OBJECTIVE Cortical thickness reductions in schizophrenia are irregularly distributed across multiple loci. The authors hypothesized that cortical connectivity networks would explain the distribution of cortical thickness reductions across the cortex, and, specifically, that cortico-cortical connectivity between loci with these reductions would be exceptionally strong and form an interconnected network. This hypothesis was tested in three cross-sectional schizophrenia cohorts: first-episode psychosis, chronic schizophrenia, and treatment-resistant schizophrenia. METHODS Structural brain images were acquired for 70 patients with first-episode psychosis, 153 patients with chronic schizophrenia, and 47 patients with treatment-resistant schizophrenia and in matching healthy control groups (N=57, N=168, and N=54, respectively). Cortical thickness was compared between the patient and respective control groups at 148 regions spanning the cortex. Structural connectivity strength between pairs of cortical regions was quantified with structural covariance analysis. Connectivity strength between regions with cortical thickness reductions was compared with connectivity strength between 5,000 sets of randomly chosen regions to establish whether regions with reductions were interconnected more strongly than would be expected by chance. RESULTS Significant (false discovery rate corrected) and widespread cortical thickness reductions were found in the chronic schizophrenia (79 regions) and treatment-resistant schizophrenia (106 regions) groups, with more circumscribed reductions in the first-episode psychosis group (34 regions). Cortical thickness reductions with the largest effect sizes were found in frontal, temporal, cingulate, and insular regions. In all cohorts, both the patient and healthy control groups showed significantly increased structural covariance between regions with cortical thickness reductions compared with randomly selected regions. CONCLUSIONS Brain network architecture can explain the irregular topographic distribution of cortical thickness reductions in schizophrenia. This finding, replicated in three distinct schizophrenia cohorts, suggests that the effect is robust and independent of illness stage.

中文翻译：

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精神分裂症中基于网络的皮质厚度减少的证据。

目的精神分裂症的皮质厚度减少在多个基因座上不规则地分布。作者假设皮质连通性网络可以解释皮质厚度减少在整个皮质的分布，特别是，随着这些减少的基因座之间的皮质皮质连通性会异常强壮，并形成一个互连的网络。在三个横断性精神分裂症队列中检验了该假设：首发性精神病，慢性精神分裂症和对治疗有抵抗力的精神分裂症。方法采集了70例首发性精神病患者，153例慢性精神分裂症患者和47例治疗难治性精神分裂症患者的结构脑图像，并匹配了健康对照组（分别为N = 57，N = 168和N = 54） ）。在横跨皮层的148个区域的患者和相应对照组之间比较了皮层厚度。皮质区域对之间的结构连接强度通过结构协方差分析进行定量。将皮层厚度减少的区域之间的连接强度与5,000套随机选择的区域之间的连接强度进行比较，以确定减少厚度的区域之间的连接是否比偶然预期的更牢固。结果在慢性精神分裂症（79个地区）和对治疗有抵抗力的精神分裂症（106个地区）组中，皮层厚度明显减少（广泛纠正），在首发精神病组（34个地区）中明显受到限制。在额叶，颞叶，扣带状和岛状区域发现皮层厚度减少，影响最大。与随机选择的区域相比，在所有队列中，患者和健康对照组均显示区域之间的结构协方差显着增加，且皮质厚度减少。结论脑网络结构可以解释精神分裂症的皮质厚度减少的不规则形貌分布。在三个不同的精神分裂症队列中重复的这一发现表明，这种作用是强有力的，并且与疾病阶段无关。与随机选择的区域相比，患者和健康对照组的皮层厚度减少区域之间的结构协方差均显着增加。结论脑网络结构可以解释精神分裂症的皮质厚度减少的不规则形貌分布。在三个不同的精神分裂症队列中重复的这一发现表明，这种作用是强有力的，并且与疾病阶段无关。与随机选择的区域相比，患者和健康对照组的皮层厚度减少区域之间的结构协方差均显着增加。结论脑网络结构可以解释精神分裂症的皮质厚度减少的不规则形貌分布。在三个不同的精神分裂症队列中重复的这一发现表明，这种作用是强有力的，并且与疾病阶段无关。