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| 題名: | 憂鬱症之中西醫觀點：探討中醫證型、基因型及臨床表現之相關性 |
| 其他題名: | The Viewpoints of Depression from Chinese and Western Medicine---Exploring the Relationship among Patterns of Chinese Medicine, Genotypes and Clinical Manifestation |
| 作者: | 藍先元(Lane,Hsien-Yuan);謝慶良(Ching-Liang Hsieh) |
| 貢獻者: | 醫學院醫學系學士班精神醫學科 |
| 關鍵詞: | 重鬱症;中醫辨證分型;基因型;憂鬱徵候群;Major Depression;genotypes, differentiation of patterns in Chinese Medicine;genotype;depressive syndromes |
| 日期: | 2004-12-31 |
| 上傳時間: | 2009-09-01 16:25:45 (UTC+8) |
| 摘要: | 一、背景分析：世界衛生組織(WHO )預測，至西元2020年時，重度憂鬱症將僅次於心血管疾病，成為影響全人類生活功能的第二大疾病。目前全世界約有3％的人口（二億人）罹患重度憂鬱症，而各種疾病引起的負荷或失能中，精神疾病是最重要的因素，在1999年已高達各種疾病或傷害所造成失能生命人年（DALYs）的11.5％，且估計至 2020年還會上升至15％，其中以重度憂鬱症最多，占36.5％，但全球重度憂鬱症患者接受有效治療者不到2 5％。國內調查則發現，18歲以上嚴重精神病的盛行率已接近1％，重度憂鬱症占3％，即台灣地區各式嚴重精神病患約十至十二萬人，重度憂鬱症患者則有三十至三十六萬人。《黃帝內經》一書中，已有木鬱、土鬱、火鬱、金鬱、水鬱及情志內鬱的論述。情志致鬱而致病的機理亦多有記載；如《素問.舉痛論》說：”心有所存，神有所歸，正氣留而不行，故氣結矣”，《素問.本病論》說：“人憂愁思慮即傷心”，“人或恚怒，氣逆上而不下，即傷肝也”。在大陸一些病歷報告中也可看到，憂鬱症患者經中醫辨證分型後可取得一定的療效（逍遙散主治憂鬱症66例臨床分析，庄逢康，1996）（祛風藥輔治憂鬱症摭拾，丁德正，1994）（枸杞柴胡湯治療更年期憂鬱症32例臨床觀察，顧文元，2002）。但在研究中醫藥之臨床論文、傳統文獻及病案記載時，並未有關於憂鬱症的客觀的證型分類及診斷基準。困難的是患者就醫時不一定會以憂鬱症的主訴來呈現或者自行表達不適的情緒。臨床上大部分的特徵是焦慮、抱怨身體不適、疲累、活性症狀(如睡眠或食慾障礙)、甚至精神病症狀。也有可能僅僅是以工作或者人際關係的困難揭露出背後更全面的問題 (Tylee. 1999) 。此外有愈來愈多證據顯示出憂鬱症和某些認知功能的相關性（Mauro 2003）；諸如選擇性專注力、口語性工作記憶、長期記憶及口語流利性（Landro et al 2001）。 本研究首先對現代精神醫學診斷確定之重鬱症患者作中醫辨證分型、嘗試建立證型診斷重鬱症之基準。其次以工具施測來量化患者臨床表現，以探討憂鬱症的情感徵候群/認知功能表現與證型之相關性。連帶研究是採集患者及相稱受試者的血液，分析憂鬱症相關基因型與臨床徵候群/證型之相關性。二、 方法與步驟：取樣對象：自93年3月至93年12月由中國醫藥大學附設醫院精神科門診陸續收集75名精神科醫師診治後符合憂鬱症診斷標準之患者，立即進行中醫辨證分型，並另取健康受試者75名(需一等親以內無重度憂鬱或精神病，且性別、年齡及教育程度相稱於實驗組)為控制組。以上個案皆在簽署告知同意術後收案診斷標準：西方醫學診斷方面，以DSM-IV準則作為診斷標準，並以HRSD及CGI之評分做疾病嚴重度的分析。中醫辨證分型和診斷標準方面，我們採用計畫初期經過文獻考據及中西醫研討會後訂定、且以單盲方式測試15位憂鬱症與15位健康控制個案經、統計分析所初步建立的憂鬱症證型基準。測量工具：21項漢氏憂鬱量表 (HRSD)， Digit span test(順背與逆背)， Wisconsin Card Sorting Test (WCST)，WAIS-R時事記憶測試，臨床整體印象（CGI），Rosenberg self-esteem Questionnaire，Parental bonding Instrument，57項Maudsley Pesonality Inventory，14項Family environment scale進行步驟： 收案後立即採血萃取白血球準備分析基因型，並且以量表或工具評分施測。分析方法：將患者及控制組各項資料輸入電腦資料庫。使用SAS統計軟體分析中醫證型與憂鬱疾患臨床表現之關係。以T檢定及卡方檢定分析診斷與認知功能相關性，並利用多變項分析法研究重度憂鬱症患者臨床徵候群與中醫辨證分型間的關係、以及憂鬱症之情感症狀與認知功能間的關係。三、預期成果：1. 初步建立中醫診斷憂鬱症之主要標準、次要標準等其他臨床評估標的2.測量重度憂鬱症患者在憂鬱期有何特定的認知功能缺損。3.了解重度憂鬱症患者認知功能的表現和其他證型/憂鬱症候群的相關性。4.若重度憂鬱症患者與控制組的特定認知功能有所差異，是否與某些基因型相關。5.認知功能表現的缺損及相關基因型將能對應於某些中醫的辨證分型。對於基因型及臨床表現相關性之初步研究將有助於整合中西醫對於憂鬱症之診斷觀念，互補互長。以此基因體研究為基礎，預期將能改進:對憂鬱症症狀表現之偵測、藥物或處方之選擇，新藥、新處方之研究，甚至病因學之了解，以做為日後中西醫學結合之治療研究基礎
Major depressive disorder is the most common mental disease and has been determined by the World Health Organization as one of the most disabling disorders in the world. It affects roughly 25% of women and 10% of men at some point in their lifetime. It is thus estimated more than 340 million people worldwide suffering from depressive disorders at any particular time. Since depression is a complex disorder with heterogeneous symptom expression, diagnosis is not always straightforward. Not infrequently, the patient does not present with complaints of depression or does not spontaneously report feelings of dysphoria. The predominant clinical features may be anxiety, physical