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Dynamic cerebral reorganization in the pathophysiology of schizophrenia: a MRI-derived cortical thickness study

  • S. Guo (a1) (a2), L. Palaniyappan (a3) (a4) (a5), P. F. Liddle (a3) and J. Feng (a2) (a6) (a7) (a8)
Abstract
Background

A structural neuroanatomical change indicating a reduction in brain tissue is a notable feature of schizophrenia. Several pathophysiological processes such as aberrant cortical maturation, progressive tissue loss and compensatory tissue increase could contribute to the structural changes seen in schizophrenia.

Method

We studied cortical thickness using surface-based morphometry in 98 clinically stable patients with schizophrenia and 83 controls. Using a pattern classification approach, we studied whether the features that discriminate patients from controls vary across the different stages of the illness. Using a covariance analysis, we also investigated if concurrent increases accompany decreases in cortical thickness.

Results

Very high levels of accuracy (96.3%), specificity (98.8%) and sensitivity (88%) were noted when classifying patients with <2 years of illness from controls. Within the patient group, reduced thickness was consistently accompanied by increased thickness in distributed brain regions. A pattern of cortical amelioration or normalization (i.e. reduced deviation from controls) was noted with increasing illness duration. While temporo-limbic and fronto-parietal regions showed reduced thickness, the occipital cortex showed increased thickness, especially in those with a long-standing illness.

Conclusion

A compensatory remodelling process might contribute to the cortical thickness variations in different stages of schizophrenia. Subtle cerebral reorganization reflecting the inherent plasticity of brain may occur concomitantly with processes contributing to tissue reduction in adult patients with schizophrenia.

