Skip to main content

Neuromorphometric Measures as Endophenotypes of Schizophrenia Spectrum Disorders

  • Chapter
The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes

Abstract

Abnormal size of cortical and subcortical brain structures is strongly associated with schizophrenia, and has also been reported in unaffected relatives of patients, and in those with associated diagnoses such as schizotypal personality disorder. Such volumetric measures have been considered as potential candidates for schizophrenia endophenotypes as they are heritable, co-segregate with the broadly defined neurocognitive and behavioral phenotypes within first degree relatives, and are frequently present in unaffected family members. In recent years, shape analyses have become of increasing interest due to their potential to precisely locate surface defects and their increased sensitivity for subtle volume changes. Statistical analysis of shape variables have recently been shown to improve the discrimination of individuals with schizophrenia from healthy controls, when included with overall volume. Computerized methods of shape analysis have been used to detect systematic differences in regional cortical thickness and gyral patterns between individuals. Methods such as large-deformation high-dimensional brain mapping and spherical harmonics have identified localized abnormalities within the hippocampus, thalamus and basal ganglia in schizophrenia, which were similar to those observed in unaffected siblings. The chapter reviews the status of current research involving both shape and volume of brain structures that applies to schizophrenia, and discusses future research directions required to establish these measures as endophenotypes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  1. Adler CM, Strakowski SM. Boundaries of schizophrenia. Psychiat Clin North Am 2003;26:1–23.

    Google Scholar 

  2. Cadenhead KS. Vulnerability markers in the schizophrenia spectrum: implications for phenomenology, genetics, and the identification of the schizophrenia prodrome. Psychiat Clin North Am 2002;25:837–853.

    Google Scholar 

  3. Siever LJ, Davis KL. The pathophysiology of schizophrenia disorders: perspectives from the spectrum. Am J Psychiat 2004;161:398–413.

    PubMed  Google Scholar 

  4. Takahashi T, Suzuki M, Zhou SY, Hagino H, Niu L, Kawasaki Y, Seto H, Kurachi M. Temporal lobe gray matter in schizophrenia spectrum: a volumetric MRI study of the fusiform gyrus, parahippocampal gyrus, and middle and inferior temporal gyri. Schizophr Res 2006;87:116–126.

    PubMed  Google Scholar 

  5. Hazlett EA, Romero MJ, Haznedar MM, New AS, Goldstein KE, Newmark RE, Siever LJ, Buchsbaum MS. Deficient attentional modulation of startle eyeblink is associated with symptom severity in the schizophrenia spectrum. Schizophr Res 2007;93:288–295.

    PubMed  Google Scholar 

  6. Potash JB, Chiu YF, MacKinnon DF, Miller EB, Simpson SG, McMahon FJ, McInnis MG, DePaulo JR Jr. Familial aggregation of psychotic symptoms in a replication set of 69 bipolar disorder pedigrees. Am J Med Genet B Neuropsychiat Genet 2003;116B(1):90–97.

    Google Scholar 

  7. McIntosh AM, Job DE, Moorhead WJ, Harrison LK, Whalley HC, Johnstone EC. Genetic liability to schizophrenia or bipolar disorder and its relationship to brain structure. Am J Med Genet B Neuropsychiat Genet 2006;141:76–83.

    Google Scholar 

  8. McDonald C, Bullmore ET, Sham PC, Chitnis X, Wickham H, Bramon E, Murray RM. Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes. Arch Gen Psychiat 2004;61:974–984.

    PubMed  Google Scholar 

  9. Ashburner J, Friston KJ. Voxel-based morphometry — the methods. Neuroimage 2000;11:805–821.

    PubMed  CAS  Google Scholar 

  10. Csernansky JG, Wang L, Jones D et al. Hippocampal deformities in schizophrenia characterized by high dimensional brain mapping. Am J Psychiat 2002;159:2000–2006.

    PubMed  Google Scholar 

  11. Csernansky JG, Schlinder MK, Splinter NR et al. Abnormalities of thalamic volume and shape in schizophrenia. Am J Psychiat 2004;161:896–902.

    PubMed  Google Scholar 

  12. Harms MP, Wang L, Mamah D, Barch DM, Thompson PA, Csernansky JG. Thalamic shape abnormalities in individuals with schizophrenia and their nonpsychotic siblings. J Neurosci 2007;27:13835–13842.

    PubMed  CAS  Google Scholar 

  13. Thompson PM, Vidal C, Giedd JN, Gochman P, Blumenthal J, Nicolson R, Toga AW, Rapoport Jl. Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proc Natl Acad Sci USA 2001;98:11650–11655.

    PubMed  CAS  Google Scholar 

  14. Narr KL, Bilder RM, Luders E, Thompson PM, Woods RP, Robinson D, Szeszko PR, Dimtcheva T, Gurbani M, Toga AW. Asymmetries of cortical shape: effects of handedness, sex and schizophrenia. Neuroimage 2007;34:939–948.

    PubMed  Google Scholar 

  15. Wang L, Hosakere M, Trein JCL, Miller A, Ratnanather JT, Barch DM, Thompson PA, Qiu A, Gado MH, Miller MI, Csernansky JG. Abnormalities of cingulate gyrus neuro-anatomy in schizophrenia. Schizophr Res 2007;93:66–78.

    PubMed  Google Scholar 

  16. Cannon TD, van Erp TG, Bearden CE et al. Early and late neurodevelopmental influences in the prodrome to schizophrenia: contributions of genes, environment, and their interactions. Schizophr Bull 2003;29:653–669.

