Associations between structural brain changes and blood neurofilament light chain protein in treatment-resistant schizophrenia

Objective: Around 30% of people with schizophrenia are refractory to antipsychotic treatment (treatment-resistant schizophrenia). Abnormal structural neuroimaging findings, in particular volume and thickness reductions, are often described in schizophrenia. Novel biomarkers of active brain pathology such as neurofilament light chain protein are now expected to improve current understanding of psychiatric disorders, including schizophrenia. This study explored whether treatment-resistant schizophrenia individuals exhibit different associations between plasma neurofilament light chain protein levels and regional cortical thickness reductions compared with controls. Methods: Plasma neurofilament light chain protein levels were measured, and T1-weighted magnetic resonance imaging sequences were obtained and processed via FreeSurfer for each participant. General linear models adjusting for age and body mass index were estimated to determine whether the interaction between diagnostic group and plasma neurofilament light chain protein level predicted lower cortical thickness across frontotemporal structures and the insula. Results: A total of 79 participants were included: 37 treatment-resistant schizophrenia and 42 healthy controls. Significant (false discovery rate-corrected) cortical thinning of the left (p = 0.005, eta(2)(p) = 0.100) and right (p = 0.002, eta(2)(p) = 0.149) insula, and left inferior temporal gyrus (p < 0.001, eta(2)(p) = 0.143) was associated with higher levels of plasma neurofilament light chain protein in treatment-resistant schizophrenia, but not in healthy controls. Conclusions: The association between regional thickness reduction of the bilateral insula and left inferior temporal gyrus with plasma neurofilament light chain protein may reflect a neuroprogressive component to schizophrenia, which is not observed in the normal population.