Copyright
Corresponding author
*Address for correspondence: Dr L. Palaniyappan MBBS, PhD, Robarts Research Institute, Western University, Room 3208, 100 Perth Drive, London, ON, N6A 5K8, Canada. (Email: lpalaniy@uwo.ca) [L.P.] (Email: jianfeng64@gmail.com) [J.F.]
References
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Ammons, RB, Ammons, CH (1962). The quick test (QT): provisional manual. Psychological Reports 11, 111161.
Andreasen, NC, Nopoulos, P, Magnotta, V, Pierson, R, Ziebell, S, Ho, B-C (2011). Progressive brain change in schizophrenia: a prospective longitudinal study of first-episode schizophrenia. Biological Psychiatry 70, 672679.
Ansell, BRE, Dwyer, DB, Wood, SJ, Bora, E, Brewer, WJ, Proffitt, TM, Velakoulis, D, McGorry, PD, Pantelis, C (2015). Divergent effects of first-generation and second-generation antipsychotics on cortical thickness in first-episode psychosis. Psychological Medicine 45, 515527.
Arndt, S, Andreasen, NC, Flaum, M, Miller, D, Nopoulos, P (1995). A longitudinal study of symptom dimensions in schizophrenia. Prediction and patterns of change. Archives of General Psychiatry 52, 352360.
Bora, E, Fornito, A, Radua, J, Walterfang, M, Seal, M, Wood, SJ, Yücel, M, Velakoulis, D, Pantelis, C (2011). Neuroanatomical abnormalities in schizophrenia: a multimodal voxelwise meta-analysis and meta-regression analysis. Schizophrenia Research 127, 4657.
Borgwardt, S, Fusar-Poli, P (2012). Third-generation neuroimaging in early schizophrenia: translating research evidence into clinical utility. British Journal of Psychiatry 200, 270272.
Brans, RGH, Kahn, RS, Schnack, HG, Baal, GCM, Van Posthuma, D, Haren, NEM, van Lepage, C, Lerch, JP, Collins, DL, Evans, AC, Boomsma, DI, Pol, HEH (2010). Brain plasticity and intellectual ability are influenced by shared genes. Journal of Neuroscience 30, 55195524.
Cardinale, F, Chinnici, G, Bramerio, M, Mai, R, Sartori, I, Cossu, M, Lo Russo, G, Castana, L, Colombo, N, Caborni, C, De Momi, E, Ferrigno, G (2014). Validation of FreeSurfer-estimated brain cortical thickness: comparison with histologic measurements. Neuroinformatics 12, 535542.
Chan, RCK, Di, X, McAlonan, GM, Gong, Q (2011). Brain anatomical abnormalities in high-risk individuals, first-episode, and chronic schizophrenia: an activation likelihood estimation meta-analysis of illness progression. Schizophrenia Bulletin 37, 177188.
Dale, AM, Fischl, B, Sereno, MI (1999). Cortical surface-based analysis: I. segmentation and surface reconstruction. NeuroImage 9, 179194.
DeLisi, LE (2008). The concept of progressive brain change in schizophrenia: implications for understanding schizophrenia. Schizophrenia Bulletin 34, 312321.
Destrieux, C, Fischl, B, Dale, A, Halgren, E (2010). Automatic parcellation of human cortical gyri and sulci using standard anatomical nomenclature. NeuroImage 53, 115.
Duvernoy, HM, Bourgouin, P (1999). The Human Brain: Surface, Three-Dimensional Sectional Anatomy with MRI, and Blood Supply. Springer-Verlag/Wien.
Ellison-Wright, I, Glahn, DC, Laird, AR, Thelen, SM, Bullmore, E (2008). The anatomy of first-episode and chronic schizophrenia: an anatomical likelihood estimation meta-analysis. American Journal of Psychiatry 165, 10151023.
Faget-Agius, C, Boyer, L, Lançon, C, Richieri, R, Fassio, E, Soulier, E, Chanoine, V, Auquier, P, Ranjeva, JP, Guye, M (2013). Structural and functional reorganization of working memory system during the first decade in schizophrenia. A cross-sectional study. Schizophrenia Research 151, 4860.
Fischl, B, Dale, AM (2000). Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proceedings of the National Academy of Sciences USA 97, 1105011055.
Fisher, M, Loewy, R, Hardy, K, Schlosser, D, Vinogradov, S (2013). Cognitive interventions targeting brain plasticity in the prodromal and early phases of schizophrenia. Annual Review of Clinical Psychology 9, 435463.
Fusar-Poli, P, Radua, J, McGuire, P, Stefan, B (2011). Neuroanatomical maps of psychosis onset: voxel-wise meta-analysis of antipsychotic-naive VBM studies. Schizophrenia Bulletin 38, 12971307.
