White matter hyperintensities and chronicity of depression

Heiden, A.; Kettenbach, Joachim; Fischer, Peter; Schein, B.; Ba‐Ssalamah, Ahmed; Frey, Richard; Naderi, Mohammad; Gulesserian, Talin; Schmid, Daniela; Trattnig, S.; Imhof, Herwig; Kasper, Siegfried

doi:10.1016/j.jpsychires.2004.07.004

Cited by 54 publications

(38 citation statements)

References 55 publications

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“…The vascular depression hypothesis has been supported by numerous studies showing that development of late-onset LLD is associated with greater severity of WMHs. Furthermore, research has demonstrated that baseline WMHs are associated with treatment outcomes in these patients (Heiden et al, 2005;O'Brien et al, 1998). Our results were able to demonstrate that non-remitters had higher baseline WMHs compared with responders, but this difference was nonsignificant.…”

Section: Discussioncontrasting

confidence: 47%

“…Furthermore, one of the most salient models of depression in older adults is the vascular depression hypothesis, which suggests that cerebrovascular ischemic damage promotes depressive symptoms Butters et al, 2008). The relationship between WMHs and the vascular depression hypothesis is further strengthened by studies demonstrating that WMHs are associated with treatment outcomes (Aizenstein et al, 2011;Firbank et al, 2007;Heiden et al, 2005;Taylor et al, 2014). However, as several other studies have failed to find the association between WMHs and depression, the vascular depression hypothesis is not universally accepted (Aizenstein et al, 2011;Dotson et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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White Matter Hyperintensity Accumulation During Treatment of Late-Life Depression

Khalaf

Edelman

Tudorascu

et al. 2015

Neuropsychopharmacol

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White matter hyperintensities (WMHs) have been shown to be associated with the development of late-life depression (LLD) and eventual treatment outcomes. This study sought to investigate longitudinal WMH changes in patients with LLD during a 12-week antidepressant treatment course. Forty-seven depressed elderly patients were included in this analysis. All depressed subjects started pharmacological treatment for depression shortly after a baseline magnetic resonance imaging (MRI) scan. At 12 weeks, patients underwent a follow-up MRI scan, and were categorized as either treatment remitters (n = 23) or non-remitters (n = 24). Among all patients, there was as a significant increase in WMHs over 12 weeks (t(46) = 2.36, P = 0.02). When patients were stratified by remission status, non-remitters demonstrated a significant increase in WMHs (t(23) = 2.17, P = 0.04), but this was not observed in remitters (t(22) = 1.09, P = 0.29). Other markers of brain integrity were also investigated including whole brain gray matter volume, hippocampal volume, and fractional anisotropy. No significant differences were observed in any of these markers during treatment, including when patients were stratified based on remission status. These results add to existing literature showing the association between WMH accumulation and LLD treatment outcomes. Moreover, this is the first study to demonstrate similar findings over a short interval (ie 12 weeks), which corresponds to the typical length of an antidepressant trial. These findings serve to highlight the acute interplay of cerebrovascular ischemic disease and LLD.

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Section: Discussioncontrasting

confidence: 47%

Section: Introductionmentioning

confidence: 99%

White Matter Hyperintensity Accumulation During Treatment of Late-Life Depression

Khalaf

Edelman

Tudorascu

et al. 2015

Neuropsychopharmacol

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“…Alterations of the integrity of white matter seem to be related to the outcome of late-life depression. 7,25 For instance, frontal microstructural white matter abnormalities may be associated with a low remission rate of late-life depression. 26 White matter abnormalities and the resulting dysfunctions of the frontosubcortical circuits at the level of the dorsolateral prefrontal cortex may affect the course of latelife depression.…”

Section: Discussionmentioning

confidence: 99%

“…7 White matter hyperintensities are conceptualized as a sign of vascular damage to brain structures, and they are known to contribute to the development of vascular depression. 8 Cerebral microbleeds (CMBs) are focal deposits of hemosiderin that indicate previous microhemorrhages.…”

