Association between different frequencies of age-related hearing loss and depression: A Mendelian randomization and observational study

BACKGROUND: Hearing loss and depression are common among older adults, but the association between different frequencies of age-related hearing loss (ARHL) and depression remains unclear, and their causal relationship is yet to be established.This study aimed to explore the association between ARHL at different frequencies and depression and evaluate their causal relationship using Mendelian randomization (MR). METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) were analyzed using multivariable logistic regression and negative binomial regression to assess the effects of low-frequency, speech-frequency, and high-frequency ARHL on depression, with subgroup analyses by race/ethnicity. GWAS data were used for MR analyses with five methods, including inverse-variance weighting (IVW) and MR-Egger regression. Sensitivity analyses assessed result robustness. RESULTS: Among 2378 participants, low-frequency and speech-frequency ARHL were associated with a 50 % (OR = 1.5, 95 % CI: 1.1-2.1) and 40 % (OR = 1.4, 95 % CI: 1.0-1.9) increased risk of depression, respectively. High-frequency ARHL showed no significant association. Subgroup analyses revealed stronger associations in Mexican Americans. MR analyses showed no causal relationship between genetically predicted ARHL and depression (IVW OR = 0.8530, 95 % CI: 0.7102-1.0244).The MR-Egger regression analysis found no evidence of horizontal pleiotropy (P > 0.05), and the heterogeneity test indicated that the random-effects IVW model was more suitable (P < 0.001). CONCLUSION: Low- and speech-frequency ARHL are associated with increased depression risk, but MR analyses do not support a causal relationship.