一項(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)所做的研究發(fā)現(xiàn),，那些后來(lái)被診斷患有自閉癥譜系障礙的孩子在嬰兒時(shí)期有過(guò)多的腦脊液及增大的大腦,，從而提出了一個(gè)可能性，即腦部的那些異常也許能作為早期識(shí)別這種神經(jīng)發(fā)育性疾病的可能的生物標(biāo)記,。
這項(xiàng)研究首次從嬰兒期開(kāi)始追蹤那些日后出現(xiàn)自閉癥的孩子的腦生長(zhǎng)軌跡,，并第一次將嬰兒期過(guò)多的腦脊液與自閉癥進(jìn)行了關(guān)聯(lián)。“出現(xiàn)自閉癥譜系疾病嬰兒的早期腦發(fā)育及軸外液體增加”于今天在網(wǎng)絡(luò)版的神經(jīng)學(xué)雜志Brain上發(fā)表,，該雜志由Oxford University Press出版,。
MIND研究所的研究部主任David Amaral共同主持了這項(xiàng)研究；他說(shuō)：“該研究首次報(bào)告了嬰兒腦部異常與自閉癥有關(guān),，且可以通過(guò)傳統(tǒng)的結(jié)構(gòu)性MRI檢測(cè)到,。”
Amaral說(shuō)：“這項(xiàng)研究提出了研發(fā)一種非常早期的檢測(cè)自閉癥譜系疾病方法的可能性。早期檢測(cè)是至關(guān)重要的,，因?yàn)樵缙诟深A(yù)可減少與自閉癥有關(guān)的認(rèn)知與行為損害,，并可能為這些孩子帶來(lái)更為積極的長(zhǎng)期轉(zhuǎn)歸。”
這項(xiàng)研究是在55名年齡在6-36個(gè)月的嬰兒中進(jìn)行的,，他們中的33人各有一位罹患自閉癥的哥哥或姐姐,。有22名嬰兒沒(méi)有該疾病家族史。
研究人員報(bào)告說(shuō),，在那些日后于24-36個(gè)月大時(shí)被診斷罹患自閉癥的高危嬰兒中檢測(cè)到腦部異常的情況顯然更為常見(jiàn),。Sally Ozonoff是精神病與行為科學(xué)系教授及研究部副主任；她共同主持了這項(xiàng)研究,。她過(guò)去所做的研究顯示,，在罹患自閉癥孩子的兄弟姐妹中的自閉癥風(fēng)險(xiǎn)比一般人群要高近20倍。美國(guó)疾病控制與預(yù)防中心將自閉癥的總體發(fā)生率定為1/88,。
過(guò)多的腦脊液和腦容量的增大是由對(duì)這些嬰兒腦部生長(zhǎng)和發(fā)育進(jìn)行定期核磁共振成像（MRI）檢測(cè)以及通過(guò)經(jīng)常性地對(duì)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)嬰兒皆在6-9個(gè)月大的時(shí)候接受他們的第一次MRI掃描,。第二次MRI掃描發(fā)生在他們12-15個(gè)月大的時(shí)候。第三次掃描是在18-24個(gè)月大之間進(jìn)行的,。這些MRIs檢查是在嬰兒自然睡著時(shí)進(jìn)行的,，檢查無(wú)需鎮(zhèn)靜和麻醉,。
在6個(gè)月大的時(shí)候，研究人員開(kāi)始對(duì)這些嬰兒的發(fā)育進(jìn)行密集的行為評(píng)估,。他們的家長(zhǎng)也定期地完成有關(guān)他們寶寶行為的調(diào)查問(wèn)卷,。這些測(cè)試一直進(jìn)行到嬰兒24個(gè)月至36個(gè)月大的時(shí)候，在那個(gè)時(shí)候,，每一個(gè)孩子都被評(píng)估是否有自閉癥譜系障礙,、其它的發(fā)育延遲或具有典型的發(fā)育。
