White matter abnormalities across the lifespan of schizophrenia: a harmonized multi-site diffusion MRI study.

Cetin-Karayumak, Suheyla; Di Biase, Maria A; Chunga, Natalia; Reid, Benjamin; Somes, Nathaniel; Lyall, Amanda E; Kelly, Sinead; Solgun, Bengisu; Pasternak, Ofer; Vangel, Mark; Pearlson, Godfrey; Tamminga, Carol; Sweeney, John A; Clementz, Brett; Schretlen, David; Viher, Petra Verena; Stegmayer, Katharina Deborah Lena; Walther, Sebastian; Lee, Jungsun; Crow, Tim; ... (2020). White matter abnormalities across the lifespan of schizophrenia: a harmonized multi-site diffusion MRI study. Molecular psychiatry, 25(12), pp. 3208-3219. Nature Publishing Group 10.1038/s41380-019-0509-y

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Several prominent theories of schizophrenia suggest that structural white matter pathologies may follow a developmental, maturational, and/or degenerative process. However, a lack of lifespan studies has precluded verification of these theories. Here, we analyze the largest sample of carefully harmonized diffusion MRI data to comprehensively characterize age-related white matter trajectories, as measured by fractional anisotropy (FA), across the course of schizophrenia. Our analysis comprises diffusion scans of 600 schizophrenia patients and 492 healthy controls at different illness stages and ages (14-65 years), which were gathered from 13 sites. We determined the pattern of age-related FA changes by cross-sectionally assessing the timing of the structural neuropathology associated with schizophrenia. Quadratic curves were used to model between-group FA differences across whole-brain white matter and fiber tracts at each age; fiber tracts were then clustered according to both the effect-sizes and pattern of lifespan white matter FA differences. In whole-brain white matter, FA was significantly lower across the lifespan (up to 7%; p < 0.0033) and reached peak maturation younger in patients (27 years) compared to controls (33 years). Additionally, three distinct patterns of neuropathology emerged when investigating white matter fiber tracts in patients: (1) developmental abnormalities in limbic fibers, (2) accelerated aging and abnormal maturation in long-range association fibers, (3) severe developmental abnormalities and accelerated aging in callosal fibers. Our findings strongly suggest that white matter in schizophrenia is affected across entire stages of the disease. Perhaps most strikingly, we show that white matter changes in schizophrenia involve dynamic interactions between neuropathological processes in a tract-specific manner.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > Translational Research Center

UniBE Contributor:

Viher, Petra; Stegmayer, Katharina Deborah Lena and Walther, Sebastian


600 Technology > 610 Medicine & health




Nature Publishing Group




Sebastian Walther

Date Deposited:

04 Nov 2019 14:25

Last Modified:

06 Dec 2020 01:30

Publisher DOI:


PubMed ID:






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