2014-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/655006摘要：[目標]本計劃使用擴散頻譜造影(diffusion spectrum imaging, DSI)及功能性磁振造影(functional MRI, fMRI)在精神分裂症患者之手足身上研究精神分裂症的風險基因對腦結構及功能的影響，並以此為依據找到大腦在結構性與功能性連結的內表現型(endophenotype)。DSI 藉由量測水分子擴散以檢測腦白質神經束的微結構狀態，而fMRI 藉由量測血氧濃度依存訊號(blood oxygenated level dependent, BOLD)以檢測腦灰質的活性。本計劃將以大腦預設迴路(default mode network, DMN)為研究重點。DMN 主要包含有中前額葉，後扣帶回，楔前葉以及側頂葉。此迴路與內省及自我指認等功能相關。近年來，DMN 已被報導在精神分裂症患者身上有顯著變化。此外我們以患者之未患病手足為研究對象將可排除因藥物治療或疾病進展所造成的變因。<br> Abstract: [Aim] This research project investigates the dosage effects of three promising vulnerability genes of schizophrenia (NRG1-P3, DISC1-2 and DISC1-27) on the brain structure and function. Diffusion spectrum imaging (DSI) and functional magnetic resonance imaging (fMRI) will be performed on unaffected siblings of the patients and normal controls. DSI examines neural tracts of the white matter by the water molecular diffusion, whereas fMRI measures cortical activity of the gray matter by the blood oxygenation level dependent (BOLD) signal. In this study, we focus on the default mode network (DMN). The DMN typically involves the medial prefrontal cortex, posterior cingulate cortices / precuneus, and lateral parietal lobule, and is considered to be related to introspective and self-referential thought. Alterations of the DMN have been robustly reported in schizophrenia patients. The unaffected siblings are recruited to minimize confounds by the medication and disease process of the illness.[Hypothesis] Based on the neurodevelopmental perspective on psychopathology of schizophrenia, our hypotheses are as follow. 1) The existence of risk gene alleles is associated with the decrease in structural connectivity, as well as, the compensatory increase in functional connectivity of the DMN. 2) The alterations in the structural and functional connectivity would be observed in the sibling group as compared with the control group, and the alterations are associated with the gene dosage. 3) The gene dosage would exhibit cascading effects on the brain structure, function and cognitive behavior. The gene dosage poses the strongest effect on the structural connectivity of the DMN, followed by the functional connectivity of the DMN, the task-negative activation of the verbal working memory affecting the taskpositive activation, and the weakest on the cognitive performance in the neuropsychological assessments.精神分裂症磁振造影功能性磁振造影