Skip to main content
Log in

Alteration of gray matter microstructure in schizophrenia

  • Original Research
  • Published:
Brain Imaging and Behavior Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Anderson, D., Ardekani, B. A., Burdick, K. E., Robinson, D. G., John, M., Malhotra, A. K., & Szeszko, P. R. (2013). Overlapping and distinct gray and white matter abnormalities in schizophrenia and bipolar I disorder. Bipolar Disorders, 15(6), 680–693. doi:10.1111/bdi.12096.

    Article  PubMed  PubMed Central  Google Scholar 

  • Andreasen, N. C. (1984a). The scale for the assessment of negative symptoms (SANS). Iowa City: University of Iowa.

    Google Scholar 

  • Andreasen, N. C. (1984b). The scale for the assessment of positive symptoms (SAPS). Iowa City: University of Iowa.

    Google Scholar 

  • Andreasen, N. C. (2010). The lifetime trajectory of schizophrenia and the concept of neurodevelopment. Dialogues in Clinical Neuroscience, 12(3), 409–415.

    PubMed  PubMed Central  Google Scholar 

  • Arnold, S. E. (2001). Contributions of neuropathology to understanding schizophrenia in late life. Harvard Review of Psychiatry, 9(2), 69–76.

    Article  CAS  PubMed  Google Scholar 

  • Assaf, Y., & Basser, P. J. (2005). Composite hindered and restricted model of diffusion (CHARMED) MR imaging of the human brain. NeuroImage, 27(1), 48–58.

    Article  PubMed  Google Scholar 

  • Assunção Leme, I. B., Gadelha, A., Sato, J. R., Ota, V. K., Mari, J., Melaragno, M. I.,… Jackowski, A. P. (2013). Is there an association between cortical thickness, age of onset, and duration of illness in schizophrenia? CNS Spectr, 18(6), 315–321.

  • Basser, P. J., & Pierpaoli, C. (1996). Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. Journal of Magnetic Resonance. Series B, 111(3), 209–219.

    Article  CAS  PubMed  Google Scholar 

  • Basser, P. J., Matielo, B., & Bihan, D. L. (1996). MR diffusion tensor spectroscopy and imaging. Biophs, 66, 259–267.

    Google Scholar 

  • Beaulieu, C. (2002). The basis of anisotropic water diffusion in the nervous system - a technical review. NMR in Biomedicine, 15(7–8), 435–455. doi:10.1002/nbm.782.

    Article  PubMed  Google Scholar 

  • Bergamino, M., Pasternak, O., Farmer, M., Shenton, M. E., & Hamilton, J. P. (2016). Applying a free-water correction to diffusion imaging data uncovers stress-related neural pathology in depression. Neurologic Clinics, 10, 336–342. doi:10.1016/j.nicl.2015.11.020.

    Google Scholar 

  • Bose, S. K., Mackinnon, T., Mehta, M. A., Turkheimer, F. E., Howes, O. D., Selvaraj, S., et al. (2009). The effect of ageing on grey and white matter reductions in schizophrenia. Schizophrenia Research, 112(1–3), 7–13.

    Article  PubMed  Google Scholar 

  • Bozikas, V. P., Kovari, E., Bouras, C., & Karavatos, A. (2002). Neurofibrillary tangles in elderly patients with late onset schizophrenia. Neuroscience Letters, 324(2), 109–112.

    Article  CAS  PubMed  Google Scholar 

  • Brans, R. G. H., van Haren, N. E. M., van Baal, G. C. M., Staal, W. G., Schnack, H. G., Kahn, R. S., & Hulshoff Pol, H. E. (2008). Longitudinal MRI study in schizophrenia patients and their healthy siblings. The British Journal of Psychiatry, 193(5), 422–423.

    Article  PubMed  Google Scholar 

  • Dacquino, C., De Rossi, P., & Spalletta, G. (2015). Schizophrenia and bipolar disorder: the road from similarities and clinical heterogeneity to neurobiological types. Clinica Chimica Acta, 449, 49–59. doi:10.1016/j.cca.2015.02.029.

