Cortical and subcortical brain morphometry differences between patients with autism spectrum disorders (ASD) and healthy individuals across the lifespan: results from the ENIGMA-ASD working group-猫眼课题宝

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2017

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D. Rooij;E. Anagnostou;C. Arango;G. Auzias;M. Behrmann;Sara;Calderoni;E. Daly;C. Deruelle;Adriana Dimartino;I. Dinstein;S. Durston;C. Ecker;D. Fair;Jennifer Fedor;J. Fitzgerald;C. Freitag;L. Gallagher;I. Gori;Shlomi Haar;Liesbeth Hoekstra;N. Jahanshad;María;Jalbrzikowski;J. Janssen;J. Lerch;B. Luna;J. McGrath;F. Muratori;C. Murphy;D. Murphy;K. O'Hearn;B. Oranje;M. Parellada;A. Retico;Pedro Rossa;K. Rubia;Devon A. Shook;Margot J. Taylor;M. Paul;Thompson;M. Tosetti;G. Wallace;Fengfeng Zhou;J. Buitelaar

目的：神经影像学研究显示，与对照组相比，患有自闭症谱系障碍（ASD）的儿童和成人的皮质和皮质下大脑区域存在结构差异。然而，研究结果并不一致，目前还不清楚这些差异是如何在整个生命周期中发展的。我们的目的是调查ASD参与者和对照组在整个生命周期中的脑形态测量学差异，来自ENIGMA-ASD工作组的大型全球样本。方法：样本包括来自49个参与地点的1571名ASD患者和1651名健康对照（年龄范围：2-64岁）。在各个研究中心使用基于经验证的自动分割软件的协调方案对MRI扫描进行预处理。大分析被用来测试病例对照差异皮质下体积，皮质厚度和表面积。使用分数多项式方法对寿命期间的脑形态测量学的发展进行建模。结果如下：病例对照大分析表明，ASD与苍白球、壳核、杏仁核和杏仁核的皮质下体积较小（效应量d=0.11至d=0.16），以及额叶皮质皮质厚度增加和颞叶皮质厚度减少（效应量d=0.20至d=-0.21）相关。年龄效应的分析表明，皮质厚度的发展在ASD中改变，最大的差异发生在青春期左右。在皮质下分区中未观察到年龄与ASD的相互作用。结论：ENIGMA-ASD工作组提供了迄今为止最大的ASD脑形态测量差异研究，使用了成熟且有效的公开分析管道。ASD受试者在纹状体、额叶皮质和颞叶皮质的认知和情感部分显示出形态学的改变。在不同的区域观察到复杂的发展轨迹，在青春期左右出现发展高峰。我们的研究结果表明，在整个生命周期中，ASD患者的纹状体、额叶和颞叶区域的异常发育存在相互作用。总之，这项研究显示了迄今为止最大样本中ASD皮质厚度和皮质下体积的异常发展，正如ENIGMA-ASD工作组所获得的那样。与对照组相比，ASD患者的壳核、杏仁核、杏仁核和苍白球体积较小，额叶皮质厚度增加，颞叶皮质厚度减少。我们的年龄分析表明，ASD的皮质下差异在整个生命周期内保持相对稳定，而ASD的皮质改变在儿童和青春期早期显示出高峰，并在成年期逐渐减少。未来的功能激活和静息状态连接研究将考虑这些成熟差异，并专注于揭示额叶，颞叶和皮质下改变之间的平衡如何影响ASD表型在整个生命周期中的表达。ASD患者的脑形态学发育在男性和女性之间没有差异。

Objective : Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorders (ASD), compared to controls. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. We aimed to investigate brain morphometry differences between participants with ASD and controls cross-sectionally across the lifespan, in a large worldwide sample from the ENIGMA-ASD Working Group. Methods : The sample comprised 1571 patients with ASD and 1651 healthy controls from 49 participating sites (age range: 2-64 years). MRI scans were preprocessed at individual sites with a harmonized protocol based on validated, automated segmentation software. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach. Results : The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala and nucleus accumbens (effect sizes d=0.11 to d=0.16), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes d=0.20 to d=-0.21). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age by ASD interactions were observed in the subcortical partitions. Conclusions : The ENIGMA-ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established and validated publicly available analysis pipeline. ASD subjects showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex and temporal cortex. Complex developmental trajectories were observed for the different regions, with a developmental peak around adolescence. Our findings suggest an interplay in the abnormal development of the striatal, frontal and temporal regions in ASD across the lifespan. conclude, this study showed the abnormal development of cortical thickness and subcortical volumes in ASD in the largest sample to date, as obtained by the ENIGMA-ASD working group. We observed smaller volumes of putamen, amygdala, nucleus accumbens and pallidum, increased frontal cortical thickness and decreased temporal cortical thickness in ASD compared to controls. Our age analyses, show that subcortical differences in ASD remain relatively stable over the lifespan, whilst cortical alterations in ASD show a peak in childhood and early adolescence, and taper off over adulthood. Future functional activation and resting-state connectivity studies will want to take into account these differences in maturation, and focus on unraveling how the balance between frontal, temporal and subcortical alterations influences the expression of the ASD phenotype across the lifespan. No differences in the development of brain morphometry was observed between males and females with ASD.

Cortical and subcortical brain morphometry differences between patients with autism spectrum disorders (ASD) and healthy individuals across the lifespan: results from the ENIGMA-ASD working group

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