Abstract
Neuroimaging studies demonstrate gray matter (GM) macrostructural abnormalities in patients with schizophrenia (SCZ). While ex-vivo and genetic studies suggest cellular pathology associated with abnormal neurodevelopmental processes in SCZ, few in-vivo measures have been proposed to target microstructural GM organization. Here, we use diffusion heterogeneity- to study GM microstructure in SCZ. Structural and diffusion magnetic resonance imaging (MRI) were acquired on a 3 Tesla scanner in 46 patients with SCZ and 37 matched healthy controls (HC). After correction for free water, diffusion heterogeneity as well as commonly used diffusion measures FA and MD and volume were calculated for the four cortical lobes on each hemisphere, and compared between groups. Patients with early course SCZ exhibited higher diffusion heterogeneity in the GM of the frontal lobes compared to controls. Diffusion heterogeneity of the frontal lobe showed excellent discrimination between patients and HC, while none of the commonly used diffusion measures such as FA or MD did. Higher diffusion heterogeneity in the frontal lobes in early SCZ may be due to abnormal brain maturation (migration, pruning) before and during adolescence and early adulthood. Further studies are needed to investigate the role of heterogeneity as potential biomarker for SCZ risk.
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Acknowledgments
This study was part of the doctoral thesis of Johanna Seitz. We thank all subjects for their participation. We also thank the clinical, research assistant, and data management staff from the Boston CIDAR study, including Bryant C, Cousin A, Francis G, Franz M, Friedman-Yakoobian M, Gibson L, Gnong-Granato A, Hiraldo M, Hornbach S, Klein K, Min G, Pilo C, Rodenhiser-Hill J, Schutt J, Sorenson S, Szent-Imry R, Thomas A, Tucker L, Wakeham C, Woodberry K. We are grateful for the hard work of many research volunteers, including Donodoe D, Feder Z, Khromina S, Molokotos E, Oldershaw A, Reading J, Piazza E, and Schanz O. Finally, we would like to thank Zuo A and Eckbo R for their support with data processing.
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This work was supported by the National Institutes of Health (grant number P50MH080272 (to MN, LJS, TP, RM, JW, RM, MES, MK), R01 MH102377 (to MK), T32MH016259–35 (to AL), K05MH070047 (to MES)); the Veterans Affairs Merit Awards (to RM, MES); R01MH074794; P41EB015902; NARSAD young investigator award (to OP); by the Else Kroener-Fresenius Stiftung, Deutschland (to IK); by the Commonwealth Research Center (SCDMH82101008006 (to RM, JW, LJS)); and by a Clinical Translational Science Award (UL1RR025758 to Harvard University and Beth Israel Deaconess Medical Center from the National Center for Research Resources (to LJS)).
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The Authors Seitz Johanna, Rathi Yogesh, Lyall Amanda, Pasternak Ofer, del Re Elisabetta C, Niznikiewicz Margaret, Nestor Paul, Seidman Larry J, Petryshen Tracey L, Mesholam-Gately Raquelle I, Wojcik Joanne, McCarley Robert W, Shenton Martha E, Koerte Inga K, and Kubicki Marek have declared that there are no conflicts of interest in relation to the subject of this study.
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Seitz, J., Rathi, Y., Lyall, A. et al. Alteration of gray matter microstructure in schizophrenia. Brain Imaging and Behavior 12, 54–63 (2018). https://doi.org/10.1007/s11682-016-9666-7
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DOI: https://doi.org/10.1007/s11682-016-9666-7