    Article  CAS  Google Scholar 

  • Desikan, R. S., Segonne, F., Fischl, B., Quinn, B. T., Dickerson, B. C., Blacker, D., et al. (2006). An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. NeuroImage, 31(3), 968–980.

    Article  PubMed  Google Scholar 

  • Egashira, K., Matsuo, K., Mihara, T., Nakano, M., Nakashima, M., Watanuki, T., et al. (2014). Different and Shared Brain Volume Abnormalities in Late- and Early-Onset Schizophrenia. Neuropsychobiology, 70(3), 142–151.

    Article  PubMed  Google Scholar 

  • Feinberg, I. (1983). Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? Journal of Psychiatric Research, 17(4), 319–334.

    Article  CAS  Google Scholar 

  • First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (2002a). Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition. (SCID-I/NP). In N. Y. S. P. Institute (Ed.), Biometrics Research. New York.

  • First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (2002b). Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition. (SCID-I/P) Biometrics Research. New York: New York State Psychiatric Institute.

  • Fjell, A. M., Westlye, L. T., Greve, D. N., Fischl, B., Benner, T., van der Kouwe, A. J., et al. (2008). The relationship between diffusion tensor imaging and volumetry as measures of white matter properties. NeuroImage, 42(4), 1654–1668. doi:10.1016/j.neuroimage.2008.06.005.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gardner, D. M., Murphy, A. L., O'Donnell, H., Centorrino, F., & Baldessarini, R. J. (2010). International consensus study of antipsychotic dosing. The American Journal of Psychiatry, 167(6), 686–693. doi:10.1176/appi.ajp.2009.09060802.

    Article  PubMed  Google Scholar 

  • Gogtay, N., Giedd, J. N., Lusk, L., Hayashi, K. M., Greenstein, D., Vaituzis, A. C., et al. (2004). Dynamic mapping of human cortical development during childhood through early adulthood. Proceedings of the National Academy of Sciences of the United States of America, 101(21), 8174–8179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • GraphPadSoftware. (2014). GraphPad Prism version 6.00 for Windows. San Diego California USA GraphPadSoftware. Retrieved from www.graphpad.com

  • Helenius, J., Soinne, L., Perkio, J., Salonen, O., Kangasmaki, A., Kaste, M., et al. (2002). Diffusion-weighted MR imaging in normal human brains in various age groups. AJNR. American Journal of Neuroradiology, 23(2), 194–199.

    PubMed  Google Scholar 

  • Hien, D., Matzner, F. J., First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (1994). Structured clinical interview for DSM-IV-child edition (1.0 ed.). New York: Columbia University.

    Google Scholar 

  • Ho, B. C., Andreasen, N. C., Ziebell, S., Pierson, R., & Magnotta, V. (2011). Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Archives of General Psychiatry, 68(2), 128–137.

    Article  PubMed  PubMed Central  Google Scholar 

  • Holz, M., Heil, S. R., & Sacco, A. (2000). Temperature-dependent self-di†usion coefficients of water and six selected molecular liquids for calibration in accurate 1H NMR PFG measurements. PCCP, 2, 4740–4742.

    Article  CAS  Google Scholar 

  • Hosmer, D. W., & Lemeshow, S. (2000). Applied logistic regression (Wiley Ed.). Hoboken, NJ.

  • Hulshoff Pol, H., & Kahn, R. S. (2008). What happens after the first episode? A review of progressive brain changes in chronically ill patients with schizophrenia. Schizophrenia Bulletin, 34(2), 354–366.

    Article  PubMed  PubMed Central  Google Scholar 

  • Huttenlocher, P. R., & Dabholkar, A. S. (1997). Regional differences in synaptogenesis in human cerebral cortex. The Journal of Comparative Neurology, 387(2), 167–178.

