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Evidence against the "normalization" prediction of the early brain overgrowth hypothesis of autism.

反对自闭症早期大脑过度生长假说 “正常化” 预测的证据。

  • 影响因子:5.99
  • DOI:10.1186/s13229-020-00353-2
  • 作者列表:"Yankowitz LD","Herrington JD","Yerys BE","Pereira JA","Pandey J","Schultz RT
  • 发表时间:2020-06-18
Abstract

BACKGROUND:The frequently cited Early Overgrowth Hypothesis of autism spectrum disorder (ASD) postulates that there is overgrowth of the brain in the first 2 years of life, which is followed by a period of arrested growth leading to normalized brain volume in late childhood and beyond. While there is consistent evidence for early brain overgrowth, there is mixed evidence for normalization of brain volume by middle childhood. The outcome of this debate is important to understanding the etiology and neurodevelopmental trajectories of ASD. METHODS:Brain volume was examined in two very large single-site samples of children, adolescents, and adults. The primary sample comprised 456 6-25-year-olds (ASD n = 240, typically developing controls (TDC) n = 216), including a large number of females (n = 102) and spanning a wide IQ range (47-158). The replication sample included 175 males. High-resolution T1-weighted anatomical MRI images were examined for group differences in total brain, cerebellar, ventricular, gray, and white matter volumes. RESULTS:The ASD group had significantly larger total brain, cerebellar, gray matter, white matter, and lateral ventricular volumes in both samples, indicating that brain volume remains enlarged through young adulthood, rather than normalizing. There were no significant age or sex interactions with diagnosis in these measures. However, a significant diagnosis-by-IQ interaction was detected in the larger sample, such that increased brain volume was related to higher IQ in the TDCs, but not in the ASD group. Regions-of-significance analysis indicated that total brain volume was larger in ASD than TDC for individuals with IQ less than 115, providing a potential explanation for prior inconsistent brain size results. No relationships were found between brain volume and measures of autism symptom severity within the ASD group. LIMITATIONS:Our cross-sectional sample may not reflect individual changes over time in brain volume and cannot quantify potential changes in volume prior to age 6. CONCLUSIONS:These findings challenge the "normalization" prediction of the brain overgrowth hypothesis by demonstrating that brain enlargement persists across childhood into early adulthood. The findings raise questions about the clinical implications of brain enlargement, since we find that it neither confers cognitive benefits nor predicts increased symptom severity in ASD.

摘要

背景: 经常被引用的自闭症谱系障碍 (ASD) 早期过度生长假说假设在生命的前 2 年存在大脑过度生长,随后是一段停滞的生长过程,导致童年晚期及以后的大脑体积正常化。虽然有一致的证据表明早期大脑过度生长,但到童年中期大脑体积正常化的证据是混杂的。这场辩论的结果对理解 ASD 的病因和神经发育轨迹很重要。 方法: 在两个非常大的儿童、青少年和成人单部位样本中检查脑体积。主要样本包括 456 名 6-25 岁的儿童 (ASD n = 240,通常为发展对照组 (TDC) n = 216),包括大量女性 (n = 102) 并跨越广泛的智商范围 (47-158)。复制样本包括 175 例男性。高分辨率 T1-weighted 解剖 MRI 图像检查全脑、小脑、脑室、灰质和白质体积的组间差异。 结果: ASD 组在两个样本中都有明显更大的总脑、小脑、灰质、白质和侧脑室容积,表明大脑容积在青年期仍然增大,而不是正常化。这些指标与诊断无明显的年龄或性别相互作用。然而,在较大样本中检测到显著的按 IQ 诊断相互作用,因此脑体积增加与 TDCs 中 IQ 较高有关,但在 ASD 组中无关。显著性区域分析表明,对于智商低于 115 的个体,ASD 的总脑体积大于 TDC,为先前不一致的脑大小结果提供了潜在的解释。在 ASD 组中未发现脑体积与自闭症症状严重程度之间的关系。 局限性: 我们的横断面样本可能不能反映大脑体积随时间的个体变化,也不能量化 6 岁前体积的潜在变化。 结论: 这些发现通过证明大脑扩大在整个儿童期持续到成年早期,挑战了大脑过度生长假说的 “正常化” 预测。这些发现提出了关于脑扩大的临床意义的问题,因为我们发现它既没有赋予认知益处,也没有预测 ASD 症状严重程度的增加。

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影响因子:5.83
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