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Abnormal relationships between local and global brain measures in subjects at clinical high risk for psychosis: a pilot study

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Abstract

We examined whether abnormal volumes of several brain regions as well as their mutual associations that have been observed in patients with schizophrenia, are also present in individuals at clinical high-risk (CHR) for developing psychosis. 3T magnetic resonance imaging was acquired in 19 CHR and 20 age- and handedness-matched controls. Volumes were measured for the body and temporal horns of the lateral ventricles, hippocampus and amygdala as well as total brain, cortical gray matter, white matter, and subcortical gray matter volumes. Relationships between volumes as well as correlations between volumes and cognitive and clinical measures were explored. Ratios of lateral ventricular volume to total brain volume and temporal horn volume to total brain volume were calculated. Volumetric abnormalities were lateralized to the left hemisphere. Volumes of the left temporal horn, and marginally, of the body of the left lateral ventricle were larger, while left amygdala but not hippocampal volume was significantly smaller in CHR participants compared to controls. Total brain volume was also significantly smaller and the ratio of the temporal horn/total brain volume was significantly higher in CHR than in controls. White matter volume correlated positively with higher verbal fluency score while temporal horn volume correlated positively with a greater number of perseverative errors. Together with the finding of larger temporal horns and smaller amygdala volumes in the left hemisphere, these results indicate that the ratio of temporal horns volume to brain volume is abnormal in CHR compared to controls. These abnormalities present in CHR individuals may constitute the biological basis for at least some of the CHR syndrome.

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References

  • Addington, J., Liu, L., Buchy, L., Cadenhead, K. S., Cannon, T. D., Cornblatt, B. A., et al. (2015). North American Prodrome longitudinal study (NAPLS 2). The Journal of Nervous and Mental Disease, 203, 328–335. doi:10.1097/NMD.0000000000000290.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bartholomeusz, C. F., Cropley, V. L., Wannan, C., Di Biase, M., McGorry, P. D., & Pantelis, C. (2016). Structural neuroimaging across early-stage psychosis: aberrations in neurobiological trajectories and implications for the staging model. The Australian and New Zealand Journal of Psychiatry. doi:10.1177/0004867416670522.

    Article  PubMed  Google Scholar 

  • Berg, E. A. (1948). A simple objective technique for measuring flexibility in thinking. The Journal of General Psychology, 39, 15–22. doi:10.1080/00221309.1948.9918159.

    Article  PubMed  CAS  Google Scholar 

  • Blokland, G. A., Mesholam-Gately, R. I., Toulopoulou, T., Del Re, E. C., Lam, M., DeLisi, L. E., et al. (2016). Heritability of neuropsychological measures in schizophrenia and nonpsychiatric populations: a systematic review and meta-analysis. Schizophrenia Bulletin. doi:10.1093/schbul/sbw146.

    Article  PubMed Central  Google Scholar 

  • Bogerts, B., Ashtari, M., Degreef, G., Alvir, J. M., Bilder, R. M., & Lieberman, J. A. (1990). Reduced temporal limbic structure volumes on magnetic resonance images in first episode schizophrenia. Psychiatry Research, 35(1), 1–13.

    Article  PubMed  CAS  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, 689–714. doi:10.1016/j.chc.2013.06.003.

    Article  PubMed  PubMed Central  Google Scholar 

  • Buchsbaum, M. S., Yang, S., Hazlett, E., Siegel, B. V. Jr., Germans, M., Haznedar, M., et al. (1997). Ventricular volume and asymmetry in schizotypal personality disorder and schizophrenia assessed with magnetic resonance imaging. Schizophrenia Research, 27(1), 45–53. doi:10.1016/S0920-9964(97)00087-X.

    Article  PubMed  CAS  Google Scholar 

  • Buckner, R. L., Head, D., Parker, J., Fotenos, A. F., Marcus, D., Morris, J. C., et al. (2004). A unified approach for morphometric and functional data analysis in young, old, and demented adults using automated atlas-based head size normalization: reliability and validation against manual measurement of total intracranial volume. NeuroImage, 23(2), 724–38.

