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Schizotypy and brain structure: a voxel-based morphometry study

Published online by Cambridge University Press:  17 November 2009

G. Modinos ,
A. Mechelli ,
J. Ormel ,
N. A. Groenewold ,
A. Aleman  and
P. K. McGuire
G. Modinos*
Affiliation:
Department of Neuroscience, University Medical Center Groningen, and BCN Neuroimaging Center, University of Groningen, Groningen, The Netherlands Department of Psychological Medicine, Section of Neuroimaging, Institute of Psychiatry, London, UK
A. Mechelli
Affiliation:
Department of Psychological Medicine, Section of Neuroimaging, Institute of Psychiatry, London, UK
J. Ormel
Affiliation:
Interdisciplinary Center of Psychiatric Epidemiology, University Medical Center Groningen, Groningen, The Netherlands
N. A. Groenewold
Affiliation:
Department of Neuroscience, University Medical Center Groningen, and BCN Neuroimaging Center, University of Groningen, Groningen, The Netherlands
A. Aleman
Affiliation:
Department of Neuroscience, University Medical Center Groningen, and BCN Neuroimaging Center, University of Groningen, Groningen, The Netherlands
P. K. McGuire
Affiliation:
Department of Psychological Medicine, Section of Neuroimaging, Institute of Psychiatry, London, UK
*
*Address for correspondence: G. Modinos, M.Sc., BCN Neuroimaging Center, University Medical Center Groningen, University of Groningen, PO Box 9700AD, Groningen, The Netherlands. (Email: [email protected])
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Abstract

Background

Schizotypy is conceptualized as a subclinical manifestation of the same underlying biological factors that give rise to schizophrenia and other schizophrenia spectrum disorders. Individuals with psychometric schizotypy (PS) experience subthreshold psychotic signs and can be psychometrically identified among the general population. Previous research using magnetic resonance imaging (MRI) has shown gray-matter volume (GMV) abnormalities in chronic schizophrenia, in subjects with an at-risk mental state (ARMS) and in individuals with schizotypal personality disorder (SPD). However, to date, no studies have investigated the neuroanatomical correlates of PS.

Method

Six hundred first- and second-year university students completed the Community Assessment of Psychic Experiences (CAPE), a self-report instrument on psychosis proneness measuring attenuated positive psychotic experiences. A total of 38 subjects with high and low PS were identified and subsequently scanned with MRI. Voxel-based morphometry (VBM) was applied to examine GMV differences between subjects with high and low positive PS.

Results

Subjects with high positive PS showed larger global volumes compared to subjects with low PS, and larger regional volumes in the medial posterior cingulate cortex (PCC) and the precuneus. There were no regions where GMV was greater in low than in high positive PS subjects.

Conclusions

These regions, the PCC and precuneus, have also been sites of volumetric differences in MRI studies of ARMS subjects and schizophrenia, suggesting that psychotic or psychotic-like experiences may have common neuroanatomical correlates across schizophrenia spectrum disorders.

Keywords

Gray matterMRIschizophreniaschizotypyvoxel-based morphometry
Type
Original Articles
Information
Psychological Medicine , Volume 40 , Issue 9 , September 2010 , pp. 1423 - 1431
Copyright
Copyright © Cambridge University Press 2009