Glahn, DC, Laird, AR, Ellison-Wright, I, Thelen, SM, Robinson, JL, Lancaster, JL, Bullmore, E, Fox, PT (2008). Meta-analysis of gray matter anomalies in schizophrenia: application of anatomic likelihood estimation and network analysis. Biological Psychiatry 64, 774781.
Goghari, VM, Rehm, K, Carter, CS, MacDonald, AW (2007). Regionally specific cortical thinning and gray matter abnormalities in the healthy relatives of schizophrenia patients. Cerebral Cortex 17, 415424.
Guo, S, Palaniyappan, L, Yang, B, Liu, Z, Xue, Z, Feng, J (2014). Anatomical distance affects functional connectivity in patients with schizophrenia and their siblings. Schizophrenia Bulletin 40, 449459.
Haijma, SV, Haren, NV, Cahn, W, Koolschijn, PCMP, Pol, HEH, Kahn, RS (2013). Brain volumes in schizophrenia: a meta-analysis in over 18 000 Subjects. Schizophrenia Bulletin 39, 11291138.
Haukvik, UK, Rimol, LM, Roddey, JC, Hartberg, CB, Lange, EH, Vaskinn, A, Melle, I, Andreassen, OA, Dale, A, Agartz, I (2014). Normal birth weight variation is related to cortical morphology across the psychosis spectrum. Schizophrenia Bulletin 40, 410419.
He, Y, Chen, ZJ, Evans, AC (2007). Small-world anatomical networks in the human brain revealed by cortical thickness from MRI. Cerebral Cortex 17, 24072419.
Ho, B-C, Andreasen, NC, 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, 128137.
Hulshoff Pol, HE, Kahn, RS (2008). What happens after the first episode? A review of progressive brain changes in chronically Ill patients with schizophrenia. Schizophrenia Bulletin 34, 354366.
Iwabuchi, S, Liddle, PF, Palaniyappan, L (2013). Clinical utility of machine learning approaches in schizophrenia: improving diagnostic confidence for translational neuroimaging. Frontiers in Neuropsychiatric Imaging and Stimulation 4, 95.
Jung, WH, Kim, JS, Jang, JH, Choi, J-S, Jung, MH, Park, J-Y, Han, JY, Choi, C-H, Kang, D-H, Chung, CK, Kwon, JS (2011). Cortical thickness reduction in individuals at ultra-high-risk for psychosis. Schizophrenia Bulletin 37, 839849.
Kasparek, T, Thomaz, CE, Sato, JR, Schwarz, D, Janousova, E, Marecek, R, Prikryl, R, Vanicek, J, Fujita, A, Ceskova, E (2011). Maximum-uncertainty linear discrimination analysis of first-episode schizophrenia subjects. Psychiatry Research: Neuroimaging 191, 174181.
Koutsouleris, N, Davatzikos, C, Borgwardt, S, Gaser, C, Bottlender, R, Frodl, T, Falkai, P, Riecher-Rössler, A, Möller, H-J, Reiser, M, Pantelis, C, Meisenzahl, E (2014). Accelerated brain aging in schizophrenia and beyond: a neuroanatomical marker of psychiatric disorders. Schizophrenia Bulletin 40, 11401153.
Koutsouleris, N, Gaser, C, Jäger, M, Bottlender, R, Frodl, T, Holzinger, S, Schmitt, GJE, Zetzsche, T, Burgermeister, B, Scheuerecker, J, Born, C, Reiser, M, Möller, H-J, Meisenzahl, EM (2008). Structural correlates of psychopathological symptom dimensions in schizophrenia: a voxel-based morphometric study. NeuroImage 39, 16001612.
Kuperberg, GR, Broome, MR, McGuire, PK, David, AS, Eddy, M, Ozawa, F, Goff, D, West, WC, Williams, SCR, Van der Kouwe, AJW, Salat, DH, Dale, AM, Fischl, B (2003). Regionally localized thinning of the cerebral cortex in schizophrenia. Archives of General Psychiatry 60, 878888.
Lawrie, SM, Olabi, B, Hall, J, McIntosh, AM, Sm, L, BO, JH, Am, M (2011). Do we have any solid evidence of clinical utility about the pathophysiology of schizophrenia? World Psychiatry 10, 19.
Leckman, JF, Sholomskas, D, Thompson, D, Belanger, A, Weissman, MM (1982). Best estimate of lifetime psychiatric diagnosis: a methodological study. Archives of General Psychiatry 39, 879883.
Levine, SZ, Lurie, I, Kohn, R, Levav, I (2011). Trajectories of the course of schizophrenia: from progressive deterioration to amelioration over three decades. Schizophrenia Research 126, 184191.
Liddle, PF, Ngan, ETC, Duffield, G, Kho, K, Warren, AJ (2002). Signs and symptoms of psychotic illness (SSPI): a rating scale. British Journal of Psychiatry 180, 4550.
Mané, A, Falcon, C, Mateos, JJ, Fernandez-Egea, E, Horga, G, Lomeña, F, Bargalló, N, Prats-Galino, A, Bernardo, M, Parellada, E (2009). Progressive gray matter changes in first episode schizophrenia: a 4-year longitudinal magnetic resonance study using VBM. Schizophrenia Research 114, 136143.