除了有10個(gè)孩子被診斷患有自閉癥之外,，有24%的高風(fēng)險(xiǎn)嬰兒及13.4%的低風(fēng)險(xiǎn)嬰兒被歸類(lèi)為患有其它類(lèi)型的發(fā)育遲緩,。有約45.5%的高風(fēng)險(xiǎn)寶寶和86%的低風(fēng)險(xiǎn)寶寶被發(fā)現(xiàn)具有正常的發(fā)育。
研究人員發(fā)現(xiàn),，到6-9個(gè)月大的時(shí)候,，那些發(fā)生自閉癥的孩子在腦部以上及周?chē)?ldquo;軸外”空間內(nèi)的腦脊液水平有所升高，而該腦脊液水平在年齡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),，在嬰兒期早期中的腦脊液越多，那個(gè)孩子在被診斷時(shí)的自閉癥癥狀就越嚴(yán)重,。
在那些后來(lái)被診斷患有自閉癥的嬰兒中,，在12-15個(gè)月大的時(shí)候及在18-24個(gè)月大的時(shí)候，其“軸外”腦脊液容量比典型發(fā)育的嬰兒平均高出33%和22%,。在6-9個(gè)月大的時(shí)候,，其軸外腦脊液容量比典型發(fā)育嬰兒要多20%。
這項(xiàng)研究還第一次提供了在24個(gè)月大之前自閉癥患兒腦部增大的MRI證據(jù),。在本研究中被診斷患有自閉癥的嬰兒在12個(gè)月大的時(shí)候,，其腦容量比典型發(fā)育嬰兒平均要大7%。
過(guò)多的軸外腦脊液及增大的腦容量在自閉癥行為學(xué)體征變得明顯之前可被檢測(cè)到,。Amaral說(shuō)：“軸外腦脊液增加及腦尺寸的增大的原因目前還不清楚,。”
早期診斷可能對(duì)那些其哥哥姐姐曾經(jīng)被診斷患有自閉癥的嬰兒有特別的裨益，但研究人員警告,，這一發(fā)現(xiàn)必須要得到重復(fù)之后才能將其用于協(xié)助ASD的早期診斷,。MIND研究所目前正在與其它的研究所合作以重復(fù)這些發(fā)現(xiàn)并評(píng)估這一生物標(biāo)記可如何準(zhǔn)確地預(yù)測(cè)日后的ASD診斷。
Ozonoff說(shuō):“了解這一針對(duì)大腦的發(fā)現(xiàn)在沒(méi)有發(fā)生自閉癥的孩子中也會(huì)出現(xiàn)的頻度是至關(guān)重要的,。就一種對(duì)預(yù)測(cè)自閉癥轉(zhuǎn)歸有用的生物標(biāo)記來(lái)說(shuō),，我們希望確定它不會(huì)產(chǎn)生一種不可接受的假陽(yáng)性水平。”
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,他說(shuō):“如果這一軸外腦脊液升高的發(fā)現(xiàn)能在更大的發(fā)生自閉癥的嬰兒樣本中得到重復(fù),，且它能與那些不發(fā)生自閉癥的嬰兒做準(zhǔn)確的區(qū)分,，那么它將具有成為一種非創(chuàng)傷性的可協(xié)助早期發(fā)現(xiàn)疾病并通過(guò)早期干預(yù)而最終改善這些孩子長(zhǎng)期轉(zhuǎn)歸的生物標(biāo)記的潛力。”（生物谷 Bioon.com）
生物谷推薦的英文摘要
Brain doi: 10.1093/brain/awt166
Early brain enlargement and elevated extra-axial fluid in infants who develop autism spectrum disorder
Mark D. Shen1, Christine W. Nordahl, Gregory S. Young1, Sandra L. Wootton-Gorges2, Aaron Lee1, Sarah E. Liston1, Kayla R. Harrington1, Sally Ozonoff1 and David G. Amaral1
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.
