一項(xiàng)發(fā)表于《腦》網(wǎng)絡(luò)版（Brain,First published online July 9,2013）的最新研究稱,，那些后來被診斷患有孤獨(dú)癥譜系障礙（ASD）的孩子在嬰兒時(shí)期存在過多的腦脊液及增大的大腦。這項(xiàng)由加州大學(xué)戴維斯分校MIND研究院的多學(xué)科研究團(tuán)隊(duì)所開展的研究提示,，上述異?；蛟S能作為早期識(shí)別這種嚴(yán)重發(fā)育障礙的潛在生物標(biāo)記。
Sally Ozonoff是該校精神病與行為科學(xué)系教授及研究部副主任,，她共同主持了該研究,。她過去所做的研究顯示，孤獨(dú)癥患兒的兄弟姐妹罹患孤獨(dú)癥的風(fēng)險(xiǎn)比一般人群要高近20倍,，根據(jù)美國疾病控制與預(yù)防中心的觀點(diǎn),，孤獨(dú)癥的總體發(fā)病率為1/88。這項(xiàng)研究納入了55名年齡在6-36個(gè)月的嬰兒,，他們中的33人各有一位罹患孤獨(dú)癥的哥哥或姐姐,，另有22名嬰兒沒有該疾病家族史。
過多的腦脊液和腦容量的增大是通過對這些嬰兒腦部生長和發(fā)育進(jìn)行定期核磁共振成像（MRI）檢測,，以及通過經(jīng)常性地對他們的認(rèn)知,、社交、溝通及運(yùn)動(dòng)能力發(fā)育進(jìn)行評(píng)估而發(fā)現(xiàn)的,。高風(fēng)險(xiǎn)及低風(fēng)險(xiǎn)嬰兒均在6-9個(gè)月大的時(shí)候接受第一次MRI掃描,，第二次發(fā)生在他們12-15個(gè)月大時(shí)，而第三次則在18-24個(gè)月大之間進(jìn)行,。這些MRI檢查在嬰兒自然睡著時(shí)進(jìn)行，無需鎮(zhèn)靜和麻醉,。
在嬰兒6個(gè)月大時(shí),，研究人員開始對這些嬰兒的發(fā)育進(jìn)行密集的行為評(píng)估。他們的家長也被要求定期完成有關(guān)他們寶寶行為的調(diào)查問卷,。這些測試一直進(jìn)行到嬰兒24個(gè)月至36個(gè)月大的時(shí)候,，屆時(shí)每個(gè)孩子都被評(píng)估是否罹患孤獨(dú)癥譜系障礙以及其它的發(fā)育延遲，或發(fā)育正常,。
研究對象中,，有10個(gè)孩子被診斷患有孤獨(dú)癥，24%的高風(fēng)險(xiǎn)嬰兒及13.4%的低風(fēng)險(xiǎn)嬰兒被判定為患有其它類型的發(fā)育遲緩,，45.5%的高風(fēng)險(xiǎn)寶寶和86%的低風(fēng)險(xiǎn)寶寶發(fā)育正常,。
6-9個(gè)月大時(shí)，那些日后罹患孤獨(dú)癥的孩子在腦部以上及周圍“軸外”空間內(nèi)的腦脊液水平有所升高，而該指標(biāo)在年齡18個(gè)月至24個(gè)月大期間仍然有異常升高,。該研究發(fā)現(xiàn),，在嬰兒早期中的腦脊液越多，被確診時(shí)的孤獨(dú)癥癥狀就越嚴(yán)重,。
在12-15個(gè)月及18-24個(gè)月大時(shí),，潛在孤獨(dú)癥患兒的“軸外”腦脊液容量比發(fā)育正常的嬰兒平均高出33%和22%；6-9個(gè)月大時(shí),，其軸外腦脊液容量比發(fā)育正常的嬰兒多20%,。
該研究首次從嬰兒期開始追蹤孤獨(dú)癥患兒的腦生長軌跡，并第一次將嬰兒期過多的腦脊液與孤獨(dú)癥聯(lián)系在一起,；這項(xiàng)研究同時(shí)第一次提供了孤獨(dú)癥患兒在24個(gè)月大之前腦部增大的MRI證據(jù)：這些嬰兒12個(gè)月大時(shí)的腦容量比發(fā)育正常的嬰兒平均大7%,。
過多的軸外腦脊液及增大的腦容量在孤獨(dú)癥行為學(xué)體征變得明顯之前即可被檢測到，但MIND研究所的研究部主任Amaral同時(shí)指出：“軸外腦脊液增加及腦尺寸的增大的原因目前還不清楚,。”
早期診斷或可使那些哥哥姐姐曾被診斷患有孤獨(dú)癥的嬰兒受益匪淺,，但研究人員警告稱，這一發(fā)現(xiàn)必須要得到重復(fù)驗(yàn)證后方能應(yīng)用于ASD的早期診斷,。MIND研究所目前正在與其它的研究所開展合作,，以重復(fù)這些發(fā)現(xiàn)并評(píng)估這一生物標(biāo)記對ASD診斷的預(yù)測價(jià)值。
Ozonoff稱：“了解這一發(fā)現(xiàn)在健康兒童中出現(xiàn)的頻度是至關(guān)重要的,。就一種對預(yù)測自閉癥轉(zhuǎn)歸有用的生物標(biāo)記來說,，我們希望確定它的假陽性水平在我們可以接受的范圍以內(nèi)。”
加州大學(xué)戴維斯分校的研究生Mark Shen是這項(xiàng)研究的主要作者,他指出：“如果這一軸外腦脊液升高的發(fā)現(xiàn)能在更大的樣本中得到重復(fù),，且能與那些未罹患孤獨(dú)癥的嬰兒做準(zhǔn)確的區(qū)分,，它將可能成為一種非創(chuàng)傷性的、可協(xié)助早期發(fā)現(xiàn)疾病并通過早期干預(yù)而最終改善長期轉(zhuǎn)歸的生物標(biāo)記,。”
“該研究首次報(bào)告了嬰兒腦部異常與孤獨(dú)癥有關(guān),，且可以通過傳統(tǒng)的結(jié)構(gòu)性MRI檢測到，”Amaral稱,，“這項(xiàng)研究提出了研發(fā)一種極早期檢測孤獨(dú)癥譜系障礙方法的可能性,。早期檢測是至關(guān)重要的，因?yàn)樵缙诟深A(yù)可減輕孤獨(dú)癥相關(guān)認(rèn)知與行為損害,，并可能為這些孩子帶來更為積極的長期預(yù)后,。”（生物谷Bioon.com）
生物谷推薦英文摘要：
Brain doi: 10.1093/brain/awt166
Early brain enlargement and elevated extra-axial fluid in infants who develop autism spectrum disorder
Mark D. Shen, Christine W. Nordahl, Gregory S. Young, Sandra L. Wootton-Gorges, Aaron Lee, Sarah E. Liston, Kayla R. Harrington1, Sally Ozonoff1 and David G. Amaral
