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Major depression and small vessel stroke: a Mendelian randomization analysis.

Huan Cai1, Biyang Cai2, Hao Zhang3

  • 1Department of Neurology, Zhongshan City People's Hospital, 2 East Sunwen Road, Zhongshan, 528403, Guangdong, China. ch.neurol@gmail.com.

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Summary

Major depressive disorder (MDD) may causally increase the risk of small vessel stroke (SVS). This genetic study found a significant association between MDD predisposition and SVS risk, suggesting potential therapeutic targets.

Keywords:
Ischemic strokeMajor depressionMendelian randomizationSingle-nucleotide polymorphismSmall vessel stroke

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Genetics

Background:

  • Observational studies suggest a link between depression and ischemic stroke, but causality is unproven.
  • Major Depressive Disorder (MDD) is a common mental health condition with significant public health implications.

Purpose of the Study:

  • To investigate the causal relationship between Major Depressive Disorder (MDD) and ischemic stroke, particularly the small vessel stroke (SVS) subtype.
  • Utilize Mendelian randomization to assess causality, overcoming limitations of observational studies.

Main Methods:

  • Employed genome-wide association study (GWAS) data for MDD from the Psychiatric Genetics Consortium, using 72 single-nucleotide polymorphisms as instrumental variables.
  • Analyzed large-scale ischemic stroke and subtype data from the MEGASTROKE consortium (34,217 cases, 406,111 controls) of European ancestry.
  • Performed primary analysis using the inverse-variance weighted method, supplemented by sensitivity analyses to ensure robustness.

Main Results:

  • A genetic predisposition to higher MDD risk was significantly associated with an increased risk of small vessel stroke (SVS) (OR, 1.33; p=0.009).
  • No significant causal association was found between MDD and large artery stroke, cardioembolic stroke, or overall ischemic stroke.
  • The observed association between MDD and SVS remained robust across multiple sensitivity analyses.

Conclusions:

  • Provided evidence supporting a potential causal effect of Major Depressive Disorder (MDD) on the risk of developing small vessel stroke (SVS).
  • Highlights the need for further research into whether interventions targeting depression could mitigate the burden of SVS.