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References

Allen, P, Laroi, F, McGuire, PK, Aleman, A (2008). The hallucinating brain: a review of structural and functional neuroimaging studies of hallucinations. Neuroscience and Biobehavioral Reviews 32, 175–191.CrossRefGoogle Scholar
APA (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV). American Psychiatric Association: Washington, DC.Google Scholar
Ashburner, J, Friston, KJ (2000). Voxel-based morphometry: the methods. NeuroImage 11, 805–821.CrossRefGoogle ScholarPubMed
Baiano, M, David, A, Versace, A, Churchill, R, Balestrieri, M, Brambilla, P (2007). Anterior cingulate volumes in schizophrenia: a systematic review and a meta-analysis of MRI studies. Schizophrenia Research 93, 1–12.CrossRefGoogle Scholar
Beck, AT, Steer, RA, Ball, R, Ranieri, WF (1996). Comparison of Beck Depression Inventories-IA and -II in psychiatric outpatients. Journal of Personality Assessment 67, 588–597.CrossRefGoogle Scholar
Blakemore, SJ, Wolpert, DM, Frith, CD (2002). Abnormalities in the awareness of action. Trends in Cognitive Sciences 6, 237–242.CrossRefGoogle ScholarPubMed
Borgwardt, SJ, Fusar-Poli, P, Radue, EW, Riecher-Rössler, A (2008 a). Insular pathology in the at-risk mental state. European Archives of Psychiatry and Clinical Neuroscience 258, 254–255.CrossRefGoogle ScholarPubMed
Borgwardt, SJ, McGuire, PK, Aston, J, Berger, G, Dazzan, P, Gschwandtner, U, Pflüger, M, D'Souza, M, Radue, EW, Riecher-Rössler, A (2007 a). Structural brain abnormalities in individuals with an at-risk mental state who later develop psychosis. British Journal of Psychiatry 51, S69–S75.CrossRefGoogle ScholarPubMed
Borgwardt, SJ, McGuire, PK, Fusar-Poli, P, Radue, EW, Riecher-Rössler, A (2008 b). Anterior cingulate pathology in the prodromal stage of schizophrenia. NeuroImage 19, 553–554.CrossRefGoogle Scholar
Borgwardt, SJ, Riecher-Rössler, A, Dazzan, P, Chitnis, X, Aston, J, Drewe, M, Gschwandtner, U, Haller, S, Pflüger, M, Rechsteiner, E, D'Souza, M, Stieglitz, RD, Radü, EW, McGuire, PK (2007 b). Regional gray matter volume abnormalities in the at-risk mental state. Biological Psychiatry 61, 1148–1156.CrossRefGoogle ScholarPubMed
Byne, W, Buchsbaum, MS, Kemether, E, Hazlett, EA, Shinwari, A, Mitropoulou, V, Siever, LJ (2001). Magnetic resonance imaging of the thalamic mediodorsal nucleus and pulvinar in schizophrenia and schizotypal personality disorder. Archives of General Psychiatry 58, 133–140.CrossRefGoogle ScholarPubMed
Cavanna, AE, Trimble, MR (2006). The precuneus: a review of its functional anatomy and behavioural correlates. Brain 129, 546–583.CrossRefGoogle ScholarPubMed
Chapman, LJ, Chapman, JP (1980). Scales for rating psychotic and psychotic-like experiences as continua. Schizophrenia Bulletin 6, 477–489.CrossRefGoogle ScholarPubMed
Chapman, LJ, Chapman, JP, Kwapil, TR, Eckblad, M, Zinser, MC (1994). Putatively psychosis-prone subjects 10 years later. Journal of Abnormal Psychology 103, 171–183.CrossRefGoogle ScholarPubMed
Dickey, CC, McCarley, RW, Voglmaier, MM, Niznikiewicz, MA, Seidman, LJ, Hirayasu, Y, Fischer, I, Teh, EK, Van Rhoads, R, Jakab, M, Kikinis, R, Jolesz, FA, Shenton, ME (1999). Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter. Biological Psychiatry 45, 1393–1402.CrossRefGoogle ScholarPubMed
