Abstract Objective Depression is the most common psychiatric comorbidity in patients with epilepsy (PWE) but remains frequently underdiagnosed. Identifying objective biomarkers may improve early detection and intervention. Neurofilament light chain (NfL), a marker of neuroaxonal injury, has been linked to both epilepsy‐related neuronal damage and depression, yet its role in comorbidity is unclear. Methods We conducted a cross‐sectional study including 152 adult PWE recruited from a large tertiary hospital in Northeast China. Depressive symptoms were assessed using the Hamilton Depression Scale (HAMD), and plasma NfL concentrations were measured by enzyme‐linked immunosorbent assay. Binary logistic regression models were applied to examine the association between plasma NfL and depressive symptoms, and linear regression models with HAMD scores as a continuous outcome were performed as sensitivity analyses. Both approaches were conducted with adjustment for potential confounders. Receiver operating characteristic (ROC) analysis was conducted to evaluate the discriminative performance of plasma NfL, and k ‐fold cross‐validation ( k = 5) was performed to assess the robustness of the ROC analysis. Results Of the 152 participants, 61 (40.1%) had depressive symptoms. Higher plasma NfL levels were independently associated with both increased odds of depressive symptoms and higher HAMD scores. ROC analysis demonstrated good discriminative accuracy (area under the curve AUC = .838), with an optimal cutoff value of 44.85 pg/mL yielding a sensitivity of .82 and a specificity of .74. The mean AUC obtained from k ‐fold cross‐validation was .842, which was consistent with the overall ROC result. Significance These findings suggest that plasma NfL may serve as a candidate biomarker for identifying comorbid depression in epilepsy and provide new insight into shared neurobiological mechanisms.
Chen et al. (2026) studied this question.