Schizophrenia is a highly heritable disorder characterized by increased cortical thinning throughout the life span. Studies have reported a shared genetic basis between schizophrenia and cortical thickness. However, no genes whose expression is related to abnormal cortical thinning in schizophrenia have been identified. We conducted linear mixed models to estimate the rates of accelerated cortical thinning across 68 regions from the Desikan-Killiany atlas in individuals with schizophrenia compared with healthy control participants from a large longitudinal sample ( = 169 and = 298, ages 16–70 years). We studied the correlation between gene expression data from the Allen Human Brain Atlas and accelerated thinning estimates across cortical regions. Finally, we explored the functional and genetic underpinnings of the genes that contribute most to accelerated thinning. We found a global pattern of accelerated cortical thinning in individuals with schizophrenia compared with healthy control participants. Genes underexpressed in cortical regions that exhibit this accelerated thinning were downregulated in several psychiatric disorders and were enriched for both common and rare disrupting variation for schizophrenia and neurodevelopmental disorders. In contrast, none of these enrichments were observed for baseline cross-sectional cortical thickness differences. Our findings suggest that accelerated cortical thinning, rather than cortical thickness alone, serves as an informative phenotype for neurodevelopmental disruptions in schizophrenia. We highlight the genetic and transcriptomic correlates of this accelerated cortical thinning, emphasizing the need for future longitudinal studies to elucidate the role of genetic variation and the temporal-spatial dynamics of gene expression in brain development and aging in schizophrenia.

中文翻译：

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精神分裂症的皮质加速变薄与精神分裂症和神经发育障碍的罕见和常见诱发变异有关

精神分裂症是一种高度遗传性疾病，其特征是整个生命周期中皮质变薄程度增加。研究报告了精神分裂症和皮质厚度之间存在共同的遗传基础。然而，尚未发现其表达与精神分裂症皮质异常变薄相关的基因。我们采用线性混合模型来估计 Desikan-Killiany 图谱中 68 个区域的精神分裂症患者与来自大型纵向样本（= 169 和 = 298，年龄 16-70 岁）的健康对照参与者相比的皮质加速变薄率。我们研究了艾伦人脑图谱的基因表达数据与皮质区域加速稀疏估计之间的相关性。最后，我们探索了对加速稀疏贡献最大的基因的功能和遗传基础。我们发现，与健康对照参与者相比，精神分裂症患者的皮质加速变薄的全球模式。表现出这种加速变薄的皮质区域表达不足的基因在几种精神疾病中下调，并且在精神分裂症和神经发育障碍中常见和罕见的破坏性变异丰富。相反，没有观察到基线横截面皮质厚度差异的这些富集。我们的研究结果表明，皮质加速变薄，而不仅仅是皮质厚度，可以作为精神分裂症神经发育障碍的信息表型。我们强调了这种加速皮质变薄的遗传和转录组相关性，强调未来需要进行纵向研究来阐明遗传变异的作用以及基因表达的时空动态在精神分裂症大脑发育和衰老中的作用。