    PubMed  Google Scholar 

  17. Weinberger DR. From neuropathology to neurodevelopment. Lancet 1995;346:552–557.

    PubMed  CAS  Google Scholar 

  18. Sisodiya SM, Free SL, Duncan JS, Stevens JM. Bilateral periventricular and subcortical heterotopias in a man with refractory epilepsy. Epilepsia 2000;41:352–354.

    PubMed  CAS  Google Scholar 

  19. Styner M, Lieberman JA, Pantazis D, Gerig G. Boundary and medial shape analysis of the hippocampus in schizophrenia. Med Image Anal 2004;8:197–203.

    PubMed  Google Scholar 

  20. Shenton ME, Gerig G, McCarley RW, Szekely G, Kikinis R. Amygdala-hippocampal shape differences in schizophrenia: the application of 3D shape models to volumetric MR data. Psychiat Res Neuroimaging 2002;115:15–35.

    Google Scholar 

  21. Mamah D, Wang L, Barch D, de Erausquin GA, Gado M, Csernansky JG. Structural analysis of the basal ganglia in schizophrenia. Schizophr Res 2007;89(1–3):59–71.

    PubMed  Google Scholar 

  22. Mamah D, Harms MP, Wang L, Barch D, Thompson P, Kim J, Miller MI, Csernansky JG. Basal ganglia shape abnormalities in the unaffected siblings of schizophrenia patients. Biol Psychiat 2008 Jul 15;64(2):111–120.

    PubMed  Google Scholar 

  23. Vetsa S, Styner M, Pizer S, Lieberman J, Gerig G. Caudate shape discrimination in schizophrenia using template-free non-parametric tests. In: MICCAI 2003; pp. 661–669.

    Google Scholar 

  24. Narr KL, Cannon TD, Woods RP, Thompson PM, Kim S, Asunction D, van Erp TGM, Poutanen V-P, Huttunen M, Lonnqvist J, Standerksjold-Nordenstam C-G, Kaprio J, Mazziotta JC, Toga AW. Genetic contributions to altered callosal morphology in schizophrenia. J Neurosci 2002;22:3720–3729.

    PubMed  CAS  Google Scholar 

  25. Narr KL, Thompson PM, Shama T, Moussai J, Zoumalan C, Rayman J, Toga AW. Three-dimensional mapping of gyral shape and cortical shape asymmetries in schizophrenia: gender effects. Am J Psychiat 2001;158:244–255.

    PubMed  CAS  Google Scholar 

  26. Gottesmann II, Gould TD. The endophenotypes concept in psychiatry: etymology and strategic intentions. Am J Psychiat 2003;160:636–645.

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  28. Shenton ME, Frumin M, McCarley RW, Maier SE, Westin C, Fischer IA, Dickey C, Kikinis R. Morphometric magnetic resonance imaging studies: findings in schizophrenia. In: Dougherty DD, Rauch SL (Eds.), Psychiatric Neuroimaging Research: Contemporary Strategies. Washington, DC: American Psychiatric Publishing, 2001; pp. 1–60.

    Google Scholar 

  29. Keshavan MS, Prasad KM, Pearlson G. Are brain structural abnormalities useful as endophenotypes in schizophrenia? Int Rev Psychiat 2007;19:397–406.

    Google Scholar 

  30. Vila-Rodriguez F, French L, Barakauskas V, Mead CL, Khorram B. Thalamic shape: a possible endophenotype. J Neurosci 2008;28:3533–3534.

    PubMed  CAS  Google Scholar 

  31. Tepest R, Wang L, Miller MI, Falkai P, Csernansky JG. Hippocampal deformities in the unaffected siblings of schizophrenia subjects. Biol Psychiat 2003;54:1234–1240.

    PubMed  Google Scholar 

  32. Downhill JE, Buchsbaum MS, Wei TS, Spiegel-Cohen J, Hazlett EA, Haznedar MM,Silverman J, Siever LJ. Shape and size of the corpus callosum in schizophrenia and schizotypal personality disorder. Schizophr Res 2000;42:193–208.

    PubMed  Google Scholar 

  33. Smith RC, Calderon M, Ravichandran GK, Largen J, Vroulis G, shvartsburd A, Gordon J, Schoolar JC. Nuclear magnetic resonance in schizophrenia: a preliminary study. Psychiat Res 1984;12:137–147.

    CAS  Google Scholar 

  34. Golland P, Grimson WE, Kikinis R. Statistical shape analysis using fixed topology skeletons: corpus callosum study. In: Kuba A (Ed.), IPMI LNCS. Berlin: Springer, 1991; Vol. 161, pp. 382–387.

    Google Scholar 

  35. Kimia B, Tannebaum A, Zucker S. Shapes, shocks and deformations: I: The components and shape and the reaction-diffusion space. Int J Comp Vision 1995;15:189–224.

    Google Scholar 

  36. Naf M, Szekely G, Kikinis R, Shenton ME, Kubler O. 3D voronoi skeletons and their usage for the characterization and recognition of 3D organ shape. Comp Vision Image Understanding 1997;66:640–646.

    Google Scholar 

  37. Bookstein FL. Landmark methods for forms without landmarks: localizing group differences in outline shape. Med Image Anal 1997;1:225–243.

    PubMed  CAS  Google Scholar 

  38. Christensen GE, Joshi SC, Miller MI. Volumetric transformation of brain anatomy. IEEE Trans Med Imag 1997;16:864–877.

    CAS  Google Scholar 

  39. Csernansky JG, Joshi SC, Wang L, Gado M, Miller JP, Grenander U, Miller MI. Hippocampal morphometry in schizophrenia by high dimensional brain mapping. PNAS 1998;95:11406–11411.

    PubMed  CAS  Google Scholar 

  40. Dale AM, Fischl B, Sereno MI. Cortical surface-based analysis. II: Inflation, flattening and a surface-based coordinate system. Neuroimage 1999;9:195–207.

