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Enlarged lateral ventricles inversely correlate with reduced corpus callosum central volume in first episode schizophrenia: association with functional measures

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Abstract

The lateral and third ventricles, as well as the corpus callosum (CC), are known to be affected in schizophrenia. Here we investigate whether abnormalities in the lateral ventricles (LVs), third ventricle, and corpus callosum are related to one another in first episode schizophrenia (FESZ), and whether such abnormalities show progression over time. Nineteen FESZ and 19 age- and handedness-matched controls were included in the study. MR images were acquired on a 3-Tesla MRI at baseline and ~1.2 years later. FreeSurfer v.5.3 was employed for segmentation. Two-way or univariate ANCOVAs were used for statistical analysis, where the covariate was intracranial volume. Group and gender were included as between-subjects factors. Percent volume changes between baseline and follow-up were used to determine volume changes at follow-up. Bilateral LV and third ventricle volumes were significantly increased, while central CC volume was significantly decreased in patients compared to controls at baseline and at follow-up. In FESZ, the bilateral LV volume was also inversely correlated with volume of the central CC. This inverse correlation was not present in controls. In FESZ, an inverse correlation was found between percent volume increase from baseline to follow-up for bilateral LVs and lesser improvement in the Global Assessment of Functioning score. Significant correlations were observed for abnormalities of central CC, LVs and third ventricle volumes in FESZ, suggesting a common neurodevelopmental origin in schizophrenia. Enlargement of ventricles was associated with less improvement in global functioning over time.

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References

  • Alexander-Bloch, A. F., Vertes, P. E., Stidd, R., Lalonde, F., Clasen, L., Rapoport, J., et al. (2013). The anatomical distance of functional connections predicts brain network topology in health and schizophrenia. Cerebral Cortex, 23(1), 127–138. doi:10.1093/cercor/bhr388.

    Article  PubMed  Google Scholar 

  • Andreasen, N. C. (1983). Scale for the Assessment of Negative Symptoms (SANS). Iowa City: University of Iowa.

  • Andreasen, N. C. (1984). Scale for the Assessment of Positive Symptoms. Iowa City: University of Iowa.

  • Arnone, D., McIntosh, A. M., Tan, G. M., & Ebmeier, K. P. (2008). Meta-analysis of magnetic resonance imaging studies of the corpus callosum in schizophrenia. Schizophrenia Research, 101(1–3), 124–132. doi:10.1016/j.schres.2008.01.005.

    Article  CAS  PubMed  Google Scholar 

  • Bergen, S. E., & Petryshen, T. L. (2012). Genome-wide association studies of schizophrenia: does bigger lead to better results? Current Opinion in Psychiatry, 25(2), 76–82. doi:10.1097/YCO.0b013e32835035dd.

    Article  PubMed  PubMed Central  Google Scholar 

  • Brent, B. K., Thermenos, H. W., Keshavan, M. S., & Seidman, L. J. (2013). Gray matter alterations in schizophrenia high-risk youth and early-onset schizophrenia: a review of structural MRI findings. Child and Adolescent Psychiatric Clinics of North America, 22(4), 689–714. doi:10.1016/j.chc.2013.06.003.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cahn, W., van Haren, N. E., Hulshoff Pol, H. E., Schnack, H. G., Caspers, E., Laponder, D. A., et al. (2006). Brain volume changes in the first year of illness and 5-year outcome of schizophrenia. The British Journal of Psychiatry, 189, 381–382. doi:10.1192/bjp.bp.105.015701.

    Article  CAS  PubMed  Google Scholar 

  • Del Re, E. C., Bergen, S. E., Mesholam-Gately, R. I., Niznikiewicz, M. A., Goldstein, J. M., Woo, T. U., et al. (2014). Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds. Transcultural Psychiatry, 4, e346. doi:10.1038/tp.2013.117.

