Plasma neurofilament light protein provides evidence of accelerated brain ageing in treatment-resistant schizophrenia

BackgroundAccelerated brain aging has been observed across multiple psychiatric disorders. Blood markers of neuronal injury such as Neurofilament Light (NfL) protein may therefore represent biomarkers of accelerated brain aging in these disorders. The current study aimed to examine whether relationships between age and plasma NfL were increased in individuals with primary psychiatric disorders compared to healthy individuals. MethodsPlasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), a large reference normative healthy control (HC) group (n= 1,926) and a locally-acquired HC sample (n = 59). A general linear model (GLM) was used to examine diagnosis by age interactions on NfL z-scores using the large normative HC sample as a reference group. Significant results were then validated using the locally-acquired HC sample. Resultsa GLM identified a significant age by diagnosis interaction for TRS vs HCs and BPAD vs HCs. Post hoc analyses revealed a positive correlation between NfL levels and age among individuals with TRS, whereas a negative correlation was found among individuals with BPAD. However, only the TRS findings were replicated using the locally-acquired HC sample. Post hoc analyses revealed that individuals with TRS aged <40 had lower NfL levels compared to same-age HCs, whereas individuals with TRS aged >40 had higher NfL levels compared to same-age HCs. ConclusionsThese findings add to the growing literature supporting the notion of accelerated brain ageing in schizophrenia-spectrum disorders.