Overview of neurofilament light chain in mental disorders

Abstract

Neurofilament light chain (NfL), released following neuroaxonal damage, serves as a biomarker in neurological diseases and shows potential in mental disorders. This narrative review aims to clarify the current research status of NfL in five mental disorders, namely depression, bipolar disorder, schizophrenia, substance use disorder, and anxiety, as well as in electroconvulsive therapy. We conducted a literature review using articles from PubMed, EMBASE, Google Scholar, and Web of Science databases. In depression, most population-based studies supported positive associations between NfL and depressive symptoms, whereas clinical findings were mixed. For bipolar disorder, most studies reported elevated NfL levels compared to healthy controls. In schizophrenia, however, more studies found no significant elevation compared with healthy controls. For substance use disorder, studies reported dynamic changes in NfL across withdrawal stages, with most evidence derived from alcohol dependence. The only study on anxiety disorder lacked patient-control comparisons. Studies on electroconvulsive therapy consistently reported no significant changes in NfL after treatment. Overall, research on NfL in mental disorders remains at a preliminary stage and requires further validation, as well as mechanistic and longitudinal studies.

Keywords: Neurofilament light chain; Mental disorders; Biomarker; Mood disorders; Schizophrenia; Substance use disorder; Electroconvulsive therapy

Core Tip: This minireview provides an overview of current findings on neurofilament light chain (NfL) in five mental disorders and electroconvulsive therapy. Heterogeneity exists across mental disorders, with mixed findings in clinical studies on depression, more consistently elevated NfL levels observed in bipolar disorder, predominantly no significant differences noted in schizophrenia, and dynamic changes observed during substance withdrawal. In contrast, studies on electroconvulsive therapy consistently show no significant changes in NfL levels. Overall, research on NfL in mental disorders remains at a preliminary stage and warrants further validation, as well as mechanistic and longitudinal studies.