    Article  Google Scholar 

  • del Re, E. C., Gao, Y., Eckbo, R., Petryshen, T. L., Blokland, G. A. M., Seidman, L. J., Konishi. J., Goldstein, J. M., McCarley, R. W., Shenton, M. E., Bouix, S. (2015a). A new MRI masking technique based on multi-atlas brain segmentation in controls and schizophrenia: a rapid and Viable alternative to manual masking. Journal of Neuroimaging, doi:10.1111/jon.12313

  • del Re, E. C., Spencer, K. M., Oribe, N., Mesholam-Gately, R. I., Goldstein, J., Shenton, M. E., et al. (2015b). Clinical high risk and first episode schizophrenia: auditory event-related potentials. Psychiatry Research, 231(2), 126–133. doi:10.1016/j.pscychresns.2014.11.012.

    Article  PubMed  Google Scholar 

  • DeLisi, L. E., Hoff, A. L., Kushner, M., Calev, A., & Stritzke, P. (1992). Left ventricular enlargement associated with diagnostic outcome of schizophreniform disorder. Biological Psychiatry, 32(2), 199–201.

    Article  CAS  PubMed  Google Scholar 

  • Faul, F., Erdfelder, E., Lang, A. G., & Buchner, A. (2007). G*power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behavior Research Methods, 39(2), 175–191.

    Article  PubMed  Google Scholar 

  • First, M. B., & Pincus, H. A. (2002). The DSM-IV text revision: rationale and potential impact on clinical practice. Psychiatric Services, 53(3), 288–292.

    Article  PubMed  Google Scholar 

  • Fischl, B., Salat, D. H., Busa, E., Albert, M., Dieterich, M., Haselgrove, C., et al. (2002). Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron, 33(3), 341–355.

    Article  CAS  PubMed  Google Scholar 

  • Fitzsimmons, J., Kubicki, M., & Shenton, M. E. (2013). Review of functional and anatomical brain connectivity findings in schizophrenia. Current Opinion in Psychiatry, 26(2), 172–187.

    Article  PubMed  Google Scholar 

  • Francis, A. N., Bhojraj, T. S., Prasad, K. M., Kulkarni, S., Montrose, D. M., Eack, S. M., et al. (2011). Abnormalities of the corpus callosum in non-psychotic high-risk offspring of schizophrenia patients. Psychiatry Research, 191(1), 9–15. doi:10.1016/j.pscychresns.2010.09.007.

    Article  PubMed  Google Scholar 

  • Fusar-Poli, P., Smieskova, R., Kempton, M. J., Ho, B. C., Andreasen, N. C., & Borgwardt, S. (2013). Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies. Neuroscience and Biobehavioral Reviews, 37(8), 1680–1691. doi:10.1016/j.neubiorev.2013.06.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Green, M. J., Cairns, M. J., Wu, J., Dragovic, M., Jablensky, A., Tooney, P. A., et al. (2013). Genome-wide supported variant MIR137 and severe negative symptoms predict membership of an impaired cognitive subtype of schizophrenia. Molecular Psychiatry, 18(7), 774–780. doi:10.1038/mp.2012.84.

    Article  CAS  PubMed  Google Scholar 

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

  • Hofer, S., & Frahm, J. (2006). Topography of the human corpus callosum revisited–comprehensive fiber tractography using diffusion tensor magnetic resonance imaging. NeuroImage, 32(3), 989–994. doi:10.1016/j.neuroimage.2006.05.044.

    Article  PubMed  Google Scholar 

  • Hollingshead, A. B. (1975). Two-factor index of social position. New Haven, CT: Yale University Press

  • Johnson, S. L., Greenstein, D., Clasen, L., Miller, R., Lalonde, F., Rapoport, J., et al. (2013). Absence of anatomic corpus callosal abnormalities in childhood-onset schizophrenia patients and healthy siblings. Psychiatry Research, 211(1), 11–16. doi:10.1016/j.pscychresns.2012.09.013.

    Article  PubMed  Google Scholar 

  • Johnstone, E. C., Crow, T. J., Frith, C. D., Husband, J., & Kreel, L. (1976). Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet, 2(7992), 924–926.

    Article  CAS  PubMed  Google Scholar 

  • Jones, S. H., Thornicroft, G., Coffey, M., & Dunn, G. (1995). A brief mental health outcome scale-reliability and validity of the global assessment of functioning (GAF). The British Journal of Psychiatry, 166(5), 654–659.

