Objective:

Previous research has demonstrated that the amygdala is enlarged in children with autism spectrum disorder (ASD). However, the precise onset of this enlargement during infancy, how it relates to later diagnostic behaviors, whether the timing of enlargement in infancy is specific to the amygdala, and whether it is specific to ASD (or present in other neurodevelopmental disorders, such as fragile X syndrome) are all unknown.

Methods:

Longitudinal MRIs were acquired at 6–24 months of age in 29 infants with fragile X syndrome, 58 infants at high likelihood for ASD who were later diagnosed with ASD, 212 high-likelihood infants not diagnosed with ASD, and 109 control infants (1,099 total scans).

Results:

Infants who developed ASD had typically sized amygdala volumes at 6 months, but exhibited significantly faster amygdala growth between 6 and 24 months, such that by 12 months the ASD group had significantly larger amygdala volume (Cohen’s d=0.56) compared with all other groups. Amygdala growth rate between 6 and 12 months was significantly associated with greater social deficits at 24 months when the infants were diagnosed with ASD. Infants with fragile X syndrome had a persistent and significantly enlarged caudate volume at all ages between 6 and 24 months (d=2.12), compared with all other groups, which was significantly associated with greater repetitive behaviors.

Conclusions:

This is the first MRI study comparing fragile X syndrome and ASD in infancy, demonstrating strikingly different patterns of brain and behavior development. Fragile X syndrome–related changes were present from 6 months of age, whereas ASD-related changes unfolded over the first 2 years of life, starting with no detectable group differences at 6 months. Increased amygdala growth rate between 6 and 12 months occurs prior to social deficits and well before diagnosis. This gradual onset of brain and behavior changes in ASD, but not fragile X syndrome, suggests an age- and disorder-specific pattern of cascading brain changes preceding autism diagnosis.

中文翻译：

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自闭症和脆性 X 综合征的皮层下大脑发育：婴儿期动态、年龄和疾病特异性轨迹的证据

 客观的：

先前的研究表明，患有自闭症谱系障碍（ASD）的儿童的杏仁核会增大。然而，这种增大在婴儿期的确切开始时间、它与以后的诊断行为有何关系、婴儿期增大的时间是否特定于杏仁核，以及它是否特定于自闭症谱系障碍（或存在于其他神经发育障碍中，例如脆性发育障碍）。 X综合症）都是未知的。

 方法：

29 名患有脆性 X 综合征的婴儿、58 名极有可能患有 ASD 但后来被诊断为 ASD 的婴儿、212 名高可能性未诊断出患有 ASD 的婴儿和 109 名对照婴儿（总共 1,099 名）在 6-24 个月大时获得了纵向 MRI扫描）。

 结果：

患有自闭症谱系障碍的婴儿通常在 6 个月大时杏仁核体积就已增大，但在 6 至 24 个月期间杏仁核生长速度明显加快，因此到 12 个月时，与所有其他组相比，自闭症谱系障碍组的杏仁核体积明显更大（科恩 d=0.56）。当婴儿被诊断患有 ASD 时，6 至 12 个月期间杏仁核的生长速度与 24 个月时更大的社交缺陷显着相关。与所有其他组相比，患有脆性 X 综合征的婴儿在 6 至 24 个月之间的所有年龄段都有持续且显着增大的尾状核体积 (d=2.12)，这与更大的重复行为显着相关。

 结论：

这是第一项比较婴儿期脆性 X 综合征和自闭症谱系障碍 (ASD) 的 MRI 研究，展示了大脑和行为发育的显着不同模式。与脆性 X 综合征相关的变化从 6 个月大时开始出现，而与自闭症谱系障碍 (ASD) 相关的变化则在出生后的头 2 年中出现，从 6 个月大时开始没有可检测到的组间差异。 6 至 12 个月期间杏仁核生长速度加快发生在社交缺陷之前和诊断之前。自闭症谱系障碍（而非脆性 X 综合征）的大脑和行为变化是逐渐发生的，这表明自闭症诊断之前存在一种年龄和疾病特异性的级联大脑变化模式。