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系統識別號 U0026-2708201301395700
論文名稱(中文) 第二色胺酸氫氧基化酶基因多型性調節兒時虐待 對台灣婦女情緒障礙之影響
論文名稱(英文) Tryptophan Hydroxylase 2 Gene Polymorphism Moderates the Effects of Childhood Maltreatment on Emotional Disorders among Women in Taiwan
校院名稱 成功大學
系所名稱(中) 行為醫學研究所
系所名稱(英) Institute of Behavioral Medicine
學年度 101
學期 2
出版年 102
研究生(中文) 謝志伸
研究生(英文) Chih-Shen Hsieh
學號 s86991031
學位類別 碩士
語文別 中文
論文頁數 64頁
口試委員 指導教授-柯慧貞
共同指導教授-張峰銘
召集委員-藍先元
口試委員-陳彰惠
中文關鍵字 第二色胺酸氫氧基化酶基因多型性  T-703G  兒時虐待  情緒障礙 
英文關鍵字 Tryptophan Hydroxylase 2 gene polymorphism  TPH2  T-703G  childhood maltreatment  emotional disorders 
學科別分類
中文摘要 背景與目的: 兒時虐待為重鬱症及焦慮性疾患之共同危險因子,然進一步研究指出兒時虐待與情緒障礙之關係可能受血清素系統基因所調控。第二色胺酸氫氧基化酶基因 (Tryptophan hydroxylase 2 gene; TPH2)之表現與人體腦內血清素合成有關,許多精神病理研究探討此基因與個體情緒失調之關聯。其中經常被討論的TPH 2單一核甘酸多型性―T-703G 被認為和個體處理情緒性刺激時杏仁核反應程度有關;T-703G帶有T對偶基因之個體在面對正、負向臉孔刺激時,杏仁核反應皆較G對偶基因個體強。本研究假設TPH2 T-703G基因型調節兒時虐待對情緒障礙之影響;亦即是於T-703G TT之參與者中,曾受兒時虐待者未來被診斷為情緒障礙之比例顯著高於未受兒虐者;於TG、GG兩基因型參與者中,有、無兒時虐待之情緒障礙診斷比例無顯著差異。

方法: 受試者皆來自1997年進行之懷孕婦女縱貫研究,共189名;受試者需完成 (1)情感性疾患及精神分裂症終生診斷手冊―中文修訂版 (Chinese modified version of the Schedule for Affective Disorders and Schizophrenia―lifetime [CM-SADS-L]),(2)兒童時期受虐經驗晤談 (Interview for Childhood Maltreatment Experiences [ICME]),(3)TPH2 T-703G基因型鑑定。在此研究中,婦女一生中曾受重鬱症或任一焦慮性疾患診斷者納入情緒障礙組 (n=110),其餘為對照組 (n=79);T-703G基因型分為TT、TG、GG三組;受虐經驗部分,於ICME兒虐晤談三題任一題答有為兒虐組,三題皆答無則為非兒虐組。

結果: 將參與者依T-703G基因型分為 TT、TG、GG三組,分別一一以卡方考驗檢定有、無兒虐經驗下情緒障礙診斷比例是否有差異;結果發現在TT基因型參與者中,曾受兒虐組於成年後情緒障礙比例高於非兒虐組;但對於TG、GG兩基因型參與者而言,有、無兒虐組之情緒障礙診斷比例皆無差異。

結論與建議: 本研究發現對於T-703G TT參與者若其曾受兒時虐待則其情緒障礙比例顯著高於未受兒虐者;故T-703G TT型可視為個體之脆弱性素質,推測具此基因型者可能對環境負向情緒刺激之處理及適應較差,進而提升個體成年後有情緒障礙之機率,其值得未來進一步探討。
英文摘要 Objective: Earlier studies have suggested that childhood maltreatment is a non-specific risk factor for various psychiatric disorders, especially major depressive disorder and anxiety disorders. However, impact of maltreatment varies from person to person, implying that genetic susceptibility might be at work. A growing body of research has been focused on the association between Tryptophan Hydroxylase 2 (TPH2) and emotional regulation. In particular, TPH2 T-703G polymorphism may influence amygdala responsiveness during the process of emotional stimuli, especially negative emotions. We aimed to test the moderating effect of TPH2 T-703G on the effects of childhood maltreatment on emotional disorders.