    Article  CAS  PubMed  Google Scholar 

  • Kempton, M. J., Stahl, D., Williams, S. C., & DeLisi, L. E. (2010). Progressive lateral ventricular enlargement in schizophrenia: a meta-analysis of longitudinal MRI studies. Schizophrenia Research, 120(1–3), 54–62. doi:10.1016/j.schres.2010.03.036.

    Article  PubMed  Google Scholar 

  • Kubicki, M., & Shenton, M. E. (2015). Editorial to special issue on "white matter pathology". Schizophrenia Research, 161(1), 1–3. doi:10.1016/j.schres.2014.12.015.

    Article  PubMed  Google Scholar 

  • Lazo, D. L. (2004). Fundamentals of sectional anatomy: an imaging approach, 1st Edition. Stamford: Cengage Learning.

  • Lett, T. A., Chakravarty, M. M., Felsky, D., Brandl, E. J., Tiwari, A. K., Goncalves, V. F., et al. (2013). The genome-wide supported microRNA-137 variant predicts phenotypic heterogeneity within schizophrenia. Molecular Psychiatry, 18(4), 443–450. doi:10.1038/mp.2013.17.

    Article  CAS  PubMed  Google Scholar 

  • Mitelman, S. A., & Buchsbaum, M. S. (2007). Very poor outcome schizophrenia: clinical and neuroimaging aspects. International Review of Psychiatry, 19(4), 345–357. doi:10.1080/09540260701486563.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mitelman, S. A., Nikiforova, Y. K., Canfield, E. L., Hazlett, E. A., Brickman, A. M., Shihabuddin, L., et al. (2009). A longitudinal study of the corpus callosum in chronic schizophrenia. Schizophrenia Research, 114(1–3), 144–153. doi:10.1016/j.schres.2009.07.021.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nakamura, M., Salisbury, D. F., Hirayasu, Y., Bouix, S., Pohl, K. M., Yoshida, T., et al. (2007). Neocortical gray matter volume in first-episode schizophrenia and first-episode affective psychosis: a cross-sectional and longitudinal MRI study. Biological Psychiatry, 62(7), 773–783. doi:10.1016/j.biopsych.2007.03.030.

    Article  PubMed  PubMed Central  Google Scholar 

  • Narr, K. L., Thompson, P. M., Sharma, T., Moussai, J., Cannestra, A. F., & Toga, A. W. (2000). Mapping morphology of the corpus callosum in schizophrenia. Cerebral Cortex, 10(1), 40–49.

    Article  CAS  PubMed  Google Scholar 

  • Narr, K. L., van Erp, T. G., Cannon, T. D., Woods, R. P., Thompson, P. M., Jang, S., et al. (2002). A twin study of genetic contributions to hippocampal morphology in schizophrenia. Neurobiology of Disease, 11(1), 83–95.

    Article  PubMed  Google Scholar 

  • Nasrallah, H. A., Jacoby, C. G., Chapman, S., & McCalley-Whitters, M. (1985). Third ventricular enlargement on CT scans in schizophrenia: association with cerebellar atrophy. Biological Psychiatry, 20(4), 443–450.

    Article  CAS  PubMed  Google Scholar 

  • Pfefferbaum, A., Sullivan, E. V., & Carmelli, D. (2004). Morphological changes in aging brain structures are differentially affected by time-linked environmental influences despite strong genetic stability. Neurobiology of Aging, 25(2), 175–183.

    Article  PubMed  Google Scholar 

  • Pfefferbaum, A., Sullivan, E. V., Swan, G. E., & Carmelli, D. (2000). Brain structure in men remains highly heritable in the seventh and eighth decades of life. Neurobiology of Aging, 21(1), 63–74.

    Article  CAS  PubMed  Google Scholar 

  • Rotarska-Jagiela, A., Schonmeyer, R., Oertel, V., Haenschel, C., Vogeley, K., & Linden, D. E. (2008). The corpus callosum in schizophrenia-volume and connectivity changes affect specific regions. NeuroImage, 39(4), 1522–1532. doi:10.1016/j.neuroimage.2007.10.063.

