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標題: | 注意力不足過動症之藥物流行病學危險因子及與其它精神疾病之關聯性研究 Pharmacoepidemiological factors for Attention-deficit/hyperactivity disorder (ADHD) and the association with other mental disease development |
作者: | Kang-Chung Yang 楊剛仲 |
指導教授: | 李克昭(Ker-Chau Li) |
關鍵字: | 注意力不足過動症,ADHD,藥物流行病學,時間相依共變數之存活分析,累計藥量, ADHD,pharmacoepidemiology,time-dependent covariates,cumulative effects, |
出版年 : | 2017 |
學位: | 博士 |
摘要: | 注意力不足過動症(Attention Deficit/Hyperactivity Disorder, ADHD)是一種神經精神疾病,其常見症狀為注意力不集中、過動與衝動。ADHD患者常伴隨著其他精神障礙如對立反抗症(Oppositional Defiant Disorder, ODD)、行為規範障礙(Conduct Disorder, CD)與焦慮症 (Anxiety Disorder, AD)。ADHD患者是否有更高的風險罹患重度憂鬱症(Major depressive disorder, MDD)及思覺失調症(Schizophrenia)則是長久以來的爭議話題。不同的結論可能來自於不同的實驗設計、不同的人群取樣及不同的研究區間。
近年來,由於藥物流行病學的發展及台灣健保資料庫的建立,我們有機會利用大量長期的保險請款資料,進行ADHD病患的長期罹病追蹤研究。我們也可藉由長期的開藥記錄,研究藥物的長期使用是否會影響ADHD罹患重度憂鬱症與思覺失調症的風險。然而,藥物使用量的分析是非常複雜的,我們需要更精細的統計分析方法,來得到更適當的風險估計。 在本篇研究中,我們先從世代研究開始,探討ADHD患者是否有更高的風險罹患重度憂鬱症(第二章)及思覺失調症(第三章);然後我們對於健保資料庫中有ADHD確診記錄的病患族群進行完整的族群描述,包含盛行率與用藥特徵分析(第四章);鑒於ADHD與其他精神疾病可能有基因上的相似性,我們也回顧了ADHD的基因體學發展,並嘗試使用Liquid association分析,探索更多潛在與ADHD有關的基因(第五章);最後我們回到藥物流行病學統計方法,討論時間相依共變數之存活分析、累計藥量的估算,以及現有統計方法的限制,並提出改善的方法(第六章)。 Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder. Patients diagnosed with ADHD were also accompanied with other comorbidities such as oppositional defiant (ODD), conduct disorder (CD), and Anxiety Disorder (AD). It has been debated for decades that whether patients with ADHD diagnosis are associated with subsequent diagnosis of depressive disorders or psychotic disorders. Inconsistent results from these studies may be caused by differences in diagnostic criteria, follow-up lengths, sample sizes, and study designs. In recent years, with the development of pharmacoepidemiology and the establishment of National Health Insurance Research Database (NHIRD), we are now able to perform national-wide cohort studies by analyzing massive claims data from National Health Insurance Research Database (NHIRD). By analyzing long-term prescription records, we are also able to study that whether medication treatments in ADHD patients affect the risk of developing subsequent depressive disorders or psychotic disorders. However, the analyses of drug usage are complex. We need more delicate statistical models to get the better hazard estimates. In this dissertation, we began with studying whether ADHD patients have higher risk of developing subsequent depressive disorders (Chapter 2) or psychotic disorders (Chapter 3). Then we summarized the diagnosis rate and prescription patterns of ADHD in recent years (Chapter 4). In view of the genetic similarity between ADHD and other mental disorders, we reviewed candidate genes reported by family or case-control studies. Then we tried to find more potential candidate genes by performing liquid association analysis (Chapter 5). Finally, we reviewed the study designs, statistical biases common in pharmacoepidemiology. We discussed the statistical methods regarding cumulative exposure as time-dependent variable in Cox proportional hazard regression and the limitation of current methods. Then we provided a new procedure to improve the analysis results (chapter 6). |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77837 |
DOI: | 10.6342/NTU201703725 |
全文授權: | 有償授權 |
顯示於系所單位: | 基因體與系統生物學學位學程 |
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