McGlashan, TH (2006). Is active psychosis neurotoxic? Schizophrenia Bulletin 32, 609613.
Mechelli, A, Riecher-Rössler, A, Meisenzahl, EM, Tognin, S, Wood, SJ, Borgwardt, SJ, Koutsouleris, N, Yung, AR, Stone, JM, Phillips, LJ, McGorry, PD, Valli, I, Velakoulis, D, Woolley, J, Pantelis, C, McGuire, P (2011). Neuroanatomical abnormalities that predate the onset of psychosis: a multicenter study. Archives of General Psychiatry 68, 489495.
Mitelman, SA, Buchsbaum, MS (2007). Very poor outcome schizophrenia: clinical and neuroimaging aspects. International Review of Psychiatry (Abingdon, England) 19, 345357.
Narr, KL, Bilder, RM, Toga, AW, Woods, RP, Rex, DE, Szeszko, PR, Robinson, D, Sevy, S, Gunduz-Bruce, H, Wang, Y-P, DeLuca, H, Thompson, PM (2005). Mapping cortical thickness and gray matter concentration in first episode schizophrenia. Cerebral Cortex 15, 708719.
Nesvåg, R, Lawyer, G, Varnäs, K, Fjell, AM, Walhovd, KB, Frigessi, A, Jönsson, EG, Agartz, I (2008). Regional thinning of the cerebral cortex in schizophrenia: effects of diagnosis, age and antipsychotic medication. Schizophrenia Research 98, 1628.
Olabi, B, Ellison-Wright, I, McIntosh, AM, Wood, SJ, Bullmore, E, Lawrie, SM (2011). Are there progressive brain changes in schizophrenia? A meta-analysis of structural magnetic resonance imaging studies. Biological Psychiatry 70, 8896.
Orrù, G, Pettersson-Yeo, W, Marquand, AF, Sartori, G, Mechelli, A (2012). Using support vector machine to identify imaging biomarkers of neurological and psychiatric disease: a critical review. Neuroscience & Biobehavioral Reviews 36, 11401152.
Palaniyappan, L, Balain, V, Liddle, PF (2012). The neuroanatomy of psychotic diathesis: a meta-analytic review. Journal of Psychiatric Research 46, 12491256.
Palaniyappan, L, Liddle, PF (2012). Aberrant cortical gyrification in schizophrenia: a surface-based morphometry study. Journal of Psychiatry & Neuroscience 37, 110119.
Quintana, J, Wong, T, Ortiz-Portillo, E, Kovalik, E, Davidson, T, Marder, SR, Mazziotta, JC (2003). Prefrontal-posterior parietal networks in schizophrenia: primary dysfunctions and secondary compensations. Biological Psychiatry 53, 1224.
Roiz-Santiáñez, R, Ayesa-Arriola, R, Tordesillas-Gutiérrez, D, Ortiz-García de la Foz, V, Pérez-Iglesias, R, Pazos, A, Sánchez, E, Crespo-Facorro, B (2014). Three-year longitudinal population-based volumetric MRI study in first-episode schizophrenia spectrum patients. Psychological Medicine 44, 15911604.
Rosa, PGP, Zanetti, MV, Duran, FLS, Santos, LC, Menezes, PR, Scazufca, M, Murray, RM, Busatto, GF, Schaufelberger, MS (2015). What determines continuing grey matter changes in first-episode schizophrenia and affective psychosis? Psychological Medicine 45, 817828.
Rose, D, Pevalin, DJ (2003). A Researcher's Guide to the National Statistics Socio-economic Classification. Sage Publications: London.
Schaufelberger, MS, Lappin, JM, Duran, FLS, Rosa, PGP, Uchida, RR, Santos, LC, Murray, RM, McGuire, PK, Scazufca, M, Menezes, PR, Busatto, GF (2011). Lack of progression of brain abnormalities in first-episode psychosis: a longitudinal magnetic resonance imaging study. Psychological Medicine 41, 16771689.
Schultz, CC, Koch, K, Wagner, G, Roebel, M, Schachtzabel, C, Gaser, C, Nenadic, I, Reichenbach, JR, Sauer, H, Schlösser, RGM (2010). Reduced cortical thickness in first episode schizophrenia. Schizophrenia Research 116, 204209.
Song, S, Zhan, Z, Long, Z, Zhang, J, Yao, L (2011). Comparative study of SVM methods combined with voxel selection for object category classification on fMRI data. PLoS ONE 6, e17191.
Sprooten, E, Papmeyer, M, Smyth, AM, Vincenz, D, Honold, S, Conlon, GA, Moorhead, TWJ, Job, D, Whalley, HC, Hall, J, McIntosh, AM, Owens, DCG, Johnstone, EC, Lawrie, SM (2013). Cortical thickness in first-episode schizophrenia patients and individuals at high familial risk: a cross-sectional comparison. Schizophrenia Research 151, 259264.
Storsve, AB, Fjell, AM, Tamnes, CK, Westlye, LT, Overbye, K, Aasland, HW, Walhovd, KB (2014). Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change. Journal of Neuroscience 34, 84888498.
