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Altered voxel-wise gray matter structural brain networks in schizophrenia: Association with brain genetic expression pattern

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Abstract

Previous seed- and atlas-based structural covariance/connectivity analyses have demonstrated that patients with schizophrenia is accompanied by aberrant structural connection and abnormal topological organization. However, it remains unclear whether this disruption is present in unbiased whole-brain voxel-wise structural covariance networks (SCNs) and whether brain genetic expression variations are linked with network alterations. In this study, ninety-five patients with schizophrenia and 95 matched healthy controls were recruited and gray matter volumes were extracted from high-resolution structural magnetic resonance imaging scans. Whole-brain voxel-wise gray matter SCNs were constructed at the group level and were further analyzed by using graph theory method. Nonparametric permutation tests were employed for group comparisons. In addition, regression modes along with random effect analysis were utilized to explore the associations between structural network changes and gene expression from the Allen Human Brain Atlas. Compared with healthy controls, the patients with schizophrenia showed significantly increased structural covariance strength (SCS) in the right orbital part of superior frontal gyrus and bilateral middle frontal gyrus, while decreased SCS in the bilateral superior temporal gyrus and precuneus. The altered SCS showed reproducible correlations with the expression profiles of the gene classes involved in therapeutic targets and neurodevelopment. Overall, our findings not only demonstrate that the topological architecture of whole-brain voxel-wise SCNs is impaired in schizophrenia, but also provide evidence for the possible role of therapeutic targets and neurodevelopment-related genes in gray matter structural brain networks in schizophrenia.

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Funding

This study was funded by grants from the National Natural Science Foundation of China (81501451 to F.L.), the Natural Science Foundation of Tianjin (16JCYBJC24200 to J.L. and 17JCZDJC35700 to C.Z.), the Tianjin Health Bureau Foundation (2014KR02 to C.Z.), the Tianjin Health Key Program (13KG118 to J.L.), and the “New Century” Talent Training Project of Tianjin Medical University General Hospital (2017 to F.L.)

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Authors and Affiliations

  1. Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, 300052, China

    Feng Liu

  2. Laboratory of Psychiatric Neuroimaging, Tianjin Mental Health Center, Tianjin Anding Hospital, Tianjin Medical University Mental Health Teaching Hospital, No. 13, Liulin Road, Hexi District, Tianjin City, 300222, China

    Hongjun Tian, Jie Li, Shen Li & Chuanjun Zhuo

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  1. Feng Liu
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  2. Hongjun Tian
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Correspondence to Chuanjun Zhuo.

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Fig. S1

Between-group comparisons of structural covariance strength (SCS) maps (left panel: mean SCS maps subtraction; right panel: raw p values obtained by permutation test) across a range of analytical approaches: (A) weighted network, correlation threshold = 0.2, voxel size = 3 × 3 × 3 mm3; (B) binarized network, correlation threshold = 0.2, voxel size = 3 × 3 × 3 mm3; (C) weighted network, correlation threshold = 0.2, voxel size = 1.5 × 1.5 × 1.5 mm3; (D) weighted network, correlation threshold = 0.1, voxel size = 3 × 3 × 3 mm3; (E) weighted network, correlation threshold = 0.3, voxel size = 3 × 3 × 3 mm3. The SCS maps were visualized with the BrainNet Viewer (Xia et al. 2013). Abbreviation: SCH, schizophrenia; HC, healthy controls; mSCS, mean structural covariance strength; L, left; R, right. (GIF 260 kb)

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Liu, F., Tian, H., Li, J. et al. Altered voxel-wise gray matter structural brain networks in schizophrenia: Association with brain genetic expression pattern. Brain Imaging and Behavior 13, 493–502 (2019). https://doi.org/10.1007/s11682-018-9880-6

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