Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study.
Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study.
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连接体结构塑造了精神分裂症的大规模皮质改变：一项全球 ENIGMA 研究。
DOI：
10.1038/s41380-024-02442-7
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发表时间：
2024
影响因子：
11
通讯作者：
Tooney,Pau
中科院分区：
文献类型：
--
作者：
Georgiadis,Foivos;Larivière,Sara;Glahn,David;Hong,LElliot;Kochunov,Peter;Mowry,Bryan;Loughland,Carmel;Pantelis,Christos;Henskens,FransA;Green,MelissaJ;Cairns,MurrayJ;Michie,PatriciaT;Rasser,PaulE;Catts,Stanley;Tooney,Pau
精神分裂症是一种典型的网络障碍，具有广泛的脑形态改变，但目前尚不清楚这些分布的改变是否有力地反映了潜在的网络布局。我们测试了精神分裂症患者的大规模结构改变是否与规范的结构和功能连接体结构有关，并系统地评估了这些网络级改变的稳健性和普适性。利用来自26个谜点的2,439名成人精神分裂症患者和2,867名健康对照的解剖磁共振扫描和来自人类连接组计划(n= 207)的标准数据，我们对照两个网络易感性模型评估了精神分裂症的结构变化：(I)中心脆弱性，它检查区域网络中心性和疾病相关变化幅度之间的关联；(Ii)震中映射，它确定其典型连接轮廓最接近与疾病相关的形态变化的区域。为了评估概括性和特异性，我们将地点、疾病阶段和个人临床因素的影响联系起来，并比较了精神分裂症和情感障碍的网络联系。我们的发现表明，与精神分裂症相关的皮质变薄在空间上与功能和结构枢纽有关，这表明高度相互关联的区域更容易受到形态变化的影响。主要是颞叶、边缘和额叶区域作为震中出现，连接特征与精神分裂症的变化模式有关。在不同地点、疾病阶段和与个别症状相关的发现中，研究结果是可靠的。此外，跨诊断比较显示，在精神分裂症和双相情感障碍中，震中中心重叠，但不是严重的抑郁障碍，这表明精神分裂症-双相情感障碍的病理生理连续性。总而言之，精神分裂症病程中的皮质改变强烈地遵循大脑网络结构，强调群体和个体水平上明显的中枢易感性和临时额叶震中。不同疾病阶段震中的细微变化表明了相互作用的病理过程，而与患者特定症状的关联支持了精神分裂症中心脆弱性和震中的额外个体间变异性。我们的工作概述了更好地理解精神分裂症的宏观结构变化和个体间变异性的潜在途径。
Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n= 207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenia’s alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work outlines potential pathways to better understand macroscale structural alterations, and inter- individual variability in schizophrenia.