    Article  PubMed  Google Scholar 

  • Cannon, T. D. (2016). Brain biomarkers of vulnerability and progression to psychosis. Schizophrenia Bulletin, 42 Suppl 1, S127–132. doi:10.1093/schbul/sbv173.

    Article  PubMed  Google Scholar 

  • Cannon, T. D., Chung, Y., He, G., Sun, D., Jacobson, A., van Erp, T. G., et al. (2015). Progressive reduction in cortical thickness as psychosis develops: a multisite longitudinal neuroimaging study of youth at elevated clinical risk. Biological Psychiatry, 77(2), 147–157. doi:10.1016/j.biopsych.2014.05.023.

    Article  PubMed  Google Scholar 

  • Chance, S. A., Esiri, M. M., & Crow, T. J. (2003). Ventricular enlargement in schizophrenia: a primary change in the temporal lobe? Schizophrenia Research, 62(1–2), 123–131.

    Article  PubMed  Google Scholar 

  • Chung, Y., Jacobson, A., He, G., van Erp, T. G. M., McEwen, S., Addington, J., et al. (2015). Prodromal symptom severity predicts accelerated gray matter reduction and third ventricle expansion among clinically high risk youth developing psychotic disorders. Molecular Neuropsychiatry, 1, 13–22. doi:10.1159/000371887.

    Article  PubMed  PubMed Central  Google Scholar 

  • Crespo-Facorro, B., Barbadillo, L., Pelayotera, J. M., & Rodriguez-Sanchez, J. M. (2007). Neuropsychological functioning and brain structure in schizophrenia. International Review of Psychiatry, 19(4), 325–336.

    Article  PubMed  Google Scholar 

  • del Re, E. C., Gao, Y., Eckbo, R., Petryshen, T. L., Blokland, G. A., Seidman, L. J., et al. (2016a). 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, 26(1), 28–36. doi:10.1111/jon.12313.

    Article  PubMed  Google Scholar 

  • del Re, E. C., Konishi, J., Bouix, S., Blokland, G. A., Mesholam-Gately, R. I., Goldstein, J., et al. (2016b). Enlarged lateral ventricles inversely correlate with reduced corpus callosum central volume in first episode schizophrenia: association with functional measures. Brain Imaging and Behavior, 10(4), 1264–1273. doi:10.1007/s11682-015-9493-2.

    Article  PubMed  PubMed Central  Google Scholar 

  • del Re, E. C., Spencer, K. M., Oribe, N., Mesholam-Gately, R. I., Goldstein, J., Shenton, M. E., et al. (2015). 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., Goldin, L. R., Hamovit, J. R., Maxwell, M. E., Kurtz, D., & Gershon, E. S. (1986). A family study of the association of increased ventricular size with schizophrenia. Archives of General Psychiatry, 43(2), 148–153.

    Article  PubMed  CAS  Google Scholar 

  • Dickey, C. C., McCarley, R. W., & Shenton, M. E. (2002). The brain in schizotypal personality disorder: a review of structural MRI and CT findings. Harvard Review of Psychiatry, 10(1), 1–15.

    Article  PubMed  PubMed Central  Google Scholar 

  • Everett, J., Lavoie, K., Gagnon, J. F., & Gosselin, N. (2001). Performance of patients with schizophrenia on the Wisconsin Card Sorting Test (WCST). Journal of Psychiatry & Neuroscience, 26(2), 123–130.

    CAS  Google Scholar 

  • First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (2002). Structured clinical interview for DSM-IV-TR axis I disorders, research version. New York: Biometrics Research, New York State Psychiatric Institute.

    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, 341–355.

    Article  PubMed  CAS  Google Scholar 

  • Frazier, J. A., Hodge, S. M., Breeze, J. L., Giuliano, A. J., Terry, J. E., Moore, C. M., et al. (2008). Diagnostic and sex effects on limbic volumes in early-onset bipolar disorder and schizophrenia. Schizophrenia Bulletin, 34, 37–46. doi:10.1093/schbul/sbm120.

