Association between methylmalonic acid and prevalence of depression in US adults: evidence from NHANES 2011–2014

<b>Background</b>: Depression is a prevalent mental disorder with high morbidity and mortality globally. Methylmalonic acid (MMA) is involved in the pathogenesis of numerous diseases. However, it is unclear whether there is an association between MMA and the prevalence of depression.<b>Methods</b>: This study enrolled 7866 US adults from the 2011-2014 survey of the National Health and Nutrition Examination Survey (NHANES). Individuals were categorized into depression group and non-depression group based on Patient's Health Questionnaire-9 (PHQ-9) score. The association between MMA concentrations and prevalence of depression was analysed by multivariate logistic and linear regression, restricted cubic spline regression, and subgroup analysis. Mediation analysis was used to explore the role of inflammation in the relationship between MMA and depression.<b>Results</b>: MMA concentrations were higher in participants with depression than those without depression. There was a positive and linear relationship of MMA concentrations with PHQ-9 score and depression risk, respectively. Moreover, the association was stable in most subgroups. Furthermore, inflammatory factors were positively correlated to MMA concentrations and prevalence of depression. In addition, white blood cell, neutrophil and alkaline phosphatase (ALP) mediated the relationship between MMA and depression.<b>Conclusion:</b> Our findings revealed that there was a linear and positive correlation between MMA and the prevalence of depression in US adults, which might be mediated by inflammation.