臺灣博碩士論文加值系統

思覺失調症是一個影響約台灣千分之五人口的複雜疾病。因為思覺失調症高度 異質性，很難去指出一個清楚的病因，而基因因素已在許多研究中被證實會造 成思覺失調症的發展。常見的思覺失調症症狀有幻覺(delusion)、妄想 (hallucination)、及認知功能障礙，其中認知功能障礙為重要的工作及生活 品質的決定因子。LASP1 為一個和許多蛋白作用的蛋白(a versatile protein)，而它的基因多型性 rs979607 已經在一個韓國研究中指出和思覺斯調 症有關，在那之後沒有更多關於 LASP1 和思覺失調症或認知功能研究發表。我 們想要知道 LASP1 基因 rs979607 是否和思覺失調症病患認知功能有關。
總共有兩百九十一位思覺失調症病患被納入實驗，而他們的認知功能和臨床表 現也由專業的精神科醫師使用正性與負性症況量表(PANSS)及負性症狀檢測量 表(SANS)評估。認知功能的分數在統計中街有標準化過。病人的 DNA 則是用 取出的血，純化出 DNA 並稀釋至 50ng/ul 的濃度。我們使用 Taqman 基因定序來 分析病人的基因型。
在兩百九十一位病人中，帶有 LASP1 rs979607 C/C 同型合子的有八十五位， C/T 異型合子有一百四十一位，T/T 同型合子有六十五位。這符合哈溫柏格定律 (Hardy-Weinberg equilibrium)(p= 0.653)。在控制了年紀、性別、教育 後，帶有 C/C 同型合子的病人在類別流暢度(category fluency)及魏式記憶 量表第三版(WMS-III)空間記憶廣度(Spatial Span)兩項測驗中比 C/T 異型合子 表現還要好(p 分別為 0.045 及 0.025)。
就作者所知這是第一個 LASP1 基因多型性及思覺失調症認知功能關聯的研究。

Schizophrenia is a complex disease that affects around 0.5% of total population in Taiwan. Schizophrenia’s heterogeneous etiology makes it difficult to define, and genetic cause has been proposed to play a crucial role in the developing of the disease. Common clinical manifestations of schizophrenia include delusions, hallucinations and cognitive deficits, with the last being an important influencer of work and life quality. Genetic polymorphism (rs979607) of LASP1 (the LIM and SH3 domain protein), which translates into the versatile protein LASP1 that interacts with many other proteins, has been implicated in human schizophrenia susceptibility in Korean population. However, no further study on schizophrenia, cognitive functions and LASP1 has been done since then. The aim of this study is to look for the possible association of the schizophrenia patients’ cognitive functions and the polymorphism of LASP1 gene (re979607).
Two hundred and ninety-one schizophrenia patients were recruited and their cognitive functions and clinical manifestations were assessed by research psychiatrists using Positive and Negative Syndrome Scale (PANSS) and Scale for Assessment of Negative Symptoms (SANS). The scores of the cognitive tests were all standardized to T-scores. The DNA in blood from patients was isolated using purification kit and was diluted to concentration of 50ng/ul. Genotyping was performed using Taqman SNP genotyping assay.
Among the 291 patients, 85 were C/C homozygotes of rs979607, 141 C/T heterozygotes, and 65 T/T homozygotes, which fits the Hardy-Weinberg equilibrium (p = 0.653). After controlling age, gender, and education, in the cognitive categories assessed, the C/C homozygotes performed better than T/T homozygotes in Category Fluency test (p=0.045) and WMS-III Spatial Span test (backward) (p=0.025).
To the best of our knowledge, this is the first study showing LASP1 (rs979607) may have potential to serve as a predictor of cognitive functions in schizophrenia patients.

Introduction 1
1.1 Dendric spines and cognitive functions 1
1.2 Dendritic spines in schizophrenia 1
1.3 The LIM and SH3 domain protein (LASP1), dendritic spines, NMDA receptor hypofunctions, and schizophrenia 1
1.4 Hypothesis 2
2. Methods 4
2.1 Participants 4
2.2 Clinical assessment 4
2.3 Measurements of cognitive functions 4
2.4 Genotyping 5
2.5 Statistical analysis 6
3. Results 7
3.1 Demographic in schizophrenia patients 7
3.2 Clinical characteristics of schizophrenia patients 7
3.3 LASP1 allele frequency distribution among different groups 7
3.4 Association between LASP1 genotypes and schizophrenia patients’ cognitive functions 8
4. Discussion 9

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