    Article  PubMed  Google Scholar 

  • Friederici, A. D. (2009). Pathways to language: fiber tracts in the human brain. Trends in Cognitive Sciences, 13(4), 175–181. doi:10.1016/j.tics.2009.01.001.

    Article  PubMed  Google Scholar 

  • Fusar-Poli, P., Bonoldi, I., Yung, A. R., Borgwardt, S., Kempton, M. J., Valmaggia, L., et al. (2012). Predicting psychosis: meta-analysis of transition outcomes in individuals at high clinical risk. Archives of General Psychiatry, 69(3), 220–229. doi:10.1001/archgenpsychiatry.2011.1472.

    Article  PubMed  Google Scholar 

  • Fusar-Poli, P., Borgwardt, S., Bechdolf, A., Addington, J., Riecher-Rossler, A., Schultze-Lutter, F., et al. (2013). The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry, 70(1), 107–120. doi:10.1001/jamapsychiatry.2013.269.

    Article  PubMed  PubMed Central  Google Scholar 

  • Fusar-Poli, P., Borgwardt, S., Crescini, A., Deste, G., Kempton, M. J., Lawrie, S., et al. (2011). Neuroanatomy of vulnerability to psychosis: a voxel-based meta-analysis. Neuroscience & Biobehavioral Reviews, 35, 1175–1185. doi:10.1016/j.neubiorev.2010.12.005.

    Article  CAS  Google Scholar 

  • Gaser, C., Nenadic, I., Buchsbaum, B. R., Hazlett, E. A., & Buchsbaum, M. S. (2004). Ventricular enlargement in schizophrenia related to volume reduction of the thalamus, striatum, and superior temporal cortex. The American Journal of Psychiatry, 161(1), 154–156. doi:10.1176/appi.ajp.161.1.154.

    Article  PubMed  Google Scholar 

  • Gilmore, J. H., Smith, L. C., Wolfe, H. M., Hertzberg, B. S., Smith, J. K., Chescheir, N. C., Evans, D. D., Kang, C., Hamer, R. M., Lin, W., & Gerig, G. (2008). Prenatal mild ventriculomegaly predicts abnormal development of the neonatal brain. Biological Psychiatry, 64, 1069–1076.

    Article  PubMed  PubMed Central  Google Scholar 

  • Giuliano, A. J., Li, H., Mesholam-Gately, R. I., Sorenson, S. M., Woodberry, K. A., & Seidman, L. J. (2012). Neurocognition in the psychosis risk syndrome: a quantitative and qualitative review. Current Pharmaceutical Design, 18(4), 399–415.

    Article  PubMed  CAS  Google Scholar 

  • Goldstein, J. M., Cherkerzian, S., & Petryshen, T. L. (2013). Sex differences in the genetic risk for schizophrenia: history of the evidence for sex-specific and sex-dependent effects. American Journal of Medical Genetic Part B: Neuropsychiatric Genetics, 162B(7), 698–710.

    Article  CAS  Google Scholar 

  • Goncalves, A. M., Dantas, Cde. R., & Banzato, C. E. (2016). Values and DSM-5: looking at the debate on attenuated psychosis syndrome. BMC Medical Ethics, 17(1), 7. doi:10.1186/s12910-016-0090-8.

  • Heaton, R. K. (2000). WCST-64: Computer version3 for windows-research edition. Odessa: Psychological Assessment Resources.

    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 (Version 1.0). New York: Columbia University.

    Google Scholar 

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

    Google Scholar 

  • Horga, G., Bernacer, J., Dusi, N., Entis, J., Chu, K., Hazlett, E. A., et al. (2011). Correlations between ventricular enlargement and gray and white matter volumes of cortex, thalamus, striatum, and internal capsule in schizophrenia. European Archives of Psychiatry and Clinical NeuroScience, 261(7), 467–476. doi:10.1007/s00406-011-0202-x.