Prospective studies of infants at risk for autism spectrum disorder have provided important clues about the early behavioural symptoms of autism spectrum disorder. Diagnosis of autism spectrum disorder, however, is not currently made until at least 18 months of age. There is substantially less research on potential brain-based differences in the period between 6 and 12 months of age. Our objective in the current study was to use magnetic resonance imaging to identify any consistently observable brain anomalies in 6–9 month old infants who would later develop autism spectrum disorder. We conducted a prospective infant sibling study with longitudinal magnetic resonance imaging scans at three time points (6–9, 12–15, and 18–24 months of age), in conjunction with intensive behavioural assessments. Fifty-five infants (33 ‘high-risk’ infants having an older sibling with autism spectrum disorder and 22 ‘low-risk’ infants having no relatives with autism spectrum disorder) were imaged at 6–9 months; 43 of these (27 high-risk and 16 low-risk) were imaged at 12–15 months; and 42 (26 high-risk and 16 low-risk) were imaged again at 18–24 months. Infants were classified as meeting criteria for autism spectrum disorder, other developmental delays, or typical development at 24 months or later (mean age at outcome: 32.5 months). Compared with the other two groups, infants who developed autism spectrum disorder (n = 10) had significantly greater extra-axial fluid at 6–9 months, which persisted and remained elevated at 12–15 and 18–24 months. Extra-axial fluid is characterized by excessive cerebrospinal fluid in the subarachnoid space, particularly over the frontal lobes. The amount of extra-axial fluid detected as early as 6 months was predictive of more severe autism spectrum disorder symptoms at the time of outcome. Infants who developed autism spectrum disorder also had significantly larger total cerebral volumes at both 12–15 and 18–24 months of age. This is the first magnetic resonance imaging study to prospectively evaluate brain growth trajectories from infancy in children who develop autism spectrum disorder. The presence of excessive extra-axial fluid detected as early as 6 months and the lack of resolution by 24 months is a hitherto unreported brain anomaly in infants who later develop autism spectrum disorder. This is also the first magnetic resonance imaging evidence of brain enlargement in autism before age 2. These findings raise the potential for the use of structural magnetic resonance imaging to aid in the early detection of children at risk for autism spectrum disorder or other neurodevelopmental disorders.
