Antidepressant use is related to larger white matter lesion volume in patients with symptomatic atherosclerotic disease: the SMART-MR study

Although a relation between depression and white matter lesions (WML) is frequently observed, the direction of causation remains unknown. We investigated whether depressed mood was associated with baseline severity and change in WML volume during 4 years of follow-up, and the relative contribution of mood symptoms and antidepressant use to this relation. Within the SMART-MR study 594 patients (58 ± 10 years) with symptomatic atherosclerotic disease had assessments of mood symptoms and antidepressant use and 1.5 T MRI at baseline and after 3.9 ± 0.4 years of follow-up. Mood symptoms were assessed using the Mental Health Index (MHI-5). Depressed mood was defined as antidepressant use and/or MHI-5 score ≤ 52. Volumetric WML measures (deep and periventricular) were obtained with automated segmentation. Linear regression analyses were adjusted for age, sex, baseline WML volume, follow-up time, vascular risk factors and infarcts. Depressed mood was not associated with larger WML volume at baseline. However, when separate contributions were distinguished, antidepressant use was associated with greater deep (B = 0.50 mL, 95 % CI 0.04-0.96) and periventricular WML volume (B = 0.47 mL, 95 % CI 0.05-0.89) at baseline, while mood symptoms were not. Antidepressants were associated with a modest but non-significant increase in progression of periventricular WML volume over 4 years of follow-up (B = 0.21 mL, 95 % CI -0.05 to 0.47). WML at baseline were not associated with new-onset depressed mood at follow-up. Antidepressants, but not mood symptoms, were associated with greater WML volume and a modest, although non-significant increase in periventricular WML volume in patients with symptomatic atherosclerotic disease. Future studies are needed to determine whether this may be a direct effect, or whether other underlying diseases for which antidepressants are prescribed influence this relation.