Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).
Am J Psychiatry. 2022 Aug;179(8):562-572. doi: 10.1176/appi.ajp.21090896. Epub 2022 Mar 25.
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.
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).
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.
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.
先前的研究表明，在自闭症谱系障碍（ASD）儿童中，杏仁核增大。然而，这种增大的确切起始时间在婴儿期，它与后来的诊断行为有何关系，婴儿期的增大时间是否特定于杏仁核，以及它是否特定于 ASD（或存在于其他神经发育障碍中，如脆性 X 综合征），这些都是未知的。
在 29 名脆性 X 综合征婴儿、58 名后来被诊断为 ASD 的高可能性 ASD 婴儿、212 名未被诊断为 ASD 的高可能性婴儿和 109 名对照婴儿（共 1099 次扫描）中，在 6-24 个月时获取纵向 MRI。
患有 ASD 的婴儿在 6 个月时杏仁核体积正常，但在 6-24 个月之间杏仁核生长速度明显更快，因此到 12 个月时，ASD 组的杏仁核体积明显更大（Cohen's d=0.56），与所有其他组相比。当婴儿被诊断为 ASD 时，6-12 个月之间的杏仁核生长速度与 24 个月时更大的社交缺陷显著相关。在 6 至 24 个月期间，患有脆性 X 综合征的婴儿的尾状核体积持续且明显增大（d=2.12），与所有其他组相比，这与更严重的重复行为显著相关。
这是第一项比较婴儿期脆性 X 综合征和 ASD 的 MRI 研究，结果显示出截然不同的大脑和行为发育模式。脆性 X 综合征相关的变化从 6 个月时就已经存在，而 ASD 相关的变化在生命的前 2 年展开，在 6 个月时没有发现可检测到的组间差异。6 至 12 个月之间杏仁核生长速度的增加发生在社交缺陷之前，并且远在诊断之前。ASD 中大脑和行为变化的这种逐渐发生，但脆性 X 综合征没有，这表明在自闭症诊断之前存在年龄和疾病特异性的级联大脑变化模式。
