Randomization and resilience of brain functional networks as systems-level endophenotypes of schizophrenia
Randomization and resilience of brain functional networks as systems-level endophenotypes of schizophrenia
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DOI：
10.1073/pnas.1502052112
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发表时间：
2015-07-21
影响因子：
11.1
通讯作者：
Bullmore, Edward T.
中科院分区：
文献类型：
--
作者：
Lo, Chun-Yi Zac;Su, Tsung-Wei;Bullmore, Edward T.
精神分裂症越来越多地被认为是一种大脑网络组织紊乱或连接障碍综合征。精神分裂症的功能磁共振成像（fMRI）网络具有异常随机拓扑结构的特点。我们检验了网络随机化是精神分裂症内在表型的假设，因此在患者的非精神病亲属中也很明显。研究对象包括25名精神分裂症患者、25名患者一级亲属和29名健康志愿者。图被用来模拟功能连接区域节点之间的一组边缘。我们估计了每个功能网络的拓扑效率、聚类、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显著的随机化的全球网络指标（减少集群，更高的效率），在度分布的转变，以更均匀的形式（更少的枢纽），在距离分布的转变（成比例的更长距离的边缘），并更大的弹性有针对性的攻击网络枢纽。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，但它们通常比患者的网络拓扑不那么异常，并且没有异常的连接距离。我们的结论是，精神分裂症与功能网络随机化的可复制和收敛证据相关，并且在非精神病亲属中也明显存在类似的拓扑特征，这表明这是系统水平的内表型或家族风险的标志物。我们推测，大脑网络的更大弹性可能会赋予非精神病亲属一些健身优势，这可以解释这种内在表型在人群中的持续存在。
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.