Systemic Inflammatory Factors and Neuropsychiatric Disorders: A Bidirectional Mendelian Randomization Study

ABSTRACT Background The present study employed Mendelian randomization to scrutinize the causal connections that may exist between 91 distinct inflammatory markers and six neuropsychiatric disorders, namely Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD), anxiety disorders (ANX), depressive disorders (DEP), and unexplained encephalopathy (UE). Discussion The methodology utilized involved the standard inverse variance weighting method within a two‐sample, two‐way Mendelian randomization framework and integrated statistics from genome‐wide association studies. To ascertain the robustness of the identified causal associations, sensitivity analyses were performed with the aid of the MR‐Egger method and the weighted median test. Conclusion The results revealed that 14 distinct systemic inflammatory modulators are potentially causally linked to the risk of developing various neuropsychiatric disorders. Specifically, five were associated with AD, eight with ANX, six with DEP, and one with UE. However, the causal associations involving systemic inflammatory markers with PD and MS require further investigation, particularly with the identification of additional significant genetic variants. Furthermore, the concentration levels of 33 systemic inflammatory factors could be modulated by the occurrence of neuropsychiatric conditions, indicated by this study. These include five affected by AD, eight by PD, six by MS, 12 by ANX, five by DEP, and five by UE.