Neurofilament light and glial fibrillary acidic protein in mood and anxiety disorders: A systematic review and meta-analysis
Matthew Kang, Jasleen Grewal, Dhamidhu Eratne, Charles B. Malpas, Wei‐Hsuan Chiu, Kasper Katisko, Eino Solje, Alexander Santillo, Philip B. Mitchell, Malcolm Hopwood, Dennis Velakoulis
Abstract
• NfL and GFAP are biomarkers of neuronal injury and inflammation. • These biomarkers are elevated in neurodegenerative disorders such as dementia. • NfL was found to be mildly elevated in bipolar disorder, but not in major depression. • There was significant heterogeneity in the studies, including the assay kits that were used. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers of neuronal injury measurable in cerebrospinal fluid (CSF) and blood. Despite their potential as diagnostic tests for neurodegenerative disorders, it is unclear how they behave in mood and anxiety disorders. We conducted a systematic review and meta -analysis to investigate whether NfL and GFAP concentrations were altered in adults with mood and anxiety disorders compared to healthy controls. We searched PubMed, Web of Science, PsycINFO, MEDLINE and Embase through August 20, 2024, and assessed relevant studies and their risk of bias. The primary outcome was the standardised mean difference (SMD) and 95 % confidence interval (95 % CI) of NfL and GFAP concentrations. Twenty-nine studies comprising 2,962 individuals (927majordepression,804bipolardisorder,and1,231controls). When we compared individuals with major depression and healthy controls, there was no difference in NfL nor GFAP levels. In individuals with bipolar disorder, NfL was significantly elevated compared to controls (SMD = 0.53; 95 % CI: 0.20, 0.85; p = 0.005). Only one study reported on NfL levels anxiety disorders. Our study informs clinicians about how to interpret these emerging biomarkers in determining whether a person’s symptoms are caused by a neurodegenerative or mood disorder. The mild elevation of NfL in bipolar disorder may suggest underlying neuroaxonal injury, warranting further research into its clinical and prognostic significance.