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confidence: 99%

Cerebral Microbleeds as a Predictor of 1-Year Outcome of Poststroke Depression

Tang

Chen²,

Liang³

et al. 2014

Stroke

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Background and Purpose-Cerebral microbleeds (CMBs) are common in stroke survivors and community-dwelling elderly.The clinical significance of CMBs in the outcome of poststroke depression (PSD) is unknown. This study examined the association between the 1-year outcome of PSD and CMBs. Methods-The study population comprised 774 Chinese patients with acute ischemic stroke who were admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong. Three and 15 months after the onset of the index stroke, a research assistant administered the locally validated 15-item Geriatric Depression Scale. PSD was defined as a Geriatric Depression Scale score of ≥7. Of the 213 patients with PSD at the 3-month follow-up, 135 (63.4%) attended the 15-month follow-up, at which time 89 (65.9%) patients remained depressed (nonremitters), and 46 (34.1%) had recovered (remitters). The presence and location of CMBs were evaluated with magnetic resonance imaging. Results-In

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“…In the Rotterdam study, which is a population-based prospective follow-up study of the entire population aged 55 years and older in Rotterdam (the Netherlands), the prevalence rate of WML was 27%, with higher prevalence among elderly people (aged 65-74 years) with higher lesional score with advanced age (Breteler et al 1994). The clinical effects of WML vary with the main impairment being detected in the cognitive functions, specially executive functions (Marshall et al 2006), with increased risk of severe depression associated with higher WML volume in anterior quadrants, in both the right and the left frontal lobes (Heiden et al 2005). Previous work by our group (Simpson et al 2009) studied gene expression changes in WML compared to both normal areas from the same brain (NAWM(L)) and normal control brains (NAWM(C)), using RNA extracted from frozen brains of the CFAS post-mortem brain bank.…”

Section: Introductionmentioning

confidence: 99%

Brain Iron Dysregulation and the Risk of Ageing White Matter Lesions

et al. 2011

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White matter lesions (WML) or leukoaraiosis is a major feature in cerebral imaging of older people, and their prevalence increases with age. The clinical effects of WML vary with the main impairment being detected in the cognitive functions, increased risk of severe depression and motor impairment. Although vascular comorbidities have been found to be the main changes in these brains, increased production of reactive oxygen species (ROS) could represent a risk factor for these lesions with elemental iron being a potential factor for ROS production. This study focuses on changes in iron, iron-regulating proteins and RNA expression of iron metabolism genes. Three groups of samples were used: WML, normal areas from lesional WM [NAWM (L)] as disease control and normal WM from control brains [NAWM(C)]. Ferric iron staining was undertaken using known Perl's reaction. Immunohistochemistry (IHC) of white matter for ceruloplasmin (Cp), haemochromatosis (HFE) and transferrin receptor (TfR) was done. Cellular localization of HFE and Cp was performed using dual-antibody IHC. Whole-genome RNA was extracted from WML, NAWM (L) and NAWM(C), and QPCR for HFE, TF, TfR, ceruloplasmin, ferritin and ferroportin was performed. Ferric iron staining shows increased diffuse iron staining among WML, followed by NAWM (L) and the least group being NAWM(C). IHC shows increased HFE and CP expression in lesional WM, while TfR shows no changes among the groups. HFE colocalized with vascular endothelium and microglia in WML and control samples, while Cp colocalized with microglia and some expression was shown by astrocytes. The mRNA expression using QPCR suggests a pattern that favours decreased intracellular iron influx, increased ferrous oxidation and increased iron export from the cells. Iron metabolism seems to be changed in brains with WML, increased elemental iron in these brains and in turn increased production of free oxidative radicals could represent a potentiating factor for the development of ageing WML.

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White matter hyperintensities and chronicity of depression

Cited by 54 publications

References 55 publications

White Matter Hyperintensity Accumulation During Treatment of Late-Life Depression

White Matter Hyperintensity Accumulation During Treatment of Late-Life Depression

Cerebral Microbleeds as a Predictor of 1-Year Outcome of Poststroke Depression

Brain Iron Dysregulation and the Risk of Ageing White Matter Lesions

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