https://scholars.lib.ntu.edu.tw/handle/123456789/83811
Title: | 右弓狀束於思覺失調症的遺傳與功能性相關之研究 Heredity and functional association of the right arcuate fasciculus in schizophrenia |
Authors: | 吳振豪 Wu, Chen-Hao |
Keywords: | 思覺失調症;內表型;特徵性指標;擴散頻譜造影;神經纖維追蹤術;功能性磁振造影;schizophrenia;endophenotype;trait marker;diffusion spectrum imaging;tractography;functional MRI | Issue Date: | 2015 | Abstract: | 特徵性指標有助於將不同的表現型區分成明確的子類型,並提供較有效率的途徑來發現該疾病的遺傳基礎。近期有關擴散磁振造影的研究,已提出白質微結構的完整度可當作思覺失調症的特徵性指標。雖然測量白質微結構完整度較佳的方法是以神經纖維追蹤術為基礎的分析,但手動的神經纖維追蹤術易受操作者影響,且當要分析大量白質束時,是非常耗時的。 在這篇研究,我們嘗試運用新的大腦神經連結自動分析方法,來找出思覺失調症的特徵性指標。我們分析一群思覺失調症患者、未發病手足與健康正常人的白質纖維束。結果發現右弓狀束的白質完整度,在患者與未發病手足,皆可觀察到顯著且呈等級的異常。我們認為,右弓狀束可能是思覺失調症的候選特徵性指標,且在建立基因型與表現型之間的關聯上,有其潛在價值。 雖然發現右弓狀束是思覺失調症的候選特徵性指標,但此白質束的結構與功能是如何改變、這些改變相互間有何關聯、以及這些改變又如何與精神病的症狀有關是不清楚的。因此,我們進行一個結合擴散磁振造影與功能性磁振造影的研究,來釐清右弓狀束的結構與功能間的關係。在我們的分析結果發現,右弓狀束的白質完整度與其相對應的功能性側化有顯著的正相關。當與臨床症狀做關聯時,右弓狀束的白質完整度以及其相對應的功能性側化皆與妄想/幻覺構面的分數呈負相關。此結果認為,右弓狀束白質結構的受損程度與其相對應的功能性側化的降低是有關的,而這兩者的改變可能會加重思覺失調症的言語性幻聽。 總結來說,這些結果呈現出右弓狀束的遺傳特性,也說明它與特定的臨床表型有關之結構與功能的複雜關係,認為右弓狀束是一個可用來篩選有關思覺失調症的基因以及早期辨識思覺失調症的特徵性指標。 Trait markers aid in the separation of heterogeneous phenotypes into distinct subtypes and provide more efficient routes for the discovery of the genetic underpinnings of disease. Recent diffusion magnetic resonance imaging (MRI) research has proposed that the microstructural integrity of white matter is a trait marker for schizophrenia. Although tractography-based analysis is a better approach for measuring the microstructural integrity of white matter, manual tractography is operator-dependent and extremely time-consuming if a large number of tracts are to be analyzed. In this study, we sought to identify the trait markers of schizophrenia using a novel, automatic tractography-based analysis method. We analyzed tract integrities in a cohort of schizophrenic patients, unaffected siblings and healthy controls. We found that the white matter integrity of the right arcuate fasciculus was significantly impaired in both unaffected siblings and schizophrenic patients in a predictable, graded pattern. Our results suggest that the right arcuate fasciculus is a candidate trait marker and could be valuable for establishing links between genetic liabilities and specific clinical phenotypes. Although the right arcuate fasciculus was identified as a candidate trait marker of schizophrenia, it is unclear how the structure and function of the white matter tract is altered, how these alterations are related to each other, and how these alterations are associated with psychotic symptoms. To address these questions, we conducted a study combining diffusion MRI and functional MRI to identify the relationships between structure and function in the right arcuate fasciculus. A positive correlation was found between the microstructural integrity of the right arcuate fasciculus and the corresponding functional lateralization. When correlated with clinical symptoms, both the microstructural integrity of the right arcuate fasciculus and the corresponding functional lateralization were negatively correlated with the delusion/hallucination dimension scores. Our results suggest that the impaired structural integrity of the right arcuate fasciculus is related to a reduction in the corresponding functional lateralization and that these alterations might aggravate auditory verbal hallucinations in schizophrenia. In summary, these results demonstrate the hereditary traits of the right arcuate fasciculus and reveal its complex structure-function relationships in relation to specific clinical phenotypes, suggesting that the right arcuate fasciculus is a trait marker that could be useful in screening for schizophrenia-related genes and in the early diagnosis of schizophrenia. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/277515 | Rights: | 論文公開時間: 2015/7/20 論文使用權限: 同意有償授權(權利金給回饋學校) |
Appears in Collections: | 醫學工程學研究所 |
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ntu-104-D99548016-1.pdf | 23.54 kB | Adobe PDF | View/Open |
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