    Article  PubMed  PubMed Central  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  PubMed  CAS  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, 654–659.

    Article  PubMed  CAS  Google Scholar 

  • Kemali, D., Maj, M., Galderisi, S., Salvati, A., Starace, F., Valente, A., et al. (1987). Clinical, biological, and neuropsychological features associated with lateral ventricular enlargement in DSM-III schizophrenic disorder. Psychiatry Research, 21, 137–149.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Keshavan, M. S., Dick, E., Mankowski, I., Harenski, K., Montrose, D. M., Diwadkar, V., & DeBellis, M. (2002). Decreased left amygdala and hippocampal volumes in young offspring at risk for schizophrenia. Schizophrenia Research, 58(2), 173–183.

    Article  PubMed  Google Scholar 

  • Kiernan, J. A. (2012). Anatomy of the temporal lobe. Epilepsy Research and Treatment, 2012, 176157. doi:10.1155/2012/176157.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Klausner, J. D., Sweeney, J. A., Deck, M. D., Haas, G. L., & Kelly, A. B. (1992). Clinical correlates of cerebral ventricular enlargement in schizophrenia. Further evidence for frontal lobe disease. The Journal of Nervous and Mental Disease, 180, 407–412.

    Article  PubMed  CAS  Google Scholar 

  • Klosterkötter, J., Hellmich, M., Steinmeyer, E. M., & Schultze-Lutter, F. (2001). Diagnosing schizophrenia in the initial prodromal phase. Archives of General Psychiatry, 58, 158–164.

    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. doi:10.1016/j.jpsychires.2005.05.005.

    Article  PubMed  Google Scholar 

  • Kubicki, M., Shenton, M. E., Maciejewski, P. K., Pelavin, P. E., Hawley, K. J., Ballinger, T., et al. (2013). Decreased axial diffusivity within language connections: a possible biomarker of schizophrenia risk. Schizophrenia Research, 148(1–3), 67–73. doi:10.1016/j.schres.2013.06.014.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Laywer, G., Nyman, H., Agartz, I., Arnborg, S., Jönsson, E. G., Sedvall, G. C., & Hall, H. (2006). Morphological correlates to cognitive dysfunction in schizophrenia as studied with Bayesian regression. BMC Psychiatry, 6, 31.

    Article  PubMed  Google Scholar 

  • Mathalon, D. H., Sullivan, E. V., Lim, K. O., & Pfefferbaum, A. (2001). Progressive brain volume changes and the clinical course of schizophrenia in men: a longitudinal magnetic resonance imaging study. Archives of General Psychiatry, 58, 148–57.

    Article  PubMed  CAS  Google Scholar 

  • McCarley, R. W., Wible, C. G., Frumin, M., Hirayasu, Y., Levitt, J. J., Fischer, I. A., et al. (1999). MRI anatomy of schizophrenia. Biological Psychiatry, 45(9), 1099–1119.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • McDonald, C., Marshall, N., Sham, P. C., Bullmore, E. T., Schulze, K., Chapple, B., et al. (2006). Regional brain morphometry in patients with schizophrenia or bipolar disorder and their unaffected relatives. The American Journal of Psychiatry, 163(3), 478–487. doi:10.1176/appi.ajp.163.3.478.

    Article  PubMed  Google Scholar 

  • Mechelli, A., Riecher-Rössler, A., Meisenzahl, E. M., Tognin, S., Wood, S. J., Borgwardt, S. J., et al. (2011). Neuroanatomical abnormalities that predate the onset of psychosis: a multicenter study. Archives of General Psychiatry, 68, 489–495. doi:10.1001/archgenpsychiatry.2011.42.

    Article  PubMed  Google Scholar 

  • Mesholam-Gately, R. I., Giuliano, A. J., Goff, K. P., Faraone, S. V., & Seidman, L. J. (2009). Neurocognition in first-episode schizophrenia: a meta-analytic review. Neuropsychology, 23(3), 315–336. doi:10.1037/a0014708.

