AbstractBackgroundDecreased caudate volumes and increased white matter lesions (WMLs) are associated both with aging and late‐life depression, but the relationship between the two is unclear. We examined the association between WML and caudate volume, hypothesizing there would be a negative association, which would be stronger for WMLs located in anterior regions. We additionally hypothesized that this association would be stronger in depressed subjects.MethodThis MRI study included 182 elderly depressed and 64 elderly control subjects. Our imaging analysis procedures divided the brain into anterior and posterior halves. WML volume in each half was calculated, as were left and right caudate volumes. A statistical model incorporating WML volumes, age, total brain volume, diagnosis, and gender was used to examine caudate volumes.ResultsWML volume was negatively associated with total and right caudate volume. This association was stronger for WMLs in the anterior half of the brain. Anterior WML volume was additionally negatively associated with right caudate volume in depressed subjects, but not in controls.ConclusionsUsing unadjusted levels of significance, WML volume is negatively associated with right caudate volume in both older populations, but with left caudate volume only in depressed individuals. When statistical corrections for multiple comparisons are used, the finding is limited to a negative association between WML volume and right caudate volume, primarily in depressed subjects. This study demonstrates one mechanism by which WMLs may disrupt frontostriatal circuits. Copyright © 2006 John Wiley & Sons, Ltd.