    PubMed  Google Scholar 

  41. Davatzikos C, Shen D, Gur RC, Wu X, Liu D, Fan Y, Hughett P, Turetsky BI, Gur RE. Whole-brain morphometric study of schizophrenia revealing a spatially complex set of focal abnormalities. Arch Gen Psychiat 2005;62:1218–1227.

    PubMed  Google Scholar 

  42. Kelemen A, Székely G, Gerig G. Elastic model-based segmentation of 3-D neuroradiological data sets. IEEE Trans Med Imag 1999 Oct;18(10):828–839.

    CAS  Google Scholar 

  43. McDonald C, Bullmore E, Sham P et al. Regional volume deviations of brain structure in schizophrenia and psychotic bipolar disorder: computational morphometry study. Br J Psychiat 2005;286:369–377.

    Google Scholar 

  44. Miller MI, Trouve A, Younes L. On the metrics and Euler– Lagrange equations of computational anatomy. Ann Rev Biomed Eng 2002;4:375–405.

    CAS  Google Scholar 

  45. Wang L, Joshi SC, Miller MI, Csernansky JG. Statistical analysis of hippocampal asymmetry in schizophrenia. Neuroimage 2001;14:531–545.

    PubMed  CAS  Google Scholar 

  46. Falkai P, Tepest R, Honer WG, Dani I, Ahle G, Pfeiffer U, Vogeley K, Schulze TRG, Rietschel M, Cordes J, Schonell H, Gaebel W, Kuhn KU, Maier W, Traber F, Block W, Schld HH, Schneider-Admann T. Shape changes in prefrontal, but not parieto-occipital regions: brains of schizophrenic patients come closer to a circle in coronal and sagittal view. Psychiat Res 2004;132:261–271.

    Google Scholar 

  47. Connor SEJ, Ng V, McDonald C, Schulze K, Morgan K, Dazzan P, Murray RM. A study of hippocampal shape anomaly in schizophrenia and in families multiply affected by schizophrenia or bipolar disorder. Neuroradiology 2004;46:523–534.

    PubMed  CAS  Google Scholar 

  48. Levitt JJ, Westin CF, Nestor PG, Estepar RS, Dickey CC, Voglmaier MM, Seidman LJ, Kikinis R, Jolesz FA, McCarley RW, Shenton ME. Shape of the caudate nucleus and its cognitive correlates in neuroleptic-naïve schizotypal personality disorder. Biol Psychiat 2004;55:177–184.

    PubMed  Google Scholar 

  49. Sandu A-L, Rasmussen I-A Jr, Lundervold A, Kreuder F, Neckelmann G, Hugdahl K, Specht K. Fractal dimension analysis of MR images reveals grey matter structure irregularities in schizophrenia. Comp Med Imaging Graphics 2008;32:150–158.

    Google Scholar 

  50. Narr KL, Bilder RM, Kim S, Thompson PM, Szeszko P, Robinson D et al. Abnormal gyral complexity in first-epi-sode schizophrenia. Biol Psychiat 2004;55:859–867.

    PubMed  Google Scholar 

  51. Ha TH, Youn T, Ha KS, Rho KS, Lee JM, Kim IY, Kim SI, Kwon JS. Gray matter abnormalities in paranoid schizophrenia and their clinical correlations. Psychiat Res 2004;132:251–260.

    Google Scholar 

  52. Khan AR, Wang L, Beg MF. FreeSurfer-initiated fully-automated subcortical brain segmentation in MRI using large deformation diffeomorphic metric mapping. Neuroimage 2008;41:735–746.

    PubMed  Google Scholar 

  53. Christensen GE, Rabbitt RD, Miller MI. A deformable neuroanatomy textbook based on viscous fluid mechanics. In: Prince J, Runolfsson T (Eds.), 27th Annual Conference on Information Sceinces and Systems. Baltimore, MD: Johns Hopkins University, 1993; pp. 211–216.

    Google Scholar 

  54. Christensen GE, Rabbitt RD, Miller MI, Joshi SC, Grenander U, Coogan TA. Topological properties of smooth anatomical maps. Boston, MA: Kluwer, 1995; pp. 101–112.

    Google Scholar 

  55. Joshi S, Miller MI, Christensen GE, Coogen TA, Grenandur U. The generalized dirichlet problem for mapping brain manifolds. Int'l Symp on Optical Science, Engineering and Instrumentation; 1995.

    Google Scholar 

  56. Miller MI, Grenander U, Osullivan JA, Snyder DL. Automatic target recognition organized via jump-diffusion algorithms. IEEE Trans Image Process 1997;6(1):157–174.

    PubMed  CAS  Google Scholar 

  57. Haller JW, Banerjee A, Christensen GE, Gado M, Joshi S, Miller MI, Sheline YI, Vannier MW, Csernansky JG. 3D hippocampal morphometry by high dimensional transformation of a neuroanatomical atlas. Radiology 1997;202:504–510.

    PubMed  CAS  Google Scholar 

  58. Mamah D, Wang L, Harms MP, Barch DM, Styner M, Lieberman J. Olanzapine and haloperidol effects on hippocampal structure in first-episode psychosis. Abstract, Society for Neuroscience Annual Meeting 2008.

    Google Scholar 

  59. Wang L, Swank JS, Glick IE, Gado MH, Miller MI, Morris JC, Csernansky JG. Changes in hippocampal volume and shape across time distinguish dementia of the Alzheimer type from healthy aging. Neuroimage 2003;20:667–682.

