Abstract WP120: Association Between Mental Disorders and Risk of Stroke: A Meta-analysis of Mendelian Randomization Studies.

Introduction: Stroke remains a leading cause of mortality and long-term disability worldwide. In recent years, mental disorders have emerged as potential contributors to cerebrovascular disease, with observational studies reporting associations between various psychiatric conditions and stroke. However, whether these associations are causal is uncertain. Hypothesis: We tested the hypothesis that genetic predisposition to mental disorders including anxiety disorders, depression, attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, and autism spectrum disorder (ASD) is a causal risk factor for stroke. This association was evaluated by systematically pooling evidence from existing Mendelian randomization (MR) studies. Methods: A systematic search of PubMed, Embase, and Cochrane databases was done through June 2025 for MR studies assessing the association between genetically predicted mental disorders and stroke. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using random-effects meta-analysis. Heterogeneity was assessed using the I 2 statistic, and p value < 0.05 was considered for statistical significance. Results: Of 638 studies found in the initial screening, 13 MR studies met inclusion criteria and were included in the meta-analysis. Our pooled analysis revealed significant association between depression and increased risk of stroke (OR 1.09, 95% CI 1.03-1.14; p < 0.01). Similarly, ADHD showed a significant association with stroke risk (OR 1.14, 95% CI 1.09-1.19; p < 0.01). In contrast, no significant associations were observed for anxiety disorders (OR 0.86, 95% CI 0.58-1.28; p = 0.45), bipolar disorder (OR 0.97, 95% CI 0.94-1.00; p = 0.06), schizophrenia (OR 1.00, 95% CI 0.99-1.02; p = 0.66) or ASD (OR 1.06, 95% CI 0.99-1.14; p = 0.07). Heterogeneity across studies was low to moderate (I 2 = 0%-46%). Conclusion: In conclusion, genetic predisposition to depression and ADHD was associated with an increased risk of stroke, suggesting a potential causal relationship. These findings suggest that incorporating psychiatric evaluation particularly for depression and ADHD into routine vascular risk assessment may improve early identification of individuals at higher risk. Further investigation is warranted to determine whether targeted management of these conditions could contribute to stroke prevention strategies.