    Article  CAS  PubMed  Google Scholar 

  • IBMCorp (2013). IBM SPSS statistics for windows, version 22.0. Armonk: IBMCorp.

    Google Scholar 

  • Jenkinson, M., Bannister, P., Brady, J. M., & Smith, S. M. (2002). Improved optimization for the robust and accurate linear registration and motion correction of brain images. NeuroImage, 17(2), 825–841.

    Article  PubMed  Google Scholar 

  • Jeste, D. V., Wolkowitz, O. M., & Palmer, B. W. (2011). Divergent trajectories of physical, cognitive, and psychosocial aging in schizophrenia. Schizophrenia Bulletin, 37(3), 451–455. doi:10.1093/schbul/sbr026.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jouan, L., Girard, S. L., Dobrzeniecka, S., Ambalavanan, A., Krebs, M. O., Joober, R., … Rouleau, G. A. (2013). Investigation of rare variants in LRP1, KPNA1, ALS2CL and ZNF480 genes in schizophrenia patients reflects genetic heterogeneity of the disease. Behav Brain Funct, 9, 9. doi:10.1186/1744-9081-9-9

  • Kalus, P., Buri, C., Slotboom, J., Gralla, J., Remonda, L., Dierks, T., et al. (2004). Volumetry and diffusion tensor imaging of hippocampal subregions in schizophrenia. Neuroreport, 15(5), 867–871.

    Article  PubMed  Google Scholar 

  • Kalus, P., Slotboom, J., Gallinat, J., Federspiel, A., Gralla, J., Remonda, L., et al. (2005a). New evidence for involvement of the entorhinal region in schizophrenia: a combined MRI volumetric and DTI study. NeuroImage, 24(4), 1122–1129.

    Article  PubMed  Google Scholar 

  • Kalus, P., Slotboom, J., Gallinat, J., Wiest, R., Ozdoba, C., Federspiel, A., et al. (2005b). The amygdala in schizophrenia: a trimodal magnetic resonance imaging study. Neuroscience Letters, 375(3), 151–156. doi:10.1016/j.neulet.2004.11.004.

    Article  CAS  PubMed  Google Scholar 

  • Kochunov, P., Chiappelli, J., Wright, S. N., Rowland, L. M., Patel, B., Wijtenburg, S. A., et al. (2014). Multimodal white matter imaging to investigate reduced fractional anisotropy and its age-related decline in schizophrenia. Psychiatry Research, 223(2), 148–156. doi:10.1016/j.pscychresns.2014.05.004.

    Article  PubMed  PubMed Central  Google Scholar 

  • Koo, B. B., Hua, N., Choi, C. H., Ronen, I., Lee, J. M., & Kim, D. S. (2009). A framework to analyze partial volume effect on gray matter mean diffusivity measurements. NeuroImage, 44(1), 136–144. doi:10.1016/j.neuroimage.2008.07.064.

    Article  PubMed  Google Scholar 

  • Kubicki, M., McCarley, R., Westin, C. F., Park, H. J., Maier, S., Kikinis, R., et al. (2007). A review of diffusion tensor imaging studies in schizophrenia. Journal of Psychiatric Research, 41(1–2), 15–30.

    Article  PubMed  Google Scholar 

  • Kubota, M., Miyata, J., Yoshida, H., Hirao, K., Fujiwara, H., Kawada, R., et al. (2011). Age-related cortical thinning in schizophrenia. Schizophrenia Research, 125(1), 21–29. doi:10.1016/j.schres.2010.10.004.

    Article  PubMed  Google Scholar 

  • Lebel, C., Walker, L., Leemans, A., Phillips, L., & Beaulieu, C. (2008). Microstructural maturation of the human brain from childhood to adulthood. NeuroImage, 40(3), 1044–1055. doi:10.1016/j.neuroimage.2007.12.053.