Szeszko, PR, Narr, KL, Phillips, OR, McCormack, J, Sevy, S, Gunduz-Bruce, H, Kane, JM, Bilder, RM, Robinson, DG (2012). Magnetic resonance imaging predictors of treatment response in first-episode schizophrenia. Schizophrenia Bulletin 38, 569578.
Takao, H, Hayashi, N, Ohtomo, K (2013). Effects of the use of multiple scanners and of scanner upgrade in longitudinal voxel-based morphometry studies. Journal of Magnetic Resonance Imaging 38, 12831291.
Tan, H-Y, Sust, S, Buckholtz, JW, Mattay, VS, Meyer-Lindenberg, A, Egan, MF, Weinberger, DR, Callicott, JH (2006). Dysfunctional prefrontal regional specialization and compensation in schizophrenia. American Journal Psychiatry 163, 19691977.
Thambisetty, M, Wan, J, Carass, A, An, Y, Prince, JL, Resnick, SM (2010). Longitudinal changes in cortical thickness associated with normal aging. NeuroImage 52, 12151223.
Tognin, S, Riecher-Rossler, A, Meisenzahl, EM, Wood, SJ, Hutton, C, Borgwardt, SJ, Koutsouleris, N, Yung, AR, Allen, P, Phillips, LJ, McGorry, PD, Valli, I, Velakoulis, D, Nelson, B, Woolley, J, Pantelis, C, McGuire, P, Mechelli, A (2014). Reduced parahippocampal cortical thickness in subjects at ultra-high risk for psychosis. Psychological Medicine 44, 489498.
Van Haren, NEM, Hulshoff Pol, HE, Schnack, HG, Cahn, W, Brans, R, Carati, I, Rais, M, Kahn, RS (2008). Progressive brain volume loss in schizophrenia over the course of the illness: evidence of maturational abnormalities in early adulthood. Biological Psychiatry 63, 106113.
Van Haren, NEM, Schnack, HG, Cahn, W, Van den Heuvel, MP, Lepage, C, Collins, L, Evans, AC, Pol, HEH, Kahn, RS (2011). Changes in cortical thickness during the course of illness in schizophrenia. Archives of General Psychiatry 68, 871880.
Venkatasubramanian, G, Jayakumar, PN, Gangadhar, BN, Keshavan, MS (2008). Automated MRI parcellation study of regional volume and thickness of prefrontal cortex (PFC) in antipsychotic-naïve schizophrenia. Acta Psychiatrica Scandinavica 117, 420431.
Veronese, E, Castellani, U, Peruzzo, D, Bellani, M, Brambilla, P (2013). Machine learning approaches: from theory to application in schizophrenia. Computational and Mathematical Methods in Medicine DOI: 10.1155/2013/867924.
Vita, A, Peri, LD, Deste, G, Sacchetti, E (2012). Progressive loss of cortical gray matter in schizophrenia: a meta-analysis and meta-regression of longitudinal MRI studies. Translational Psychiatry 2, e190.
Weinberger, DR, McClure, RK (2002). Neurotoxicity, neuroplasticity, and magnetic resonance imaging morphometry: what is happening in the schizophrenic brain? Archives of General Psychiatry 59, 553558.
Xiao, Y, Lui, S, Deng, W, Yao, L, Zhang, W, Li, S, Wu, M, Xie, T, He, Y, Huang, X, Hu, J, Bi, F, Li, T, Gong, Q (2015). Altered cortical thickness related to clinical severity but not the untreated disease duration in schizophrenia. Schizophrenia Bulletin 41, 201210.
Yoon, U, Lee, J-M, Im, K, Shin, Y-W, Cho, BH, Kim, IY, Kwon, JS, Kim, SI (2007). Pattern classification using principal components of cortical thickness and its discriminative pattern in schizophrenia. NeuroImage 34, 14051415.
Zarogianni, E, Moorhead, TWJ, Lawrie, SM (2013). Towards the identification of imaging biomarkers in schizophrenia, using multivariate pattern classification at a single-subject level. NeuroImage: Clinical 3, 279289.
Zhang, Y, Lin, L, Lin, C-P, Zhou, Y, Chou, K-H, Lo, C-Y, Su, T-P, Jiang, T (2012). Abnormal topological organization of structural brain networks in schizophrenia. Schizophrenia Research 141, 109118.
Zipparo, L, Whitford, TJ, Redoblado Hodge, MA, Lucas, S, Farrow, TFD, Brennan, J, Gomes, L, Williams, LM, Harris, AWF (2008). Investigating the neuropsychological and neuroanatomical changes that occur over the first 2–3 years of illness in patients with first-episode schizophrenia. Progress in Neuro-Psychopharmacology & Biological Psychiatry 32, 531538.
Zipursky, RB, Reilly, TJ, Murray, RM (2013). The myth of schizophrenia as a progressive brain disease. Schizophrenia Bulletin 39, 13631372.
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