    PubMed  CAS  Google Scholar 

  60. Brechbuhler C, Gerig G, Kubler O. Parameterization of closed surfaces for 3-D shape description. CVGIP: Image Understanding 1995;61:154–170.

    Google Scholar 

  61. Styner M, Lieberman JA, McClure RK, Weinberger DR, Jones DW, Gerig G. Morphometric analysis of lateral ventricles in schizophrenia and healthy controls regarding genetic and disease-specific factors. PNAS 2005;102:4872–4877.

    PubMed  CAS  Google Scholar 

  62. Styner M, Oguz I, Xu S, Pantazis D, Gerig G. Statistical group differences in anatomical shape analysis using hotelling T 2 metric. Proc SPIE Med Imaging, 2007;6512:65123Z-1–65123Z-11.

    Google Scholar 

  63. Pantazis D, Leahy RM, Nichols TM, Styner M. Statistical Surface Based Morphometry Using a Non-parametric Approach, IEEE Symposium on Biomedical Imaging ISBI 2004,1283–1286.

    Google Scholar 

  64. Styner M, Xu SC, El-Sayed M, Gerig G. Correspondence Evaluation in Local Shape Analysis and Structural Subdivision, IEEE Symposium on Biomedical Imaging ISBI 2007, 1192–1195.

    Google Scholar 

  65. Pizer S, Fritsch D, Yushkevich P, Johnson V, Chaney E. Segmentation, registration, and measurement of shape variation via image object shape. IEEE Trans Med Imaging 1999;18:851–865.

    PubMed  CAS  Google Scholar 

  66. Styner M, Gerig G, Lieberman J, Jones D, Weinberger D. Statistical shape analysis of neuroanatomical structures based on medial models. Med Image Anal 2003;7:207–220.

    PubMed  CAS  Google Scholar 

  67. Thompson PM, Hayashi KM, de Zubicaray G. Dynamics of gray matter loss in Alzheimer's disease. J Neurosci 2003;23:994–1005.

    PubMed  CAS  Google Scholar 

  68. Vidal CN, Rapoport JL, Hayashi KM, Geaga JA, Sui Y, McLemore LE, Alaghaband Y, Giedd JN, Gochman P, Blumenthal J, Gogtay N, Nicolson R, Toga AW, Thompson PM. Dynamically spreading frontal and cingulate deficits mapped in adolescents with schizophrenia. Arch Gen Psychiat 2006;63:25–34.

    PubMed  Google Scholar 

  69. Thompson PM, Woods RP, Mega MS, Toga AW. Mathematical/computational challenges in creating deformable and probabilistic atlases of human brain. Hum Brain Mapp 2000;9:81–92.

    PubMed  CAS  Google Scholar 

  70. Sowell ER, Thompson PM, Tessner KD, Toga AW. Mapping continued brain growth and gray matter density reduction in dorsal frontal cortex: inverse relationships during postado-lescent brain maturation. J Neurosci 2001;21:8819–8829.

    PubMed  CAS  Google Scholar 

  71. Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, van der Kouwe A, Killany R, Kennedy D, Klaveness S, Montillo A, Makris N, Rosen B, Dale AM. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 2002;33:341–355.

    PubMed  CAS  Google Scholar 

  72. Joshi M, Cui J, Doolittle K, Joshi S, Van Essen D, Wang L, Miller MI. Brain segmentation and the generation of cortical surfaces. Neuroimage 1999;9:461–476.

    PubMed  CAS  Google Scholar 

  73. Miller MI, Massie AB, Ratnanather JT, Botteron KN, Csernansky JG. Bayesian construction of geometrically based cortical thickness metrics. Neuroimage 2000;12:676–687.

    PubMed  CAS  Google Scholar 

  74. Ratnanather JT, Wang L, Nebel MB, Hosakere M, Han X, Csernansky JG, Miller MI. Validation of semiautomated methods for quantifying cingulate cortical metrics in schizophrenia. Psychiat Res 2004;132:53–68.

    Google Scholar 

  75. Van Essen DC, Maunsell JHR. Two-dimensional maps of the cerebral cortex. J Comp Neurol 1980;191:255–281.

    PubMed  Google Scholar 

  76. Van Essen DC, Drury HA, Joshi S, Miller MI. Functional and structural mapping of human cerebral cortex: solutions are in the surfaces. Proc Natl Acas Sci USA 1998;95:788–795.

    Google Scholar 

  77. Van Leemput K, Maes F, Vandermeulen D, Suetens P. A unifying framework for partial volume segmentation of brain MR images. IEEE Trans Med Imag 2003;22:105–119.

    Google Scholar 

  78. Miller MI, Hosakere M, Barker AR et al. Labeled cortical mantle distance maps in the cingulate quantify cortical differences distinguishing dementia of the Alzheimer type and healthy aging. Proc Nat Acad Sci 2003;100:15172–15177.

    PubMed  CAS  Google Scholar 

  79. Harms MP, Campanella C, Wang L, Aldridge K, Moffitt AJ, Kuelper J, Ratnanather JT, Miller MI, Barch DM, Csernansky JG. Abnormalities of prefrontal cortex neuroanatomy in siblings at risk for schizophrenia. Society for Neuroscience Annual Meeting Abstr 2008, Washington, DC.

    Google Scholar 

  80. Ratnanather JT, Barta PE, Honeycutt NA, Lee N, Morris HM, Dziorny AC, Hurdal MK, Pearlson GD, Miller MI. Dynamic programming generation of boundaries of local coordinatized submaniforlds in the neocortex: application to the planum temporale. Neuroimage 2003;209:359–377.

    Google Scholar 

  81. Shen D, Davatzikos C. Very high-resolution morphometry using mass-preserving deformations and HAMMER elastic registration. Neuroimage 2003;18:28–41.

