White matter integrity and depressive symptoms in cerebral small vessel disease: The RUN DMC study

Ingeborg W.M. van Uden, Anil M. Tuladhar, Karlijn F. de Laat, Anouk G.W. van Norden, David G. Norris, Ewoud J. van Dijk, Indira Tendolkar, Frank-Erik de Leeuw*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

42 Citations (Scopus)
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Objective: Depressive symptoms are common in elderly with cerebral small vessel disease (SVD). As not every individual with SVD experiences depressive symptoms, other factors might play a role. We therefore investigated the white matter (WM) integrity of the white matter tracts in elderly with depressive symptoms, independent of global cognitive function, by applying the tract-based spatial statistics (TBSS).

Design: Prospective cohort study with cross-sectional baseline data.

Setting: Radboud University Nijmegen Medical Centre, The Netherlands.

Participants: 438 individuals aged between 50-85 years, with SVD without dementia.

Measurements: Diffusion tensor imaging parameters and depressive symptoms, assessed with the Center for Epidemiologic Studies Depression Scale.

Results: Compared with non-depressed participants (N = 287), those with depressive symptoms (N = 151) had lower fractional anisotropy in the genu and body of the corpus callosum, bilateral inferior fronto-occipital fasciculus, uncinate fasciculus, and corona radiata. These differences disappeared after adjustment for white matter hyperintensities (WMH) and lacunar infarcts. Mean-, axial-and radial diffusivity were higher in these areas in participants with depressive symptoms. After additional adjustment for WMH and lacunar infarcts, the changes observed in radial diffusivity also disappeared. Adding global cognition as confounding variable altered the diffusion parameters only slightly.

Conclusion: This study indicates that elderly with depressive symptoms show a lower WM integrity, independent of global cognitive function, and that the presence of SVD is mostly responsible, affecting the fronto-subcortical regions and hereby disrupting the neural circuitry involved in mood regulation.

Original languageEnglish
Pages (from-to)525-535
Number of pages11
JournalAmerican journal of geriatric psychiatry
Issue number5
Publication statusPublished - 1 May 2015


  • Depressive symptoms
  • DTI
  • Elderly
  • Small vessel disease
  • TBSS
  • 2023 OA procedure


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