White matter hyperintensity progression and late-life depression outcomes

Context: White matter hyperintensities (WMHs) are bright foci seen in the parenchyma of the brain on T2-weighted cranial magnetic resonance imaging (MRI) scans and are associated with geriatric depression. Because they are associated with age, they should increase in number and size over time. To our knowledge, this is the first longitudinal, volumetric MRI study of WMHs in depression. Objective: To determine if WMH progression over 2 years influences depression outcomes. Design: Over 2 years, depressed subjects received antidepressant treatment according to a naturalistic somatic treatment algorithm designed to offer the best possible treatment to the individual. After the treatment period, depressed subjects were dichotomized based on whether they had reached and sustained remission during this period. Participants: One hundred thirty-three subjects aged 60 years or older meeting DSM-IV criteria for major depressive disorder. Measures: Cranial MRI was obtained at baseline and approximately 2 years later. White matter hyperintensity volume was measured in each hemisphere using a semiautomated segmentation process. Outcomes: Subjects were dichotomized based on achieving or not achieving remission of depressive symptoms, defined as a Montgomery-Asberg Depression Rating Scale score of 8 or less. Results: The depressed subgroup that achieved and sustained remission had significantly less increases in WMH volume (11.5%) than did the group that did not achieve or sustain remission (31.6%) (P=.01). In a regression model, greater change in WMH volume was significantly associated with failure to sustain remission (P=.004) even when controlling for baseline depression severity, medical illness severity, age, sex, and race. Education was associated with achieving and sustaining remission (P=.02). Conclusions: 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.