    Article  PubMed  Google Scholar 

  • Miller, T. J., McGlashan, T. H., Woods, S. W., Stein, K., Driesen, N., Corcoran, C. M., et al. (1999). Symptom assessment in schizophrenic prodromal states. The Psychiatric Quarterly, 70, 273–287.

    Article  PubMed  CAS  Google Scholar 

  • Molina, V., Reig, S., Sarramea, F., Sanz, J., Francisco Artaloytia, J., Luque, R., et al. (2003). Anatomical and functional brain variables associated with clozapine response in treatment-resistant schizophrenia. Psychiatry Research, 124, 153–161.

    Article  PubMed  CAS  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, 773–783. doi:10.1016/j.biopsych.2007.03.030.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nesvåg, R., Bergmann, Ø., Rimol, L. M., Lange, E. H., Haukvik, U. K., Hartberg, C. B., et al. (2012). A 5-year follow-up study of brain cortical and subcortical abnormalities in a schizophrenia cohort. Schizophrenia Research, 142, 209–216. doi:10.1016/j.schres.2012.10.004.

    Article  PubMed  Google Scholar 

  • Pearlson, G. D., Kim, W. S., Kubos, K. L., Moberg, P. J., Jayaram, G., Bascom, M. J., et al. (1989). Ventricle-brain ratio, computed tomographic density, and brain area in 50 schizophrenics. Archives of General Psychiatry, 46, 690–697.

    Article  PubMed  CAS  Google Scholar 

  • Reite, M., Reite, E., Collins, D., Teale, P., Rojas, D. C., & Sandberg, E. (2010). Brain size and brain/intracranial volume ratio in major mental illness. BMC Psychiatry, 10, 79. doi:10.1186/1471-244X-10-79.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rosa, P. G., Schaufelberger, M. S., Uchida, R. R., Duran, F. L., Lappin, J. M., Menezes, P. R., et al. (2010). Lateral ventricle differences between first-episode schizophrenia and first-episode psychotic bipolar disorder: a population-based morphometric MRI study. The World Journal of Biological Psychiatry, 11(7), 873–887. doi:10.3109/15622975.2010.486042.

  • Rossi, A., Stratta, P., Mancini, F., Gallucci, M., Mattei, P., Core, L., et al. (1994). Magnetic resonance imaging findings of amygdala-anterior hippocampus shrinkage in male patients with schizophrenia. Psychiatry Research, 52, 43–53.

    Article  PubMed  CAS  Google Scholar 

  • Schultze-Lutter, F., Addington, J., Ruhrmann, S., & Klosterkötter, J. (2007). The schizophrenia proneness instrument, adult version (SPI-A). Rome: Giovanni Fioriti Editore.

  • Seidman, L. J., Faraone, S. V., Goldstein, J. M., Goodman, J. M., Kremen, W. S., Toomey, R., et al. (1999). Thalamic and amygdala–hippocampal volume reductions in first-degree relatives of patients with schizophrenia: an MRI-based morphometric analysis. Biological Psychiatry, 46(7), 941–954.

  • Seidman, L. J., Shapiro, D. I., Stone, W. S., Woodberry, K. A., Ronzio, A., Cornblatt, B. A., et al. (2016). Association of neurocognition with transition to psychosis: baseline functioning in the second phase of the north American prodrome longitudinal study. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2016.2479.

    Article  PubMed Central  PubMed  Google Scholar 

  • Seitz, J., Zuo, J. X., Lyall, A. E., Makris, N., Kikinis, Z., Bouix, S., Pasternak, O., Fredman, E., Duskin, J., Goldstein, J. M., Petryshen, T. L., Mesholam-Gately, R. I., Wojcik, J., McCarley, R. W., Seidman, L. J., Shenton, M. E., Koerte, I. K., & Kubicki, M. (2016). Tractography analysis of 5 white matter bundles and their clinical and cognitive correlates in early-course schizophrenia. Schizophrenia Bulletin, 42(3), 762–71.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shenton, M. E., Kikinis, R., Jolesz, F. A., Pollak, S. D., LeMay, M., Wible, C. G., et al. (1992). Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study. The New England Journal of Medicine, 327(9), 604–612. doi:10.1056/NEJM199208273270905.

