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

Molecular Psychiatry volume 25, pages 3208–3219 (2020)Cite this article

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Abstract

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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Code availability

Our multi-site diffusion MRI harmonization software is available per request. Please request an access through e-mail: skarayumak@bwh.harvard.edu.

Notes

  1. early onset, first episode, early course, chronic

  2. Forceps major (posterior forceps), forceps minor (anterior forceps), for the rest left and right hemisphere separately: cingulum (cingulate gyrus portion (CING1) and hippocampal (CING2) portion separately), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), uncinate fasciculus (UF).

  3. Bonferroni correction was performed to control for the number of fibers and whole-brain (n = 15).

References

  1. Mueser KT, McGurk SR. Schizophrenia. Lancet. 2004;363:2063–72.

    PubMed  Google Scholar 

  2. Kubicki M, McCarley R, Westin C-F, Park H-J, Maier S, Kikinis R, et al. A review of diffusion tensor imaging studies in schizophrenia. J Psychiatr Res. 2007;41:15–30.

    PubMed  Google Scholar 

  3. Shenton ME, Dickey CC, Frumin M, McCarley RW. A review of MRI findings in schizophrenia. Schizophr Res. 2001;49:1–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Menon RR, Barta PE, Aylward EH, Richards SS, Vaughn DD, Tien AY, et al. Posterior superior temporal gyrus in schizophrenia: grey matter changes and clinical correlates. Schizophr Res. 1995;16:127–35.

    CAS  PubMed  Google Scholar 

  5. Schnack HG, van Haren NEM, Nieuwenhuis M, Hulshoff Pol HE, Cahn W, Kahn RS. Accelerated Brain Aging in Schizophrenia: A Longitudinal Pattern Recognition Study. Am J Psychiatry. 2016;173:607–16.

    PubMed  Google Scholar 

  6. Mitelman SA, Canfield EL, Newmark RE, Brickman AM, Torosjan Y, Chu K-W, et al. Longitudinal Assessment of Gray and White Matter in Chronic Schizophrenia: A Combined Diffusion-Tensor and Structural Magnetic Resonance Imaging Study. Open Neuroimag J. 2009;3:31–47.

    PubMed  PubMed Central  Google Scholar 

  7. Ohtani T, Bouix S, Hosokawa T, Saito Y, Eckbo R, Ballinger T, et al. Abnormalities in white matter connections between orbitofrontal cortex and anterior cingulate cortex and their associations with negative symptoms in schizophrenia: a DTI study. Schizophr Res. 2014;157:190–7.

    PubMed  PubMed Central  Google Scholar 

  8. Ohtani T, Bouix S, Lyall AE, Hosokawa T, Saito Y, Melonakos E, et al. Abnormal white matter connections between medial frontal regions predict symptoms in patients with first episode schizophrenia. Cortex. 2015;71:264–76.

    PubMed  PubMed Central  Google Scholar 

  9. Kochunov P, Hong LE. Neurodevelopmental and neurodegenerative models of schizophrenia: white matter at the center stage. Schizophr Bull. 2014;40:721–8.

    PubMed  PubMed Central  Google Scholar 

  10. Friston K, Brown HR, Siemerkus J, Stephan KE. The dysconnection hypothesis (2016). Schizophr Res. 2016;176:83–94.

    PubMed  PubMed Central  Google Scholar 

  11. Keshavan MS. Development, disease and degeneration in schizophrenia: a unitary pathophysiological model. J Psychiatr Res. 1999;33:513–21.

    CAS  PubMed  Google Scholar 

  12. Xiao Y, Sun H, Shi S, Jiang D, Tao B, Zhao Y, et al. White matter abnormalities in never-treated Patients with long-term schizophrenia. Am J Psychiatry. 2018;175:1129–36.

    PubMed  Google Scholar 

  13. McGrath JJ, Féron FP, Burne THJ, Mackay-Sim A, Eyles DW. The neurodevelopmental hypothesis of schizophrenia: a review of recent developments. Ann Med. 2003;35:86–93.

    PubMed  Google Scholar 

  14. Murray RM, Castle D, O’Callaghan E, Lewis S. Classifying schizophrenia into neurodevelopmental and adult onset forms. Schizophr Res. 1992;6:170.

    Google Scholar 

  15. Fatemi SH, Folsom TD. The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophr Bull. 2009;35:528–48.

    PubMed  PubMed Central  Google Scholar 

  16. van Haren NEM, Hulshoff Pol HE, Schnack HG, Cahn W, Brans R, Carati I, et al. Progressive brain volume loss in schizophrenia over the course of the illness: evidence of maturational abnormalities in early adulthood. Biol Psychiatry. 2008;63:106–13.