    Article  PubMed  Google Scholar 

  • Salat, D. H., Tuch, D. S., Greve, D. N., van der Kouwe, A. J., Hevelone, N. D., Zaleta, A. K., et al. (2005). Age-related alterations in white matter microstructure measured by diffusion tensor imaging. Neurobiology of Aging, 26(8), 1215–1227. doi:10.1016/j.neurobiolaging.2004.09.017.

    Article  CAS  PubMed  Google Scholar 

  • Schizophrenia Psychiatric Genome-Wide Association Study, C (2011). Genome-wide association study identifies five new schizophrenia loci. Nature Genetics, 43(10), 969–976. doi:10.1038/ng.940.

    Article  Google Scholar 

  • Schizophrenia Working Group of the Psychiatric Genomics, C (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511(7510), 421–427. doi:10.1038/nature13595.

    Article  Google Scholar 

  • Serpa, M. H., Schaufelberger, M. S., Rosa, P. G., Duran, F. L., Santos, L. C., Muray, R. M., et al. (2012). Corpus callosum volumes in recent-onset schizophrenia are correlated to positive symptom severity after 1 year of follow-up. Schizophrenia Research, 137(1–3), 258–259. doi:10.1016/j.schres.2012.02.027.

    Article  PubMed  Google Scholar 

  • Shenton, M. E., Dickey, C. C., Frumin, M., & McCarley, R. W. (2001). A review of MRI findings in schizophrenia. Schizophrenia Research, 49(1–2), 1–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silber, J., Lim, D. A., Petritsch, C., Persson, A. I., Maunakea, A. K., Yu, M., et al. (2008). miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Medicine, 6(14). doi:10.1186/1741-7015-6-14.

  • Stoll, A. L. (2009). The psychopharmacology reference card, 1989–2009. Belmont, MA: McLean Hospital.

  • van Haren, N. E., 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 

  • Wechsler, D. (1999). Wechsler abbreviated scale of intelligence. New York: Psychological Corporation, Harcourt Brace.

  • Whitford, T. J., Ford, J. M., Mathalon, D. H., Kubicki, M., & Shenton, M. E. (2012). Schizophrenia, myelination, and delayed corollary discharges: a hypothesis. Schizophrenia Bulletin, 38(3), 486–494. doi:10.1093/schbul/sbq105.

    Article  PubMed  Google Scholar 

  • Whitford, T. J., Kubicki, M., Schneiderman, J. S., O’Donnell, L. J., King, R., Alvarado, J. L., et al. (2010). Corpus callosum abnormalities and their association with psychotic symptoms in patients with schizophrenia. Biological Psychiatry, 68(1), 70–77. doi:10.1016/j.biopsych.2010.03.025.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wilkinson, G. S, Robertson, G. J. (2006). Wide range achievement test, Fourth edition. Lutz, FL: Psychological Assessment Resources.

  • Witelson, S. F. (1989). Hand and sex differences in the isthmus and genu of the human corpus callosum. A postmortem morphological study. Brain, 112 (Pt 3), 799–835.

  • Woodruff, P. W., McManus, I. C., & David, A. S. (1995). Meta-analysis of corpus callosum size in schizophrenia. Journal of Neurology, Neurosurgery, and Psychiatry, 58(4), 457–461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woods, S. W. (2003). Chlorpromazine equivalent doses for the newer atypical antipsychotics. Journal of Clinical Psychiatry, 64(6), 663–667.

  • Wright, C., Calhoun, V. D., Ehrlich S., Wang L., Turner J. A., and Bizzozero N. I. (2015). Meta gene set enrichment analyses link miR-137-regulated pathways with schizophrenia risk. Frontiers in Genetics, 6, 147.

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Acknowledgments

We thank all subjects who participated in the study. We also thank the clinical, research assistant, and data management staff from the Boston CIDAR study, including.

