BackgroundSeveral studies have reported smaller hippocampal volume (HcV) in depression patients; however, the temporality of the association remains unknown. One proposed hypothesis is that depression may cause HcV loss. This study evaluates whether previous depression and recent depressive symptoms are associated with HcV and HcV loss.MethodWe used a prospective cohort of older adults (n= 1328; age = 65–80 years) with two cerebral magnetic resonance imaging examinations at baseline and 4-year follow-up. Using multivariable linear regression models, we estimated, in stratified analyses by gender, the association between indicators of history of depression and its severity (age at onset, recurrence, hospitalization for depression), proximal depressive symptoms [Center for Epidemiologic Studies-Depression (CES-D) scale], baseline antidepressant use, and the outcomes: baseline HcV and annual percentage change in HcV.ResultsAt baseline, women with more depressive symptoms had smaller HcV [−0.05 cm³, 95% confidence interval (CI) −0.1 to −0.01 cm³per 10-unit increase in CES-D scores]. History of depression was associated with a 0.2% faster annual HcV loss in women (95% CI 0.01–0.36%). More baseline depressive symptoms and worsening of these symptoms were also associated with accelerated HcV loss in women. No associations were observed in men. Treatment for depression was associated with slower HcV loss in women and men.ConclusionsWhile only concomitant depressive symptoms were associated with HcV, both previous depression and more proximal depressive symptoms were associated with faster HcV loss in women.