Lei Du, Li Wenbin, Tallman Maxwell J, Patino L Rodrigo, McNamara Robert K, Strawn Jeffrey R, Klein Christina C, Nery Fabiano G, Fleck David E, Qin Kun, Ai Yuan, Yang Jing, Zhang Wenjing, Lui Su, Gong Qiyong, Adler Caleb M, Sweeney John A, DelBello Melissa P
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Huaxi MR Research Center (HMRRC), Department of Radiology, The Center for Medical Imaging, West China Hospital of Sichuan University, Chengdu, P. R. China.
Neuropsychopharmacology. 2021 Jun;46(7):1315-1323. doi: 10.1038/s41386-021-00989-5. Epub 2021 Mar 22.
The goals of the current study were to determine whether topological organization of brain structural networks is altered in youth with bipolar disorder, whether such alterations predict treatment outcomes, and whether they are normalized by treatment. Youth with bipolar disorder were randomized to double-blind treatment with quetiapine or lithium and assessed weekly. High-resolution MRI images were collected from children and adolescents with bipolar disorder who were experiencing a mixed or manic episode (n = 100) and healthy youth (n = 63). Brain networks were constructed based on the similarity of morphological features across regions and analyzed using graph theory approaches. We tested for pretreatment anatomical differences between bipolar and healthy youth and for changes in neuroanatomic network metrics following treatment in the youth with bipolar disorder. Youth with bipolar disorder showed significantly increased clustering coefficient (C) (p = 0.009) and characteristic path length (L) (p = 0.04) at baseline, and altered nodal centralities in insula, inferior frontal gyrus, and supplementary motor area. C, L, and nodal centrality of the insula exhibited normalization in patients following treatment. Changes in these neuroanatomic parameters were correlated with improvement in manic symptoms but did not differ between the two drug therapies. Baseline structural network matrices significantly differentiated medication responders and non-responders with 80% accuracy. These findings demonstrate that both global and nodal structural network features are altered in early course bipolar disorder, and that pretreatment alterations in neuroanatomic features predicted treatment outcome and were reduced by treatment. Similar connectome normalization with lithium and quetiapine suggests that the connectome changes are a downstream effect of both therapies that is related to their clinical efficacy.
本研究的目的是确定双相情感障碍青年的脑结构网络拓扑组织是否发生改变，这种改变是否能预测治疗结果，以及它们是否能通过治疗恢复正常。双相情感障碍青年被随机分配接受喹硫平或锂盐的双盲治疗，并每周进行评估。从患有混合或躁狂发作的双相情感障碍儿童和青少年（n = 100）以及健康青年（n = 63）中收集高分辨率MRI图像。基于各区域形态特征的相似性构建脑网络，并使用图论方法进行分析。我们测试了双相情感障碍青年与健康青年治疗前的解剖学差异，以及双相情感障碍青年治疗后神经解剖网络指标的变化。双相情感障碍青年在基线时聚类系数（C）（p = 0.009）和特征路径长度（L）（p = 0.04）显著增加，岛叶、额下回和辅助运动区的节点中心性发生改变。治疗后患者岛叶的C、L和节点中心性恢复正常。这些神经解剖学参数的变化与躁狂症状的改善相关，但两种药物治疗之间没有差异。基线结构网络矩阵以80%的准确率显著区分了药物反应者和无反应者。这些发现表明，在双相情感障碍病程早期，整体和节点结构网络特征均发生改变，神经解剖学特征的治疗前改变可预测治疗结果，且治疗后有所减轻。锂盐和喹硫平类似的连接组正常化表明，连接组变化是两种疗法的下游效应，与它们的临床疗效相关。
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