Relationship between baseline white-matter changes and development of late-life depressive symptoms: 3-year results from the LADIS study

Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
Psychological Medicine (Impact Factor: 5.94). 09/2009; 40(4):603-10. DOI: 10.1017/S0033291709990857
Source: PubMed


Growing evidence suggests that cerebral white-matter changes and depressive symptoms are linked directly along the causal pathway. We investigated whether baseline severity of cerebral white-matter changes predict longer-term future depressive outcomes in a community sample of non-disabled older adults.
In the Leukoaraiosis and Disability in the Elderly (LADIS) study, a longitudinal multi-centre pan-European study, 639 older subjects underwent baseline structural magnetic resonance imaging (MRI) and clinical assessments. Baseline severity of white-matter changes was quantified volumetrically. Depressive outcomes were assessed in terms of depressive episodes and depressive symptoms, as measured by the Geriatric Depression Scale (GDS). Subjects were clinically reassessed annually for up to 3 years. Regression models were constructed to determine whether baseline severity of white-matter changes predicted future depressive outcomes, after controlling for confounding factors.
Baseline severity of white-matter changes independently predicted depressive symptoms at both 2 (p<0.001) and 3 years (p=0.015). Similarly, white-matter changes predicted incident depression (p=0.02). Over the study period the population became significantly more disabled (p<0.001). When regression models were adjusted to account for the influence of the prospective variable transition to disability, baseline severity of white-matter changes no longer predicted depressive symptoms at 3 years (p=0.09) or incident depression (p=0.08).
Our results support the vascular depression hypothesis and strongly implicate white-matter changes in the pathogenesis of late-life depression. Furthermore, the findings indicate that, over time, part of the relationship between white-matter changes and depression may be mediated by loss of functional activity.

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    • "This suggests that WMHs may play a causal role for the development of depression in some individuals. By demonstrating that greater WMHs severity precedes and increases the risk for depression, these data provide strong support for the vascular depression hypothesis (Teodorczuk 2007, 2010). "
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    ABSTRACT: There are no cross-sectional or longitudinal epidemiological studies present on MRI-defined vascular depression in community populations. The purpose of this study was to estimate the prevalence rates of both vascular and non-vascular late life depression (LLD) at baseline, to examine the natural course of LLD, and to investigate the influence of White matter hyperintensities (WMHs) on depression after three years. The baseline study employed a two-stage design, Phase I population survey (n=783) and Phase II diagnostic evaluation (n=122). In the 3-year follow-up study, baseline participants completing the second phase were reassessed with the same methodology. WMHs severity was rated visually by the modified Fazekas scale and WMHs volume was calculated using an automated method. The prevalence rates of vascular major depressive disorder (MDD) and vascular non-major depressive disorder (nMDD) were 2.39% (56.2% of MDD) and 4.24% (34.0% of nMDD). Subjects with a score of 2 or more on the modified Fazekas scale in either deep white matter hyperintensities or subcortical gray matter ratings had an 8.1 times greater risk of developing a depressive disorder in the 3-year follow-up study. Greater Log WMHs volume (odds ratio=5.78, 95% CI, 1.04-31.72) at baseline was an independent predictor for depressive disorder in the 3-year assessment. Response rate and follow-up rate were relatively low. Vascular depression is common and makes up about a half of MDD in elders. Greater WMHs severity is a crucial factor predicting future depression risk, which supports the previous vascular depression hypothesis. Copyright © 2015 Elsevier B.V. All rights reserved.
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    • "It is associated with white matter lesions (WMLs), lacunar infarcts, and, more recently, microbleeds [2]–[4]. CM manifests itself in manifold clinical symptoms including gait disorders, [5] urinary disturbances, [6] depression [7] and cognitive decline [8]–[10]. Because CM patients are such a heterogeneous group, clinicians may not consider this diagnosis and may miss important opportunities for intervention. "
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    Full-text · Article · Feb 2013 · PLoS ONE
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    • "Although the direction of causation between WMHs and depression has not yet been completely clarified, longitudinal studies shed light on the progression and predictive value of WMHs in depression (Teodorczuk et al., 2010). "
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    ABSTRACT: The aim of this study was to evaluate excitatory/inhibitory intracortical circuit changes in patients with vascular depression, and whether there are any interhemispheric differences of motor cortical excitability. Fifteen vascular depressed elderly (VD), ten nondepressed subcortical vascular disease patients (SVD) and ten age-matched controls underwent bilateral motor threshold and paired-pulse studies. They were also assessed for their brain vascular burden at MRI and neuropsychological profile. Executive dysfunction and apathy were significantly higher in VD; we were unable to find significant differences in resting motor threshold, cortical silent period and paired-pulse curves between VD, SVD and controls, and between the two hemispheres in the VD group. Our findings might suggest that neurophysiological mechanisms underlying VD differ from those previously reported in Major Depression (reduced excitability in the left hemisphere) and seem to be similar to those of patients with SVD. Our findings also, support the "vascular depression" hypothesis, suggesting that in VD patients the depressive syndrome is not the primary disease but can be considered as one of the clinical manifestations in the wide symptom spectrum of the cerebral small vessel disease.
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