Association of Serum Neurofilament Light Chain with Depressive Symptoms: a population-based study

Background: Neurofilament light chain proteins (NfL) are widely accepted biomarkers of neuronal injury, and depressive symptoms are related to neuronal injury. Nevertheless, evidences of the association between NfL and depressive symptoms are still limited. This is the first population-based study to examine the association between NfL and depressive symptoms in general population. Methods We included 1907 participants with measurement of serum NfL from the 2013–2014 U.S. National Health and Nutrition Examination Survey. Depressive symptoms were measured by the 9-item Patient Health Questionnaire. Logistic regression models were conducted to examine associations between serum NfL levels and depressive symptoms. Restricted cubic spline regressions were applied to estimate the possible nonlinear relationships between them. Results Increased serum NfL were associated with higher risk of depressive symptoms after adjusted for confounder factors (per SD: odds ratios [OR] = 1.16, 95% confidence intervals [CI]: 1.02–1.34). Individuals with higher serum NfL (> 21.8 pg/ml, the upper 20% quantile) had a higher likelihood of depressive symptoms compared to normal counterparts (OR = 1.50, 95% CI: 1.01–2.22), and sensitivity analysis using different grouping criteria provided similar results. Furthermore, restricted cubic spline regression analysis demonstrated that a near-linear association occurred between serum NfL and the risk of depressive symptoms (P-nonlinear = 0.681, P-overall < 0.001). Conclusions This study found linear association between serum NfL levels and depressive symptoms in general population. Our findings support that serum NfL levels may be a novel biomarker for depressive symptoms, further studies are needed to validate our findings underlying this association.