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Background: Cerebral small vessel diseases (SVD) are associated with poststroke depressive symptoms (PDS). The mechanisms underlying the association between SVD burden and PDS are unclear. This study investigated the clinical pathways linking SVD burden to PDS.Method: A cohort of 563 patients with acute ischemic stroke were examined at three and fifteen months after stroke. PDS was measured with the 15-item Geriatric Depression Scale (GDS). Cognitive and physical functions were assessed with the Mini-Mental State Examination and the modified Rankin Scale, respectively. All patients received MRI scans at baseline. Infarct volumes and the four SVD markers (lacunae, white matter hyperintensities, cerebral microbleeds, and perivascular spaces) were assessed on magnetic resonance imaging. SVD burden was defined as a latent variable encompassing the information about all four SVD markers in structural equation modeling (SEM). SEM was further employed to examine the direct and indirect linking pathways between SVD burden, infarct volumes, stroke severity, poststroke cognitive and physical dysfunctions, and PDS.Results: The latent SVD burden was directly associated with more severe PDS at the 3-month follow-up (path coefficient=0.11), while SVD burden and PDS at the 15-month were mainly linked through PDS at the 3-month follow-up (path coefficient=0.48). The volume of acute infarcts and impaired physical functions predominantly mediated the association between SVD burden and PDS at 3-month follow-up. Physical and cognitive functions 15 months after stroke mainly bridged the link between SVD burden and the PDS at the 15-month follow-up.Limitations: The study included patients with mild stroke, which reduced the generalizability of the findings.Conclusions: SVD burden not only directly determines poststroke depressive symptoms, but also worsens acute stroke lesions, stroke severity, and poststroke neurological deficits, thereby contributing further to the development of PDS over the first 15 months after stroke. [ABSTRACT FROM AUTHOR]