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博碩士論文 etd-0630101-214211 詳細資訊
Title page for etd-0630101-214211
論文名稱
Title
精神分裂症患者事象聽覺誘發電位與染色體末端長度之分析
Analysis of event-related potentials and telomere length in schizophrenic patients
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
53
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2001-06-05
繳交日期
Date of Submission
2001-06-30
關鍵字
Keywords
認知功能退化、染色體末端長度、精神分裂症、P300潛時
telomere length, schizophrenia, P300 latency, cognitive deficit
統計
Statistics
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The thesis/dissertation has been browsed 5849 times, has been downloaded 8294 times.
中文摘要
中文摘要
染色體末端(telomere)位於每一條染色體兩端,由一連串短而一再重複的核甘酸系列和蛋白質所組成,可維持染色體的穩定性,一般成熟的體細胞缺乏telomerase的活性,因此,人體的telomere會隨著年齡增加,細胞分裂次數的增加而變短,當telomere短到某個程度時,細胞就不再分裂而成衰老細胞最後死亡。因此,telomere長度的縮短對人體細胞而言提供了一個老化的訊號。
精神分裂症是一種思考、知覺障礙,以及不適當或遲鈍情感的精神疾病,在所有精神疾病中佔最多數。平均約二十幾歲發病,大部分喪失工作能力且須終生治療。精神分裂症患者的認知功能障礙是眾所周知的症狀之一,認知功能障礙是一種老化的症狀,因此是否與telomere有關?為本研究的目的。
本研究分兩部份進行,第一部份為了解精神分裂症是否較常人的老化速度快,因此以神經電氣生理學的P300潛時來作為評估的工具,研究的對象為精神分裂症患者153位(男44位,女109位),平均年齡38.4±8.5歲;正常對照組101位,男37位,女76位平均年齡38.1±11.1歲。將精神分裂症組依據治療後的整體功能評分再分成治療反應好者91位;治療反應差者62位。三組在年齡、性別上沒有統計學上的差異;精神分裂症治療反應差者的P300潛時最長,反應好者次之,正常組最短;正常人的P300潛時隨著年齡增加一歲延長1.2毫秒。在精神分裂症患者除了年齡的影響外,整體功能愈好者其P300潛時較不會延長。
由所收集的資料分析,精神分裂症患者治療反應差者(整體功能得分低者),以神經電生理學的聽覺P300波型的變化來評估,是屬於老化最快速的族群,因此進一步進行第二部份老化標的染色體末端長度的研究。
第二部份的研究對象取自第一部份的個案,以年齡、性別配對選取精神分裂症患者48位(男11位,女37位),平均年齡37.9±7.8歲;正常對照組48位,男11位,女37位平均年齡37.9±7.8歲。將精神分裂症組依據治療後的整體功能評分再分成治療反應好者34位;治療反應差者14位。三組在年齡、性別上沒有統計學上的差異;正常人的telomere 長度,隨著年齡增加一歲縮短89bp;精神分裂症治療反應差的一組的其telomere長度最短;精神分裂症患者的telomere長度與年齡無關,但與發病年齡、整體功能有關,發病年齡愈晚,整體功能愈好,telomere長度愈長。
精神分裂症患者對於治療反應最差的一組,以telomere長度來評估是老化最快速的一組,應屬於Kraepelin所稱的早發型癡呆患者,屬於較同質性的一群。

