Cortical profiles of numerous psychiatric disorders and normal development share a common pattern
Cortical profiles of numerous psychiatric disorders and normal development share a common pattern
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DOI：
10.1038/s41380-022-01855-6
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发表时间：
2022-11-15
影响因子：
11
通讯作者：
Garavan, Hugh
中科院分区：
文献类型：
--
作者：
Cao, Zhipeng;Cupertino, Renata B.;Garavan, Hugh
发育和精神病理学之间的关联的神经生物学基础仍然知之甚少。在这里，我们确定了一个共同的空间模式的皮质厚度（CT）的规范发展和几个精神和神经系统疾病。将主成分分析（PCA）应用于Desikan-Killiany图谱中68个区域的CT，这些区域来自三个大规模数据集，共包括41，075名神经典型参与者。PCA产生了一个空间上广泛的第一主成分（PC 1），是跨数据集的重现。然后，将来自健康成年参与者的PC 1与与精神和神经障碍相关的CT差异模式进行比较，所述CT差异模式包括来自七个ENIGMA疾病相关工作组的总共14，886例病例和20，962例对照，正常成熟和衰老包括来自ABCD研究（R）和IMAGEN发育研究的总共17，697次扫描，以及17，来自ENIGMA寿命工作组的075名参与者，以及来自艾伦人脑图谱的基因表达图谱。结果显示，大量的空间之间的对应关系PC 1和广泛的低CT观察到许多精神疾病。此外，PC 1模式也与规范性成熟和老化的空间格局。转录分析确定了一组基因，包括KCNA 2，KCNS 1和KCNS 2的表达模式密切相关的PC 1的空间模式。基因类别富集分析表明，PC 1的转录相关性被富集到多个基因本体论类别，并且在儿童晚期开始特别过度表达，与青春期前到青春期过渡期间显著的皮质成熟和精神病理学的出现相一致。总的来说，本研究报告了一个可重复的潜在模式的CT，捕捉区域间配置文件的皮质变化，在规范的大脑成熟和频谱的精神疾病。PC 1相关基因表达的青春期时间暗示了在青春期出现的精神疾病的发病机制中的神经发育中断。
The neurobiological bases of the association between development and psychopathology remain poorly understood. Here, we identify a shared spatial pattern of cortical thickness (CT) in normative development and several psychiatric and neurological disorders. Principal component analysis (PCA) was applied to CT of 68 regions in the Desikan-Killiany atlas derived from three large-scale datasets comprising a total of 41,075 neurotypical participants. PCA produced a spatially broad first principal component (PC1) that was reproducible across datasets. Then PC1 derived from healthy adult participants was compared to the pattern of CT differences associated with psychiatric and neurological disorders comprising a total of 14,886 cases and 20,962 controls from seven ENIGMA disease-related working groups, normative maturation and aging comprising a total of 17,697 scans from the ABCD Study (R) and the IMAGEN developmental study, and 17,075 participants from the ENIGMA Lifespan working group, as well as gene expression maps from the Allen Human Brain Atlas. Results revealed substantial spatial correspondences between PC1 and widespread lower CT observed in numerous psychiatric disorders. Moreover, the PC1 pattern was also correlated with the spatial pattern of normative maturation and aging. The transcriptional analysis identified a set of genes including KCNA2, KCNS1 and KCNS2 with expression patterns closely related to the spatial pattern of PC1. The gene category enrichment analysis indicated that the transcriptional correlations of PC1 were enriched to multiple gene ontology categories and were specifically over-represented starting at late childhood, coinciding with the onset of significant cortical maturation and emergence of psychopathology during the prepubertal-to-pubertal transition. Collectively, the present study reports a reproducible latent pattern of CT that captures interregional profiles of cortical changes in both normative brain maturation and a spectrum of psychiatric disorders. The pubertal timing of the expression of PC1-related genes implicates disrupted neurodevelopment in the pathogenesis of the spectrum of psychiatric diseases emerging during adolescence.