環境賀爾蒙PCBs/PCDFs之暴露與神經認知發展初探

Abstract

背景: 1979年，台灣中部地區發生米糠油中毒事件，約兩千名當地居民食用到多氯聯苯 (PCBs)及多氯呋喃 (PCDFs)汙染之米糠油因而導致中毒事件。過去之研究發現，經胎盤而暴露的油症子代比起對照組有智力發展遲緩現象，此智力的發展遲緩問題，甚至在女性中毒後七至十二年所生的小孩仍會發生，為了解子代成年後智力方面是否仍受影響，因此對成年後的子代進行較明確之評估。研究目的預探討: 1. 以預測之血中PCBs/PCDFs濃度探討與第二代智力分數之間是否有劑量效應關係? 2. 以熱刺激誘發電位檢查 (Contact Heat Evoke Potential) 評估PCBs/PCDFs暴露是否會影響第二代痛覺傳導通路脊髓丘腻束至週邊傳導神經電位之振幅及潛伏期改變? 3. 以功能性磁振造影 (Functional Magnetic Resonance Imaging)儀器結合圖形配對測驗 (Picture task) 及回推記憶測驗 (2-back task) 評估是否PCBs/PCDFs暴露可導致第二代其空間旋轉功能以及記憶功能的特定皮質區之血流(活化)量的改變? 方法: 研究對象為經胎盤而暴露的油症第二代與他們的鄰居對照組。在研究目的1中，針對油症第二代110位與其對照組124位作比較，以母親血中多氯聯苯及多氯呋喃濃度與其魏氏兒童智力量表比較。在研究目的2及3之中，自304位19至32歲男性從中挑選出暴露組及對照組共21位。使用神經影像學技術，包括功能性磁振造影（fMRI）研究腻部功能血流活化情形。另外，也使用熱刺激誘發電位檢查 (CHEP)來評估神經感覺，以及魏氏成人智力量表 (WAIS)評估成年智力狀況，並結合問卷及過去母親血中濃度量測得到完整訊息。 結果: 在年齡6至15歲之油症子代分析，其智力影響在不同性別之間非常不同，男性為行為智力(PIQ)，而女性在語言智力(VIQ)之影響較為顯著。特定之智力分數影響，與特定之PCBs化學同源物有相關性。在研究目的2及3中，成年後的魏氏智力分數仍可看出油症者較低的趨勢。且熱刺激誘發電位小神經纖維的腳部振幅較對照組為低。fMRI可看到在picture match task時的活化區於大腻皮質中的空間處理區域頂葉(parietal lobe)兩組人皆有活化(p<0.001)，兩組人相減之後(Contrast)可得到油症組較對照組顯著活化區域為小腻(Cerebellum) (p<0.001)，對照組較油症組顯著活化區域為海馬迴(Hippocampus) (p<0.001)，杏仁核(Amygdala) (p<0.001)。本研究對於油症子代孩童神經認知影響使用有效的工具檢測出與其對照組之差異性，但實際上的機制，以及此研究族群是否足以推估至整個油症子代，甚至是整個受多氯聯苯或戴奧辛類化合物暴露之族群，都是接下來還需繼續努力的方向。

Background: In 1979, approximately 2000 people in central Taiwan were accidentally exposed polychlorinated biphenyls (PCBs) and dibenzofurans (PCDFs) due to ingest the contaminated rice oil. Children born to exposed mothers after the exposure event were thus prenatally exposed. We followed up these children for health effects and found poorer neurocognitive development. The effect is still presence in the prenatal exposed child after the event about 7~12 years. We would like to know the adult IQ of the prenatal exposed second generation, and assess the neurocognitive effect of second generation comprehensively. The study aim is：1. Whether the dose - effect relationship was found between IQ and predicted PCBs/PCDFs concentration? 2. Whether PCBs/PCDFs exposure could affect the nerve conduction potential situation? 3. Whether PCBs/PCDFs exposure was associated with activation changes in specific brain regions of cortical? Method: The study sample is prenatal exposed people and their matched controls. In the study aim 1, there are 110 prenatal exposed people and 124 matched controls. Assess the relationship between the predicted PCBs/PCDFs concentration and the child IQ. In the study aim 2 and 3, among the 304 prenatal exposed people that we follow up regularly, and the age range from19 to 32 years, we select 10 young men and their matched controls 11 volunteer. We propose to utilize the recently advanced neuroimaging technologies, namely, functional magnetic resonance imaging (fMRI) to examine the functional activations. In addition, Wechsler Adult Intelligence Scale (WAIS) and contact heat evoke potential (CHEP) used to follow the participants’ neurocognitive functioning. Result: Among Yucheng children, males and females were affected rather differently in IQ. Some subscales of WISC-R were negatively related to mothers’ serum levels of PCB congeners 138, 153, 157, and 180. Among adults, Wechsler intelligence scores were lower in Yucheng boys as compared to their controls. The amplitudes of the contact heat evoke potential in legs of Yucheng men was found to be lower than those in the controls (p=0.03). In functional MRI, the parietal activation with picture task (p<0.001) was found in both groups. Yucheng men had higher activation in cerebellum than their controls in the contrast results (p<0.001), and had lower activation in hippocampus, amygdala than their controls (p<0.001). We conclude that IQ was affected in the second generation of Yucheng women. These effects were dose-related to maternal exposure levels. Reduced evoke potential amplitude induced by heat exposure was seen in Yucheng second generation. Using functional activation studies, different regions of activation were seen in Yucheng and their controls. Further studies with larger number of participants are warranted to confirm this finding.