The World Journal of Biological Psychiatry | March 30, 2021

Liu YL, Bavato F, Chung AN, Liu TH, Chen YL, Huang MC and Quednow BB

World J Biol Psychiatry. 2021:1-28

DOI: 10.1080/15622975.2021.1907709

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 characterize 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<.001). A multivariate regression showed that age (p<.05) and lifetime history of major depressive disorder (MDD) (p<.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<.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.