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

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