    PubMed  Google Scholar 

  82. Jang D-P, Kim J-J, Chung T-S, An SK, Jung YC, Lee J-L, Lee J-M, Kim I-Y, Kim SI. Shape deformation of the insula in schizophrenia. Neuroimage 2006;32:220–227.

    PubMed  Google Scholar 

  83. Narr KL,Thompson PM, Sharma T, Moussai J, Blanton R, Anvar B, Edris A, Krupp R, Rayman J, Khaledy M, Toga AW. Three-dimensional mapping of temporo-limbic regions and the lateral ventricles in schizophrenia: gender effects. Biol Psychiat 2001;50:84–97.

    PubMed  CAS  Google Scholar 

  84. Buchsbaum M, Yang S, Hazlett E, Siegel B, Germans M, Haznedar M, O'Flaithbheartaigh S, Wei T, Silverman J, Siever LJ. Ventricular volume and asymmetry in schizotypal personality disorder and schizophrenia assessed with magnetic resonance imaging. Schizophr Res 1997;27:45–53.

    PubMed  CAS  Google Scholar 

  85. DeQuardo JR, Tandon R, Brunberg JA, Green WD, Bookstein FL. Spatial relationships of neuroanatomic landmarks in schizophrenia. Psychiat Res Neuroimaging 1996;67:81–95.

    Google Scholar 

  86. DeQuardo JR, Keshavan MS, Bookstein FL, Bagwell WW, Green WD, Sweeney JA, Haas GL, Tandon R, Schooler NR, Pettegrew JW. Landmark-based morphometric analysis of first-episode schizophrenia. Biol Psychiat 1999;45:1321–1328.

    Google Scholar 

  87. Frumin M, Golland P, Kikinis R, Hirayasu Y, Salisbury DF, Hennen J, Dickey CC, Anderson M, Jolesz FA, Grimson WEL, McCarley RW, Shenton ME. Shape differences in the corpus callosum in first-episode schizophrenia and first-episode psychotic affective disorder. Am J Psychiat 2002;159:866–868.

    PubMed  Google Scholar 

  88. Steen RG, Mull C, McClure R, Hamer RM, Lieberman JA. Brain volume in first-episode schizophrenia: systematic review and meta-analysis of magnetic resonance imaging study. Br J Psychiat 2006;188:510–518.

    Google Scholar 

  89. Wright IC, Rabe-Hesketh S, Woodruff PWR, David AS, Murray RM, Bullmore ET. Meta-analysis of regional brain volumes in schizophrenia. Am J Psychiat 2000;157:16–25.

    PubMed  CAS  Google Scholar 

  90. Woodruff PWR, McManus IC, David AS. Meta-analysis of corpus callosum size in schizophrenia. J Neurol Neurosurg Psychiat 1995;58:457–461.

    PubMed  CAS  Google Scholar 

  91. Harrison PJ. The neuropathology of schizophrenia: a critical review of the data and their interpretation. Brain 1999;122:593–624.

    PubMed  Google Scholar 

  92. McIntosh A, Lawrie S. Structural magnetic resonance imaging. In: Lawrie S, Johnstone E, Weinberger D (Eds.), Schizophrenia from Neuroimaging to Neuroscience. Oxford: Oxford University Press; 2004.

    Google Scholar 

  93. Jacobsen LK, Giedd JN, Vaituzis AC et al. Temporal lobe morphology in childhood-onset schizophrenia. Am J Psychiat 1996;153:355–361.

    PubMed  CAS  Google Scholar 

  94. DeLisi LE, Sakuma M, Tew W, Kushner M, Hoff AL, Grimson R. Schizophrenia as a chronic active brain process: a study of progressive brain structural change subsequent to the onset of schizophrenia. Psychiat Res 1997;74:129–140.

    Google Scholar 

  95. Theberge J, Williamson KE, Aoyama N, Drost DJ, Manchandra R, Malla AK et al. Longitudinal grey-matter and glutamatergic losses in first-episode schizophrenia. Br J Psychiat 2007;191:325–334.

    Google Scholar 

  96. Van Haren NEM, Cahn W, Hulshoff Pol HE, Schnack HG, Caspers E, Lemstra A. Brain volumes as predictor of outcome in recent-onset schizophrenia: a multi-central MRI study. Schizophr Res 2003;64:41–52.

    PubMed  Google Scholar 

  97. Lieberman J, Tollefson GD, Charles C, Zipursky R, Sharma T, Kahn RS et al. Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch Gen Psychiat 2005;62:361–370.

    PubMed  CAS  Google Scholar 

  98. Wood SJ, Yucel M, Velakoulis D, Phillips LJ, Yung AR, Brewer W, McGorry PD, Pantelis C. Hippocampal and anterior cingulate morphology in subjects at ultra-high-risk for psychosis: the role of family history of psychotic illness. Schizophr Res 2005;75:295–301.

    PubMed  Google Scholar 

  99. Van Erp TG, Saleh PA, Rosso IM, Huttunen M, Lonnqvist J, Pirkola T, Salonen O, Valanne L, Poutanen VP, Standerstskjold-Nordenstam CG, Cannon TD. Contributions of genetic risk and fetal hypoxia to hippocampal volume in patients with schizophrenia or schizoaffective disorder, their unaffected siblings and healthy unrelated volunteers. Am J Psychiat 2002;159:1514–1520.

    PubMed  Google Scholar 

  100. Noga JT, Bartley AJ, Jones DW, Torrey EF, Weinberger DR. Cortical gyral anatomy and gross brain dimensions in monozygotic twins discordant for schizophrenia. Schizophr Res 1996;22:27–40.

