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Brain Imaging and Behavior

, Volume 12, Issue 1, pp 54–63 | Cite as

Alteration of gray matter microstructure in schizophrenia

  • Johanna Seitz
  • Yogesh Rathi
  • Amanda Lyall
  • Ofer Pasternak
  • Elisabetta C. del Re
  • Margaret Niznikiewicz
  • Paul Nestor
  • Larry J. Seidman
  • Tracey L. Petryshen
  • Raquelle I. Mesholam-Gately
  • Joanne Wojcik
  • Robert W. McCarley
  • Martha E. Shenton
  • Inga K. Koerte
  • Marek Kubicki
Original Research

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.

Keywords

Diffusion MRI Heterogeneity Schizophrenia Neurodevelopment Gray matter 

Notes

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.

Compliance with ethical standards

Funding

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)).

Disclosure of potential conflicts of interest

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.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11682_2016_9666_MOESM1_ESM.docx (17 kb)
ESM 1 (DOCX 16 kb)
11682_2016_9666_MOESM2_ESM.docx (18 kb)
ESM 2 (DOCX 18 kb)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Johanna Seitz
    • 1
    • 2
  • Yogesh Rathi
    • 1
  • Amanda Lyall
    • 1
    • 3
  • Ofer Pasternak
    • 1
    • 4
  • Elisabetta C. del Re
    • 1
    • 5
  • Margaret Niznikiewicz
    • 5
  • Paul Nestor
    • 5
    • 6
  • Larry J. Seidman
    • 3
    • 7
  • Tracey L. Petryshen
    • 8
    • 9
  • Raquelle I. Mesholam-Gately
    • 7
  • Joanne Wojcik
    • 7
  • Robert W. McCarley
    • 5
    • 10
  • Martha E. Shenton
    • 1
    • 4
    • 10
  • Inga K. Koerte
    • 1
    • 2
  • Marek Kubicki
    • 1
    • 3
    • 4
  1. 1.Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Harvard Medical SchoolBrigham and Women’s HospitalBostonUSA
  2. 2.Department of Child and Adolescent Psychiatry, Psychosomatic and PsychotherapyLudwig- Maximilians- UniversitätMunichGermany
  3. 3.Department of Psychiatry, Harvard Medical SchoolMassachusetts General HospitalBostonUSA
  4. 4.Department of Radiology, Harvard Medical SchoolBrigham and Women’s HospitalBostonUSA
  5. 5.Clinical Neuroscience Division, Laboratory of Neuroscience, VA Boston Healthcare SystemBrocktonUSA
  6. 6.Department of PsychologyUniversity of MassachusettsBostonUSA
  7. 7.Beth Israel Deaconess Medical Center Public Psychiatry Division at the Massachusetts Mental Health Center Harvard Medical SchoolBostonUSA
  8. 8.Psychiatric and Neurodevelopmental Genetic Unit, Department of Psychiatry and Center for Human Genetic ResearchMassachusetts General HospitalBostonUSA
  9. 9.Stanley Center for Psychiatric ResearchBroad Institute of MIT and HarvardCambridgeUSA
  10. 10.VA Boston Healthcare System, Brockton DivisionBrocktonUSA

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