Dinstein Ilan, Haar Shlomi, Atsmon Shir, Schtaerman Hen
Psychology Department, Ben Gurion University, Beer Sheva, 84105 Israel.
Cognitive and Brain Sciences Department, Ben Gurion University, Beer Sheva, 84105 Israel.
Mol Autism. 2017 Mar 23;8:15. doi: 10.1186/s13229-017-0129-9. eCollection 2017.
Large controversy exists regarding the potential existence and clinical significance of larger brain volumes in toddlers who later develop autism. Assessing this relationship is important for determining the clinical utility of early head circumference (HC) measures and for assessing the validity of the early overgrowth hypothesis of autism, which suggests that early accelerated brain development may be a hallmark of the disorder.
We performed a retrospective comparison of HC, height, and weight measurements between 66 toddlers who were later diagnosed with autism and 66 matched controls. These toddlers represent an unbiased regional sample from a single health service provider in the southern district of Israel. On average, participating toddlers had >8 measurements between birth and the age of two, which enabled us to characterize individual HC, height, and weight development with high precision and fit a negative exponential growth model to the data of each toddler with exceptional accuracy.
The analyses revealed that HC sizes and growth rates were not significantly larger in toddlers with autism even when stratifying the autism group based on verbal capabilities at the time of diagnosis. In addition, there were no significant correlations between ADOS scores at the time of diagnosis and HC at any time-point during the first 2 years of life.
These negative results add to accumulating evidence, which suggest that brain volume is not necessarily larger in toddlers who develop autism. We believe that conflicting results reported in other studies are due to small sample sizes, use of misleading population norms, changes in the clinical definition of autism over time, and/or inclusion of individuals with syndromic autism. While abnormally large brains may be evident in some individuals with autism and more clearly visible in MRI scans, converging evidence from this and other studies suggests that enlarged HC is not a common etiology of the entire autism population. Early HC measures, therefore, offer very limited clinical utility for assessment of autism risk in the general population.
对于后来发展为自闭症的幼儿大脑体积是否更大及其临床意义,存在很大争议。评估这种关系对于确定早期头围(HC)测量的临床效用以及评估自闭症早期过度生长假说的有效性很重要,该假说表明早期大脑加速发育可能是该疾病的一个标志。
我们对66名后来被诊断为自闭症的幼儿和66名匹配的对照组幼儿的头围、身高和体重测量值进行了回顾性比较。这些幼儿代表了以色列南部地区一家单一医疗服务提供者的无偏区域样本。平均而言,参与研究的幼儿在出生至两岁之间有超过8次测量,这使我们能够高精度地描述个体的头围、身高和体重发育情况,并以极高的准确性将负指数生长模型拟合到每个幼儿的数据中。
分析显示,即使根据诊断时的语言能力对自闭症组进行分层,自闭症幼儿的头围大小和生长速度也没有显著更大。此外,诊断时的ADOS分数与生命最初2年中任何时间点的头围之间均无显著相关性。
这些阴性结果进一步证明了越来越多的证据表明,患自闭症的幼儿大脑体积不一定更大。我们认为,其他研究报告的相互矛盾的结果是由于样本量小、使用误导性的人群标准、自闭症临床定义随时间的变化和/或纳入了患有综合征性自闭症的个体。虽然在一些自闭症个体中可能明显存在大脑异常增大,在MRI扫描中更清晰可见,但来自本研究和其他研究的一致证据表明,头围增大不是整个自闭症人群的常见病因。因此,早期头围测量在评估一般人群自闭症风险方面的临床效用非常有限。