    PubMed  CAS  Google Scholar 

  101. Van Haren NE, Picchioni MM, McDonald C, Marshall N, Davis N, Ribchester T, Hulshoff Pol HE, Sharma T, Sham P, Kahn RS, Murray R. A controlled study of brain structure in monozygotic twins concordant and discordant for schizophrenia. Biol Psychiat 2004;56:454–461.

    PubMed  Google Scholar 

  102. Baare WF, van Oel CJ, Hulshoff Pol HE et al. Volumes of brain structures in twins discordant for schizophrenia. Arch Gen Psychiat 2001;58:33–40.

    PubMed  CAS  Google Scholar 

  103. Seidman LJ, Faraone SV, Goldsein JM, Kremen WS, Horton NJ, Makris N, Toomey R, Kennedy D, Caviness VS, Tsuang MT. Left hippocampal volume as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric study of nonpsychotic first-degree relatives. Arch Gen Psychiat 2002;59:839–849.

    PubMed  Google Scholar 

  104. Lawrie SM, Whalley HC, Abukmeil SS, Kestelman JN, Donnelly L, Miller P et al. Brain structure, genetic liability and psychotic symptoms in subjects at high risk of developing schizophrenia. Biol Psychiat 2001;49:811–823.

    PubMed  CAS  Google Scholar 

  105. Boos HBM, Aleman A, Cahn W, Kahn RS. Brain volumes in relatives of patients with schizophrenia: a meta-analysis. Schizophr Res 2006;81:41.

    Google Scholar 

  106. Dickey CC, Shenton ME, Hirayasu Y, Fischer I, Voglmaier MM, Niznikiewicz MA, Seidman LJ, Fraone S, McCarley RW. Large CSF volume not attributable to ventricular volume in schizotypal personality disorder. Am J Psychiat 2000;157:48–54.

    PubMed  CAS  Google Scholar 

  107. Koo MS, Dickey CC, Park HJ, Kubicki M, Ji NY, Bouix S, Pohl KM, Levitt JJ, Nakamura M, Shenton ME, McCarley RW. Smaller neocortical gray matter and larger sulcal cere-brospinal fluid volumes in neuroleptic-naive women with schizotypal personality disorder. Arch Gen Psychiat 2006 Oct;63(10):1090–1100.

    PubMed  Google Scholar 

  108. Davidson LL, Heinrichs RW. Quantification of frontal and temporal lobe brain-imaging findings in schizophrenia: a meta-analysis. Psychiat Res 2003;122:69–87.

    Google Scholar 

  109. Rapoport JL, Giedd JN, Blumenthal J, Hamburger S, Jeffries N, Fernandez T et al. Progressive cortical change during adolescence in childhood-onset schizophrenia: a longitudinal magnetic resonance imaging study. Arch Gen Psychiat 1999;56:649–654.

    PubMed  CAS  Google Scholar 

  110. Goghari VM, Rehm K, Carter CS, MacDonald AW 3rd. Regionally specific cortical thinning and gray matter abnormalities in the healthy relatives of schizophrenia patients. Cereb Cortex 2007;17:315–324.

    Google Scholar 

  111. Lawrie SM, Whalley HC, Abukmeil SS, Kestelman JN, Miller P, Best JJ, Owens DG, Johnstone EC. Temporal lobe volume changes in people at high risk of schizophrenia with psychotic symptoms. Br J Psychiat 2002;181:138–143.

    Google Scholar 

  112. Downhill JE, Buchsbaum MS, Hazlett EA, Barth S, Lees-Roitman S, Nunn M, Lekarev O, Wei T, Siever LJ. Temporal lobe volume determined by magnetic resonance imaging in schizotypal personality disorder and schizophrenia. Schizophr Res 2001;48:187–199.

    PubMed  Google Scholar 

  113. Gur RE, Turetsky BI, Cowell PE, Finkelman C, Maany V, Grossman RI, Arnold SE, Bilker WB, Gur RC. Temporolimbic volume reductions in schizophrenia. Arch Gen Psychiat 2000;57:769–775.

    PubMed  CAS  Google Scholar 

  114. Bogerts B, Ashtari M, Degreef G et al. Reduced temporal limbic structure volumes on magnetic resonance images in first episode schizophrenia. Psychiat Res 1990;35:1–13.

    CAS  Google Scholar 

  115. Flaum M, O'Leary DS, Swayze VW 2nd, Miller DD, Arndt S, Andreasen NC. Symptom dimensions and brain morphology in schizophrenia and related psychotic disorders. J Psychiat Res 1995;29:261–276.

    PubMed  CAS  Google Scholar 

  116. Barta PE, Pearlson GD, Powers RE et al. Auditory hallucinations and smaller superior or temporal gyral volume in schizophrenia. Am J Psychiat 1990;147:1457–1462.

    PubMed  CAS  Google Scholar 

  117. Kawasaki Y, Maeda Y, Urata K et al. A quantitative magnetic resonance imaging study of patients with schizophrenia. Eur Arch Psychiat Clin Neurosci 1993;242:268–272.

    CAS  Google Scholar 

  118. Rossi A, Stratta P, Mancini F et al. Magnetic resonance imaging findings of amygdala-anterior hippocampus shrinkage in male patients with schizophrenia. Psychiat Res 1994;52:43–53.

    CAS  Google Scholar 

  119. Shenton ME, Kikinis R, Jolesz FA et al. Abnormalities of the left temporal lobe and thought disorder in schizophrenia: a quantitative magnetic resonance imaging study. N Engl J Med 1992;327:604–612.

    PubMed  CAS  Google Scholar 

  120. Lee J-M, Kim SH, Jang DP, Ha TH, Kim J-J, Kim IY, Kwon JS, Kim SI. Deformable model with surface registration for hippocampal shape deformity analysis in schizophrenia. Neuroimage 2004;22:831–840.

