Abnormal structural networks characterize major depressive disorder: a connectome analysis

Biol Psychiatry. 2014 Oct 1;76(7):567-74. doi: 10.1016/j.biopsych.2014.02.018. Epub 2014 Mar 6.


Background: Major depressive disorder (MDD) has been shown to be associated with a disrupted topological organization of functional brain networks. However, little is known regarding whether these changes have a structural basis. Diffusion tensor imaging (DTI) enables comprehensive whole-brain mapping of the white matter tracts that link regions distributed throughout the entire brain, the so-called human connectome.

Methods: We examined whole-brain structural networks in a cohort of 95 MDD outpatients and 102 matched control subjects. Structural networks were represented by an 84 × 84 connectivity matrix representing probabilistic white matter connections between 84 parcellated cortical and subcortical regions using DTI tractography. Network-based statistics were used to assess differences in the interregional connectivity matrix between the two groups, and graph theory was used to examine overall topological organization.

Results: Our network-based statistics analysis demonstrates lowered structural connectivity within two distinct brain networks that are present in depression: the first primarily involves the regions of the default mode network and the second comprises the frontal cortex, thalamus, and caudate regions that are central in emotional and cognitive processing. These two altered networks were observed in the context of an overall preservation of topology as reflected as no significant group differences for the graph-theory measures.

Conclusions: This is the first report to use DTI to show the structural connectomic alterations present in MDD. Our findings highlight that altered structural connectivity between nodes of the default mode network and the frontal-thalamo-caudate regions are core neurobiological features associated with MDD.

Trial registration: ClinicalTrials.gov NCT00693849.

Keywords: Biomarker; connectome; diffusion tensor imaging; graph theory; major depressive disorder; network based statistics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain / pathology*
  • Connectome*
  • Depressive Disorder, Major / pathology*
  • Diffusion Tensor Imaging
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Net / pathology*
  • Statistics as Topic
  • White Matter / pathology
  • Young Adult

Associated data

  • ClinicalTrials.gov/NCT00693849