Ketamine-dependent patients with persistent psychosis have higher neurofilament light chain levels than patients with schizophrenia.

People who develop persistent psychosis from heavy, chronic ketamine use show the highest blood levels of neurofilament light chain (NFL), a marker of nerve cell damage, compared to ketamine users without persistent psychosis, people with schizophrenia, and healthy controls. NFL levels averaged 24.5 pg/mL in ketamine users with persistent psychosis, 12.9 pg/mL in those without, 9.2 pg/mL in schizophrenia patients, and 6.2 pg/mL in controls. Ketamine dependence was linked to higher NFL than schizophrenia, and the elevated NFL in those with persistent psychosis suggests a distinct neurobiological basis for this condition, even though its symptoms resemble schizophrenia.

Study at a glance

Abstract

Ketamine can induce persisting psychosis in a subset of individuals who use it chronically and heavily. Previously, we found that the psychopathology and cognitive impairments in patients with ketamine dependence (KD) exhibiting persistent psychosis (KPP) bear resemblances with schizophrenia, albeit with less severity in those with no persistent psychosis (KNP). Furthermore, we also showed that patients with KD had higher blood levels of neurofilament light chain (NFL), a biomarker for neuroaxonal injury, compared to healthy controls. In this study, we aimed to investigate the differences in NFL levels between patients with KPP and KNP while comparing the levels of individuals with schizophrenia and healthy controls. We enrolled 64 treatment-seeking ketamine-dependent patients (53 with KNP and 11 with KPP), 37 medication-free patients with schizophrenia, and 80 healthy controls. Blood NFL levels were measured by single molecule array immunoassay. NFL levels were highest in the KPP subgroup, followed by the KNP subgroup, and then the schizophrenia and control groups (mean ± SD: 24.5 ± 24.7, 12.9 ± 10.9, 9.2 ± 12.2, and 6.2 ± 2.2 pg/mL, respectively), with no significant difference observed between the schizophrenia and control groups. We found that KD is associated with higher NFL levels compared to schizophrenia, with the KPP subgroup showing the most consistent alterations. The observation of accentuated neuroaxonal pathology in individuals with KPP implies that this clinical manifestation is associated with a specific neurobiological phenotype, despite prior evidence suggesting syndromal similarity between schizophrenia and KPP.