Downhill, Jr. JE, Buchsbaum, MS, Hazlett, EA, Barth, S, Lees Roitman, S, Nunn, M, Lekarev, O, Wei, T, Shihabuddin, L, Mitropoulou, V, Silverman, J, Siever, LJ (2001). Temporal lobe volume determined by magnetic resonance imaging in schizotypal personality disorder and schizophrenia. Schizophrenia Research 48, 187–199.CrossRefGoogle Scholar
Flaum, M, O'Leary, DS, Swayze, VW 2nd, Miller, DD, Arndt, S, Andreasen, NC (1995). Symptom dimensions and brain morphology in schizophrenia and related psychotic disorders. Journal of Psychiatric Research 29, 261–276.CrossRefGoogle ScholarPubMed
Fornito, A, Yung, AR, Wood, SJ, Phillips, LJ, Nelson, B, Cotton, S, Velakoulis, D, McGorry, PD, Pantelis, C, Yücel, M (2008). Anatomic abnormalities of the anterior cingulated cortex before psychosis onset: an MRI study of ultra-high-risk individuals. Biological Psychiatry 64, 758–765.CrossRefGoogle ScholarPubMed
Fransson, P, Marrelec, G (2008). The medial precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: evidence from a partial correlation network analysis. NeuroImage 42, 1178–1184.CrossRefGoogle Scholar
Garner, B, Pariante, CM, Wood, SJ, Velakoulis, D, Phillips, L, Soulsby, B, Brewer, WJ, Smith, DJ, Dazzan, P, Berger, GE, Yung, AR, van den Buuse, M, Murray, R, McGorry, PD, Pantelis, C (2005). Pituitary volume predicts future transition to psychosis in individuals at ultra-high risk of developing psychosis. Biological Psychiatry 58, 417–423.CrossRefGoogle ScholarPubMed
Garrity, AG, Pearlson, GD, McKiernan, K, Lloyd, D, Kiehl, KA, Calhoun, VD (2007). Aberrant ‘default mode’ functional connectivity in schizophrenia. American Journal of Psychiatry 164, 450–457.CrossRefGoogle ScholarPubMed
Good, CD, Johnsrude, IS, Ashburner, J, Henson, RN, Friston, KJ, Frackowiak, RS (2001). A voxel-based morphometric study of ageing in 465 normal adult human brains. NeuroImage 14, 21–36.CrossRefGoogle ScholarPubMed
Gotay, N, Giedd, JN, Lusk, L, Hayashi, KM, Greenstein, D, Vaituzis, AC, Nugent, TF 3rd, Herman, DH, Clasen, LS, Toga, AW, Rapoport, JL, Thompson, PM (2004). Dynamic mapping of human cortical development during childhood and through early adulthood. Proceedings of the National Academy of Sciences USA 101, 8174–8179.CrossRefGoogle Scholar
Hanssen, M, Bak, M, Bijl, R, Vollebergh, W, Van Os, J (2005). The incidence and outcome of subclinical psychotic experiences in the general population. British Journal of Clinical Psychology 44, 181–191.CrossRefGoogle ScholarPubMed
Hazlett, EA, Buchsbaum, MS, Haznedar, MM, Newmark, R, Goldstein, KE, Zelmanova, Y, Glanton, CF, Torosjan, Y, New, AS, Lo, JN, Mitropoulou, V, Siever, LJ (2008). Cortical gray and white matter volume in unmedicated schizotypal and schizophrenia patients. Schizophrenia Research 101, 111–123.CrossRefGoogle ScholarPubMed
Hulshoff Pol, HE, Schnack, HG, Mandl, RC, van Haren, NE, Koning, H, Collins, DL, Evans, AC, Kahn, RS (2001). Focal gray matter density changes in schizophrenia. Archives of General Psychiatry 58, 1118–1125.CrossRefGoogle ScholarPubMed
Jahshan, CS, Sergi, MJ (2007). Theory of mind, neurocognition, and functional status in schizotypy. Schizophrenia Research 89, 278–286.CrossRefGoogle ScholarPubMed
Job, DE, Whalley, HC, Johnstone, EC, Lawrie, SM (2005). Grey matter changes over time in high-risk subjects developing schizophrenia. NeuroImage 25, 1023–1030.CrossRefGoogle ScholarPubMed
