Background

Cerebral overgrowth is frequently reported in children but not in adults with autism spectrum disorder (ASD). This suggests that early cerebral overgrowth is followed by normalization of cerebral volumes. However, this notion is predicated on cross-sectional research that is vulnerable to sampling bias. For example, autistic individuals with disproportionate megalencephaly, a subgroup with higher rates of intellectual disability and larger cerebral volumes, may be underrepresented in studies of adolescents and adults. Furthermore, extant studies have cohorts that are predominately male, thus limiting knowledge of cerebral growth in females with ASD.

Methods

Growth of total cerebral volume, gray matter (GM) volume, and white matter volume as well as proportion of GM to total cerebral volume were examined in a longitudinal sample comprising 273 boys (199 with ASD) scanned at up to four time points (mean ages = 38, 50, 64, and 137 months, respectively) and 156 girls (95 with ASD) scanned at up to three time points (mean ages = 39, 53, and 65 months, respectively) using mixed-effects modeling.

Results

In boys with ASD, cerebral overgrowth in the ASD with disproportionate megalencephaly subgroup was predominately driven by increases in GM and persisted throughout childhood without evidence of volumetric regression or normalization. In girls with ASD, cerebral volumes were similar to those in typically developing girls, but growth trajectories of GM and white matter were slower throughout early childhood. The proportion of GM to total cerebral volume declined with age at a slower rate in autistic boys and girls relative to typically developing control subjects.

Conclusions

Longitudinal evidence does not support the notion that early brain overgrowth is followed by volumetric regression, at least from early to late childhood.

中文翻译：

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自闭症谱系障碍男孩和女孩儿童期大脑发育的纵向评估

背景

自闭症谱系障碍 (ASD) 的儿童经常报告大脑过度生长，但成人则没有。这表明早期脑过度生长之后是脑容量的正常化。然而，这一概念是基于容易受到抽样偏差影响的横断面研究。例如，患有不成比例的巨脑畸形的自闭症患者（智力残疾率较高且脑容量较大的亚组）在青少年和成人研究中的代表性可能不足。此外，现有研究的队列主要是男性，因此限制了对患有 ASD 的女性大脑发育的了解。

方法

在包括 273 名男孩（199 名患有 ASD）的纵向样本中，在最多四个时间点（平均年龄分别为 38、50、64 和 137 个月）和 156 名女孩（95 名患有 ASD）使用混合效应模型在最多三个时间点（平均年龄分别为 39、53 和 65 个月）进行扫描。

结果

在患有 ASD 的男孩中，具有不成比例的巨脑畸形亚组的 ASD 中的脑过度生长主要是由 GM 的增加驱动的，并且在整个童年时期都持续存在，没有体积回归或正常化的证据。在患有 ASD 的女孩中，脑容量与正常发育的女孩相似，但在整个儿童早期，GM 和白质的生长轨迹较慢。相对于正常发育的对照受试者，自闭症男孩和女孩的 GM 占大脑总体积的比例随着年龄的增长而下降，速度较慢。

结论

纵向证据不支持早期大脑过度生长之后体积退化的观点，至少从儿童早期到晚期。