Abstract
Telomere, the ends of chromosomes, consists of simple hexameric repeats. In human, TTAGGG repeat is found at the ends of all chromosomes. Telomeres progressively shorten with age in somatic cells, because the insufficient telomerase activity fails to compensate the progressive telomeric erosion. Thus, the reduction of telomeric length in senescent cells is believed to result from active cell division that erodes chromosomal termini. The telomere length supposed to have been an evaluation tool for aging in human.
Schizophrenia is a thought, perception disorder, generally regarded as an illness with onset in late adolescence or early adult life with a prevalence rate of 1%. Although the long-term course of schizophrenia shows great heterogeneity among patients, a significant number of patients experience very poor outcomes, shows severe cognitive impairment that is suggestive of a progressive neurodegenerative disorder. The aim of this study is to explore the relationship between neurodegenerative process and telomere length in schizophrenic patients. The latency of P300 event-related potentials is prolonged in disorders associated with neural damage and degeneration and also becomes prolonged in the course of aging process.
This study is separated as two parts: first part, using the event-related potentials P300 latency as a tool to evaluate the cognitive dysfunction and aging process in schizophrenics. One hundred and fifty three long-term hospitalization chronic schizophrenics were recruited as the experimental group of this research, including 44 male and 109 female patients with mean age of 38.4 years. These patients were divided into 2 groups according to the different responses to treatment, global assessment functional scale (GAF): 91 with good response to treatment; 62 with poor response to treatment. The normal control group included 101 normal people, male 37 and female 76, with mean age of 38.1 years. The event-related potentials was elicited by auditory oddball paradigm.
The P300 latency prolonged in these two schizophrenic patients. The longest P300 latency was found in the poor response schizophrenic group. The shortest P300 latency was found in the normal group. Linear regression coefficients were computed to determine the slope of component P300 latency on age and other factors. The slope of P300 latency on age in normal control group is 1.2 ms/y. In schizophrenic groups, not only the age, but the GAF as the most contributing factors in the neurodegenerative process.
Second part, the subjects were selected from part one, 48 chronic schizophrenia whose mean age was 37.9 years and 48 age-, handedness-, and gender-matched normal control subjects. The schizophrenic patients were divided into 2 groups according to the different responses to treatment: 34 with good response to treatment; 14 with poor response to treatment. The telomere length, measured by assay of terminal restriction fragments (TRFs), was determined in HinfI-digested DNA by Southern blot analysis using a (TTAGGG)4 probe. The shortest TRF length was found in the poor response schizophrenic group. There was no difference between the good response schizophrenic group and normal control group. TRF length in peripheral leukocytes obtained from normal control group decreased by approximately 89bP per year. In schizophrenic groups, the TRF length was found that not the age, but the age onset and GAF as the most contributing factors in linear regression model.
This study shows that the poor response schizophrenic patients have the most rapid neurodegenerative process in P300 latency and TRF length evaluation. It implicates the homogeneous group, and can be considered as the kraepelinian schizophrenics, very poor outcome group.

目次 Table of Contents
目 錄
中文摘要 5
英文摘要 7
壹、前言 9
一、 染色體末端 9
二、 精神分裂症與遺傳 10
三、 老化的神經電生理學標的(事象相關誘發電位, event-related potentials, ERPs) 12
四、 精神分裂症的認知功能缺失 16
貳、研究目的: 18
一、 第一部份 18
二、 第二部份 18
參、實驗材料與方法 19
一、 事象聽覺誘發電位 19
二、染色體末端長度的測量 20
二、統計分析 25
肆、研究成果 26
一、 第一部份 26
二、 第二部份 30
伍、討論 38
一、 正常組的Telomere變化 38
二、 P300與Telomere變化之比較 39
三、 精神分裂症組的Telomere變化 40
四、其他有關Telomere變化之研究 42
陸、結論 44
柒、參考文獻 45
捌、附錄 52
附錄一、簡短精神症狀評量表(BPRS) 52
附錄二、總體功能評估表(GAF) 53
表 次
表 1. 染色體末端長度隨年齡的變化 10
表 2. 事象聽覺誘發電位的組成波形與年齡的關係 15
表3. 相同研究條件下P300潛值隨年齡增加而延長 16
表 4. 第一部份研究對象之基本資料 27
表 5. 事象聽覺誘發電位P300潛時在三組之比較 28
表 6.正常組複迴歸分析結果 28
表 7. 精神分裂症組複迴歸分析結果 29
表 8. 精神分裂症組刪除病程後之複迴歸分析結果 29
表 9. 第二部份研究對象之基本資料 31
表 10. TELOMERE長度在三組之比較 32
表 11.正常組複迴歸分析結果 33
表 12. 精神分裂症組分析變項間的PEARSON相關分析 35
表 13. 精神分裂症組TELOMERE長度複迴歸分析結果 36
表 14. 研究對象預測年齡之比較 37
圖 次
圖 1. 事象聽覺誘發電位之正常分布圖 14
圖 2. A REPRESENTATIVE SOUTHERN BLOT ANALYSIS DEMONSTRATING LENGTH OF TELOMERIC REPEATS IN NORMAL INDIVIDUALS.. 23
圖 3. A REPRESENTATIVE SOUTHERN BLOT ANALYSIS DEMONSTRATING LENGTH OF TELOMERIC REPEATS IN SCHIZOPHRENIC PATIENTS. 24
圖 4. LENGTHS OF TRFS IN PERIPHERAL LEUKOCYTE OBTAINED FROM HEALTHY VOLUNTEERS……………………... ……..33
圖 5. 正常組TELOMERE長度(TRF)隨年齡變化之趨勢圖…. 34
圖 6. 精神分裂症組TELOMERE長度與影響因素之相對分布圖… 36


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