Shifting priorities: highly conserved behavioral and brain network adaptations to chronic stress across species.


Journal Article

Parallel clinical and preclinical research have begun to illuminate the biological basis of stress-related disorders, including major depression, but translational bridges informing discrete mechanistic targets for intervention are missing. To address this critical need, we used structural MRI in a mouse model and in a large human sample to examine stress effects on brain structure that may be conserved across species. Specifically, we focused on a previously unexplored approach, whole-brain structural covariance, as it reflects synchronized changes in neuroanatomy, potentially due to mutual trophic influences or shared plasticity across regions. Using the unpredictable chronic mild stress (UCMS) paradigm in mouse we first demonstrate that UCMS-induced elevated behavioral emotionality correlates with increased size of the amygdala and other corticolimbic regions. We further identify focal increases in the amygdala's 'hubness' (degree and strength) set against the background of a global stress-related loss of network clustering and modularity. These macroscopic changes are supported on the molecular level by increased postsynaptic density-95 protein in the amygdala, consistent with stress-induced plastic changes and synaptic strengthening. Finally, we provide clinical evidence that strikingly similar structural network reorganization patterns exist in young adults reporting high childhood trauma and increased mood symptoms. Collectively, we provide initial translational evidence for a conserved stress-related increase in amygdala-centered structural synchrony, as measured by enhanced structural covariance, which is paralleled by a decrease in global structural synchrony. This putative trade-off reflected in increased amygdala-centered plastic changes at the expense of global structural dedifferentiation may represent a mechanistic pathway for depression and related psychopathology.

Full Text

Duke Authors

Cited Authors

  • Nikolova, YS; Misquitta, KA; Rocco, BR; Prevot, TD; Knodt, AR; Ellegood, J; Voineskos, AN; Lerch, JP; Hariri, AR; Sibille, E; Banasr, M

Published Date

  • January 22, 2018

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • 26 -

PubMed ID

  • 29353879

Pubmed Central ID

  • 29353879

Electronic International Standard Serial Number (EISSN)

  • 2158-3188

International Standard Serial Number (ISSN)

  • 2158-3188

Digital Object Identifier (DOI)

  • 10.1038/s41398-017-0083-5


  • eng