    PubMed  Google Scholar 

  17. French L, Gray C, Leonard G, Perron M, Pike GB, Richer L, et al. Early cannabis use, polygenic risk score for schizophrenia and brain maturation in adolescence. JAMA Psychiatry. 2015;72:1002–11.

    PubMed  PubMed Central  Google Scholar 

  18. Cropley VL, Klauser P, Lenroot RK, Bruggemann J, Sundram S, Bousman C, et al. Accelerated gray and white matter deterioration with age in schizophrenia. Am J Psychiatry. 2017;174:286–95.

    PubMed  Google Scholar 

  19. Gama C. 175.4 The relationship of aging and inflammatory biomarkers to gray matter volume and episodic memory performance in schizophrenia: evidence of pathological accelerated aging. Schizophr Bull. 2017;43:S90.

    PubMed Central  Google Scholar 

  20. Sexton CE, Walhovd KB, Storsve AB, Tamnes CK, Westlye LT, Johansen-Berg H, et al. Accelerated changes in white matter microstructure during aging: a longitudinal diffusion tensor imaging study. J Neurosci. 2014;34:15425–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Xiao Y, Sun H, Shi S, Jiang D, Tao B, Zhao Y, et al. White matter abnormalities in never-treated patients with long-term schizophrenia. Am J Psychiatry. 2018;175:1129–36. appiajp201817121402

    PubMed  Google Scholar 

  22. Meng L, Li K, Li W, Xiao Y, Lui S, Sweeney JA, et al. Widespread white-matter microstructure integrity reduction in first-episode schizophrenia patients after acute antipsychotic treatment. Schizophr Res. 2018. https://doi.org/10.1016/j.schres.2018.08.021.

  23. Thompson PM, Stein JL, Medland SE, Hibar DP, Vasquez AA, Renteria ME, et al. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data. Brain Imaging Behav. 2014;8:153–82.

    PubMed  PubMed Central  Google Scholar 

  24. Jahanshad N, Kochunov PV, Sprooten E, Mandl RC, Nichols TE, Almasy L, et al. Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: a pilot project of the ENIGMA–DTI working group. NeuroImage. 2013;81:455–69.

    PubMed  PubMed Central  Google Scholar 

  25. Blokland GAM, del Re EC, Mesholam-Gately RI, Jovicich J, Trampush JW, Keshavan MS, et al. The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) consortium: a collaborative cognitive and neuroimaging genetics project. Schizophr Res. 2018;195:306–17.

    PubMed  Google Scholar 

  26. Seidman LJ, Giuliano AJ, Meyer EC, Addington J, Cadenhead KS, Cannon TD, et al. Neuropsychology of the prodrome to psychosis in the NAPLS consortium: relationship to family history and conversion to psychosis. Arch Gen Psychiatry. 2010;67:578–88.

    PubMed  PubMed Central  Google Scholar 

  27. Cheng W, Palaniyappan L, Li M, Kendrick KM, Zhang J, Luo Q, et al. Addendum: Voxel-based, brain-wide association study of aberrant functional connectivity in schizophrenia implicates thalamocortical circuitry. NPJ Schizophr. 2018;4:19.

    PubMed  PubMed Central  Google Scholar 

  28. Loughland C, Draganic D, McCabe K, Richards J, Nasir A, Allen J, et al. Australian Schizophrenia Research Bank: a database of comprehensive clinical, endophenotypic and genetic data for aetiological studies of schizophrenia. Aust N Z J Psychiatry. 2010;44:1029–35.

    PubMed  Google Scholar 

  29. Elliott LT, Sharp K, Alfaro-Almagro F, Shi S, Miller KL, Douaud G, et al. Genome-wide association studies of brain imaging phenotypes in UK Biobank. Nature. 2018;562:210–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Tamminga CA, Pearlson G, Keshavan M, Sweeney J, Clementz B, Thaker G. Bipolar and schizophrenia network for intermediate phenotypes: outcomes across the psychosis continuum. Schizophr Bull. 2014;40:S131–7.

    PubMed  PubMed Central  Google Scholar 

  31. Cetin Karayumak S, Bouix S, Ning L, James A, Crow T, Shenton M, et al. Retrospective harmonization of multi-site diffusion MRI data acquired with different acquisition parameters. Neuroimage. 2019;184:180–200.

    PubMed  Google Scholar 

  32. Mirzaalian H, Ning L, Savadjiev P, Pasternak O, Bouix S, Michailovich O, et al. Inter-site and inter-scanner diffusion MRI data harmonization. Neuroimage. 2016;135:311–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Mirzaalian H, Ning L, Savadjiev P, Pasternak O, Bouix S, Michailovich O, et al. Multi-site harmonization of diffusion MRI data in a registration framework. Brain Imaging Behav. 2017;12:284–95.

