title: Trait-Related Cortical-Subcortical Dissociation in Bipolar Disorder: Analysis of Network Degree Centrality.
abstract: BACKGROUND
  Bipolar disorder is a systemic brain disorder. Accumulated evidence suggested that cortical-subcortical imbalance could be a trait-related pathogenic factor of bipolar disorder. Degree centrality, a robust index of focal connectivity in which the number of direct connections from one node to all nodes is counted, has not previously been studied in bipolar disorder as a whole.
  
  
  METHODS
  Resting state functional magnetic resonance imaging was performed on 52 patients with DSM-IV bipolar I disorder and 70 healthy controls recruited between September 2009 and July 2014. Degree centrality was calculated within cerebral gray matter for each subject and compared between patients with bipolar disorder and healthy controls. Hub distributions of both groups were explored. Effects of medication exposure and mood state on degree centrality, as well as cortical-subcortical degree centrality correlations, were explored.
  
  
  RESULTS
  Compared to healthy controls, patients with bipolar disorder exhibited significant decrease in degree centrality in cortical regions, including the middle temporal pole, inferior temporal gyrus, and ventral prefrontal cortex, but showed significant increase in degree centrality mainly in subcortical regions, including caudate, thalamus, parahippocampal gyrus, hippocampi, anterior cingulate, insula, and amygdala, and a small portion of cortical regions, such as superior and middle frontal gyrus (P < .05, corrected). Spatial distributions of the 2 groups were very similar. No significant effects of medication exposure or mood state on degree centrality were found. Patients with bipolar disorder also showed significant decrease in cortical-subcortical degree centrality correlation (P = .003).
  
  
  CONCLUSIONS
  These findings further contribute to the mounting evidence of cortical-subcortical dissociation in bipolar disorder pathophysiology. In addition, this study supports the continued development and implementation of graph-based techniques to enhance our understanding of the underlying neural mechanisms in mental disorders such as bipolar disorder, which are increasingly viewed as systemic brain disorders rather than disorders arising from disruption within a single structure or a limited number of structures. Due to the heterogeneity of our sample, as well as the small sample size of each medication and mood state subgroups, further investigation is needed to support our findings.
authors.affiliation: Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Fay Y
authors.initials: FY
authors.lastname: Womer
authors.affiliation: Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Lingtao
authors.initials: L
authors.lastname: Kong
authors.affiliation: Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Gerontology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Yifang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Dahai
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Bai
authors.affiliation: Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Chang
authors.affiliation: Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Guoguang
authors.initials: G
authors.lastname: Fan
authors.affiliation: Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.affiliation: The First Affiliated Hospital of China Medical University, 155 Nanjing North St, Heping District, Shenyang, Liaoning, China. yanqingtang@163.com.|Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.|Department of Gerontology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Tang
authors.affiliation: The First Affiliated Hospital of China Medical University, 155 Nanjing North St, Heping District, Shenyang, Liaoning, China. fei.wang@mail.cmu.edu.cn.|Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.|Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects / Q000502:physiology; D001714:Bipolar Disorder / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D004292:Dominance, Cerebral / Q000502:physiology; D005260:Female; D066128:Gray Matter / Q000503:physiopathology; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology*; D011619:Psychotropic Drugs / Q000627:therapeutic use; D012016:Reference Values; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D011619:Psychotropic Drugs