White Matter Hyperintensity Progression and Late-Life Depression Outcomes

Taylor, Warren D.; Steffens, David C.; MacFall, James R.; McQuoid, Douglas R.; Payne, Martha E.; Provenzale, James M.; Krishnan, K. Ranga Rama

doi:10.1001/archpsyc.60.11.1090

Cited by 212 publications

(166 citation statements)

References 62 publications

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“…Individuals who demonstrate a lack of persistence in a testing situation may be more likely to have problems with treatment adherence and other functional abilities. Like the task impersistence reported in the current study, poor treatment response and functional performance deficits have been found to be associated with white matter lesions at least partly involving the frontal lobes (Steffens et al, 2002a;Taylor et al, 2003). With additional research to clarify the construct, it is possible that task impersistence may be considered a marker for underlying prefrontal pathology and a higher risk of adverse clinical outcomes.…”

Section: Discussionsupporting

confidence: 58%

“…Multiple areas of the frontostriatal pathway are involved in the process of planning, initiating, and maintaining complex behavioral responses, including orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior cingulate (Rogers et al, 1998). White matter lesions in these broader brain regions are more prominent in depressed older adults relative to nondepressed elders (Taylor et al, 2005), and like initiation deficits, are associated with greater risk for adverse outcomes in depression, such as poor treatment response (Alexopoulos et al, 2002a;Taylor et al, 2003) and functional impairment (Steffens et al, 2002a). Identifying neuropsychological performances that are sensitive to prefrontal vascular pathology would be useful for characterizing individuals with this form of late-life depression.…”

Section: Introductionmentioning

confidence: 99%

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Prefrontal White Matter Lesions and Prefrontal Task Impersistence in Depressed and Nondepressed Elders

Potter

Blackwell

McQuoid

et al. 2007

Neuropsychopharmacol

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Poor task persistence is often observed among depressed individuals, and may be associated with some of the same frontal regions that are involved in depression. The current study explored the association between white-matter lesion volume in prefrontal cortex and noncompletion rates on a complex neurocognitive task among older adults in a treatment study for depression. Older adults in treatment for depression (n ¼ 83) and nondepressed (n ¼ 47) elders were administered the Stockings of Cambridge subtest (SoC) of the Cambridge Automated Neuropsychological Testing Battery (CANTAB) and completed a brain magnetic resonance imaging scan as part of an ongoing research study. Noncompletion of the SoC occurred in approximately 19% of depressed participants (16/83) and only 2% of nondepressed participants (1/47), which was statistically significant. In multivariate models, failure to complete the SoC was consistently and significantly associated with greater volume of white matter lesions in the anterior-most region of prefrontal cortex, particularly in the left hemisphere, and with greater age. Although SoC completion was not significantly associated with depression severity, noncompletion rates were significantly higher among unremitted individuals and those with comorbid anxiety at study entry. The inability to initiate behavior sufficient to sustain a complex neurocognitive task is a characteristic of geriatric depression which may be associated with integrity of left-prefrontal regions. Future research should investigate whether task impersistence is a construct that generalizes to other neurocognitive tasks, and if it is associated with other adverse outcomes in geriatric depression related to cerebrovascular pathology, such as poor treatment response.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Prefrontal White Matter Lesions and Prefrontal Task Impersistence in Depressed and Nondepressed Elders

Potter

Blackwell

McQuoid

et al. 2007

Neuropsychopharmacol

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“…The inability to demonstrate a statistically significant difference was likely due to a relatively short follow-up period and a sample size insufficient to detect a difference over the study period; however, the change we report is comparable to that found in other longitudinal studies investigating either total (Taylor et al, 2003a) or deep white matter lesion volume (Cook et al, 2004). Other studies have demonstrated that WMLs do increase in severity and volume over time, and that greater change is associated with depression outcomes (Nebes et al, 2002;Taylor et al, 2003c).…”

