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研究生:宋之維
研究生(外文):Chih-Wei Sung
論文名稱:心率變異與類胰島素生長因子在輕微腦創傷病人產生情緒失調之相關性研究
論文名稱(外文):Heart rate variability and serum level of insulin-like growth factor-1 are correlated with emotional disorders in patients suffering a mild traumatic brain injury
指導教授:王家儀王家儀引用關係
指導教授(外文):Jia-Yi Wang
口試委員:吳勝男張榮善
口試委員(外文):Sheng-Nan WuJung-Shan Chang
口試日期:2015-05-22
學位類別:碩士
校院名稱:臺北醫學大學
系所名稱:醫學科學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:中文
論文頁數:69
中文關鍵詞:腦創傷類胰島素生長因子心率變異情緒失調
外文關鍵詞:traumatic brain injuryheart rate variabilityemotional disorderinsulin-like growth factor-1
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腦創傷 (traumatic brain injury, TBI) 是一種因外力撞擊而造成的腦部傷害,臨床上可依嚴重程度自輕度至重度分為不同等級。輕微腦創傷 (mild traumatic brain injury, mTBI) 病人往往因為神經學症狀輕微,經治療後返回社區。然而,這些病人臨床上於創傷後短時間內往往會伴隨著一些症狀,例如:焦慮、憂鬱之情緒失調,輕則影響生活品質,重則有自傷或是傷人的行為產生,醫學上仍缺乏有效性的預測工具與預防方法。
生物標誌對於輕微腦創傷病人族群神經學後遺症之診斷扮演重要的地位,腦垂體功能低下症常常是輕微腦創傷病人於一個月之後常見的生理性失調,本研究中聚焦於促腎上腺皮質激素 (ACTH)、褪黑激素 (Melatonin)、皮質醇 (Cortisol)、類胰島素生長因子 (IGF-1) 之創傷後變化,探討其變化與伴隨之情緒失調之關係。此外,心率變異分析 (Heart rate variability;HRV) 應用於病人診斷自律神經失調之輔助,已有相當研究證明輕微腦創傷病人其HRV頻域參數可作為預測憂鬱或焦慮之指標,本研究立基於過去之研究成果,進一步欲探討輕度腦創傷伴隨情緒失調患者其與心率變異功率頻譜分析以及生物標誌之相關性。
本研究經台北醫學大學聯合人體試驗委員會審核通過,於三家附設醫院於2010年1月至2014年12月收案之輕度頭部外傷的病人 (實驗組) 與健康自願受測者 (控制組),根據審核通過的納入與排除準則,於填寫同意書後,進行抽血、HRV量測、問卷評估,整個研究期間採取定期門診追蹤,於創傷後第六週進行相同項目的檢驗,取得兩個時間點 (受傷後一週、六週) 資料後進行統計分析。我們證實輕微腦創傷病人相較於健康成人更易產生如焦慮 (p < 0.001)、憂鬱 (p < 0.01) 之情緒失序,輕微腦創傷病人其心率變異呈現較為顯著的功率頻譜衰減 (p < 0.01),顯示有顯著的自主神經功能失調。進一步分析這些可能之生物標誌,我們發現促腎上腺皮質激素在腦創傷後顯著上升,但類胰島素生長因子濃度卻在腦創傷後顯著下降 (p < 0.001),顯示其可作為腦創傷預後的指標。此外,類胰島素生長因子在第一週與第六週皆與心率變異頻域參數呈現高度正相關 (p < 0.001)。我們亦發現心率變異分析具有非侵入性之優點,相較於使用血液標誌作為預後指標,有著較佳的預測性與便利性。
Patients who have experienced a mild traumatic brain injury (mTBI) are susceptible to emotional disturbances, in particular, anxiety or depression. Because of its noninvasive advantage, the frequency-domain analysis of heart rate variability (HRV) has gained its popularity in clinical setting as a functional indicator of autonomic nervous function in psychiatric research. The association between emotional disorders and autonomic dysfunction has attracted increasing attention since epidemiological studies have reported that patients with depression have an augmented risk of cardiovascular disorders. We therefore explored the potential biomarkers for emotional disorders in mTBI patients by analyzing the frequency domain of HRV and serum concentrations of neurohormones.
We recruited mTBI patients and healthy controls with informed consent from 2010 to 2014 at their first visit (1st week) and 6-week follow-up. Anxiety or depression was evaluated by the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI), respectively. The standard frequency-domain analysis consists of the variance in R–R interval values, total power (TP), very low frequency (VLF), low frequency (LF), high frequency (HF), and the ratio of LF to HF (LF/HF). We found that mTBI patients were more vulnerable to anxiety (p < 0.001) or depression (p < 0.01) than healthy controls. Reduced HRV was noted in mTBI patients compared to healthy controls (p < 0.01). Serum levels of Adrenocorticotropic hormone (ACTH) were higher while insulin-like growth factor 1 (IGF-1) were lower in mTBI patients compared to healthy controls (p < 0.001), but melatonin and cortisol levels were unaltered. In a correlation analysis, only IGF-1 was positively correlated with HRV in mTBI patients (p < 0.001). Both HRV and IGF-1 were correlated with depression while only HRV was correlated with anxiety in mTBI patients. Spearman’s rank correlation coefficients were higher in correlation of HRV and BDI scores (r = 0.39, p < 0.05) than in that of serum levels of IGF-1 (r = 0.31, p < 0.05). Furthermore, HRV has advantages of being non-invasive, time-saving and cost-effective compared with serum levels of IGF-1. HRV may be considered a bio-signal biomarker for late anxiety or depression in mTBI patients.
圖目錄 i
表目錄 ii
縮寫表 iii
中文摘要 iv
Abstract v
誌謝 vi
第一章 緒論 1
第一節 腦創傷 1
第二節 輕微腦創傷之後遺症 3
第三節 輕微腦創傷與自主神經系統失調 5
第四節 輕微腦創傷潛在的生物標誌 7
第五節 研究假設、目標與預期結果 9
第二章 研究方法與材料 12
第一節 研究設計 12
第二節 研究族群 12
第三節 心率變異分析 14
第四節 問卷評估 20
第五節 血漿生物標誌的抽取與檢驗原理 21
第六節 統計方法 24
第三章 研究結果 31
第一節 輕微腦創傷病人相較於健康成人更易產生情緒失序 31
第三節 心率變異頻域參數與焦慮、憂鬱量表分數呈現中度負相關 35
第四節 類胰島素生長因子濃度在腦創傷後顯著下降 35
第五節 類胰島素生長因子與焦慮、憂鬱量表分數呈現負相關 37
第六節 類胰島素生長因子與心率變異頻域參數呈現高度正相關 37
第七節 心率變異分析有著較佳的預測性 39
第四章 討論 41
第一節 研究結果之分析與批判 41
第二節 臨床意義 43
第三節 研究限制 44
第四節 未來展望 46
第五章 結論 48
參考文獻 59
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