Shared genetic risk factors for depression and stroke

Background: The comorbidity of major depressive disorder (MDD) and stroke are common in clinic. There is a growing body of evidence suggesting a bi-directional relationship between stroke and depression. However, the mechanisms underlying the relationship between MDD and stroke are poorly investigated. Considering that both MDD and stroke can be heritable and are influenced by multiple risk genes, shared genetic risk factors between MDD and stroke may exist. Objective: The objective is to review the existing evidence for common genetic risk factors for both MDD and stroke and to outline the possible pathophysiological mechanisms mediating this association. Methods: A systematic review and meta-analysis was performed. Gene association studies regarding stroke and depression were searched in the database PubMed, CNKI, and Chinese Biomedical Literature Database before December 2018. Statistical analysis was performed using the software Revman 5.3. Results: Genetic polymorphisms of 4 genes, methylenetetrahydrofolate reductase (MTHFR) and apolipoprotein E (ApoE) have been demonstrated to associate with the increased risk for both MDD and stroke, while the association between identified polymorphisms in angiotensin converting enzyme (ACE) and serum paraoxonase (PON1) with depression is still under debate, for the existing studies are insufficient in sample size. These results suggest the possible pathophysiological mechanisms that are common to these two disorders, including immune-inflammatory imbalance, increased oxidative and nitrative stress, dysregulation of lipoprotein and lipid metabolism, and changes of cerebrovascular morphology and function. Other associated genes with few or conflicting results have also been included, and a few studies have investigated the effects of the described polymorphisms on MDD and stroke comorbidity, such as post stroke depression. Conclusion: These findings suggest that shared genetic pathways may contribute to the comorbidity of MDD and stroke. Studies to evaluate the shared genetic variations between MDD and stroke may provide insights into the molecular mechanisms that trigger disease progression.