Late-life Depression and Cerebral Perfusion

The long-term goal is to determine if decreased blood flow to the brain (cerebral
hypoperfusion) is predictive of antidepressant outcomes in late-life depression (LLD).
Studies in younger adult report that successful antidepressant treatment is associated with
increases in cerebral blood flow, with no change in blood flow being observed in
nonresponders. Thus cerebral hypoperfusion may be a biomarker of poor response to
antidepressants. In LLD, this may occur secondarily to underlying vascular disease. If LLD
is characterized by cerebral hypoperfusion and it does have predictive power to identify
individuals who will poorly respond to conventional antidepressants, this would support the
study of interventions that improve cerebral perfusion and may improve antidepressant
outcomes.

As an initial step in this research, this pilot study will utilize MRI to examine if resting
blood flow deficits predict and persist with antidepressant nonremission in an elderly
population. The rationale for this proposal is that it will guide the design and power
requirements of a larger, definitive trial examining the relationship between cerebral
perfusion and depression outcomes. Importantly, support for this mechanism being linked to
LLD would also support studies examining the antidepressant efficacy of drugs that may
improve cerebral perfusion.

The primary purpose of this pilot study is a) to demonstrate feasibility by recruiting,
scanning, and treating depressed elders; and b) to acquire preliminary data for competitive
grant submissions.

SPECIFIC AIM: To use MRI to test for differences in cerebral perfusion between individuals
who do and do not remit to a 8-week course of sertraline.