自闭症谱系障碍患者与健康个体在整个生命周期的大脑皮质和皮质下形态计量学差异：来自 ENIGMA ASD 工作组的结果。
Cortical and Subcortical Brain Morphometry Differences Between Patients With Autism Spectrum Disorder and Healthy Individuals Across the Lifespan: Results From the ENIGMA ASD Working Group.
机构信息
From the Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behavior, Donders Center for Cognitive Neuroimaging, Radboud University Medical Center, Nijmegen, the Netherlands; the Karakter Child and Adolescent Psychiatry University Center, Nijmegen; the Bloorview Research Institute, University of Toronto, Toronto; the Child and Adolescent Psychiatry Department, Gregorio Marañón General University Hospital, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid; Institut de Neurosciences de la Timone, Aix Marseille Université, CNRS, Marseille, France; the Department of Psychology, Carnegie Mellon University, Pittsburgh; the IRCCS Stella Maris Foundation, Pisa, Italy; the Department of Forensic and Neurodevelopmental Sciences and the Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology, and Neuroscience, King's College London; the Institute for Pediatric Neuroscience, Child Study Center, NYU Langone Health, New York; the Department of Psychology and Department of Brain and Cognitive Sciences, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer Sheva, Israel; Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, the Netherlands; the Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, University Hospital, Goethe University Frankfurt am Main, Frankfurt, Germany; the Department of Behavioral Neuroscience, Oregon Health and Science University, Portland; the Department of Psychiatry, University of Pittsburgh, Pittsburgh; the Department of Psychiatry, School of Medicine, and the Trinity College Institute of Neuroscience, Trinity College, Dublin; the National Institute for Nuclear Physics, Pisa Division, Pisa, Italy; the Mouse Imaging Centre and the Department of Diagnostic Imaging, Hospital for Sick Children, University of Toronto, Toronto; the Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; the Behavioural Genetics Clinic, Adult Autism Service, Behavioural and Developmental Psychiatry Clinical Academic Group, South London and Maudsley Foundation NHS Trust, London; the Laboratory of Neuroimaging, University of São Paulo Medical School, São Paulo, Brazil; the Imaging Genetics Center, Mark and Mary Stevens Institution for Neuroimaging and Informatics, University of Southern California, Marina del Rey; the Department of Speech, Language, and Hearing Sciences, George Washington University, Washington, D.C.; the College of Computer Science and Technology and the Key Laboratory of Symbolic Computation and Knowledge Engineering of the Ministry of Education, Jilin University, Changchun, Jilin, China.
出版信息
Am J Psychiatry. 2018 Apr 1;175(4):359-369. doi: 10.1176/appi.ajp.2017.17010100. Epub 2017 Nov 17.
OBJECTIVE
Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group.
METHOD
The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. 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 [Cohen's d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). 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, validated, publicly available analysis pipeline. ASD patients 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. These findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan.
目的
神经影像学研究表明，与健康受试者相比，自闭症谱系障碍（ASD）儿童和成人的皮质和皮质下脑区存在结构差异。然而，研究结果并不一致，目前尚不清楚这些差异在整个生命周期中是如何发展的。作者在来自增强神经影像学遗传学通过荟萃分析（ENIGMA）ASD 工作组的一个大型跨国样本中，对 ASD 患者和健康对照者进行了一生中的大脑形态差异的横断面研究。
方法
该样本包括来自 49 个参与地点的 1571 名 ASD 患者和 1651 名健康对照者（年龄范围为 2-64 岁）。MRI 扫描在各个地点根据基于验证的自动分割软件程序的标准化协议进行预处理。使用 mega 分析来测试亚皮质体积、皮质厚度和表面积的病例对照差异。使用分数多项式方法对大脑形态随时间的变化进行建模。
结果
病例对照 mega 分析表明，ASD 与苍白球、壳核、杏仁核和伏隔核的体积较小（效应大小[Cohen's d]，0.13 至-0.13），以及额叶皮质的皮质厚度增加和颞叶皮质的厚度减少（效应大小，-0.21 至 0.20）有关。年龄效应分析表明，ASD 患者的皮质厚度发育发生了改变，最大的差异发生在青春期前后。在亚皮质分区中没有观察到年龄与 ASD 的相互作用。
结论
ENIGMA ASD 工作组提供了迄今为止关于 ASD 大脑形态差异的最大研究，使用了一个成熟、经过验证、公开可用的分析管道。ASD 患者在纹状体的认知和情感部分、额叶和颞叶皮质表现出形态异常。观察到不同区域的复杂发育轨迹，在青春期前后达到发育高峰。这些发现表明，ASD 患者在整个生命周期中，纹状体、额叶和颞叶区域的异常发育存在相互作用。
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