Job, DE, Whalley, HC, McConell, S, Glabus, M, Johnstone, EC, Lawrie, SM (2003). Voxel-based morphometry of grey matter densities in subjects at high risk of schizophrenia. Schizophrenia Research 64, 1–13.CrossRefGoogle ScholarPubMed
Kawasaki, Y, Suzuki, M, Nohara, S, Hagino, H, Takahashi, T, Matsui, M, Yamashita, I, Chitnis, XA, McGuire, PK, Seto, H, Kurachi, M (2004). Structural brain differences in patients with schizophrenia and schizotypal disorder demonstrated by voxel-based morphometry. European Archives of Psychiatry and Clinical Neuroscience 254, 406–414.CrossRefGoogle ScholarPubMed
Konings, M, Bak, M, Hanssen, M, van Os, J, Krabbendam, L (2006). Validity and reliability of the CAPE: a self-report instrument for the measurement of psychotic experiences in the general population. Acta Psychiatrica Scandinavica 114, 55–61.CrossRefGoogle Scholar
Koo, MS, Levitt, JJ, Salisbury, DF, Nakamura, M, Shenton, ME, McCarley, RW (2008). A cross-sectional and longitudinal magnetic resonance imaging study of cingulate gyrus gray matter volume abnormalities in first-episode schizophrenia and first-episode affective psychosis. Archives of General Psychiatry 65, 746–760.CrossRefGoogle ScholarPubMed
Kubicki, M, Shenton, ME, Salisbury, DF, Hirayasu, Y, Kasai, K, Kikinis, R, Jolesz, FA, McCarley, RW (2002) Voxel-based morphometric analysis of gray matter in first episode schizophrenia. NeuroImage 17, 1711–1719.CrossRefGoogle ScholarPubMed
Langdon, R, Coltheart, M (1999). Mentalising, schizotypy, and schizophrenia. Cognition 71, 43–71.CrossRefGoogle ScholarPubMed
Langdon, R, Coltheart, M (2001). Visual perspective-taking and schizotypy: evidence for a simulation-based account of mentalizing in normal adults. Cognition 82, 1–26.CrossRefGoogle ScholarPubMed
Langdon, R, Coltheart, M (2004). Recognition of metaphor and irony in young adults: the impact of schizotypal personality traits. Psychiatry Research 125, 9–20.CrossRefGoogle ScholarPubMed
Lawrie, SM, Whalley, H, Kestelman, JN, Abukmeil, SS, Byrne, M, Hodges, A, Rimmington, JE, Best, JJ, Owens, DG, Johnstone, EC (1999). Magnetic resonance imaging of brain in people at high risk of developing schizophrenia. Lancet 353, 30–33.CrossRefGoogle ScholarPubMed
Lewandowski, KE, Barrantes-Vidal, N, Nelson-Gray, RO, Clancy, C, Kepley, HO, Kwapil, TR (2006). Anxiety and depression symptoms in psychometrically identified schizotypy. Schizophrenia Research 83, 225–235.CrossRefGoogle ScholarPubMed
McGorry, PD, Singh, BS (1995). Schizophrenia: risk and possibility. In Handbook of Studies on Preventive Psychiatry (ed. Raphael, B. and Burrows, G. D.), pp. 491–514. Elsevier: Amsterdam.Google Scholar
Mechelli, A, Price, CJ, Friston, KJ, Ashburner, J (2005). Voxel-based morphometry of the human brain: methods and applications. Current Medical Imaging Reviews 1, 105–133.CrossRefGoogle Scholar
Meisenzhal, EM, Koutsouleris, N, Gaser, C, Bottlender, R, Schmitt, GJ, McGuire, P, Decker, P, Burgermeister, B, Born, C, Reiser, M, Möller, HJ (2008). Structural brain alterations in subjects at high-risk of psychosis: a voxel-based morphometric study. Schizophrenia Research 102, 150–162.CrossRefGoogle Scholar
Mitelman, SA, Shihabuddin, L, Brickman, AM, Hazlett, EA, Buchsbaum, MS (2005). Volume of the cingulate and outcome in schizophrenia. Schizophrenia Research 7, 91–108.CrossRefGoogle Scholar