    Article  CAS  PubMed  Google Scholar 

  • Lee, K., Yoshida, T., Kubicki, M., Bouix, S., Westin, C. F., Kindlmann, G., et al. (2009). Increased diffusivity in superior temporal gyrus in patients with schizophrenia: a Diffusion Tensor Imaging study. Schizophrenia Research, 108(1–3), 33–40.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lewis, D. A., & Levitt, P. (2002). Schizophrenia as a disorder of neurodevelopment. Annual Review of Neuroscience, 25(1), 409–432.

    Article  CAS  PubMed  Google Scholar 

  • Liang, S. G., & Greenwood, T. A. (2015). The impact of clinical heterogeneity in schizophrenia on genomic analyses. Schizophrenia Research, 161(2–3), 490–495. doi:10.1016/j.schres.2014.11.019.

    Article  PubMed  Google Scholar 

  • McEvoy, J. P. (2007). The importance of early treatment of schizophrenia. Behavioral Healthcare, 27(4), 40–43.

    PubMed  Google Scholar 

  • Metzler-Baddeley, C., O’Sullivan, M. J., Bells, S., Pasternak, O., & Jones, D. K. (2012). How and how not to correct for CSF-contamination in diffusion MRI. NeuroImage, 59(2), 1394–1403.

    Article  PubMed  Google Scholar 

  • Mills, R. (1973). Self-Diffusion in Normal and Heavy Water. The Journal of Physical Chemistry, 77(5).

  • Moriya, J., Kakeda, S., Abe, O., Goto, N., Yoshimura, R., Hori, H., et al. (2010). Gray and white matter volumetric and diffusion tensor imaging (DTI) analyses in the early stage of first-episode schizophrenia. Schizophrenia Research, 116(2–3), 196–203.

    Article  PubMed  Google Scholar 

  • Napal, O., Ojeda, N., Elizagárate, E., Peña, J., Ezcurra, J., & Gutiérrez, M. (2012). The course of the schizophrenia and its impact on cognition: a review of literature. Actas Españolas de Psiquiatría, 40(4), 198–220.

    PubMed  Google Scholar 

  • Nesvag, R., Schaer, M., Haukvik, U. K., Westlye, L. T., Rimol, L. M., Lange, E. H., et al. (2014). Reduced brain cortical folding in schizophrenia revealed in two independent samples. Schizophrenia Research, 152(2–3), 333–338.

    Article  PubMed  Google Scholar 

  • Nonaka, S., Ichinose, H., Kinoshita, H., & Nakane, H. (2013). Epidemiology of schizophrenia. Nihon Rinsho, 71(4), 583–588.

    PubMed  Google Scholar 

  • Olabi, B., Ellison-Wright, I., McIntosh, A. M., Wood, S. J., Bullmore, E., & Lawrie, S. M. (2011). Are there progressive brain changes in schizophrenia? A meta-analysis of structural magnetic resonance imaging studies. Biological Psychiatry, 70(1), 88–96.

    Article  PubMed  Google Scholar 

  • Park, J. Y., Park, H. J., Kim, D. J., & Kim, J. J. (2014). Positive symptoms and water diffusivity of the prefrontal and temporal cortices in schizophrenia patients: a pilot study. Psychiatry Research, 224(1), 49–57. doi:10.1016/j.pscychresns.2014.07.003.

    Article  PubMed  Google Scholar 

  • Pasternak, O., Sochen, N., Gur, Y., Intrator, N., & Assaf, Y. (2009). Free water elimination and mapping from diffusion MRI. Magnetic Resonance in Medicine, 62(3), 717–730. doi:10.1002/mrm.22055.

