Neurofilaments light: Possible biomarker of brain modifications in bipolar disorder

Introduction: Brain white matter (WM) abnormalities are biomarkers that seem to be involved in bipolar disorder (BD) aetiology and maintenance. Evidences suggest a possible association between neurodegeneration, neuroaxonal alterations and BD. A biomarker that is recently drawing attention is neurofilaments light (NfL) chain, a cytoskeletal intermediate filament protein expressed in neurons. To investigate neuroimaging alterations associated with BD, we studied the association between NfL levels and WM microstructure. Methods: NfL plasma quantification was performed in a sample of 45 depressed BD patients compared with 29 healthy controls (HC) using Quanterix SIMOA assay. Statistical analysis were conducted to evaluate NfL levels differences between BD patients and controls. Analyses of the diffusion data were performed using Tract Based Spatial Statistics (TBSS) on Diffusion Tensor images acquired using a 3.0 Tesla MR scanner. Results: Patients had higher NfL levels than HC (9.13 ± 4.78 vs 4.28 ± 2.39 pg/ml; p < 0.001). The separate-slopes analysis of variance showed a significant interaction of age with diagnosis (Likelihood-ratio test: χ2 = 27.52, p < 0.0001) with significant effects only in the BD sample (p = 0.023). The TBSS analysis, performed within the BD sample, showed a significant positive correlation between NfL levels and axial diffusivity (AD) in a wide single cluster encompassing several tracts. Discussion: Our results suggest that the physiological age-dependent increment of NfL level is augmented in BD, possibly because of increased remodelling and plasticity processes related to an accelerated ageing condition. The positive association between NfL levels and AD, may reflect a condition of remyelination and axonal regeneration.