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Objective The neurodevelopmental hypothesis of psychosis suggests that disrupted white matter ( WM) maturation underlies disease onset. In this longitudinal study, we investigated WM connectivity and compared WM changes between individuals at ultra-high-risk for psychosis ( UHR) and healthy controls ( HCs). Method Thirty UHR individuals and 23 HCs underwent MR diffusion tensor imaging before and after 12 months of non-manualized standard care. Positive and negative symptoms and level of functioning were assessed. Tract-based spatial statistics were employed. Results During 12 months, none of the UHR individuals transitioned to psychosis. Both UHR individuals and HCs increased significantly in fractional anisotropy ( FA). UHR individuals showed significant FA increases predominantly in the left superior longitudinal fasciculus ( SLF) ( P = 0.01), and HCs showed significant FA increases in the left uncinate fasciculus ( P = 0.03). Within UHR individuals, a significant positive correlation between FA change and age was observed predominantly in the left SLF ( P = 0.02). Within HCs, no significant correlation between FA change and age was observed. No significant correlations between baseline FA and clinical outcomes were observed; however, FA changes were significantly positively correlated to changes in negative symptoms ( P = 0.04). Conclusion As normal brain maturation occurs in a posterior to frontal direction, our findings could suggest disturbed WM maturation in UHR individuals. [ABSTRACT FROM AUTHOR]

BackgroundIndividuals at ultra-high-risk (UHR) for psychosis present with emerging symptoms and decline in functioning. Previous univariate analyses have indicated widespread white matter (WM) aberrations in multiple brain regions in UHR individuals and patients with schizophrenia. Using multivariate statistics, we investigated whole brain WM microstructure and associations between WM, clinical symptoms, and level of functioning in UHR individuals.MethodsForty-five UHR individuals and 45 matched healthy controls (HCs) underwent magnetic resonance diffusion tensor imaging (DTI) at 3 Tesla. UHR individuals were assessed with the Comprehensive Assessment of At-Risk Mental States, Scale for the Assessment of Negative Symptoms, and Social and Occupational Functioning Assessment Scale. Partial least-squares correlation analysis (PLSC) was used as statistical method.ResultsPLSC group comparisons revealed one significant latent variable (LV) accounting for 52% of the cross-block covariance. This LV indicated a pattern of lower fractional anisotropy (FA), axial diffusivity (AD), and mode of anisotropy (MO) concomitant with higher radial diffusivity (RD) in widespread brain regions in UHR individuals compared with HCs. Within UHR individuals, PLSC revealed five significant LVs associated with symptoms and level of functioning. The first LV accounted for 31% of the cross-block covariance and indicated a pattern where higher symptom score and lower level of functioning correlated to lower FA, AD, MO, and higher RD.ConclusionsUHR individuals demonstrate complex brain patterns of WM abnormalities. Despite the subtle psychopathology of UHR individuals, aberrations in WM appear associated with positive and negative symptoms as well as level of functioning. [ABSTRACT FROM AUTHOR]