Potential causal link observed between depression on cerebral small vessel disease: Study

A new study published in the Journal of Stroke and Cerebrovascular Diseases showed a possible link between cerebral small vessel disease (cSVD) and genetic susceptibility to depression.

The degenerative condition known as cerebral small vessel disease (cSVD) affects the brain's tiny blood vessels and is linked to a higher risk of stroke and dementia. White matter hyperintensities (WMH), cerebral microbleeds (CMBs), dilated perivascular spaces, and lacunar infarcts are some of the magnetic resonance imaging (MRI) characteristics that define cSVD.

Finding the risk factors for cSVD is essential to lessening its increasing burden because there are now no viable treatments for it. Few studies have looked at depression as a risk factor for cSVD, despite the fact that cSVD has been associated with an elevated risk of depression. Despite the small patient sample and unclear causality, one cross-sectional investigation found a correlation between depression and cSVD in individuals without type 2 diabetes.

A meta-analysis of genome-wide association studies of depression (371,184 patients and 978,703 controls) yielded genetic tools for depression liability. The relationships between genetic susceptibility to depression and cSVD radiographic measures (white matter hyperintensity [WMH] volume, cerebral microbleeds [CMBs], and burden of perivascular spaces [PVS]) and clinical outcomes (small vessel stroke [SVS], deep intracerebral hemorrhage [ICH]) were investigated using Mendelian randomization (MR). The random-effects inverse-variance weighted technique was used for the primary analysis. Sensitivity analyses were performed to see how resilient the results were to MR assumption breaches.

A greater risk of SVS (odds ratio [OR], 1.36; 95% CI], 1.14-1.62; P = 5.4 x 10-4) and deep ICH (OR, 1.82; 95% CI, 1.14–2.89; P = 0.012) was linked to genetic vulnerability to depression. In line with this discovery, increased WMH volume (β, 0.09; 95% CI, 0.02–0.16; P = 0.017) was linked to genetic vulnerability to depression, but not to CMBs or PVS (P > 0.05).

Overall, evidence for a possible causal relationship between depression liability and cSVD was discovered in this study. Given the prevalence of depression and cSVD worldwide, more investigation into possible common processes and treatment approaches is necessary.

Source:

Wang, M., Daghlas, I., & Wei, N. (2025). Genetic liability to depression and cerebral small vessel disease: A Mendelian randomization study. Journal of Stroke and Cerebrovascular Diseases: The Official Journal of National Stroke Association, 108385, 108385. https://doi.org/10.1016/j.jstrokecerebrovasdis.2025.108385