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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., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Functional disconnectivity during the resting state has been observed in subjects with major depressive disorder (MDD), and in subjects at high genetic risk for major depression during task performance. It is hypothesized that functional impairments in certain brain areas are present in patients with MDD and in their first-degree relatives. To test this hypothesis, an analysis of regional homogeneity (ReHo) of the whole brain was performed on 45 subjects. Compared with the control group, subjects with MDD and those at high risk for MDD exhibited significantly decreased ReHo in the right insula and in the left cerebellum. These abnormalities may play an important role in the pathophysiology of depression.