Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, PR China.
College of Computer Science and Technology, Taiyuan University of Technology, Taiyuan 030024, PR China.
Psychiatry Res. 2014 Sep 30;223(3):210-7. doi: 10.1016/j.pscychresns.2014.05.010. Epub 2014 Jun 2.
GSK3β genotypes may interact with major depressive disorder (MDD) and may have a role in determining regional gray matter volume differences from healthy comparison subjects. However, any associations of GSK3β genotypes with MDD related to abnormal functional brain activity have yet to be elucidated. In the present study, resting state functional brain networks were constructed by thresholding partial correlation matrices of 90 regions. Differences in the network features of GSK3β-rs6438552 genotypes were tested, and a 2×2 analysis of variance was performed to identify the main effects of genotypes, disease status, and their interactions in MDD. Compared with CC carriers, T+ carriers with MDD showed increased nodal centralities in many brain regions-mainly the limbic system, thalamus and parts of the parietal, temporal, occipital, and frontal regions. Decreased nodal centralities predominantly occurred in the sensorimotor area and parts of the frontal, occipital, and temporal lobes. Significant interactions between genotypes and disease status were found in the left thalamus, left superior occipital gyrus, and left inferior parietal lobe. Only altered nodal centrality in the left angular gyrus was negatively correlated with scores on the Hamilton Depression Rating Scale. Our results suggest the GSK3β genotypic effect of rs6438552 and its interaction with disease status may contribute to the altered topological organization of resting state functional brain networks in MDD patients.
GSK3β 基因型可能与重度抑郁症（MDD）相互作用，并可能在确定与健康对照受试者的区域灰质体积差异方面发挥作用。然而，GSK3β 基因型与与异常功能脑活动相关的 MDD 的任何关联尚未阐明。在本研究中，通过对 90 个区域的部分相关矩阵进行阈值处理构建了静息状态功能脑网络。测试了 GSK3β-rs6438552 基因型的网络特征差异，并进行了 2×2 方差分析，以确定基因型、疾病状态及其在 MDD 中的相互作用的主要影响。与 CC 携带者相比，患有 MDD 的 T+携带者在许多大脑区域的节点中心度增加-主要是边缘系统、丘脑和部分顶叶、颞叶、枕叶和额叶区域。节点中心度降低主要发生在感觉运动区和部分额叶、枕叶和颞叶。在左侧丘脑、左侧顶上回和左侧顶下小叶中发现了基因型和疾病状态之间的显著相互作用。只有左侧角回的节点中心度改变与汉密尔顿抑郁评定量表的评分呈负相关。我们的研究结果表明，rs6438552 的 GSK3β 基因型效应及其与疾病状态的相互作用可能导致 MDD 患者静息状态功能脑网络拓扑组织的改变。
