Neurofilament Light Protein as a Biomarker in Severe Mental Disorders: A Systematic Review

Severe mental disorders (SMDs), such as schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD), are heterogeneous psychiatric diseases that impose a significant societal burden due to their chronic disabling nature. There are no objective and reliable diagnostic tests for SMDs; thus, there is an urgent need for specific biomarkers to improve diagnosis, treatment, and resource allocation. Neurofilaments, found in cerebrospinal fluid and blood, offer reliable diagnostic and prognostic potential. This review discusses the link between neurofilament light chain (NfL) involvement in psychiatric and neurodegenerative diseases and gives insights into the diagnostic and prognostic value of NfL in SMDs. This systematic review searched PubMed, Scopus, and Web of Science databases to answer the research question "Are NfL levels higher in individuals with SMDs compared to healthy controls?" using terms related to neurofilament, SMDs, SZ, BD, and depression. Of 8577 initial papers, 115 were relevant. After exclusions and manual additions, 17 articles were included. Studies indicate elevated NfL levels in SMDs compared to healthy controls, suggesting its potential as a biomarker for SMDs and for distinguishing neurodegenerative diseases from psychiatric disorders. However, further longitudinal research is needed to confirm its reliability for differential diagnosis, disease prediction, and treatment assessment in psychiatry.