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Trajectories in Cerebral Blood Flow Following Antidepressant Treatment in Late-Life Depression: Support for the Vascular Depression Hypothesis.

ABSTRACT: OBJECTIVE:Studies have identified longitudinally that there exists an association between depression, cerebral blood flow (CBF), and white matter hyperintensities that are thought to be due to vascular pathologies in the brain. However, the changes in CBF, a measure that reflects cerebrovascular integrity, following pharmacotherapy are not well understood. In this study, we investigated the dynamic CBF changes over the course of antidepressant treatment and the association of these changes with depressive symptoms. METHODS:We used pseudocontinuous arterial spin labeling to investigate CBF changes in a sample of older patients (? 50 years of age; N = 46; 29 female) with a DSM-IV diagnosis of major depressive disorder. Participants had 5 magnetic resonance imaging scans (at baseline, the day after receiving a placebo, the day after receiving a first dose of venlafaxine, a week after starting venlafaxine treatment, and at the end of trial [12 weeks]). Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate depression severity and treatment outcome. We investigated the association between changes in depression severity with changes in voxel-wise CBF while adjusting for potential confounding factors. RESULTS:Increased CBF in the middle and posterior cingulate between baseline and end of treatment was significantly associated with percent decrease in MADRS score, independent of sex and Mini-Mental State Examination score (5,000 permutations, cluster forming threshold P < .005, family-wise error P < .05). No significant effects were detected between baseline and other scans (ie, placebo, acute [single dose], or subacute [after a week]). CONCLUSIONS:Regional CBF increases were associated with decreases in depressive symptoms. This observation is consistent with the vascular depression hypothesis in late-life depression. TRIAL REGISTRATION:ClinicalTrials.gov identifiers: NCT00892047 and NCT01124188.

SUBMITTER: Wei W

PROVIDER: S-EPMC6419103 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Trajectories in Cerebral Blood Flow Following Antidepressant Treatment in Late-Life Depression: Support for the Vascular Depression Hypothesis.

Wei Wenjing W Karim Helmet T HT Lin Chemin C Mizuno Akiko A Andreescu Carmen C Karp Jordan F JF Reynolds Charles F CF Aizenstein Howard J HJ

The Journal of clinical psychiatry 20181023 6

<h4>Objective</h4>Studies have identified longitudinally that there exists an association between depression, cerebral blood flow (CBF), and white matter hyperintensities that are thought to be due to vascular pathologies in the brain. However, the changes in CBF, a measure that reflects cerebrovascular integrity, following pharmacotherapy are not well understood. In this study, we investigated the dynamic CBF changes over the course of antidepressant treatment and the association of these chang ...[more]

PMID: 30358242

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Project description:ContextResearch on vascular depression has used 2 approaches to subtype late-life depression, based on executive dysfunction or white matter hyperintensity severity.ObjectiveTo evaluate the relationship of neuropsychological performance and white matter hyperintensity with clinical response in late-life depression.DesignTwo-site, prospective, nonrandomized controlled trial.SettingOutpatient clinics at Washington University and Duke University.ParticipantsA total of 217 subjects aged 60 years or older met DSM-IV criteria for major depression, scored 20 or more on the Montgomery-Asberg Depression Rating Scale (MADRS), and received vascular risk factor scores, neuropsychological testing, and magnetic resonance imaging; they were excluded for cognitive impairment or severe medical disorders. Fazekas rating was conducted to grade white matter hyperintensity lesions. Intervention Twelve weeks of sertraline treatment, titrated by clinical response. Main Outcome Measure Participants' MADRS scores over time.ResultsBaseline neuropsychological factor scores correlated negatively with baseline Fazekas scores. A mixed model examined effects of predictor variables on MADRS scores over time. Baseline episodic memory (P = .002), language (P = .007), working memory (P = .01), processing speed (P < .001), executive function factor scores (P = .002), and categorical Fazekas ratings (P = .05) predicted MADRS scores, controlling for age, education, age of onset, and race. Controlling for baseline MADRS scores, these factors remained significant predictors of decrease in MADRS scores, except for working memory and Fazekas ratings. Thirty-three percent of subjects achieved remission (MADRS < or =7). Remitters differed from nonremitters in baseline cognitive processing speed, executive function, language, episodic memory, and vascular risk factor scores.ConclusionsComprehensive neuropsychological function and white matter hyperintensity severity predicted MADRS scores prospectively over a 12-week treatment course with selective serotonin reuptake inhibitors in late-life depression. Baseline neuropsychological function differentiated remitters from nonremitters and predicted time to remission in a proportional hazards model. Predictor variables correlated highly with vascular risk factor severity. These data support the vascular depression hypothesis and highlight the importance of linking subtypes based on neuropsychological function and white matter integrity.Trial registrationclinicaltrials.gov Identifier: NCT00045773.

Dataset Information

Trajectories in Cerebral Blood Flow Following Antidepressant Treatment in Late-Life Depression: Support for the Vascular Depression Hypothesis.

Publications

Trajectories in Cerebral Blood Flow Following Antidepressant Treatment in Late-Life Depression: Support for the Vascular Depression Hypothesis.

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