    PubMed  Google Scholar 

  121. Kim SH, Lee JM, Kim HP, Jang DP, Shin YW, Ha TH, Kim JJ, Kim IY, Kwon JS, Kim SI. Asymmetry analysis of deformable hippocampal model using the principal component in schizophrenia. Hum Brain Mapp. 2005 Aug;25(4):361–369.

    PubMed  Google Scholar 

  122. Goldberg TE, Ragland JD, Tortey EF, Gold JM, Bigelow LB, Weinberger DR. Neuropsychological assessment of monozygotic twins discordant for schizophrenia. Arch Gen Psychiat 1990;47:1066–1072.

    PubMed  CAS  Google Scholar 

  123. Weinberger DR, Zigun JR, Bartley AJ, Jones DW, Torrey EF. Anatomical abnormalities in the brains of monozygotic twins discordant and concordant for schizophrenia. Clin Neuropsychopharmacol 1992;15(Suppl 1 Pt A):122A–123A.

    Google Scholar 

  124. Nestor PG, Shenton ME, McCarley RW, Harrison J, Smith RS, O'Donnell B, Kimble M, Kikinis R, Jolesz FA. Neuropsychological correlates of MRI temporal abnormalities in schizophrenia. Am J Psychiat 1993;150:1849–1855.

    PubMed  CAS  Google Scholar 

  125. Powell HW, Koepp MJ, Symms MR, Boulby PA, Salek-Haddadi A, Thompson PJ, Duncan JS, Richardson MP. Material-specific lateralization of memory encoding in the medial temporal lobe: blocked versus event-related design. Neuroimage 2005;27:231–239.

    PubMed  CAS  Google Scholar 

  126. Toulopoulou T, Morris RG, Rabe-Hesketh S, MurrayRM. Selectivity of verbal memory deficit in schizophrenic patients and their relatives. Am J Med Genet B Neuropsychiat Genet 2003;116:1–7.

    Google Scholar 

  127. Sitskoorn MM, Aleman A, Ebisch SJ, Appels MC, Kahn RS. Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis. Schizophr Res 2004;71:285–295.

    PubMed  Google Scholar 

  128. Geuze E, Vermetten E, Bremner JD. MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. Mol Psychiat 2005 Feb;10(2):160–184.

    Google Scholar 

  129. Goldberg TE, Torrey EF, Berman KF, Weinberger DR. Relations between neuropsychological performance and brain morphological and physiological measures in monozygotic twins discordant for schizophrenia. Psychiat Res 1994;55:51–61.

    CAS  Google Scholar 

  130. Gur RE, Maany V, Mozley PD, Swanson C, Bilker W, Gur RC. Subcortical MRI volumes in neuroleptic-naïve and treated patients with schizophrenia. Am J Psychiat 1998;155:1711–1717.

    PubMed  CAS  Google Scholar 

  131. O'Driscoll GA, Florencio PS, Gagnon D, Wolff A-LV, Benkelfat C, Mikula L et al. Amygdala-hippocampal volume and verbal memory in first-degree relatives of schizophrenic patients. Psychiat Res Neuroimaging 2001;107:75–85.

    Google Scholar 

  132. Dickey CC, McCarley RW, Voglmaier MM, Niznikiewicz MA, Seidman LJ, Hirayasu Y, Fischer I, The EK, Van Rhoads R, Jakab M, Kikinis R, Jolesz FA, Shenton ME. Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter. Biol Psychiat 1999;45: 1393–1402.

    PubMed  CAS  Google Scholar 

  133. Dickey CC, McCarley RW, Xu ML, Seidman LJ, Voglmaier MM, Niznikiewicz MA, Connor E, Shenton M. MRI abnormalities of the hippocampus and cavum septum pellucid in females with schizotypal personality disorder. Schizophr Res 2007;89:49–58.

    PubMed  Google Scholar 

  134. Caetano S, Hatch J, Brambilla P, Sassi R, Nicoletti M, Mallinger A, Frank E, Kupfer D, Keshavan M, Soares J. Anatomical MRI study of hippocampus and amygdala in patients with current and remitted major depression. Psychiat Res Neuroimaging 2004;132:141–147.

    Google Scholar 

  135. McCarley RW, Wible CG, Frumin M, Hirayasu Y, Levitt JJ, Fischer IA, Shenton ME. MRI anatomy of schizophrenia. Rev Biol Psychiat 1999;45:1099–1119.

    CAS  Google Scholar 

  136. Goghari VM, Rehm K, Carter CS, MacDonald AW. Sulcal thickness as a vulnerability indicator of schizophrenia. Br J Psychiat 2007;191:229–233.

    Google Scholar 

  137. Rajarethinam R, Sahni S, Rosenberg DR, Keshavan MS. Reduced superior temporal gyrus volume in young offspring of patients with schizophrenia. Am J Psychiat 2004;161:1121–1124.

    PubMed  Google Scholar 

  138. Kwon JS, McCarley RW, Anderson JE, Hirayasu Y, Fischer IA, Kikinis R, Jolesz FA, Shenton ME. Left planum temporal volume reduction in schizophrenia. Arch Gen Psychiat 1999;56:142–148.

    PubMed  CAS  Google Scholar 

  139. Barta PE, Pearlson GD, Brill LB, Royall R, McGilchrist, IK, Pulver AE, Powers RE, Casanova MF, Tien AY, Frangou S, Petty PG. Planum temporal asymmetry reversal in schizophrenia: replication and relationship to gray matter abnormalities. Am J Psychiat 1997;154:661–667.

