Cortical remodelling in childhood is associated with genes enriched for neurodevelopmental disorders

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 hierarchical, 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 the underlie cortical morphology as alterations in cortical thickness can act as a potential phenotypic marker of several common neurodevelopmental and psychiatric disorders. In this study, we combine MRI acquired from a typically-developing childhood population with 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 neurons, involved in synaptic remodeling, 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.

近年来，研究人员借助磁共振成像（Magnetic Resonance Imaging, MRI）衍生的指标，对儿童与青少年时期的皮层发育特征进行了系统刻画。皮层厚度的变化在生命的前二十年最为显著，且重现了皮层的层级化遗传组织模式，这凸显了基因表达在整个生命周期中对皮层结构差异的潜在早期影响。深入阐明皮层形态学背后的潜在神经生物学机制具有重要意义，因为皮层厚度的异常可作为多种常见神经发育障碍与精神疾病的潜在表型标志物。本研究将从典型发育儿童队列中获取的磁共振成像数据与基因表达数据库相结合，旨在验证如下假说：神经发育障碍共有的异常机制，由发育早期表达的基因所编码，且这些基因隶属于与儿童时期典型皮层重塑相关的基因集合。本研究发现，发育中皮层的变薄速率差异，与基因表达的空间分布梯度显著相关。在皮层加速变薄区域高表达的基因，主要在神经元中表达，参与突触重塑过程，并与常见的认知障碍及神经发育障碍密切相关。此外，本研究还鉴定出一类在产前阶段高表达的基因子集，它们同时与发育性皮层形态学特征及神经发育障碍存在关联。