complaints, fatigue, vegetative symptoms, or psychosis. Alternatively, problems at work or in relationships may be the only overt clue of a more pervasive underlying problems (Tylee 1999). Besides, there is increasing evidence suggesting that depression is associated with a certain degree of cognitive dysfunction (Mauro et al 2003), such as selective attention, verbal working memory, long-term memory and verbal fluency (Landro et al 2001). There is strong evidence implying that genetic variation plays an important role in inter-individual differences in medication response as well as toxicity (Basile et al 2002). The rapidly evolving disciplines of pharmacogenetics and pharmacogenomics seek to uncover this genetic variation in order to predict treatment outcomes (Staddon et al 2002). There is no data at this stage to reveal whether patients with major depressive disorder can be well differentiated into specific patterns of Chinese Medicine. We hope to examine the relationship between depressive syndromes and patterns of Chinese-Medicine in the diagnosis of depression Further investigation, including association studies with genotyping, more thorough neurocognitive assessment and functional brain imaging, may be conducted on the basis of the preliminary results. We hypothesize that (1) Major depression is associated with specific cognitive dysfunctions (2) the manifestation of these cognitive impairments could be partially accounted for by genetic polymorphisms. (3) These genetic polymorphisms may be compatible with some patterns of Chinese Medicine. The efforts of improved understanding of genotyping and clinical symptomatology will contribute to more integrated diagnosis and better prediction of medicine efficacy on depression treatment. This is a one-year proposal. 75 patients with acute stage of major depressive disorder will be invited to take part in this project. They have to meet the diagnostic criteria of major depressive disorder in DSM-IV while those with bipolar depression or organic mood disorders will be excluded. They have to be 18~65 years old, free from any psychotropic agent for at least 2 weeks, physically healthy on medical history and physical examination. Their laboratory parameters have to be within normal limits. Healthy controls, matched in gender, age and educational level, and without history of major psychiatric disorders in heir first-degree relatives, will be recruited from the staff of CMUH. They have to be competent for full understanding of the study and give written informed consent. All these studies are performed after their agreement. During the baseline visit, the patients will be categorized according to patterns of Chinese Medicine and evaluated with the standard rating scales including Hamilton Rating Scale for depression, and Investigator- and patient-rated Clinical Global Impression scale. The patients and the healthy controls will also undergo neuropsychological tests while their blood would be collected for genotyping. All the data will be collected and analyzed to test our hypothesis. |
| 顯示於類別: | [醫學系] 研究計畫
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