Lo Chun-Yi Zac, Su Tsung-Wei, Huang Chu-Chung, Hung Chia-Chun, Chen Wei-Ling, Lan Tsuo-Hung, Lin Ching-Po, Bullmore Edward T
Institute of Neuroscience, National Yang-Ming University, Taipei 11221, Taiwan;
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 11221, Taiwan;
Proc Natl Acad Sci U S A. 2015 Jul 21;112(29):9123-8. doi: 10.1073/pnas.1502052112. Epub 2015 Jul 6.
Schizophrenia is increasingly conceived as a disorder of brain network organization or dysconnectivity syndrome. Functional MRI (fMRI) networks in schizophrenia have been characterized by abnormally random topology. We tested the hypothesis that network randomization is an endophenotype of schizophrenia and therefore evident also in nonpsychotic relatives of patients. Head movement-corrected, resting-state fMRI data were acquired from 25 patients with schizophrenia, 25 first-degree relatives of patients, and 29 healthy volunteers. Graphs were used to model functional connectivity as a set of edges between regional nodes. We estimated the topological efficiency, clustering, degree distribution, resilience, and connection distance (in millimeters) of each functional network. The schizophrenic group demonstrated significant randomization of global network metrics (reduced clustering, greater efficiency), a shift in the degree distribution to a more homogeneous form (fewer hubs), a shift in the distance distribution (proportionally more long-distance edges), and greater resilience to targeted attack on network hubs. The networks of the relatives also demonstrated abnormal randomization and resilience compared with healthy volunteers, but they were typically less topologically abnormal than the patients' networks and did not have abnormal connection distances. We conclude that schizophrenia is associated with replicable and convergent evidence for functional network randomization, and a similar topological profile was evident also in nonpsychotic relatives, suggesting that this is a systems-level endophenotype or marker of familial risk. We speculate that the greater resilience of brain networks may confer some fitness advantages on nonpsychotic relatives that could explain persistence of this endophenotype in the population.
精神分裂症越来越被认为是一种脑网络组织障碍或失连接综合征。精神分裂症患者的功能磁共振成像(fMRI)网络具有异常随机的拓扑结构。我们检验了这样一个假设,即网络随机化是精神分裂症的一种内表型,因此在患者的非精神病性亲属中也很明显。我们从25名精神分裂症患者、25名患者的一级亲属和29名健康志愿者身上获取了经头部运动校正的静息态fMRI数据。使用图来将功能连接建模为区域节点之间的一组边。我们估计了每个功能网络的拓扑效率、聚类系数、度分布、弹性和连接距离(以毫米为单位)。精神分裂症组表现出全局网络指标的显著随机化(聚类减少、效率提高),度分布向更均匀的形式转变(枢纽节点减少),距离分布转变(比例上更多的长距离边),以及对网络枢纽的靶向攻击具有更大的弹性。与健康志愿者相比,亲属的网络也表现出异常的随机化和弹性,但它们的拓扑异常通常比患者的网络要小,并且没有异常的连接距离。我们得出结论,精神分裂症与功能网络随机化的可重复和趋同证据相关,并且在非精神病性亲属中也明显存在类似的拓扑特征,这表明这是一种系统水平的内表型或家族风险标志物。我们推测,脑网络更大的弹性可能赋予非精神病性亲属一些适应性优势,这可以解释这种内表型在人群中的持续存在。