Exploring the Causal Relationships Between Psychiatric Disorders and Diabetic Retinopathy: A Mendelian Randomization Study

Background: Diabetic retinopathy (DR) is a major complication of diabetes that leads to vision impairment and blindness. This study aims to assess the causal relationships between genetically predicted psychiatric disorders and DR risk, as well as the reverse causal effect of DR on psychiatric disorders.

Methods: A 2-sample bidirectional Mendelian randomization (MR) analysis was conducted using genetic variants from large-scale genome-wide association studies as instrumental variables. Exposures included genetically predicted anxiety, attention deficit hyperactivity disorder (ADHD), depression, bipolar disorder, obsessive-compulsive disorder (OCD), personality disorders, and schizophrenia. Causal effects were assessed using inverse variance weighted, MR-Egger, and weighted median methods while addressing pleiotropy and confounding.

Results: The MR analysis identified ADHD as a significant protective factor for DR (odds ratio [OR]=0.913, 95% confidence interval (CI): 0.870-0.957, P < .001). No evidence of a causal relationship was found between DR and other psychiatric disorders, including bipolar disorder (P=.335), depression (P=.188), OCD (P=.931), personality disorders (P=.465), schizophrenia (P=.314), or genetically predicted anxiety (P=.374). Additionally, reverse MR analysis found no evidence that DR causally influences mental health disorders.

Conclusion: These findings suggest that ADHD may exert a protective causal effect on the risk of diabetic retinopathy, underscoring the need to further investigate ADHD-related neuroendocrine and vascular mechanisms in DR pathogenesis.