Ziyuan Yang, Yandan Shi, Jiayu Wu, Jinqing Su, Yuyao He, Jinhua Hu, Lingyun Xue, Sha Liao, Xiuxian Lu, Xiqi Zhu
CSVD is robustly associated with depression, with the magnitude of this association varying by CSVD imaging markers, population groups and depression types. These findings may have potential implications for recognizing depressive symptoms in individuals with CSVD. However, given the observational nature of the available evidence, the temporal and causal relationship between CSVD and depression remains uncertain, and a potentially bidirectional association cannot be excluded. Future longitudinal studies with standardized imaging protocols and depression assessments are warranted.
BACKGROUND: Cerebral small vessel disease (CSVD) may contribute to depression, but the magnitude and consistency of this association across different CSVD markers, depression subtypes and population groups have not been fully quantified.
METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched up to March 2026. Studies reporting multivariable-adjusted effect estimates for CSVD imaging markers and depression were included. A random-effects model was used to pool odds ratio (OR) with 95% confidence interval (CI). Subgroup analyses, sensitivity analyses and publication bias tests were performed.
RESULTS: CSVD was significantly associated with depression (pooled OR = 1.66; 95% CI: 1.48-1.87). Positive associations were observed for composite CSVD burden scores (OR = 2.62) and across individual imaging markers, including white matter hyperintensities (WMH, OR = 1.40), enlarged perivascular spaces (EPVS, OR = 1.74), and cerebral microbleeds (CMB, OR = 2.06). In contrast, lacunar infarcts (LI) showed no significant association (OR = 1.25; p = 0.344). Subgroup analyses showed variations in the pooled associations across different populations and depression subtypes. The pooled OR was 2.17 in Asian populations and 1.39 in non-Asian populations. For depression subtypes, the pooled OR was 2.00 for post-stroke depression (PSD) and 1.44 for incident depression. Sensitivity analyses confirmed the robustness of the findings.
CONCLUSION: CSVD is robustly associated with depression, with the magnitude of this association varying by CSVD imaging markers, population groups and depression types. These findings may have potential implications for recognizing depressive symptoms in individuals with CSVD. However, given the observational nature of the available evidence, the temporal and causal relationship between CSVD and depression remains uncertain, and a potentially bidirectional association cannot be excluded. Future longitudinal studies with standardized imaging protocols and depression assessments are warranted.