    Article  PubMed  CAS  Google Scholar 

  • Smieskova, R., Fusar-Poli, P., Allen, P., Bendfeldt, K., Stieglitz, R. D., Drewe, J., et al. (2010). Neuroimaging predictors of transition to psychosis–a systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews, 34, 1207–1222. doi:10.1016/j.neubiorev.2010.01.016.

    Article  PubMed  CAS  Google Scholar 

  • Spreen, O., & Strauss, E. (1991). A compendium of neuropsychological tests. New York: Oxford University Press.

    Google Scholar 

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

    Google Scholar 

  • Tamminga, C. A., Stan, A. D., & Wagner, A. D. (2010). The hippocampal formation in schizophrenia. The American Journal of Psychiatry, 167, 1178–1193. doi:10.1176/appi.ajp.2010.09081187.

    Article  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Toulopoulou, T., Grech, A., Morris, R. G., Schulze, K., McDonald, C., Chapple, B., Rabe-Hesketh, S., & Murray, R. M. (2010).The relationship between volumetric brain changes and cognitive function: a family study on schizophrenia. Biological Psychiatry, 56(6), 447–53.

    Article  Google Scholar 

  • van Erp, T. G. M., Hibar, D. P., Rasmussen, J. M., Glahn, D. C., Pearlson, G. D., Andreassen, O. A., et al. (2015). Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. Molecular Psychiatry. doi:10.1038/mp.2015.63.

    Article  PubMed  PubMed Central  Google Scholar 

  • Van Horn, J. D., & McManus, I. C. (1992). Ventricular enlargement in schizophrenia. A meta-analysis of studies of the ventricle: brain ratio (VBR). The British Journal of Psychiatry, 160, 687–697.

    Article  PubMed  Google Scholar 

  • Velakoulis, D., Wood, S. J., Wong, M. T. H., McGorry, P. D., Yung, A., Phillips, L., et al. (2006). Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals. Archives of General Psychiatry, 63, 139–149. doi:10.1001/archpsyc.63.2.139.

    Article  PubMed  Google Scholar 

  • von Hohenberg, C. C., Pasternak, O., Kubicki, M., Ballinger, T., Vu, M.-A., Swisher, T., et al. (2014). White matter microstructure in individuals at clinical high risk of psychosis: a whole-brain diffusion tensor imaging study. Schizophrenia Bulletin, 40, 895–903. doi:10.1093/schbul/sbt079.

    Article  Google Scholar 

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

  • Wilkinson, G. S., & Robertson, G. J. (2006). Wide range achievement test, 4th edn. Lutz: Psychological Assessment Resources.

  • Williams, A. O., Reveley, M. A., Kolakowska, T., Ardern, M., & Mandelbrote, B. M. (1985). Schizophrenia with good and poor outcome. II: Cerebral ventricular size and its clinical significance. The British Journal of Psychiatry, 146, 239–246.

    Article  PubMed  CAS  Google Scholar 

  • Wood, S. J., Pantelis, C., Velakoulis, D., Yücel, M., Fornito, A., & McGorry, P. D. (2008). Progressive changes in the development toward schizophrenia: studies in subjects at increased symptomatic risk. Schizophrenia Bulletin, 34, 322–329. doi:10.1093/schbul/sbm149.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Woods, S. W., Addington, J., Cadenhead, K. S., Cannon, T. D., Cornblatt, B. A., Heinssen, R., Perkins, D. O., Seidman, L. J., Tsuang, M. T., Walker, E. F., & McGlashan, T. H. (2009). Validity of the prodromal risk syndrome for first psychosis: findings from the North American prodrome longitudinal study. Schizophrenia Bulletin, 35(5), 894–908. doi:10.1093/schbul/sbp027.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yotsutsuji, T., Saitoh, O., Suzuki, M., Hagino, H., Mori, K., Takahashi, T., et al. (2003). Quantification of lateral ventricular subdivisions in schizophrenia by high-resolution three-dimensional magnetic resonance imaging. Psychiatry Research, 122(1), 1–12.

