Immune-metabolic perspective on the association of seven psychiatric disorders and five common auditory diseases: a bidirectional two-sample Mendelian randomization study and mediation analysis.

Introduction: Although the relationship between psychiatric disorders and common auditory diseases has been discovered in observational studies, the causal linkage between them remains inconclusive.

Methods: The bidirectional two-sample Mendelian randomization (MR) analysis was performed, drawing on the most recent and expansive genome-wide association studies (GWAS) data for seven psychiatric disorders and five common auditory diseases. Additionally, a mediation analysis was conducted using data on 731 immune cell phenotypes and 1400 metabolite levels to explore potential mediating factors influencing the causal pathways.

Results: Autism Spectrum Disorder (ASD) could increase the risk of presbycusis (odds ratio [OR] = 1.161 [95 % confidence interval (CI), 1.042-1.295], P-value = 0.007) through CD25 on CD45RA- CD4 not regulatory T cell (Mediation effect β = 0.017), and Major Depressive Disorder (MDD) could increase the risk of vertigo (OR = 1.215 [95 % CI, 1.043-1.415], P-value = 0.012) through CD33+ HLA DR+ CD14dim Absolute Count (Mediation effect β = 0.007). Alzheimer's Disease (AD) could reduce the risk of presbycusis through four metabolite levels related to lipid metabolism. And Bipolar Disorder I (BD I) could reduce the risk of vertigo, as well as sudden sensorineural hearing loss (SSNHL) could reduce the risk of Post Traumatic Stress Disorder (PTSD).

Conclusion: This study underscores the intricate causal links between psychiatric disorders and auditory diseases. Mediation analyses indicate that immune cells are facilitators of positive effects, while metabolite levels play a protective role. These insights offer potential pathways for more effective clinical diagnosis and treatment.