Ann Cousins, PhD, APRN, Michelle Friedman-Yakoobian, PhD, Anthony J. Giuliano, PhD, Matcheri Keshavan, MD, Janine Rodenhiser-Hill, PhD, Kristen A. Woodberry, MSW, PhD, Andréa Gnong-Granato,MSW, Lauren Gibson, EdM, Sarah Hornbach, BA, Julia Schutt,BA, Kristy Klein, PhD, Maria Hiraldo, PhD, Grace Francis, PhD, Corin Pilo, LMHC, Rachael Serur, BS, Reka Szent-Imry, BA, Shannon Sorenson, BA, Grace Min, EdM, Alison Thomas, BA, Chelsea Wakeham, BA, Caitlin Bryant, BS, and Molly Franz, BA. Finally, we are grateful for the hard work of many research volunteers, including Zach Feder, Elizabeth Piazza, Julia Reading, Devin Donohoe, Sylvia Khromina, Alexandra Oldershaw, and Olivia Schanz.

Contributors

E.C. del Re designed this study, analyzed the data, and wrote the manuscript; J. Konishi helped with data analysis; S. Bouix helped with MRI tools and edited the manuscript; G. Blokland, O. Pasternak, J. Goldstein, M. Kubicki, Y. Hirayasu and Margaret Niznikiewicz edited the manuscript; R. Mesholam-Gately and L. Seidman recruited the subjects, collected clinical data, edited the manuscript and contributed funding (LJS); T. Petryshen edited the manuscript and contributed funding for this project; M. Shenton and R. McCarley contributed funding for this research project and contributed to manuscript writing and data analysis.

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Authors and Affiliations

  1. Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare System, Brockton Division, Brockton, MA, USA

    Elisabetta C. del Re, Jun Konishi, Margaret Niznikiewicz & Robert W. McCarley

  2. Harvard Medical School, Boston, MA, USA

    Elisabetta C. del Re, Jun Konishi, Margaret Niznikiewicz & Robert W. McCarley

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

    Elisabetta C. del Re, Jun Konishi, Sylvain Bouix, Marek Kubicki, Ofer Pasternak & Martha E. Shenton

  4. VA Boston Healthcare System, Brockton Division, Brockton, MA, USA

    Elisabetta C. del Re, Jun Konishi, Margaret Niznikiewicz, Martha E. Shenton & Robert W. McCarley

  5. Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA

    Gabriëlla A. M. Blokland & Tracey Petryshen

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

    Gabriëlla A. M. Blokland, Larry J. Seidman & Tracey Petryshen

  7. Massachusetts Mental Health Center Division of Public Psychiatry, Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Raquelle I. Mesholam-Gately, Joanne Wojcik & Larry J. Seidman

  8. Brigham and Women’s Hospital, Connors Center for Women’s Health and Gender Biology, Boston, MA, USA

    Jill Goldstein

  9. Departments of Psychiatry and Medicine, Harvard Medical School, Boston, MA, USA

    Jill Goldstein

  10. Department of Psychiatry, Graduate School of Medicine, Yokohama City University, Yokohama, Japan

    Yoshio Hirayasu

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

    Martha E. Shenton

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  1. Elisabetta C. del Re
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  15. Robert W. McCarley
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Correspondence to Elisabetta C. del Re.

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Role of funding source

This study was conducted in part by the P50 MH080272 Boston Center for Intervention Development and Applied Research (Boston CIDAR; RWM PI, MES, LJS, RI-M-G, JG, TLP), entitled: “Longitudinal Assessment and Monitoring of Clinical Status and Brain Function in Adolescents and Adults.” This work was also supported in part by R01 MH40799 (RWM) and R01MH092380 (TLP) from National Institutes of Health, by the Commonwealth Research Center (SCDMH82101008006, 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 (LJS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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All authors declare that they do not have conflicts of interest.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.

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del Re, E.C., Konishi, J., Bouix, S. et al. Enlarged lateral ventricles inversely correlate with reduced corpus callosum central volume in first episode schizophrenia: association with functional measures. Brain Imaging and Behavior 10, 1264–1273 (2016). https://doi.org/10.1007/s11682-015-9493-2

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