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

白质 部分各向异性 神经病理学 磁共振弥散成像 精神分裂症(面向对象编程) 神经科学 心理学 精神病 胼胝体 扩散成像 纤维束成像 磁共振成像 医学 病理 疾病 精神科 放射科
作者
Suheyla Cetin‐Karayumak,Maria A. Di Biase,Natalia Chunga,Benjamin Reid,Nathaniel Somes,Amanda E. Lyall,Sinéad Kelly,Bengisu Solgun,Ofer Pasternak,Mark Vangel,Godfrey D. Pearlson,Carol A. Tamminga,John A. Sweeney,Brett A. Clementz,David Schretlen,Petra Viher,Katharina Stegmayer,Sebastian Walther,Jung Sun Lee,Tim Crow,Anthony James,Aristotle N. Voineskos,Robert Boyer,Philip R. Szeszko,Anil K. Malhotra,Rachal Hegde,Robert W. McCarley,Matcheri S. Keshavan,Martha E. Shenton,Yogesh Rathi,Marek Kubicki
出处
期刊:Molecular Psychiatry [Springer Nature]
卷期号:25 (12): 3208-3219 被引量:122
标识
DOI:10.1038/s41380-019-0509-y
摘要

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.
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