    Article  PubMed  Google Scholar 

  • Ziermans, T. B., Schothorst, P. F., Schnack, H. G., Koolschijn, P. C., Kahn, R. S., van Engeland, H., et al. (2012). Progressive structural brain changes during development of psychosis. Schizophrenia Bulletin, 38(3), 519–530. doi:10.1093/schbul/sbq113.

    Article  PubMed  Google Scholar 

  • Zipursky, R. B., Lim, K. O., Sullivan, E. V., Brown, B. W., & Pfefferbaum, A. (1992). Widespread cerebral gray matter volume deficits in schizophrenia. Archives of General Psychiatry, 49(3), 195–205. doi:10.1001/archpsyc.1992.01820030027004.

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Acknowledgements

We are grateful to the study participants, the investigators, the research assistants and the PIs of the CIDAR study for making this project possible. We also thank the clinical and data management staff from the Boston CIDAR study, including Caitlin Bryant, BS, Ann Cousins, PhD, APRN, Grace Francis, PhD, Molly Franz, BA, Michelle Friedman-Yakoobian, PhD, Lauren Gibson, EdM, Anthony Giuliano, PhD, Andréa Gnong-Granato,MSW, Maria Hiraldo, PhD, Sarah Hornbach, BA, Kristy Klein, PhD, Grace Min, EdM, Corin Pilo-Comtois, LMHC, Janine Rodenhiser-Hill, PhD, Julia Schutt, BA, Shannon Sorenson, BA, Reka Szent-Imry, BA, Alison Thomas, BA, Lynda Tucker, Chelsea Wakeham, BA, and Joanne D. Wojcik, PhD, APRN. 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, Elena Molokotos, and Olivia Schanz.

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    Authors and Affiliations

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

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

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

      Jun Konishi, Elisabetta C. del Re, Sylvain Bouix & Martha E. Shenton

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

      Jun Konishi & Yoshio Hirayasu

    4. Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA

      Gabriëlla A. M. Blokland & Tracey L. Petryshen

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

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

    6. Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, MA, USA

      Raquelle Mesholam-Gately, Kristen Woodberry & Larry J. Seidman

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

      Jill Goldstein

    8. 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 Radiology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA

      Martha E. Shenton

    11. Research and Development, VA Boston Healthcare System, Boston, MA, USA

      Martha E. Shenton

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    1. Jun Konishi
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    2. Elisabetta C. del Re
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    12. Martha E. Shenton
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    13. Robert W. McCarley
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    Corresponding author

    Correspondence to Elisabetta C. del Re.

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    Funding

    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 R01MH40799 (RWM) and R01MH092380 (TLP) from National Institutes of Health, by the Commonwealth Research Center (SCDMH82101008006, LJS), by a VA Merit Award (MES), 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). This work was also supported in part by R21 MH109819 (ECdR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

    Conflict of interest

    No conflict of interest has been reported by any of the authors of the study.

    Informed consent and ethical approval

    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 1964 and its later amendments (1975), and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.

    Additional information

    Jun Konishi and Elisabetta C. del Re are co-first authors.

    Martha E. Shenton and Robert W. McCarley are co-last authors.

    Robert W. McCarley died before publication of this work was completed.

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    Konishi, J., del Re, E.C., Bouix, S. et al. Abnormal relationships between local and global brain measures in subjects at clinical high risk for psychosis: a pilot study. Brain Imaging and Behavior 12, 974–988 (2018). https://doi.org/10.1007/s11682-017-9758-z

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