語意處理作為思覺失調症的一種內生表現型

Semantic processing as a neuro-cognitive endophenotype of schizophrenia

劉允中(Yun-Chung Liu)

指導教授 ： 周泰立

國立臺灣大學/理學院/心理學研究所/碩士(2015年)

https://doi.org/10.6342/NTU.2015.00866

摘要

目的：思覺失調症是我們所知遺傳性最高的精神疾患之一。在病理研究中，學者提出內生表現型（Endophenotype）的概念，用以測量外顯病徵與基因訊息之間細微的神經生物�認知表現型，進一步對病理有更深的了解。混亂的語言�行為是思覺失調症的五大症狀之一，但是，語言處理缺損與思覺失調症基因的關係尚不清楚，因此，本研究藉由檢驗思覺失調症病人、未患病手足以及一般未患病者的語意處理表現和其神經生理基礎，探討語意處理和思覺失調症基因的關係。方法：利用功能性磁振造影（functional Magnetic Resonance Imaging）技術檢驗思覺失調症病人（平均年齡 為32.9，標準差為5.1）組、未患病手足組（平均年齡為34.0歲，標準差為6.6歲）、一般正常人組（平均年齡為33.0，標準差為4.9）的語意處理歷程。三組（各29人）的智力分數、年齡沒有顯著差異，皆慣用右手。在磁振造影掃描的同時，受試者要完成中文語意聯想作業，亦即螢幕上出現的前後兩個中文字有沒有意義關聯。此外，將腦部活動大小程度與魏氏智力測驗第三版（WAIS-III）、思覺失調症正負性症狀量表（PANSS）作相關，以探討大腦活動與認知功能�病人症狀之間的關聯。結果：在語意判斷作業中，病人組的正確率、反應時間都較手足組為低，而手足組的表現與一般正常人組則沒有顯著差異。在進行中文語意處理時，病人組在左腦額下迴（IFG，BA45）、左腦顳中迴（MTG，BA 21）的活動較手足組、一般正常人組為高；另一方面，一般正常人組在左腦頂下小葉（IPL，BA39）的活化程度顯著地較病人組與手足組為高。此外，病人組在左側額下迴的活化程度與症狀量表思緒混亂（conceptual disorganization）分數呈正相關，控制組在左側顳中迴的活化程度與魏氏智力測驗中記憶廣度的分數呈負相關。結論：本研究發現思覺失調症病人與手足在語意處理時不同的神經生理機制。病人左側額下迴與顳中迴的活化程度較高，顯示他們在進行語意判斷作業時，需要花費更多精力來提取與儲存語意訊息。其中，病人左側額下迴的活化與病人思緒混亂程度呈正相關，顯示隨著症狀的嚴重性，此區域的過度活躍程度會更加明顯，而一般正常人顳中迴的活化程度較低，此處的活化又與魏氏智力測驗的記憶廣度分數呈現負相關，顯示一般正常人的記憶廣度越高，在語意表徵的儲存不需花費太多資源，病人組則沒有觀察到此一相關。另一方面，一般正常人進行語意測驗時在左側頂下小葉的活化程度較高，這個區域與跨感官語言資訊整合、空間注意力與自我概念的訊息應用有關，顯示病人和手足在進行語意聯想判斷時，可能運用不同的策略。本研究區別出語意處理時病人獨特的神經機制，與疾病狀態有關，同時，也發現手足與病人相似的神經機制，支持語意處理的部分神經機制受到與基因遺傳影響，是思覺失調症的一種內生表現型。

關鍵字

思覺失調症 ； 語意處理 ； 內生表現型 ； 功能性磁振造影

並列摘要

Introduction: Schizophrenia is characterized as a highly heritable disorder. Endophenotypes have been proposed to seek for measurable components between symptoms and genotype in schizophrenia. Disorganized speech/thought is one of the core symptoms of schizophrenia. These symptoms are related to the loosening association among concepts seen in patients with schizophrenia. However, whether semantic association is an endophenotype of schizophrenia remains unclear. We aimed to investigate the underlying neural mechanism of semantic processing in patients with schizophrenia, their unaffected siblings, and healthy controls. Methods: Functional magnetic resonance imaging (fMRI) was used to assess patients with schizophrenia (mean age = 32.9 years, SD = 5.1), their siblings (mean age = 34.0 years, SD = 6.6), and healthy controls (mean age = 33.03 years, SD = 4.9). The three groups (n = 29 each) were matched in IQ, age, and handedness (all right-handed). Participants were instructed to judge whether two Chinese characters were related in meaning while brain activation patterns were recorded. In addition, the magnitude of brain activation was correlated with scores of the WAIS-III and Positive and Negative Syndrome Scale (PANSS) to examine the relationship between brain activity and cognitive functions/symptoms of schizophrenia. Results: In the semantic judgment task, the patients showed lower accuracy rate and longer reaction time than the siblings. However, there was no difference in behavioral performance between siblings and controls. In addition, the patients showed greater activation in the left inferior frontal gyrus (IFG, BA 45) and the left middle temporal gyrus (MTG, BA 21) as compared to the siblings and controls. In contrast, the controls showed greater activation in the left inferior parietal lobule (IPL, BA 39) as compared to the other two groups. Furthermore, there was a positive correlation between the index of conceptual disorganization in the PANSS and left IFG activation in patients, as well as a negative correlation between the Digit Span score in the WAIS-III and left MTG activation in controls. Conclusions: This study reveals different biological mechanisms of semantic processing in patients and their siblings. The patients produced greater activation in left IFG/MTG, suggesting that they need more effort to retrieve semantic information and search relevant semantic representations during semantic judgments. Relative to the controls and siblings, greater activation in the patients may be treated as a state marker of schizophrenia. Moreover, the patients produced less activation in left IPL. This region is involved in higher level linguistic information integration, spatial-attentional network, and self-perception. This difference indicates that the siblings and patients may be applying a different strategy when doing the semantic judgment task. Relative to the controls, greater activation in the patients and siblings may be treated a trait marker of schizophrenia regarding semantic impairments.

並列關鍵字

schizophrenia, semantic processing, endophenotype, fMRI

參考文獻

Lee, S.H., Chen, S.Y., & Chou, T.L. (2009). Effect of vocabulary size on semantic processing of Chinese characters for fifth graders and adults. Formosa Journal of Mental Health. 22(4), 345-382.

Andreasen, C. N., & Grove, W. M. (1986). Thought, language, and communication in schizophrenia: diagnosis and prognosis. Schizophrenia bulletin, 12(3), 348-359.

Binder, J. R., Frost, J. A., Hammeke, T. A., Cox, R. W., Rao, S. M., and Prieto, T. (1997). Human brain language areas identified by functional magnetic resonance imaging. The Journal of Neuroscience. 17(1), 353-362.

Booth, R. J., Lu, D., Burman, D. D., Jin, Z., … Liu, L. (2006). Specialization of phonological and semantic processing in Chinese word reading. Brain Research, 1071(1), 197-207.

Burock, M. A., Buckne, R. L., Woldorff, M. G., Rosen, B. R., & Dale, A. M. (1998). Randomized event-related experimental designs allow for extremely rapid presentation rates using functional MRI. Neuroreport, 9, 3735-3739.