022) and men (OR=0.033, 95% CI=0.003-0.37, P=0.006). Conclusion: Our findings support that HTR2A T102C polymorphism influences the susceptibility to antipsychotics-induced TD in the chronic schizophrenic patients in Taiwan. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T04:44:19Z (GMT). No. of bitstreams: 1 ntu-98-P96846004-1.pdf: 1375144 bytes, checksum: 2ed7c732690903b7fbbca6f7f5a1087a (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | 目錄
口試委員會審定書 誌謝 中文摘要 英文摘要 第一章 研究背景....................................................................................1 第一節 抗精神病藥物的發展與作用機轉..........................................2 1.1.1 精神分裂症的多巴胺假說…………………………………..2 1.1.2 抗精神病藥物的療效機轉及其副作用……………………..3 第二節 錐體外路徑副作用的分類與評估..........................................5 1.2.1 分類與診斷準則……………………………………………..5 1.2.2 錐體外路徑副作用的評估工具……………………………..7 1.2.3 錐體外路徑副作用的病理機轉與基因相關性研究………..9 第三節 抗精神病藥物所引發之遲發性運動異常........................…10 1.3.1 遲發性運動異常的簡介……………………………………10 1.3.2 遲發性運動異常的盛行率與嚴重性………………………11 第四節 遲發性運動異常相關文獻之回顧…………………………12 1.4.1 遲發性運動異常的危險因子………………………………12 1.4.2 遲發性運動異常的病理機轉假說…………………………17 VI 1.4.3 遲發性運動異常的病理機轉與基因相關性研究………. …19 第二章 研究目的..................................................................................25 第三章 材料與方法..............................................................................26 第一節 研究設計................................................................................26 第二節 研究族群及收案標準……………………………………..26 3.2.1 研究族群…………………………………………………..26 3.2.2 收案標準…………………………………………………..27 第三節 研究進行方式……………………………………………..28 3.3.1 資料收集…………………………………………………..28 3.3.2 診斷與TD病例之標認………………………………… ..28 3.3.3 主要的研究變項…………………………………………..30 3.3.4 基因分析…………………………………………………..31 第四節 統計方法…………………………………………………..32 第五節 樣本數的估計……………………………………………..34 第四章 結果..........................................................................................35 第一節 描述性資料…………………………………………………35 第二節 Genottype and allllelle 的頻率與分布………………………..35 4.2.1 哈温平衡測試………………………………………………..35 VII 4.2.2 Genotype and allele的頻率與分布………………………….36 第三節 調整干擾因子……………………………………………....37 4.3.1 血清素2A接受體基因多型性………………………………37 4.3.2 血清素運送基因多型性……………………………………..38 4.3.3 血清素2C接受體基因多型性………………………………39 第四節 次族群分析………………………………………………..39 4.4.1 血清素2A接受體基因多型性………………………………39 4.4.2 血清素運送基因多型性……………………………………..40 4.4.3 血清素2C接受體基因多型性………………………………40 第五章 討論…………………………………………………………..41 第一節 描述性說明本研究主要結果……………………………....41 第二節 相較於過去的研究………………………………………..42 第三節 生物學的機轉……………………………………………..44 第四節 臨床意涵…………………………………………………..45 第五節 本研究之優勢……………………………………………..45 第六節 本研究之限制……………………………………………..46 第七節 未來研究方向……………………………………………..48 第八節 結論………………………………………………………..48 VIII TABLES....................................................................................................50 I . Comparison of AIMS and ESRS ………………………………….50 II. Comparison of DSM-IV and ICD-10……………………………..51 III. Literature review of 5-HT polymorphisms and TD ……………...52 IV. Characteristics of serotonin SNPs ……………………………….54 V. Basic characteristics of schizophrenic patients with and without TD …………………………………………………………………....55 VI. Results of the Hardy-Weinberg equilibrium test in the study population………………………………………………………56 VII. Genotype and allele frequencies in schizophrenic patients with and without TD……………………………………………………...57 VIII. The coefficient, standard error of mean, significant level, and odds ratio for TD in the study participants Table VIII-1A. Co-dominant mode of HTR2A……………………...58 Table VIII-1B. Additive mode of HTR2A…………………………..59 Table VIII-1C. Dominant mode of HTR2A…………………………60 Table VIII-1D. Recessive mode of HTR2A…………………………61 Table VIII-2A. Co-dominant mode of 5-HTTLPR………………….62 Table VIII-2B. Additive mode of 5-HTTLPR………………………63 Table VIII-2C. Dominant mode of 5-HTTLPR……………………..64 Table VIII-2D. Recessive mode of 5-HTTLPR……………………..65 Table IX. The estimated parameters, odds ratios, 95%CIs of the polymorphism for the risk of TD after adjustment for age and gender, education years, marital status, job status, alcohol drinking, smoking, diabetes Table IX-1. HTR2A …………………………………………………66 Table IX-2. 5-HTTLPR ……………………………………………...67 Table X. Logistic regression models for participants with and without TD Table X-1. HTR2A…………………………………………………...68 Table X-2. 5-HTTLPR……………………………………………….69 IX Table XI. The odds ratios, 95%CIs of the polymorphism for the risk of TD according to age group and gender Table XI-1. HTR2A…………………………………………………..70 Table XI-2. 5-HTTLPR………………………………………………71 X FIGURES..................................................................................................72 Figure 1. Mechanisms and possible interactions in TD 72 Figure 2. Flow diagram of patients enrollment in the study 73 Figure 3. Sample size estimation based on minor allele frequency and relative risk 74 Figure 4. Power estimation based on minor allele frequency and relative risk 75 參考文獻………………………………………………………………..76 附錄……………………………………………………………………..86 | |
| dc.language.iso | zh-TW | |
| dc.title | 血清素接受體及運送基因多型性與慢性精神分裂症病患之遲發性運動異常之相關性研究 | zh_TW |
| dc.title | Association study of serotonin receptor and transporter
gene polymorphisms with tardive dyskinesia in chronic schizophrenia | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 賴美淑,程蘊菁 | |
| dc.contributor.oralexamcommittee | 洪成志,李永凌 | |
| dc.subject.keyword | 遲發性運動異常,精神分裂症,血清素第2A 型接受體基因,血清素運送基因,血清素第2C型接受體基因,多型性, | zh_TW |
| dc.subject.keyword | Tardive dyskinesia,Schizophrenia,Serotonin 2A receptor gene,Serotonin transporter gene,Serotonin 2C receptor gene,Polymorphism, | en |
| dc.relation.page | 91 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2009-08-04 | |
| dc.contributor.author-college | 公共衛生學院 | zh_TW |
| dc.contributor.author-dept | 預防醫學研究所 | zh_TW |
| 顯示於系所單位： | 流行病學與預防醫學研究所 | |
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