Palmen, SJ, Hulshoff Pol, HE, Kemner, C, Schnack, HG, Janssen, J, Kahn, RS, van Engeland, H (2004). Larger brains in medication naive high-functioning subjects with pervasive developmental disorder. Journal of Autism and Developmental Disorders 34, 603–613.CrossRefGoogle ScholarPubMed
Pantelis, C, Velakoulis, D, McGorry, PD, Wood, SJ, Suckling, J, Phillips, LJ, Yung, AR, Bullmore, ET, Brewer, W, Soulsby, B, Desmond, P, McGuire, PK (2003). Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 361, 281–288.CrossRefGoogle ScholarPubMed
Phillips, LJ, Velakoulis, D, Pantelis, C, Wood, S, Yuen, HP, Yung, AR, Desmond, P, Brewer, W, McGorry, PD (2002). Non-reduction in hippocampal volume is associated with higher risk of psychosis. Schizophrenia Research 58, 145–158.CrossRefGoogle ScholarPubMed
Platek, SM, Gallup, GG Jr. (2002). Self-face recognition is affected by schizotypal personality traits. Schizophrenia Research 57, 81–85.CrossRefGoogle ScholarPubMed
Raine, A, Lencz, T, Yaralian, P, Bihrle, S, LaCasse, L, Ventura, J, Colletti, P (2002). Prefrontal structural and functional deficits in schizotypal personality disorder. Schizophrenia Bulletin 28, 501–513.CrossRefGoogle ScholarPubMed
Raine, A, Sheard, C, Reynolds, GP, Lencz, T (1992). Prefrontal structural and functional deficits associated with individual differences in schizotypal personality. Schizophrenia Research 7, 237–247.CrossRefGoogle ScholarPubMed
Rapoport, JL, Giedd, JN, Blumenthal, J, Hamburger, S, Jeffries, N, Fernandez, T, Nicolson, R, Bedwell, J, Lenane, M, Zijdenbos, A, Paus, T, Evans, A (1999). Progressive cortical change during adolescence in childhood-onset schizophrenia. A longitudinal magnetic resonance imaging study. Archives of General Psychiatry 56, 649–654.CrossRefGoogle ScholarPubMed
Shapleske, J, Rossell, SL, Chitnis, XA, Suckling, J, Simmons, A, Bullmore, ET, Woodruff, PW, David, AS (2002). A computational morphometric MRI study of schizophrenia: effects of hallucinations. Cerebral Cortex 12, 1331–1341.CrossRefGoogle ScholarPubMed
Shenton, ME, Dickey, CC, Frumin, M, McCarley, RW (2001). A review of MRI findings in schizophrenia. Schizophrenia Research 49, 1–52.CrossRefGoogle ScholarPubMed
Shin, SE, Lee, JS, Kang, MH, Kim, CE, Bae, JN, Jung, G (2005). Segmented volumes of cerebrum and cerebellum in first episode schizophrenia with auditory hallucinations. Psychiatry Research 138, 33–42.CrossRefGoogle ScholarPubMed
Siever, LJ, Koenigsberg, HW, Harvey, P, Mitropoulou, V, Laruelle, M, Abi-Dargham, A, Goodman, M, Buchsbaum, M (2002). Cognitive and brain function in schizotypal personality disorder. Schizophrenia Research 54, 157–167.CrossRefGoogle ScholarPubMed
Sirigu, A, Daprati, E, Pradat-Diehl, P, Franck, N, Jeannerod, M (1999). Perception of self-generated movement following left parietal lesion. NeuroImage 23, 1192–1202.Google Scholar
Sowell, ER, Levitt, J, Thompson, PM, Holmes, CJ, Blanton, RE, Kornsand, DS, Caplan, R, McCracken, J, Asarnow, R, Toga, AW (2000). Brain abnormalities in early-onset schizophrenia spectrum disorder observed with statistical parametric mapping of structural magnetic resonance images. American Journal of Psychiatry 157, 1475–1484.CrossRefGoogle ScholarPubMed
Stefanis, NC, Hanssen, M, Smirnis, NK, Avramopoulos, DA, Evdokimidis, IK, Stefanis, CN, Verdoux, H, Van Os, J (2002). Evidence that three dimensions of psychosis have a distribution in the general population. Psychological Medicine 32, 347–358.CrossRefGoogle ScholarPubMed