Section: Discussioncontrasting

confidence: 56%

“…White and gray matter hyperintense lesions are more severe in older depressed subjects than nondepressed subjects (Krishnan et al, 1988;Dolan et al, 1990;Fujikawa et al, 1993;Krishnan, 1993;Greenwald et al, 1996;Steffens et al, 1999;Kumar et al, 2000;Tupler et al, 2002;Taylor et al, 2005), and are more severe in late-onset than early-onset elderly depressed subjects (Figiel et al, 1991;Hickie et al, 1995;Salloway et al, 1996;Krishnan et al, 1997;Lavretsky et al, 1998;de Groot et al, 2000;Tupler et al, 2002). Increases in WML severity over time are additionally associated with new onset of depression (Lavretsky et al, 1999;Nebes et al, 2002) and poorer outcomes to antidepressant therapy (Simpson et al, 1997;O'Brien et al, 1998;Taylor et al, 2003c), although some have not found a relationship between WML severity and treatment outcomes (Salloway et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Lobar Distribution of Lesion Volumes in Late-Life Depression: The Biomedical Informatics Research Network (BIRN)

MacFall

Taylor

Rex

et al. 2005

Neuropsychopharmacol

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White matter hyperintense lesions on T2-weighted images are associated with late-life depression. Little work has been carried out examining differences in lesion location between elderly individuals with and without depression. In contrast to previous studies examining total brain white matter lesion volume, this study examined lobar differences in white matter lesion volumes derived from brain magnetic resonance imaging. This study examined 49 subjects with a DSM-IV diagnosis of major depression and 50 comparison subjects without depression. All participants were age 60 years or older. White matter lesion volumes were measured in each hemisphere using a semiautomated segmentation process and localized to lobar regions using a lobar atlas created for this sample using the imaging tools provided by the Biomedical Informatics Research Network (BIRN). The lobar lesion volumes were compared against depression status. After controlling for age and hypertension, subjects with depression exhibited significantly greater total white matter lesion volume in both hemispheres and in both frontal lobes than did control subjects. Although a similar trend was observed in the parietal lobes, the difference did not reach a level of statistical significance. Models of the temporal and occipital lobes were not statistically significant. Older individuals with depression have greater white matter disease than healthy controls, predominantly in the frontal lobes. These changes are thought to disrupt neural circuits involved in mood regulation, thus increasing the risk of developing depression.

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“…4,5 In clinical samples, progression of MRI white matter lesions is related to lack of response to antidepressants or recurrence of depression. 6 However, in these samples nearly all subjects received pharmacological treatment. The effect of antidepressant medications on progression of brain vascular disease defined by MRI is unclear.…”

mentioning

confidence: 99%

Antidepressant Treatment and Worsening White Matter on Serial Cranial Magnetic Resonance Imaging in the Elderly

Steffens

Chung

Krishnan

et al. 2008

Stroke

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Background and Purpose-In some studies, late life depression is associated with white matter lesions on MRI. The effect of different classes of antidepressants on progression of white matter lesions is unknown. Selective serotonergic reuptake inhibitors (SSRIs) may decrease platelet aggregation. We hypothesized that Cardiovascular Health Study participants taking SSRIs would less often have worsening white matter on serial MRI than participants not on antidepressants. Methods-Among 1826 participants who were not using an antidepressant at initial MRI scan, we examined the association of worsening in white matter grade from initial to follow-up MRI scans, 5 years apart on average, and antidepressant use between the scans. Logistic regression models were used, controlling for a variety of potential confounding variables. Results-Use of any antidepressant during the period of study was associated with worsening white matter. In a multivariable model, risk was slightly increased, not reduced, with use of serotonergic agents (OR 1.36, 95% CI 0.87 to 2.12) and was significantly increased with the use of tricyclic antidepressants (OR 1.77, 95% CI 1.07 to 2.94). Conclusions-The

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White Matter Hyperintensity Progression and Late-Life Depression Outcomes

Abstract: Greater progression of WMH volume is associated with poor outcomes in geriatric depression. Future work is needed to develop means of slowing the rate of WMH progression and to determine whether this will lead to improved depression outcomes in elderly persons.

Cited by 212 publications

References 62 publications

Prefrontal White Matter Lesions and Prefrontal Task Impersistence in Depressed and Nondepressed Elders

Prefrontal White Matter Lesions and Prefrontal Task Impersistence in Depressed and Nondepressed Elders

Lobar Distribution of Lesion Volumes in Late-Life Depression: The Biomedical Informatics Research Network (BIRN)

Antidepressant Treatment and Worsening White Matter on Serial Cranial Magnetic Resonance Imaging in the Elderly

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