2011-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649716摘要：精神分裂症病人有異常的菸鹼酸皮膚紅腫反應，已在過去研究中被重複證實，且被視為是精神分裂症脂質代謝異常的標記。然而先前研究侷限於使用了不夠敏感的半量化測量方法，同時對精神分裂症而言，異常菸鹼酸皮膚紅腫反應是否是一個穩定特徵或是會隨著時間變動的標記，仍有待更仔細的研究。此外，在精神分裂症出現紅腫反應減弱現象的生化機轉，以及它與精神分裂症型態學或神經心理功能異常的關係仍須進一步闡明。在本研究計畫中，我們提出使用菸鹼酸皮膚測試作為精神分裂症的罹病易感受標記，將其應用在四個不同的研究樣本。計畫目標如下：(1)評估一個直接、量化且標準化的皮膚溫度變化之測量方法，其結果是否與目測之紅腫評分結果一致；(2)比較急性精神分裂症病人與其他情感性疾患的菸鹼酸皮膚紅腫反應之穩定性，並研究異常紅腫反應與紅血球細胞膜脂肪酸濃度、磷脂水解酶A2活性與所使用精神藥物的相關；(3)評估國中生的菸鹼酸紅腫反應，並研究其皮膚紅腫反應與精神病理學和細微體質特徵異常的關係；(4)利用先前的一個全國性家族研究-台灣精神分裂症連鎖分析之研究，針對精神分裂症病人與其一等親家屬進行菸鹼酸皮膚測試的擴大收案，並使用菸鹼酸紅腫反應作為分組依據，去降低個案在病因上的異質性，以進行全基因體之家族連鎖分析。此三年計畫共包含四個部分：(1)利用紅外線攝溫影像技術對30位正常組個案做菸鹼酸皮膚紅腫反應測量的先導型研究(第一年)；(2)比較四組個案(50位精神分裂症病人、50位躁鬱症病人、50位重度憂鬱症病人和50位正常組個案)的生化研究(第一年到第三年)；(3)900位國中生的學校研究(第一年到第三年)；(4)1512位多發性精神分裂症家庭成員之家族遺傳研究(第一年到第三年)。前三個部分將收集新的研究對象，第四個部分則針對我們先前已做過全基因體掃描、但尚未做菸鹼酸皮膚測試的多發性精神分裂症患者家庭予以追踨施測該項皮膚測試。預期本計畫有助於瞭解影響菸鹼酸皮膚紅腫反應的生化變化及可能的基因位置，並進一步評估其在精神分裂症之病因上所可能扮演的角色。<br> Abstract: Impaired flush response to niacin skin test has been repeatedly shown in schizophrenia patients and postulated as a marker for lipid metabolism abnormality in schizophrenia. However, previous studies were limited in the insensibility of measuring the skin flush response by using a semi-quantitative method and whether this abnormality is a trait or a state-dependent marker for schizophrenia has not been thoroughly investigated. Furthermore, the underlying biochemical mechanisms of the attenuated niacin flush response and its relation to other observed morphological or neuropsychological abnormalities in schizophrenia remain to be clarified. In this project, we propose to address above research questions by using niacin skin test as a marker of vulnerability for schizophrenia in four different study samples. The specific aims of this project are as follows: 1) To assess whether the rating of a direct, quantitative, and standardized method in measuring skin temperature change is consistent with the visual rating of skin flush response to niacin; 2) To assess the stability of niacin flush response impairment in acutely psychotic patients with schizophrenia, to compare with that in patients with affective disorders, and to investigate the relationships of abnormal flush response to red blood cell membrane fatty acid levels, the activity of a key enzyme in lipid metabolism, phospholipase A2 (PLA2), and the use of psychotropic medications; 3) To assess the flush responses to niacin skin patch in junior high school students and to investigate the association of induced skin response with psychopathology and minor physical anomalies; and 4) To assess the niacin flush response impairment in schizophrenia patients and their first-degree relatives recruited by a previous nation-wide family study, the Taiwan Schizophrenia Linkage Study, and to conduct family-based genome-wide genetic linkage study using niacin flush response to reduce etiological heterogeneity in subjects. This 3-year proposal contains four components: (1) a pilot study of 30 normal subjects on infrared thermography for skin flush measurement (year 1); (2) a biochemical study comparing four groups of subjects (50 schizophrenia patients, 50 bipolar patients, 50 major depressive patients, and 50 healthy controls, conducted from year 1- year 3); (3) a school study of 900 junior high school students (year 1-3); and (4) a family-genetic study of 1512 subjects from multiple-affected schizophrenia families (year1-year3). The first three components will recruit new subjects, whereas component 4 (family-genetic study) takes advantage of our existing cohort of affected schizophrenia sib-pair families used in our previous whole genome scan. The anticipated results include that we can have a better understanding on the underlying biochemical and genetic factors influencing the magnitude of the flush response to niacin skin test, and whether impaired flush response to niacin is associated with the etiology of schizophrenia.