Donovan Alex P A, Basson M Albert
Department of Craniofacial Development and Stem Cell Biology, and MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK.
J Anat. 2017 Jan;230(1):4-15. doi: 10.1111/joa.12542. Epub 2016 Sep 12.
Autism Spectrum Disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders that are diagnosed solely on the basis of behaviour. A large body of work has reported neuroanatomical differences between individuals with ASD and neurotypical controls. Despite the huge clinical and genetic heterogeneity that typifies autism, some of these anatomical features appear to be either present in most cases or so dramatically altered in some that their presence is now reasonably well replicated in a number of studies. One such finding is the tendency towards overgrowth of the frontal cortex during the early postnatal period. Although these reports have been focused primarily on the presumed pathological anatomy, they are providing us with important insights into normal brain anatomy and are stimulating new ideas and hypotheses about the normal trajectory of brain development and the function of specific anatomical brain structures. The use of model systems that include genetic model organisms such as the mouse and, more recently, human induced pluripotent stem cell-derived brain organoids to model normal and pathological human cortical development, is proving particularly informative. Here we review some of the neuroanatomical alterations reported in autism, with a particular focus on well-validated findings and recent advances in the field, and ask what these observations can tell us about normal and abnormal brain development.
自闭症谱系障碍(ASD)是一组异质性的神经发育障碍,仅根据行为进行诊断。大量研究报告了自闭症患者与神经典型对照组个体之间的神经解剖学差异。尽管自闭症具有巨大的临床和遗传异质性,但其中一些解剖学特征似乎在大多数病例中都存在,或者在某些病例中发生了显著改变,以至于现在在许多研究中都得到了相当好的重复验证。一个这样的发现是出生后早期额叶皮质有过度生长的趋势。尽管这些报告主要集中在推测的病理解剖学上,但它们为我们提供了关于正常脑解剖学的重要见解,并激发了关于脑发育正常轨迹和特定脑解剖结构功能的新想法和假设。使用包括小鼠等遗传模式生物以及最近的人类诱导多能干细胞衍生的脑类器官在内的模型系统来模拟正常和病理性人类皮质发育,已被证明特别有启发性。在这里,我们回顾自闭症中报告的一些神经解剖学改变,特别关注经过充分验证的发现和该领域的最新进展,并探讨这些观察结果能告诉我们关于正常和异常脑发育的哪些信息。