Patterns of white matter (WM) integrity in individuals at ultra high-risk for psychosis (UHR) and associations to level of functioning and clinical symptoms

Kristine Krakauer1,2,3, Bjørn H. Ebdrup2,4, Birte Glenthøj2,4, Jayachandra Raghava2,3,4, Dorte Nordholm1,2, Lasse Randers1,2, Egill Rostrup3, Merete Nordentoft1,2; 1Mental Health Centre Copenhagen, Copenhagen University Hospital, DK-2900, Hellerup, Denmark, 2Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, DK-2600 Glostrup, 3Functional Imaging Unit, Department of Diagnostics, Copenhagen University Hospital, DK-2600 Glostrup, Denmark, 4Centre for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Centre Glostrup, Copenhagen University Hospital, DK-2600 Glostrup, Denmark

Background: UHR-individuals start having symptoms and decline in functioning around early adolescence. An important neurodevelopmental change in this period is WM-development, and disruption in this could play a role in the dysfunctions. WM-abnormalities are well known in schizophrenia but scarcely studied in UHR, and the link between WM-abnormalities, level of functioning, and symptomatology is poorly understood. Methods: Forty-five UHR-individuals and 45 healthy controls (HCs) underwent Magnetic Resonance Imaging and psychopathological testing. Using the multivariate partial least square (PLS) we compared patterns of WM-integrity obtained with diffusion tensor imaging (DTI) in UHR-individuals and HCs, and investigated if these were related to level of functioning and symptomatology. Preliminary results: Comparing patterns of WM-connectivity in UHR-individuals and HCs revealed one significant latent variable (LV) accounting for 60% of the variance. This showed that UHR-individuals had lower fractional anisotropy (FA) and mode of anisotropy (MO) and higher mean diffusivity (MD) and radial diffusivity (RD) predominantly in the posterior part of the brain, while the opposite was seen in the anterior part of the brain. Correlating WM-connectivity to symptomatology and level of functioning showed four significant LVs. LV1 accounted for 33% of the variance and identified a global pattern of WM-connectivity where both severity of negative(SANS) and positive(CAARMS) symptoms correlated negatively to FA and MO but positively to MD and RD, while level of functioning(SOFAS) displayed opposite correlations. Conclusion: Our results imply that WM-abnormalities, possibly related to dysmyelination or changes in fiber-structure, are present in UHR-individuals at baseline and seem to be related to symptomatology.

Topic Area: Ultra High Risk / Prodromal Research

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