Exploration of the relationship between autoimmune neurologic diseases and mental disorders: evidence from Mendelian...

Traditional epidemiologic studies suggest that autoimmune neurologic diseases may be associated with mental disorders (MDs). We used Mendelian randomization (MR) studies to explore the causal relationship between autoimmune neurologic diseases and MDs from the genetic perspective.

In our study, autoimmune neurologic diseases include multiple sclerosis (MS), neuromyelitis optica (NMO), and myasthenia gravis (MG); MDs include anxiety, major depressive disorder (MDD), attention deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar affective disorder (BIP). A two-sample MR approach was used to explore causal relationships. The inverse variance weighted (IVW) method was the primary method for MR analysis. In addition, we included all MG datasets for meta-analysis after MR analysis with ADHD.

Regarding the causal effects of MDs on autoimmune neurologic diseases, our analyses revealed a causal relationship between genetically predicted ADHD and MG (OR 2.250; 95% CI 1.267-3.998; p = 0.006), and no potential genetic causal relationships were found between the other diseases. However, according to the MR‒Egger analysis, there was no indication of directional pleiotropy. For the causal effects of autoimmune neurologic diseases on MDs, no potential genetic causal relationships were identified between any of the diseases. We performed a meta-analysis for MG and ADHD, there was no significant genetic causal relationship between ADHD and MG (OR 1.30 (95% CI 0.95-1.79); p = 0.10).

This study revealed that there was no genetic mechanism linking autoimmune neurologic diseases and MDs to each other. These findings provide a foundation for the prevention and treatment of comorbid conditions in clinical research.