Studies of white matter microstructure in depression typically show alterations in individuals with depression, but they are frequently limited by small sample sizes and the absence of longitudinal measures of depressive symptoms. Depressive symptoms are dynamic, however, and understanding the neurobiology of different trajectories could have important clinical implications. We examined associations between current and longitudinal measures of depressive symptoms and white matter microstructure (fractional anisotropy and mean diffusivity [MD]) in the UK Biobank Imaging Study. Depressive symptoms were assessed on two to four occasions over 5.9 to 10.7 years (n = 18,959 individuals on at least two occasions, n = 4444 on four occasions), from which we derived four measures of depressive symptomatology: cross-sectional measure at the time of scan and three longitudinal measures, namely trajectory and mean and intrasubject variance over time. Decreased white matter microstructure in the anterior thalamic radiation demonstrated significant associations across all four measures of depressive symptoms (MD: βs = .020-.029, pcorr < .030). The greatest effect sizes were seen between white matter microstructure and longitudinal progression (MD: βs = .030-.040, pcorr < .049). Cross-sectional symptom severity was particularly associated with decreased white matter integrity in association fibers and thalamic radiations (MD: βs = .015-.039, pcorr < .041). Greater mean and within-subject variance were mainly associated with decreased white matter microstructure within projection fibers (MD: βs = .019-.029, pcorr < .044). These findings indicate shared and differential neurobiological associations with severity, course, and intrasubject variability of depressive symptoms. This enriches our understanding of the neurobiology underlying dynamic features of the disorder. Copyright © 2019 Society of Biological Psychiatry. All rights reserved.