Lacunar Infarcts in Deep White Matter Are Associated with Higher and More Fluctuating Depressive Symptoms During Three Years Follow-up

Background: Disruption of frontal-subcortical circuits by cerebral small-vessel disease is thought to predispose to depression characterized by motivational symptoms. We examined the influence of lacunar infarcts and white matter lesions (WML) on severity and course of depressive symptoms during 3 years follow-up. Methods: Within the SMART-Medea study, analyses were performed in 650 patients with symptomatic atherosclerotic disease (62 +/- 9 years). Volumetric WML measures (deep and periventricular) were obtained with 1.5T magnetic resonance imaging at baseline; infarcts were rated visually. Depressive symptoms were assessed with Patient Health Questionnaire-9 at baseline and during five follow-up times and categorized into motivational and mood scores. Results: Using generalized estimating equation models, a relation between lacunar infarcts in deep white matter and an increased severity (mean difference = 1.47,95% confidence interval .33-2.60) and more fluctuating course (p value interaction infarcts * time = .04) of depressive symptoms during follow-up was found, adjusted for age, sex, education, vascular risk, and cognition. This relation was primarily driven by motivational symptoms. Lacunar infarcts were not associated with severity or course of depressive symptoms. Deep WML were associated with a more fluctuating but not more severe course of depressive symptoms. Excluding patients with major depressive disorder did not change the results. Conclusions: In patients with symptomatic atherosclerotic disease and relatively mild depressive symptoms, depressive symptoms, characteristic of motivational problems, remained higher during 3 years follow-up in patients with lacunar infarcts in deep white matter and that symptoms everity fluctuated over time.