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

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; <i>p</i> = 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); <i>p</i> = 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.

传统流行病学研究提示，自身免疫性神经系统疾病可能与精神障碍（mental disorders, MDs）存在关联。本研究采用孟德尔随机化（Mendelian randomization, MR）方法，从遗传学层面探讨自身免疫性神经系统疾病与精神障碍之间的因果关系。本研究涉及的自身免疫性神经系统疾病包括多发性硬化（multiple sclerosis, MS）、视神经脊髓炎（neuromyelitis optica, NMO）及重症肌无力（myasthenia gravis, MG）；精神障碍则涵盖焦虑症、重度抑郁症（major depressive disorder, MDD）、注意缺陷多动障碍（attention deficit/hyperactivity disorder, ADHD）、精神分裂症及双相情感障碍（bipolar affective disorder, BIP）。本研究采用双样本孟德尔随机化方法探究因果关联，以逆方差加权（inverse variance weighted, IVW）法作为MR分析的核心方法。此外，在针对注意缺陷多动障碍与重症肌无力完成MR分析后，我们纳入所有重症肌无力数据集进行了荟萃分析。在精神障碍对自身免疫性神经系统疾病的因果效应方面，分析结果显示，遗传学预测的注意缺陷多动障碍与重症肌无力之间存在因果关联（比值比OR=2.250；95%置信区间CI：1.267–3.998；*p*=0.006），其余疾病组合未发现潜在的遗传因果关系。不过，MR-Egger回归分析结果未提示存在方向性多效性。在自身免疫性神经系统疾病对精神障碍的因果效应方面，本研究未在任意疾病组合中发现潜在的遗传因果关系。针对重症肌无力与注意缺陷多动障碍的荟萃分析结果显示，二者间未存在显著的遗传因果关联（OR=1.30（95%CI：0.95–1.79）；*p*=0.10）。本研究表明，自身免疫性神经系统疾病与精神障碍之间并不存在相互关联的遗传机制。上述研究结果为临床研究中共病患者的防治工作提供了理论依据。