title: A combined study of GSK3β polymorphisms and brain network topological metrics in major depressive disorder.
abstract: 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.
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Zhifen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Computer Science and Technology, Taiyuan University of Technology, Taiyuan 030024, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Cao
authors.affiliation: College of Computer Science and Technology, Taiyuan University of Technology, Taiyuan 030024, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Radiology, Shanxi Provincial Hospital, Taiyuan 030012, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Aixia
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan 030001, PR China. Electronic address: krangzhang_sxmu@vip.163.com.
authors.forename: Kerang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D058068:Endophenotypes; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D005838:Genotype; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008032:Limbic System / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009778:Occipital Lobe / Q000473:pathology; D010296:Parietal Lobe / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D013702:Temporal Lobe / Q000473:pathology; D013788:Thalamus / Q000473:pathology
chemical_list: C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: Brain functional network; Glycogen synthase kinase-3β gene; Major depression; Neuroimaging endophenotype