    Article  PubMed  Google Scholar 

  • Pasternak, O., Koerte, I. K., Bouix, S., Fredman, E., Sasaki, T., Mayinger, M., et al. (2014). Hockey Concussion Education Project, Part 2. Microstructural white matter alterations in acutely concussed ice hockey players: a longitudinal free-water MRI study. Journal of Neurosurgery, 120(4), 873–881. doi:10.3171/2013.12.JNS132090.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pasternak, O., Westin, C. F., Dahlben, B., Bouix, S., & Kubicki, M. (2015). The extent of diffusion MRI markers of neuroinflammation and white matter deterioration in chronic schizophrenia. Schizophrenia Research, 161(1), 113–118. doi:10.1016/j.schres.2014.07.031.

    Article  PubMed  Google Scholar 

  • Petanjek, Z., Judas, M., Simic, G., Rasin, M. R., Uylings, H. B., Rakic, P., & Kostovic, I. (2011). Extraordinary neoteny of synaptic spines in the human prefrontal cortex. Proceedings of the National Academy of Sciences of the United States of America, 108(32), 13281–13286.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pierpaoli, C., & Basser, P. J. (1996). Toward a quantitative assessment of diffusion anisotropy. Magnetic Resonance in Medicine, 36(6), 893–906.

    Article  CAS  PubMed  Google Scholar 

  • (2011) Progressive brain change in schizophrenia: a prospective longitudinal study of first-episode schizophrenia, 7, 70 Cong. Rec. 672–679.

  • Rapoport, J. L., Addington, A. M., Frangou, S., & Psych, M. R. (2005). The neurodevelopmental model of schizophrenia: update 2005. Molecular Psychiatry, 10(5), 434–449.

    Article  CAS  PubMed  Google Scholar 

  • Rapoport, J. L., Giedd, J. N., & Gogtay, N. (2012). Neurodevelopmental model of schizophrenia: update 2012. Molecular Psychiatry, 17(12), 1228–1238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rathi, Y., Pasternak, O., Savadjiev, P., Michailovich, O., Bouix, S., Kubicki, M., et al. (2014). Gray matter alterations in early aging: a diffusion magnetic resonance imaging study. Human Brain Mapping, 35(8), 3841–3856. doi:10.1002/hbm.22441.

    Article  CAS  PubMed  Google Scholar 

  • Ratnasingham, S., Cairney, J., Manson, H., Rehm, J., Lin, E., & Kurdyak, P. (2013). The burden of mental illness and addiction in Ontario. Canadian Journal of Psychiatry, 58(9), 529–537.

    Article  PubMed  Google Scholar 

  • Roberts, G., & Harrison, B. J. (2000). Gliosis and its implications for the disease process. In B. J. Harrison & G. Roberts (Eds.), The neuropathology of schizophrenia: Progress and interpretation (pp. 137–150). New York: Oxford Univ. Press.

    Google Scholar 

  • Roberts, R. C., Barksdale, K. A., Roche, J. K., & Lahti, A. C. (2015). Decreased synaptic and mitochondrial density in the postmortem anterior cingulate cortex in schizophrenia. Schizophr Res.

  • Rössler, W., Salize, H. J., van Os, J., & Riecher-Rössler, A. (2005). Size of burden of schizophrenia and psychotic disorders. European Neuropsychopharmacology: The Journal of the Eurpoean College of Neuropsychopharmacology, 15(4), 399–400. doi:10.1016/j.euroneuro.2005.04.009.

    Article  Google Scholar 

  • Shin, Y. W., Kwon, J. S., Ha, T. H., Park, H. J., Kim, D. J., Hong, S. B., et al. (2006). Increased water diffusivity in the frontal and temporal cortices of schizophrenic patients. NeuroImage, 30(4), 1285–1291.

    Article  PubMed  Google Scholar 

  • Sipos, A., Rasmussen, F., Harrison, G., Tynelius, P., Lewis, G., Leon, D. A., & Gunnell, D. (2004). Paternal age and schizophrenia: a population based cohort study. BMJ, 329(7474), 1070.

