Research paperFrontocingulate cerebral blood flow and cerebrovascular reactivity associated with antidepressant response in late-life depression

•Vascular pathology is greater in and mechanistically related to late-life depression.•Cerebrovascular reactivity (CVR) is a measure of dynamic vascular processes.•Frontocingulate cerebral blood flow (CBF) is associated with antidepressant response.•Greater CBF may reflect greater regional metabolic activity.

BackgroundVascular pathology is common in late-life depression (LLD) and may contribute to alterations in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). In turn, such hemodynamic deficits may adversely affect brain function and clinical course. The goal of this study was to examine whether altered cerebral hemodynamics in depressed elders predicted antidepressant response.Methods21 depressed elders completed cranial 3 T MRI, including a pseudo-continuous Arterial Spin Labeling (pcASL) acquisition on both room air and during a hypercapnia challenge. Participants then completed 12 weeks of open-label sertraline. Statistical analyses examined the relationship between regional normalized CBF and CVR values and change in Montgomery-Asberg Depression Rating Scale (MADRS) and tested for differences based on remission status.Results10 participants remitted and 11 did not. After controlling for age and baseline MADRS, greater change in MADRS with treatment was associated with lower pre-treatment normalized CBF in the caudal anterior cingulate cortex (cACC) and lateral orbitofrontal cortex (OFC), as well as lower CVR with hypercapnia in the caudal medial frontal gyrus (cMFG). After controlling for age and baseline MADRS score, remitters exhibited lower CBF in the cACC and lower CVR in the cMFG.LimitationsOur sample was small, did not include a placebo arm, and we examined only specific regions of interest.ConclusionsOur findings suggest that increased perfusion of the OFC and the ACC is associated with a poor antidepressant response. They do not support that vascular pathology as measured by CBF and CVR negatively affects acute treatment outcomes.