Strauss, JS (1969). Hallucinations and delusions as points on continua function. Archives of General Psychiatry 21, 581–586.CrossRefGoogle ScholarPubMed
Suzuki, M, Zhou, SY, Hagino, H, Niu, L, Takahashi, T, Kawasaki, Y, Matsui, M, Seto, H, Ono, T, Kurachi, M (2005 a). Morphological brain changes associated with Schneider's first-rank symptoms in schizophrenia: a MRI study. Psychological Medicine 35, 549–560.CrossRefGoogle ScholarPubMed
Suzuki, M, Zhou, SY, Takahashi, T, Hagino, H, Kawasaki, Y, Niu, L, Matsui, M, Seto, H, Kurachi, M (2005 b). Differential contributions of prefrontal and temporolimbic pathology to mechanisms of psychosis. Brain 128, 2109–2122.CrossRefGoogle ScholarPubMed
Thompson, PM, Vidal, C, Giedd, JN, Gochman, P, Blumenthal, J, Nicolson, R, Toga, AW, Rapoport, JL (2001). Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proceedings of the National Academy of Sciences USA 98, 11650–11655.CrossRefGoogle ScholarPubMed
Van Os, J, Hanssen, M, Bijl, RV, Ravelli, A (2000). Strauss (1969) revisited: a psychosis continuum in the general population? Schizophrenia Research 45, 11–20.CrossRefGoogle ScholarPubMed
Van Os, J, Linscott, RJ, Myin-Germeys, I, Delespaul, P, Krabbendam, L (2009). A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness-persistence-impairment model of psychotic disorder. Psychological Medicine 39, 179–195.CrossRefGoogle ScholarPubMed
Velakoulis, D, Wood, SJ, Wong, MT, McGorry, PD, Yung, A, Phillips, L, Smith, D, Brewer, W, Proffitt, T, Desmond, P, Pantelis, C (2006). Hippocampal and amygdala volumes according to psychosis stage and diagnosis. Archives of General Psychiatry 63, 139–149.CrossRefGoogle ScholarPubMed
Verdoux, H, van Os, J (2002). Psychotic symptoms in non-clinical populations and the continuum of psychosis. Schizophrenia Research 54, 59–65.CrossRefGoogle ScholarPubMed
Wright, IC, Ellison, ZR, Sharma, T, Friston, KJ, Murray, RM, McGuire, PK (1999). Mapping of grey matter changes in schizophrenia. Schizophrenia Research 35, 1–14.CrossRefGoogle ScholarPubMed
Wright, IC, Rabe-Hesketh, S, Woodruff, PW, David, AS, Murray, RM, Bullmore, ET (2000). Meta-analysis of regional brain volumes in schizophrenia. American Journal of Psychiatry 157, 16–25.CrossRefGoogle ScholarPubMed
Young, AH, Blackwood, DH, Roxborough, H, McQueen, JK, Martin, MJ, Kean, D (1991). A magnetic resonance imaging study of schizophrenia: brain structure and clinical symptoms. British Journal of Psychiatry 158, 158–164.CrossRefGoogle ScholarPubMed
Yung, AR, Phillips, LJ, McGorry, PD, McFarlane, CA, Francey, S, Harrigan, S, Patton, GC, Jackson, HJ (1998). Prediction of psychosis. A step towards indicated prevention of schizophrenia. British Journal of Psychiatry. Supplement 172, 14–20.CrossRefGoogle ScholarPubMed
Yung, AR, Phillips, LJ, Yuen, HP, Francey, SM, McGarlane, CA, Hallgren, M, McGorry, PD (2003). Psychosis prediction: 12-month follow-up of a high-risk (‘prodromal’) group. Schizophrenia Research 60, 21–32.CrossRefGoogle ScholarPubMed
Zhou, SY, Suzuki, M, Takahashi, T, Hagino, H, Kawasaki, Y, Matsui, M, Seto, H, Kurachi, M (2007). Parietal lobe volume deficits in schizophrenia spectrum disorders. Schizophrenia Research 89, 35–48.CrossRefGoogle ScholarPubMed