    Article  PubMed  PubMed Central  Google Scholar 

  • Spoletini, I., Cherubini, A., Banfi, G., Rubino, I. A., Peran, P., Caltagirone, C., & Spalletta, G. (2011). Hippocampi, thalami, and accumbens microstructural damage in schizophrenia: a volumetry, diffusivity, and neuropsychological study. Schizophrenia Bulletin, 37(1), 118–130.

    Article  PubMed  Google Scholar 

  • Sullivan, P. F., Kendler, K. S., & Neale, M. C. (2003). Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Archives of General Psychiatry, 60(12), 1187–1192.

    Article  PubMed  Google Scholar 

  • Teffer, K., & Semendeferi, K. (2012). Human prefrontal cortex: evolution, development, and pathology. Progress in Brain Research, 195, 191–218. doi:10.1016/B978-0-444-53860-4.00009-X.

    Article  PubMed  Google Scholar 

  • TheMathWorks. MATLAB and Statistics Toolbox Release 2012b. Natick, Massachusetts, United States: TheMathWorks.

  • Thermenos, H. W., Keshavan, M. S., Juelich, R. J., Molokotos, E., Whitfield-Gabrieli, S., Brent, B. K., et al. (2013). A review of neuroimaging studies of young relatives of individuals with schizophrenia: a developmental perspective from schizotaxia to schizophrenia. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 162B(7), 604–635. doi:10.1002/ajmg.b.32170.

    Article  CAS  Google Scholar 

  • van Haren, N. E. M., Hulshoff Pol, H. E., Schnack, H. G., Cahn, W., Brans, R., Carati, I., et al. (2008). Progressive brain volume loss in schizophrenia over the course of the illness: evidence of maturational abnormalities in early adulthood. Biological Psychiatry, 63(1), 106–113.

    Article  PubMed  Google Scholar 

  • Vogeley, K., Schneider-Axmann, T., Pfeiffer, U., Tepest, R., Bayer, T. A., Bogerts, B., et al. (2000). Disturbed gyrification of the prefrontal region in male schizophrenic patients: A morphometric postmortem study. The American Journal of Psychiatry, 157(1), 34–39.

    Article  CAS  PubMed  Google Scholar 

  • Vollmar, C., O'Muircheartaigh, J., Barker, G. J., Symms, M. R., Thompson, P., Kumari, V., et al. (2010). Identical, but not the same: intra-site and inter-site reproducibility of fractional anisotropy measures on two 3.0 T scanners. NeuroImage, 51(4), 1384–1394.

    Article  PubMed  PubMed Central  Google Scholar 

  • Walker-Samuel, S., Orton, M., Boult, J. K., & Robinson, S. P. (2011). Improving apparent diffusion coefficient estimates and elucidating tumor heterogeneity using Bayesian adaptive smoothing. Magnetic Resonance in Medicine, 65(2), 438–447. doi:10.1002/mrm.22572.

    Article  PubMed  Google Scholar 

  • Weinberger, D. R. (1987). Implications of normal brain development for the pathogenesis of schizophrenia. Archives of General Psychiatry, 44(7), 660–669.

    Article  CAS  PubMed  Google Scholar 

  • Whiteford, H. A., Degenhardt, L., Rehm, J., Baxter, A. J., Ferrari, A. J., Erskine, H. E., et al. (2013). Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet, 382(9904), 1575–1586. doi:10.1016/S0140-6736(13)61611-6.

    Article  PubMed  Google Scholar 

  • Wilkinson, G. (1993). The wide range achievement test- revision 3. Wilmington: Jastak Association.

    Google Scholar 

  • Zhu, J., Zhuo, C., Qin, W., Wang, D., Ma, X., Zhou, Y., & Yu, C. (2014). Performances of diffusion kurtosis imaging and diffusion tensor imaging in detecting white matter abnormality in schizophrenia. Neurologic Clinics, 7, 7170–7176.

    Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marek Kubicki.

Ethics declarations

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.

Electronic supplementary material

ESM 1

(DOCX 16 kb)

ESM 2

(DOCX 18 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11682-016-9666-7

Keywords

Navigation