Anatomical integration and rich-club connectivity in euthymic bipolar disorder

S. O'Donoghue*, L. Kilmartin, D. O'Hora, L. Emsell, C. Langan, S. McInerney, N. J. Forde, A. Leemans, B. Jeurissen, G. J. Barker, P. McCarthy, D. M. Cannon, C. McDonald

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Although repeatedly associated with white matter microstructural alterations, bipolar disorder (BD) has been relatively unexplored using complex network analysis. This method combines structural and diffusion magnetic resonance imaging (MRI) to model the brain as a network and evaluate its topological properties. A group of highly interconnected high-density structures, termed the ‘rich-club’, represents an important network for integration of brain functioning. This study aimed to assess structural and rich-club connectivity properties in BD through graph theory analyses. Method: We obtained structural and diffusion MRI scans from 42 euthymic patients with BD type I and 43 age- and gender-matched healthy volunteers. Weighted fractional anisotropy connections mapped between cortical and subcortical structures defined the neuroanatomical networks. Next, we examined between-group differences in features of graph properties and sub-networks. Results: Patients exhibited significantly reduced clustering coefficient and global efficiency, compared with controls globally and regionally in frontal and occipital regions. Additionally, patients displayed weaker sub-network connectivity in distributed regions. Rich-club analysis revealed subtly reduced density in patients, which did not withstand multiple comparison correction. However, hub identification in most participants indicated differentially affected rich-club membership in the BD group, with two hubs absent when compared with controls, namely the superior frontal gyrus and thalamus. Conclusions: This graph theory analysis presents a thorough investigation of topological features of connectivity in euthymic BD. Abnormalities of global and local measures and network components provide further neuroanatomically specific evidence for distributed dysconnectivity as a trait feature of BD.

Original languageEnglish
Pages (from-to)1609-1623
Number of pages15
JournalPsychological Medicine
Issue number9
Publication statusPublished - Jul 2017


  • Bipolar disorder
  • diffusion tensor imaging
  • graph theory
  • magnetic resonance imaging
  • network analysis
  • Humans
  • Middle Aged
  • Magnetic Resonance Imaging/methods
  • Male
  • Bipolar Disorder/diagnostic imaging
  • Nerve Net/diagnostic imaging
  • Brain/diagnostic imaging
  • Adult
  • Female
  • Diffusion Magnetic Resonance Imaging/methods


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