Association between serum neurofilament light chains and depression: A cross-sectional study based on NHANES 2013-2014 database

Background: Serum neurofilament light chain (sNfl), identified as a promising biomarker, is a protein released into the bloodstream post-axonal damage. Studies on its correlation with depression, however, remains scarce. The purpose of this study was to investigate the potential relationship between sNfL levels and risk of depression among a representative segment of the U. S. populace. Methods: This study included 1,909 participants from the 2013-2014 National Health and Nutrition Examination Survey. The 9-item Patient Health Questionnaire (PHQ-9 scale) assessed depression symptoms, while sNfl concentrations were measured using the Attelica fully automated immunoassay system. The logistic regression, restricted cubic splines (RCS), and subgroup analysis were performed to assess the relationship between sNfL, lnsNfL (log-transformed values of sNfl), and depression. Results: After adjusting for sociodemographic variables, lifestyle, and chronic conditions, sNfl and lnsNfL levels positively correlated with depression. A unit increase in sNfL and lnsNfL levels was linked to a 0.7 % and 33.8 % rise in depression risk, respectively [OR (95 % CI): 1.007 (1.000, 1.014), p = 0.041 for sNfl; 1.338 (1.015, 1.764), p = 0.039 for lnsNfl]. Additionally, a positive linear association was observed between lnsNfl levels and the risk of depression (p for overall = 0.039, p for nonlinear = 0.189 in RCS). No significant differences were observed across subgroups between lnsNfl and depression, with no significant impact on this relationship from subgroups (All p for interaction >0.05). Conclusion: The findings of our study suggest a significant positive correlation between sNfl and depression, warranting further investigation into the molecular dynamics linking sNfL to depression and subgroup variability.