Neurofilament light and glial fibrillary acidic protein in mood and anxiety disorders: A systematic review and meta-analysis

Abstract

BackgroundNeurofilament 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.MethodsThe study was prospectively registered on PROSPERO (CRD42023434617). We followed the PRISMA guidelines, searched PubMed, Web of Science, PsycINFO, MEDLINE and Embase up to the 31/05/2023, 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, which was pooled using a random-effects model adopting the restricted maximum likelihood estimator.ResultsTwenty-one studies met inclusion criteria, comprising of 2327 individuals (695 major depression, 502 bipolar disorder, and 1130 controls). When we compared people with major depression and controls, there was no difference in NfL (SMD = 0.29; 95% CI: -0.10, 0.68) nor GFAP (SMD = 0.47; 95% CI: -0.74, 1.68). In people with bipolar disorder, NfL was significantly elevated compared to controls (SMD = 0.58; 95% CI: 0.16, 0.99). However, the subgroup analysis including more sensitive assay kits (blood Simoa and CSF ELISA), found no significant difference (SMD = 0.40; 95% CI: -0.04, 0.85). Only one study studied GFAP in bipolar disorder. No studies explored NfL nor GFAP concentrations in anxiety disorders.DiscussionWe found that NfL and GFAP concentrations were not elevated in depression. In bipolar disorder, NfL concentration was elevated, though not in the sensitivity analysis. 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.