In Pursuit of Neurophenotypes: The Consequences of Having Autism and a Big Brain
In Pursuit of Neurophenotypes: The Consequences of Having Autism and a Big Brain
复制标题
DOI：
10.1002/aur.1755
复制
发表时间：
2017-05-01
期刊：
影响因子：
4.7
通讯作者：
Nordahl, Christine Wu
中科院分区：
文献类型：
--
作者：
Amaral, David G.;Li, Deana;Nordahl, Christine Wu
一个共识已经出现，尽管共同的核心特征，自闭症谱系障碍（ASD）有多种病因和各种遗传和生物学特征。ASD可能存在亚型的事实使开发有效疗法的尝试变得复杂。加州大学戴维斯分校MIND研究所自闭症表型组项目是对自闭症儿童和年龄匹配的典型发育对照组的纵向，多学科分析;近400个家庭参与了这项研究。总体目标是收集足够的生物学，医学和行为数据，以定义有临床意义的ASD亚型。一个合理的假设是，自闭症的不同亚型将表现出不同的大脑组织或发育改变模式，即，不同的神经表型在这篇评论中，我们讨论了一种被定义为巨脑畸形的神经表型，或具有与身体大小不成比例的大脑大小。我们发现，15%的自闭症男孩表现出这种神经表型，尽管在女孩中远不常见。我们回顾行为和医学特征的大脑组的男孩与自闭症相比，那些典型的大小的大脑。虽然发育正常的个体的大脑大小与认知功能呈正相关，但患有自闭症和大脑较大的儿童残疾更严重，预后更差。这项研究表明，自闭症的表型分型，像基因分型一样，需要大量的受试者。此外，由于大脑和行为的关系可能出现在不同的时间在发展过程中，这项工作突出了纵向分析进行有意义的表型。(C)2017年国际自闭症研究学会，Wiley Periodicals，Inc。
A consensus has emerged that despite common core features, autism spectrum disorder (ASD) has multiple etiologies and various genetic and biological characteristics. The fact that there are likely to be subtypes of ASD has complicated attempts to develop effective therapies. The UC Davis MIND Institute Autism Phenome Project is a longitudinal, multidisciplinary analysis of children with autism and age-matched typically developing controls; nearly 400 families are participating in this study. The overarching goal is to gather sufficient biological, medical, and behavioral data to allow definition of clinically meaningful subtypes of ASD. One reasonable hypothesis is that different subtypes of autism will demonstrate different patterns of altered brain organization or development i.e., different neurophenotypes. In this Commentary, we discuss one neurophenotype that is defined by megalencephaly, or having brain size that is large and disproportionate to body size. We have found that 15% of the boys with autism demonstrate this neurophenotype, though it is far less common in girls. We review behavioral and medical characteristics of the large-brained group of boys with autism in comparison to those with typically sized brains. While brain size in typically developing individuals is positively correlated with cognitive function, the children with autism and larger brains have more severe disabilities and poorer prognosis. This research indicates that phenotyping in autism, like genotyping, requires a very substantial cohort of subjects. Moreover, since brain and behavior relationships may emerge at different times during development, this effort highlights the need for longitudinal analyses to carry out meaningful phenotyping. (C) 2017 International Society for Autism Research, Wiley Periodicals, Inc.