Neurofilament light chain as novel blood biomarker of disturbed neuroaxonal integrity in patients with ketamine dependence

Abstract

Objectives Chronic and heavy ketamine use has been associated with persistent neurocognitive impairment and structural brain abnormalities. Blood levels of neurofilament light chain (NFL) was recently proposed as a measure of axonal integrity in several neuropsychiatric disorders. We aimed to characterise the axonal neurotoxicity of chronic ketamine use and its relationship to relevant clinical outcomes. Methods We enrolled 65 treatment-seeking ketamine-dependent patients (55 males and 10 females) and 60 healthy controls (51 males and 9 females). Blood NFL levels measured by single molecule array (SiMoA) immunoassay. We compared NFL levels between groups and used regression analyses to identify clinical variables related to NFL levels. Results Ketamine-dependent patients had significantly higher NFL levels compared to controls (p < 0.001). A multivariate regression showed that age (p < 0.05) and lifetime history of major depressive disorder (MDD) (p < 0.01) predicted high NFL blood levels in patients. Subsequent group comparisons showed that specifically ketamine-dependent patients with a lifetime history of MDD had significantly increased NFL levels than those without (p < 0.05). Conclusions These results suggest substantial neuroaxonal alterations following chronic and heavy ketamine use. The pronounced increase of NFL levels in the MDD subgroup warrants further investigation of a potential neuroaxonal vulnerability of depressed patients to ketamine.