雙極症腦源神經滋養因子濃度與認知的相關性由腦源神經滋養因子基因多型性調控:一個12周追蹤研究

Genetic modulation of correlation between cognition and brain derived neurotrophic factor in bipolar disorder: A 12-week follow-up study

李聖玉(Sheng-Yu Lee)

指導教授 ： 陳正生

高雄醫學大學/醫學院/醫學研究所博士班/博士(2018年)

摘要

研究目的: 雙極症病患常出現認知功能受損，即使在症狀緩解期，認知受損常無改善。由於神經退化被認為是雙極症的病因之一，因此，影響神經元生長、發展與生存的腦源神經滋養因子，也被認為可以做為雙極症的症狀或診斷的生物標記，惟並不具有特異性。影響腦源神經滋養因子分泌的基因，被認為不但影響認知功能，也曾被發現與雙極症的病因相關。然而，過去並沒有長期追蹤研究，探討影響腦源神經滋養因子分泌的基因，在雙極症患者的認知功能及周邊血液中的腦源神經滋養因子濃度的關係上，所扮演的角色。本研究探討目的將探討腦源神經滋養因子基因多型性(Brain-derived neurotrophic factor (BDNF) Val66Met) (rs6265) 如何調控12周追蹤後，血漿中腦源神經滋養因子的濃度的變化與認知功能及生活品質變化的相關性。
方法: 收集初次診斷為雙極症的病患，在基準點ii及第1, 2, 4, 8, 12周，評估其臨床嚴重度及抽血測量血漿中腦源神經滋養因子的濃度。在基準點抽血分析BDNF Val66Met基因多型性的基因型。在基準點及實驗結束(第12周)時評估認知功能(包含威斯康辛卡片測驗和連續注意力測驗)以及生活品質。最後分析認知功能及生活品質在12周的變化與腦源神經滋養因子濃度變化的相關性。
結果: 本研究一共收集541位雙極症患者，其中355位(65.6%)完成12周的追蹤。分析完成12周追蹤的個案，發現血漿中腦源神經滋養因子的濃度增加與威斯康辛卡片測驗的進步成顯著相關(p = 0.00037)，而以雙極症亞型及BDNF Val66Met基因型分層後，發現相關僅出現在第一型雙極症且有Val/Met 基因型個案中(p = 0.008)。
結論: 血漿中腦源神經滋養因子的濃度增加與威斯康辛卡片測驗的進步相關，且受BDNF Val66Met基因型調控。

關鍵字

雙極症 ； 腦源神經滋養因子 ； 認知功能 ； 威斯康辛卡片測驗 ； 連續注意力測驗 ； BDNF Val66Met基因多型性

並列摘要

Objectives: Neurodegeneration has been regarded as pathogenesis for bipolar disorder (BD). Brain-derived neurotrophic factor (BDNF) were proposed as biomarkers of BD. Cognitive deficits frequently remained even in remitted BD. Genes related to secretion of neurotrophic factors were reported to play important role in the etiology of BD, while also modulate the association between BDNF level and cognitive function. However, no longitudinal associations were reported in past studies. In the current study, we investigated the effect of the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) on correlation between changes in plasma BDNF levels with cognitive function and quality of life (QoL) after 12 weeks of treatment.
Methods: Patients with a first diagnosis of BD were recruited. Symptom severity and l plasma BDNF levels were examined during weeks 0, 1, 2, 4, 8, and 12. The genotype of the BDNF Val66Met polymorphism was determined. The Wisconsin Card Sorting Test (WCST), and the Conners’ Continuous Performance Test (CPT) and QoL were assessed at baseline and endpoint. Changes in cognitive function and QoL over 12 weeks were reduced using factor analysis for the evaluation of their correlations with changes in plasma BDNF.
Results: Five hundred forty-one BD patients were recruited and 355 (65.6%) of them completed the 12-week follow-up. We analyzed only those who completed the 12-week follow-up. Increases in plasma BDNF levels with improvement in WCST were significantly correlated (p = 0.00037). After stratification of BD subtypes and BDNF genotypes, this correlation was significant only in BD-I and the Val/Met genotype (p = 0.008).
Conclusion: We concluded that changes in plasma BDNF levels significantly correlated with changes in WCST scores in BD and is moderated by the BDNF Val66Met polymorphism and the subtype of BD.

並列關鍵字

Bipolar disorder ； BDNF ； cognitive function ； WCST ； CPT ； polymorphism ； BDNF Val66Met polymorphism

參考文獻

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