Neural substrates for late-life depression: A selective review of structural neuroimaging studies

Yong Ku Kim, Kyu Man Han

Research output: Contribution to journalReview articlepeer-review

35 Citations (Scopus)


Recent neuroimaging studies have characterized the pathophysiology of late-life depression (LLD) as a dysfunction of the brain networks involved in the regulation of emotion, motivational behavior, cognitive control, executive function, and self-referential thinking. In this article, we reviewed LLD-associated structural neuroimaging markers such as white matter hyperintensity (WMH), white matter integrity measured by diffusion tensor imaging, cortical and subcortical volumes, and cortical thickness, which may provide a structural basis for brain network dysfunction in LLD. LLD was associated with greater severity or volumes of deep, periventricular, or overall WMH and with decreased white matter integrity in the brain regions belonging to the fronto-striatal-limbic circuits and reduced white matter tract integrity which connects these circuits, such as the cingulum, corpus callosum, or uncinate fasciculus. Decreased volumes or cortical thickness in the prefrontal cortex, orbitofrontal cortex, anterior and posterior cingulate cortex, several temporal and parietal regions, hippocampus, amygdala, striatum, thalamus, and the insula were associated with LLD. These structural neuroimaging findings were also associated with cognitive dysfunction, which is a prominent clinical feature in LLD. Several structural neuroimaging markers including the WMH burden, white matter integrity, and cortical and subcortical volumes predicted antidepressant response in LLD. These structural neuroimaging findings support the hypothesis that disruption of the brain networks involved in emotion regulation and cognitive processing by impaired structural connectivity is strongly associated with the pathophysiology of LLD.

Original languageEnglish
Article number110010
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Publication statusPublished - 2021 Jan 10
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.


  • Antidepressant
  • Geriatric depression
  • Late-life depression
  • Magnetic resonance imaging
  • Structural neuroimaging
  • White matter hyperintensity

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry


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