一项发表于《脑》网络版（Brain,First published online July 9,2013）的最新研究称，那些后来被诊断患有孤独症谱系障碍（ASD）的孩子在婴儿时期存在过多的脑脊液及增大的大脑。这项由加州大学戴维斯分校MIND研究院的多学科研究团队所开展的研究提示，上述异常或许能作为早期识别这种严重发育障碍的潜在生物标记。
Sally Ozonoff是该校精神病与行为科学系教授及研究部副主任，她共同主持了该研究。她过去所做的研究显示，孤独症患儿的兄弟姐妹罹患孤独症的风险比一般人群要高近20倍，根据美国疾病控制与预防中心的观点，孤独症的总体发病率为1/88。这项研究纳入了55名年龄在6-36个月的婴儿，他们中的33人各有一位罹患孤独症的哥哥或姐姐，另有22名婴儿没有该疾病家族史。
过多的脑脊液和脑容量的增大是通过对这些婴儿脑部生长和发育进行定期核磁共振成像（MRI）检测，以及通过经常性地对他们的认知、社交、沟通及运动能力发育进行评估而发现的。高风险及低风险婴儿均在6-9个月大的时候接受第一次MRI扫描，第二次发生在他们12-15个月大时，而第三次则在18-24个月大之间进行。这些MRI检查在婴儿自然睡着时进行，无需镇静和麻醉。
在婴儿6个月大时，研究人员开始对这些婴儿的发育进行密集的行为评估。他们的家长也被要求定期完成有关他们宝宝行为的调查问卷。这些测试一直进行到婴儿24个月至36个月大的时候，届时每个孩子都被评估是否罹患孤独症谱系障碍以及其它的发育延迟，或发育正常。
研究对象中，有10个孩子被诊断患有孤独症，24%的高风险婴儿及13.4%的低风险婴儿被判定为患有其它类型的发育迟缓，45.5%的高风险宝宝和86%的低风险宝宝发育正常。
6-9个月大时，那些日后罹患孤独症的孩子在脑部以上及周围“轴外”空间内的脑脊液水平有所升高，而该指标在年龄18个月至24个月大期间仍然有异常升高。该研究发现，在婴儿早期中的脑脊液越多，被确诊时的孤独症症状就越严重。
在12-15个月及18-24个月大时，潜在孤独症患儿的“轴外”脑脊液容量比发育正常的婴儿平均高出33%和22%；6-9个月大时，其轴外脑脊液容量比发育正常的婴儿多20%。
该研究首次从婴儿期开始追踪孤独症患儿的脑生长轨迹，并第一次将婴儿期过多的脑脊液与孤独症联系在一起；这项研究同时第一次提供了孤独症患儿在24个月大之前脑部增大的MRI证据：这些婴儿12个月大时的脑容量比发育正常的婴儿平均大7%。
过多的轴外脑脊液及增大的脑容量在孤独症行为学体征变得明显之前即可被检测到，但MIND研究所的研究部主任Amaral同时指出：“轴外脑脊液增加及脑尺寸的增大的原因目前还不清楚。”
早期诊断或可使那些哥哥姐姐曾被诊断患有孤独症的婴儿受益匪浅，但研究人员警告称，这一发现必须要得到重复验证后方能应用于ASD的早期诊断。MIND研究所目前正在与其它的研究所开展合作，以重复这些发现并评估这一生物标记对ASD诊断的预测价值。
Ozonoff称：“了解这一发现在健康儿童中出现的频度是至关重要的。就一种对预测自闭症转归有用的生物标记来说，我们希望确定它的假阳性水平在我们可以接受的范围以内。”
加州大学戴维斯分校的研究生Mark Shen是这项研究的主要作者,他指出：“如果这一轴外脑脊液升高的发现能在更大的样本中得到重复，且能与那些未罹患孤独症的婴儿做准确的区分，它将可能成为一种非创伤性的、可协助早期发现疾病并通过早期干预而最终改善长期转归的生物标记。”
“该研究首次报告了婴儿脑部异常与孤独症有关，且可以通过传统的结构性MRI检测到，”Amaral称，“这项研究提出了研发一种极早期检测孤独症谱系障碍方法的可能性。早期检测是至关重要的，因为早期干预可减轻孤独症相关认知与行为损害，并可能为这些孩子带来更为积极的长期预后。”（生物谷Bioon.com）
生物谷推荐英文摘要：
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.