    Google Scholar 

  34. Satterthwaite TD, Elliott MA, Ruparel K, Loughead J, Prabhakaran K, Calkins ME, et al. Neuroimaging of the Philadelphia Neurodevelopmental Cohort. Neuroimage. 2014;86:544–53.

    PubMed  Google Scholar 

  35. Satterthwaite TD, Connolly JJ, Ruparel K, Calkins ME, Jackson C, Elliott MA, et al. The Philadelphia Neurodevelopmental Cohort: a publicly available resource for the study of normal and abnormal brain development in youth. Neuroimage. 2016;124:1115–9.

    PubMed  Google Scholar 

  36. Smith SM. Fast robust automated brain extraction. Hum Brain Mapp. 2002;17:143–55.

    PubMed  PubMed Central  Google Scholar 

  37. Behrens TEJ, Woolrich MW, Jenkinson M, Johansen-Berg H, Nunes RG, Clare S, et al. Characterization and propagation of uncertainty in diffusion-weighted MR imaging. Magn Reson Med. 2003;50:1077–88.

    CAS  PubMed  Google Scholar 

  38. Avants BB, Yushkevich P, Pluta J, Minkoff D, Korczykowski M, Detre J, et al. The optimal template effect in hippocampus studies of diseased populations. Neuroimage. 2010;49:2457–66.

    PubMed  Google Scholar 

  39. Varentsova A, Zhang S, Arfanakis K. Development of a high angular resolution diffusion imaging human brain template. Neuroimage. 2014;91:177–86.

    PubMed  PubMed Central  Google Scholar 

  40. Avants BB, Tustison NJ, Song G, Cook PA, Klein A, Gee JC. A reproducible evaluation of ANTs similarity metric performance in brain image registration. Neuroimage. 2011;54:2033–44.

    PubMed  Google Scholar 

  41. Lebel C, Gee M, Camicioli R, Wieler M, Martin W, Beaulieu C. Diffusion tensor imaging of white matter tract evolution over the lifespan. Neuroimage. 2012;60:340–52.

    CAS  PubMed  Google Scholar 

  42. Yeatman JD, Wandell BA, Mezer AA. Lifespan maturation and degeneration of human brain white matter. Nat Commun. 2014;5:4932.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Cox SR, Ritchie SJ, Tucker-Drob EM, Liewald DC, Hagenaars SP, Davies G, et al. Ageing and brain white matter structure in 3,513 UK Biobank participants. Nat Commun. 2016;7:13629.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Tønnesen S, Kaufmann T, Doan NT, Alnæs D, Córdova-Palomera A, Meer D, et al. White matter aberrations and age-related trajectories in patients with schizophrenia and bipolar disorder revealed by diffusion tensor imaging. Sci Rep. 2018;8:14129.

    PubMed  PubMed Central  Google Scholar 

  45. Lebel C, Walker L, Leemans A, Phillips L, Beaulieu C. Microstructural maturation of the human brain from childhood to adulthood. Neuroimage. 2008;40:1044–55.

    CAS  PubMed  Google Scholar 

  46. Le Bihan D, Mangin JF, Poupon C, Clark CA, Pappata S, Molko N, et al. Diffusion tensor imaging: concepts and applications. J Magn Reson Imaging. 2001;13:534–46.

    PubMed  Google Scholar 

  47. Voineskos AN, Lobaugh NJ, Bouix S, Rajji TK, Miranda D, Kennedy JL, et al. Diffusion tensor tractography findings in schizophrenia across the adult lifespan. Brain. 2010;133:1494–504.

    PubMed  PubMed Central  Google Scholar 

  48. Whitford TJ, Kubicki M, Schneiderman JS, O’Donnell LJ, King R, Alvarado JL, et al. Corpus callosum abnormalities and their association with psychotic symptoms in patients with schizophrenia. Biol Psychiatry. 2010;68:70–7.

    PubMed  PubMed Central  Google Scholar 

  49. Ellison-Wright I, Glahn DC, Laird AR, Thelen SM, Bullmore E. The anatomy of first-episode and chronic schizophrenia: an anatomical likelihood estimation meta-analysis. Am J Psychiatry. 2008;165:1015–23.

    PubMed  PubMed Central  Google Scholar 

  50. Konopaske GT, Dorph-Petersen K-A, Sweet RA, Pierri JN, Zhang W, Sampson AR, et al. Effect of chronic antipsychotic exposure on astrocyte and oligodendrocyte numbers in macaque monkeys. Biol Psychiatry. 2008;63:759–65.

    CAS  PubMed  Google Scholar 

  51. Kubicki M, Lyall AE. Antipsychotics and their impact on cerebral white matter: part of the problem or part of the solution? Am J Psychiatry. 2018;175:1056–7.

