title: Depression in small-vessel disease relates to white matter ultrastructural damage, not disability.
abstract: OBJECTIVE
  To determine whether cerebral small-vessel disease (SVD) is a specific risk factor for depression, whether any association is mediated via white matter damage, and to study the role of depressive symptoms and disability on quality of life (QoL) in this patient group.
  
  
  METHODS
  Using path analyses in cross-sectional data, we modeled the relationships among depression, disability, and QoL in patients with SVD presenting with radiologically confirmed lacunar stroke (n = 100), and replicated results in a second SVD cohort (n = 100). We then compared the same model in a non-SVD stroke cohort (n = 50) and healthy older adults (n = 203). In a further study, to determine the role of white matter damage in mediating the association with depression, a subgroup of patients with SVD (n = 101) underwent diffusion tensor imaging (DTI).
  
  
  RESULTS
  Reduced QoL was associated with depression in patients with SVD, but this association was not mediated by disability or cognition; very similar results were found in the replication SVD cohort. In contrast, the non-SVD stroke group and the healthy older adult group showed a direct relationship between disability and depression. The DTI study showed that fractional anisotropy, a marker of white matter damage, was related to depressive symptoms in patients with SVD.
  
  
  CONCLUSIONS
  These results suggest that in stroke patients without SVD, disability is an important causal factor for depression, whereas in SVD stroke, other factors specific to this stroke subtype have a causal role. White matter damage detected on DTI is one factor that mediates the association between SVD and depression.
authors.affiliation: From the Stroke and Dementia Research Centre (R.L.B., V.H., A.J.L.), St George's, University of London; University of Cambridge (H.S.M.), Department of Neurology, Cambridge Biomedical Campus; and Department of Psychology (R.G.M.), Institute of Psychiatry, King's College London, UK. rbrookes@sgul.ac.uk.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Brookes
authors.affiliation: From the Stroke and Dementia Research Centre (R.L.B., V.H., A.J.L.), St George's, University of London; University of Cambridge (H.S.M.), Department of Neurology, Cambridge Biomedical Campus; and Department of Psychology (R.G.M.), Institute of Psychiatry, King's College London, UK.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Herbert
authors.affiliation: From the Stroke and Dementia Research Centre (R.L.B., V.H., A.J.L.), St George's, University of London; University of Cambridge (H.S.M.), Department of Neurology, Cambridge Biomedical Campus; and Department of Psychology (R.G.M.), Institute of Psychiatry, King's College London, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
authors.affiliation: From the Stroke and Dementia Research Centre (R.L.B., V.H., A.J.L.), St George's, University of London; University of Cambridge (H.S.M.), Department of Neurology, Cambridge Biomedical Campus; and Department of Psychology (R.G.M.), Institute of Psychiatry, King's College London, UK.
authors.forename: Robin G
authors.initials: RG
authors.lastname: Morris
authors.affiliation: From the Stroke and Dementia Research Centre (R.L.B., V.H., A.J.L.), St George's, University of London; University of Cambridge (H.S.M.), Department of Neurology, Cambridge Biomedical Campus; and Department of Psychology (R.G.M.), Institute of Psychiatry, King's College London, UK.
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Markus
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology / Q000523:psychology; D059345:Cerebral Small Vessel Diseases / Q000473:pathology* / Q000523:psychology*; D003071:Cognition; D003430:Cross-Sectional Studies; D003863:Depression / Q000209:etiology* / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D011788:Quality of Life; D012720:Severity of Illness Index; D059409:Stroke, Lacunar / Q000473:pathology / Q000523:psychology; D013997:Time Factors; D066127:White Matter / Q000473:pathology*