Two patterns of abnormal FA with different radial features and their relation to polygenic risks in first-episode schizophrenia and unaffected siblings.

BACKGROUND

White matter microstructure abnormalities have been widely observed in schizophrenia, closely associated with clinical symptoms and cognitive deficits. While various alterations have been suggested, the nature of their specific patterns and underlying processes remains unclear. Thus, this study aims to identify these patterns and explore their associations with polygenic burden, cognition, and clinical symptoms.

METHODS

336 participants (133 first-episode schizophrenia [FES], 49 unaffected siblings [SB], and 154 healthy controls [HC]) underwent MRI scanning, clinical and cognitive assessments, and genetic sequencing. DTI preprocessing was performed using the FMRIB Software Library. Group comparisons for fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), mean diffusivity (MD) and mode of anisotropy (MO), and correlation analysis between white matter abnormalities and PRS, clinical symptoms, and cognitive features were conducted.

RESULTS

Two patterns of reduced FA with differing radial features in FES were observed: 1) "FA + RD" pattern with reduced FA and increased RD, including fornix, left stria terminalis, left posterior corona radiata, left retrolenticular part of the internal capsule, and left cerebral peduncle; 2) "FA-only" pattern with reduced FA but normal RD, including left superior fronto-occipital fasciculus, left cingulate gyrus, left posterior thalamic radiation, left superior longitudinal fasciculus, left inferior cerebellar peduncle, bilateral sagittal stratum, bilateral superior corona radiata, and genu of the corpus callosum. FA of the white matter skeleton was negatively correlated with PRS, clinical symptoms, and duration of illness, but positively correlated with cognitive features. In addition, SB showed reduced FA in left sagittal stratum, left posterior thalamic radiation, and left superior longitudinal fasciculus.

CONCLUSION

Our study observed two diffusion patterns of reduced FA with different radial features, of which the abnormalities were associated with polygenic burden, clinical symptoms and cognitive deficits. However, further direct evidence is required to validate and extend these findings.