Material and methods: The participants consisted of 189 peripartum women, recruited from a longitudinal cohort study in 1997. Participants who received more than one lifetime major depressive disorder or anxiety disorders diagnosis were classified as the emotional disorder group (n=110), and others were grouped in the comparison group (n=79).

Results: Our finding indicated that among the T-703G TT carriers, women who had experienced childhood maltreatment had a significantly higher probability of developing emotional disorders as compared to those who did not have such experiences. However, among the TG and, GG groups, this effect was not detected.

Conclusion: As impied in the diathesis-stress model, the T-703G TT genotype might be considered a genetic susceptibility; when carriers are exposed to childhood maltreatment, this susceptibility will significantly increase their risk of emotional disorders.
論文目次 中文摘要 I
Abstract III
誌謝 IV
目錄 V
表目錄 VIII
圖目錄 VIII
附錄 VIII
第一章 緒論 1
第一節 情緒障礙之探討 1
一、重鬱症之定義-臨床表現及盛行率 1
二、焦慮性疾患之定義-臨床表現及盛行率 2
三、重鬱症與焦慮性疾患之共病 3
四、情緒障礙之定義 5
第二節 兒時虐待與情緒障礙之探討 7
一、 兒時虐待之定義 7
(一) 身體虐待 8
(二) 身體忽略 8
(三) 情緒虐待 9
(四) 情緒忽略 9
二、 兒時虐待之盛行率 10
三、 兒時虐待與情緒障礙之關聯 11
四、兒時虐待與大腦功能、結構之關聯 11
(一) 杏仁核 12
(二) 海馬迴 13
五、血清素系統基因多型性調節兒時虐待對情緒障礙之影響 13
第三節 第二色胺酸氫氧基化酶基因與情緒障礙之探討 15
一、血清素之合成 15
二、第二色胺酸氫氧基化酶基因 (Tryptophan Hydroxylase 2 Gene; TPH2) 15
三、T-703G基因多型性與大腦結構、功能之關聯 16
第四節 研究目的與假設 19
一、研究目的 19
二、研究假設 19
第二章 工具及方法 20
第一節 研究參與者 20
第二節 研究工具 21
一、情緒障礙診斷之測量: 本研究採情感性疾患及精神分裂症終生診斷手冊 ―中文修訂版 (CM-SADS-L) 21
二、兒時受虐之測量: 本研究採兒童時期受虐經驗晤談 (ICME)及中文版兒童受虐問卷 (CMQ) 21
(一) 兒童時期受虐經驗晤談 (ICME) 21
(二) 中文版兒童受虐問卷 (CMQ) 22
三、TPH2單一核甘酸基因多型性分析 22
第三節 研究程序 24
第四節 統計分析 25
第三章 研究結果 26
第一節 ICME與CMQ之效標關聯效度 26
第二節 人口學及臨床變項之分析 27
第三節 研究結果分析 28
一、T-703G基因型對情緒障礙之主要效果 28
二、兒時虐待對情緒障礙之主要效果 28
三、T-703G基因型調節兒時虐待對情緒障礙之影響 28
第四章 討論 29
第一節 研究主要發現 29
第二節 研究結果解釋與未來研究方向 30
第三節 研究限制 32
第四節 研究貢獻及應用 33
第五章 參考文獻 34
中文文獻 34
英文文獻 35

表目錄
表一 情緒障礙組、對照組之人口學及臨床變項 52
表二 T-703G基因型對情緒障礙之主要效果 54
表三 兒虐環境對情緒障礙之主要效果 55
表四 T-703G基因型之環境/診斷列聯表 56

圖目錄
圖一 血清素之兩合成路徑及兩系統各別影響範圍 57
圖二 研究相關單一核甘酸多型性 (SNPs)與第二色胺酸氫氧基化酶基因外顯子
(Exon)/內含子 (Intron)之相對位置 58
圖三 T-703G各基因型於有/無兒虐環境下之情緒障礙百分比 59

附錄
附錄一 學齡前期兒童虐待量表 60

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