Cortical remodelling in childhood is associated with genes enriched for neurodevelopmental disorders
Cortical remodelling in childhood is associated with genes enriched for neurodevelopmental disorders
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DOI：
10.1016/j.neuroimage.2020.116803
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发表时间：
2020-07-15
期刊：
影响因子：
5.7
通讯作者：
Seal, M. L.
中科院分区：
文献类型：
--
作者：
Ball, G.;Seidlitz, J.;Seal, M. L.
近年来，使用磁共振成像（MRI）衍生的指标来描述儿童和青少年时期的皮质发育。皮层厚度的变化在生命的前20年是最大的，概括了皮层的遗传组织，突出了基因表达对皮层结构差异的潜在早期影响。重要的是进一步了解这些变化背后可能的神经生物学机制，因为皮层厚度可能在几种常见的神经发育和精神疾病中发生改变。在这项研究中，我们将从大量典型发育的儿童群体（n = 768）获得的MRI与全面的人类基因表达数据库相结合，以验证神经发育障碍常见的破坏机制是由发育早期表达的基因编码的，并嵌套在与儿童时期典型皮质重塑相关的基因中。我们发现，发育中的皮层的不同变薄率与基因表达的空间变化梯度有关。在加速变薄区域高度表达的基因主要在皮质神经元中表达，参与突触重塑，并与常见的认知和神经发育障碍有关。此外，我们确定了在产前高度表达的基因亚群，这些基因亚群与发育性皮层形态和神经发育障碍共同相关。
Cortical development during childhood and adolescence has been characterised in recent years using metrics derived from Magnetic Resonance Imaging (MRI). Changes in cortical thickness are greatest in the first two decades of life and recapitulate the genetic organisation of the cortex, highlighting the potential early impact of gene expression on differences in cortical architecture over the lifespan. It is important to further our understanding of the possible neurobiological mechanisms that underlie these changes as cortical thickness may be altered in several common neurodevelopmental and psychiatric disorders.In this study, we combine MRI acquired from a large typically-developing childhood population (n = 768) with comprehensive human gene expression databases to test the hypothesis that disrupted mechanisms common to neurodevelopmental disorders are encoded by genes expressed early in development and nested within those associated with typical cortical remodelling in childhood.We find that differential rates of thinning across the developing cortex are associated with spatially-varying gradients of gene expression. Genes that are expressed highly in regions of accelerated thinning are expressed predominantly in cortical neurons, involved in synaptic remodelling, and associated with common cognitive and neurodevelopmental disorders. Further, we identify subsets of genes that are highly expressed in the prenatal period and jointly associated with both developmental cortical morphology and neurodevelopmental disorders.