運用事件關聯電位探究思覺失調症患者的聽覺感覺門控缺損

Investigation of Auditory Sensory Gating Deficits in Schizophrenia Patients Using Event-Related Potentials

沈政男(Chen-Lan Shen)

指導教授 ： 周泰立

國立臺灣大學/理學院/心理學研究所/碩士(2020年)

https://doi.org/10.6342/NTU202001581

摘要

背景：思覺失調症的致病機轉，從基因型到表現型，如此複雜曲折，以至於需要內在表現型居中充當橋樑。感覺門控用來描述在訊息處理中，濾除多餘或不必要刺激的神經學歷程，而感覺門控缺損可能促使思覺失調症患者產生症狀。在反映感覺門控的三個聽覺事件關聯電位中，P50 隱含感覺訊息的前注意力過濾，而 N100/P200 反映注意力的啟動與派用流程。雖然 P50 門控降低已在思覺失調症患者被廣泛證實，先前關於 N100 的研究並無定論，而 P200 則很少被研究。此研究目的在於探討思覺失調症患者與控制組受試者比較起來，是否有 P50、N100與 P200 門控缺損。方法：我們將控制組受試者與臨床狀況穩定的思覺失調症患者納入研究。對於中段潛時誘發電位，包括 P50、N100 與 P200，我們使用聽覺成對拍答聲典範（paired-click paradigm）予以測量，且無注意力操控。感覺門控參數包括 S1 幅度、S2 幅度、幅度差異（S1-S2）與門控比率（S2/S1）。我們也評估思覺失調症病患 PANSS 得分與感覺門控的相關性。結果：104 位病患與102 位控制組受試者接受試驗。相較於控制組，思覺失調症患者有顯著的 P50、N100 與 P200 的感官門控缺損，並且由較大的門控比率與較小的幅度差異反映出來。進一步分析發現，跟控制組比較起來，思覺失調症患者的 P50 S2 幅度較大，而 N100 與 P200 的 S1 幅度較小，顯示 P50 與 N100/P200 的門控缺損可能肇因於不同神經生理學機制。我們並未發現感覺門控指標與思覺失調症正性或負性症狀群的相關性，但我們發現 P200 S2 幅度與 Bell 的情緒不適因子以及 Wallwork的憂鬱因子有負相關。結論：此研究擁有目前為止，採用被動、無分心因子的成對拍答聲典範，來進行 P50、N100 與P200 綜合分析的最大取樣數量。思覺失調症患者表現出一種獨特的聽覺感官門控缺損型態，也就是 P50 的重複抑制缺損與N100 及 P200 的刺激登錄缺損。此一感覺門控缺損型態，如果進一步獲得驗證，將有助於在臨床診斷上鑑別思覺失調症與其他精神疾病。思覺失調症患者在整個訊息處理的中段潛時範圍內，都出現感官門控缺損。這些結果顯示，感覺門控缺損乃思覺失調症病患的瀰漫性缺損，而非僅限於訊息處理的前注意力期。既然P200 的效果量相當大，而且無須額外測量，我們建議未來對 P50、N100 與 P200進行進一步的整體性研究。

關鍵字

事件關聯電位 ； P50 ； N100 ； P200 ； 成對拍答聲典範 ； 思覺失調症 ； 感覺門控

並列摘要

Background: The pathogenesis of schizophrenia, from genotypes to phenotypes, is so complicated and convoluted that endophenotypes may serve as an in-between bridge. Event-related potential (ERP) has been used to investigate neurophysiological endophenotypes. Sensory gating means neurological processes of filtering out redundant or unnecessary stimuli during information processing to avoid sensory overloading, which may contribute to the symptoms of schizophrenia. Among the components of auditory event-related potentials during mid to late latency, P50 implies pre-attentional filtering of sensory information and N100 as well as P200 reflect attention triggering and allocation processes. Although diminished P50 gating has been extensively documented in schizophrenia patients, previous studies on N100 were inconclusive, and P200 has been scantily examined. This study aimed to investigate whether schizophrenia patients have P50, N100, and P200 gating deficits compared with healthy controls. Methods: Control subjects and clinically stable schizophrenia patients were recruited. The mid-latency auditory evoked potentials, including P50, N100, and P200 were generated using the auditory-paired click paradigm without attention manipulation. Sensory gating parameters included S1 amplitude, S2 amplitude, amplitude difference (S1-S2), and gating ratio (S2/S1) were measured. We also evaluated the correlations of schizophrenia patients‟ PANSS scores with sensory gating indices. Results: 103 patients and 101 control subjects were recruited. Compared to the healthy controls, schizophrenia patients had significant sensory gating deficits in P50, N100, and P200, reflected by larger gating ratios and smaller amplitude differences. Further analysis revealed that the S2 amplitude of P50 was larger, while the S1 amplitude of N100/P200 was smaller in schizophrenia patients than in healthy controls. We found no correlations between sensory gating indices and schizophrenia positive or negative symptom clusters. However, we found a negative correlation between the P200 S2 amplitude and Bell‟s emotional discomfort factor/ Wallwork‟s depressed factor. Conclusion: This study has the largest sample size till date to analyze P50, N100, and P200 collectively by adopting the passive auditory paired-click paradigm without distractors. The schizophrenia patients had demonstrated a unique pattern of sensory gating deficits, including repetition suppression deficits in P50 and stimulus registration deficits in N100/200. This pattern of sensory gating deficits, if further validated, may help differentiate schizophrenia from other mental disorders in clinical diagnosis. These results suggest that sensory gating is a pervasive cognitive abnormality in schizophrenia patients rather than limited to the pre-attentive phase of information processing. Since P200 exhibited a large effect size and did not require additional time during recruitment, future studies of measuring P50-N100-P200 collectively are highly recommended.

並列關鍵字

event-related potentials ； P50 ； N100 ； P200 ； paired click paradigm ； schizophrenia ； sensory gating

參考文獻

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