    PubMed  Google Scholar 

  52. Kyriakopoulos M, Samartzis L, Dima D, Hayes D, Corrigall R, Barker G, et al. P03-111 - Does antipsychotic medication affect white matter in schizophrenia and bipolar disorder? a review of diffusion tensor imaging literature. Eur Psychiatry. 2011;26:1280.

    Google Scholar 

  53. Kelly S, Jahanshad N, Zalesky A, Kochunov P, Agartz I, Alloza C, et al. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group. Mol Psychiatry. 2018;23:1261–9.

    CAS  PubMed  Google Scholar 

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Acknowledgements

We gratefully acknowledge funding provided by the following National Institutes of Health (NIH) grants: R01MH102377, K24MH110807 (PI: Dr. Marek Kubicki), R01MH119222 (PI: Dr. Yogesh Rathi), R03 MH110745, K01 MH115247–01A1 (PI: Dr. Amanda Lyall), VA Merit Award and U01 MH109977 (PI: Dr. Martha Shenton), R01MH108574 (PI: Dr. Pasternak), MRC G0500092 (PI: Dr. Anthony James), R01MH076995, P30MH090590, P50MH080173 (PI: Dr. Philip Szeszko), R01MH092440, R01MH078113 (PI: Dr. Matcheri Keshavan), R01MH077851 (PI: Dr. Carol Tamminga), R01MH077945 (PI: Dr. Godfrey Pearlson), R01MH077852 (PI: Dr. Gunvant Thaker), R01MH077862 (PI: Dr. John Sweeney). We also acknowledge funding provided by the Swiss National Science Foundation (SNF) grant 152619 (PI: Dr. Sebastian Walther) and National Research Foundation of Korea (NRF) grant NRF-2012R1A1A1006514) (PI: Dr. Jungsun Lee).

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Author notes

  1. Dr. McCarley passed away in 2018.

Authors and Affiliations

  1. Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, MA, Boston, USA

    Suheyla Cetin-Karayumak, Maria A. Di Biase, Natalia Chunga, Benjamin Reid, Nathaniel Somes, Amanda E. Lyall, Sinead Kelly, Ofer Pasternak, Martha Shenton, Yogesh Rathi & Marek Kubicki

  2. Department of Neurology, University of Rochester Medical Center, NY, Rochester, USA

    Natalia Chunga

  3. MGH Institute of Health Professions, MA, Charlestown, USA

    Nathaniel Somes

  4. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Amanda E. Lyall, Ofer Pasternak, Martha Shenton, Yogesh Rathi & Marek Kubicki

  5. Department of Psychiatry, Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, MA, USA

    Sinead Kelly, Rachal Hegde & Matcheri Keshavan

  6. Hacettepe Medical School, Altındağ, Turkey

    Bengisu Solgun

  7. Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Ofer Pasternak, Martha Shenton, Yogesh Rathi & Marek Kubicki

  8. Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Mark Vangel

  9. Department of Psychiatry, Yale University, New Haven, CT, USA

    Godfrey Pearlson

  10. Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, USA

    Carol Tamminga

  11. Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA

    John A. Sweeney

  12. Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens, USA

    Brett Clementz

  13. Department of Psychiatry and Behavioral Sciences, Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, USA

    David Schretlen

  14. University of Bern, University Hospital of Psychiatry, Bern, Switzerland

    Petra Verena Viher, Katharina Stegmayer & Sebastian Walther

  15. Department of Psychiatry, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

    Jungsun Lee

  16. Department of Psychiatry, SANE POWIC, Warneford Hospital, University of Oxford, Oxford, UK

    Tim Crow & Anthony James

  17. Centre for Addiction and Mental Health; Department of Psychiatry, University of Toronto, Toronto, Canada

    Aristotle Voineskos

  18. Maryland Psychiatric Research Center, Catonsville, USA

    Robert W. Buchanan

  19. Department of Psychiatry, Icahn School of Medicine at Mount Sinai; Mental Illness Research, Education and Clinical Center, James J. Peters VA Medical Center, New York, USA

    Philip R. Szeszko

  20. The Feinstein Institute for Medical Research and Zucker Hillside Hospital, Manhasset, USA

    Anil K. Malhotra

  21. VA Boston Healthcare System, Harvard Medical School, Boston, USA

    Martha Shenton

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  1. Suheyla Cetin-Karayumak
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Correspondence to Suheyla Cetin-Karayumak.

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Cetin-Karayumak, S., Di Biase, M.A., Chunga, N. et al. White matter abnormalities across the lifespan of schizophrenia: a harmonized multi-site diffusion MRI study. Mol Psychiatry 25, 3208–3219 (2020). https://doi.org/10.1038/s41380-019-0509-y

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