    PubMed  CAS  Google Scholar 

  140. Petty RG, Barta PE, Pearlson GD, McGilchrist IK, Lewis RW, Tien AY, Pulver A, Vaughn DD, Casanova MF, Powers RE. Reversal of asymmetry of the planum temporal in schizophrenia. Am J Psychiat 1995;152:715–721.

    PubMed  CAS  Google Scholar 

  141. Rossi A, Stratta P, Mattei P, Cupillari M, Bozzao A, Gallucci M, Casacchia M. Planum temporale in schizophrenia: a magnetic resonance study. Schizophr Res 1992;7:19–22.

    PubMed  CAS  Google Scholar 

  142. DeLisi LE, Hoff AL, Neale C, Kushner M. Asymmetries in the superior temporal lobe in male and female first-episode schizophrenic patients: measures of the planum temporale and superior temporal gyrus by MRI. Schizophr Res 1994;12:19–28.

    Google Scholar 

  143. Hirayasu Y, McCarley RW, Salisbury DF, Tanaka S, Kwon JS, Frumin M, Snyderman D, Yurgelun-Todd D, Kikinis R, Jolesz FA, Shenton ME. Planum temporale and Heschl's gyrus volume reduction in schizophrenia: a magnetic resonance imaging study of first-episode patients. Arch Gen Psychiat 2000;57:692–699.

    PubMed  CAS  Google Scholar 

  144. Frangou S, Sharma T, Sigmudsson T, Barta P, Pearlson G, Murray RM. The Maudsley Family Study. 4. Normal planum temporale asymmetry in familial schizophrenia. A volumetric MRI study. Br J Psychiat 1997 Apr;170:328–333.

    CAS  Google Scholar 

  145. Dickey CC, McCarley RW, Voglmaier MM, Frumin M, Niznikiewicz MA, Hirayasu Y, Fraone S, Seidman LJ, Shenton ME. Smaller left Heschl's gyrus volume in patients with schizotypal personality disorder. Am J Psychiat 2002 Sept;159(9):1521–1527.

    PubMed  Google Scholar 

  146. Shenton ME, Wible CG, McCarley RW. A review of magnetic resonance imaging studies of brain abnormalities in schizophrenia. In: Rama Krishnan KR, Doraiswamy PM (Eds.), Brain Imaging in Clinical Psychiatry. New York: Marcel Dekker, 1997; pp. 297–380.

    Google Scholar 

  147. Kuperberg GR, Broome MR, McGuire PK, David AS, Eddy M, Ozawa F, Goff D, West WC, Williams SC, van der Kouwe AJ, Salat DH, Dale AM, Fischl B. Regionally localized thinning of the cerebral cortex in schizophrenia. Arch Gen Psychiat 2003 Sep;60(9):878–888.

    PubMed  Google Scholar 

  148. Honey GD, Sharma T, Suckling J, Giampietro V, Soni W, Williams SC, Bullmore ET. The functional neuroanatomy of schizophrenic subsyndromes. Psychol Med 2003 Aug;33(6):1007–1018.

    PubMed  CAS  Google Scholar 

  149. Paillère-Martinot M, Caclin A, Artiges E, Poline JB, Joliot M, Mallet L, Recasens C, Attar-Lévy D, Martinot JL. Cerebral gray and white matter reductions and clinical correlates in patients with early onset schizophrenia. Schizophr Res 2001 May 30;50(1–2):19–26.

    PubMed  Google Scholar 

  150. Ananth H, Popescu I, Critchley HD, Good CD, Frackowiak RS, Dolan RJ. Cortical and subcortical gray matter abnormalities in schizophrenia determined through structural magnetic resonance imaging with optimized volumetric voxel-based morphometry. Am J Psychiat 2002 Sept;159(9):1497–1505.

    PubMed  Google Scholar 

  151. Ho B-C, Andreasen NC, Nopoulos P, Arndt S, Magnotta V, Flaum M. Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia. Arch Gen Psychiat 2003;60:585–594.

    PubMed  Google Scholar 

  152. Lieberman JA, Phillips M, Gu H, Stroup S, Zhang P, Kong L, Ji Z, Koch G, Hamer RM. Atypical and conventional antipsychotic drugs in treatment-naïve first-episode schizophrenia: a 52-week randomized trial of clozapine vs. chlorpromazine. Neuropsychopharmacology 2003;28:995–1003.

    PubMed  CAS  Google Scholar 

  153. Cannon TD, Thompson PM, van Erp TG, Toga AW, Poutanen VP, Huttunen M, Lonnqvist J, Standerskjold-Nordenstam CG, Narr KL, Khaledy M, Zoumalan CI, Dail R, Kaprio J. Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia. Proc Natl Acad Sci USA 2002;99:3228–3233.

    PubMed  CAS  Google Scholar 

  154. Pantelis C, Velakoulis D, McGorry PD. Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 2003;361:281–288.

    PubMed  Google Scholar 

  155. Job DE, Whalley HC, McConnnell S, Glabus MF, Johnstone EC, Lawrie SM. Voxel based morphometry of grey matter densities in subjects at high risk of schizophrenia. Schizophr Res 2003;64:1–13.

    PubMed  Google Scholar 

  156. Diwadkar VA, Montrose DM, Dworakowski D, Sweeney JA, Keshavan MS. Genetically predisposed offspring with schizotypal features: an ultra high-risk group of schizophrenia? Prog Neuropsychopharmacol Biol Psychiat 2006;30:23–238.

    Google Scholar 

  157. Siever LJ, Buchsbaum MS, Shihabuddin L, Downhill J, Byne WM, Hazlett EA. Cortical and subcortical volumes in patients with schizotypal personality disorder (abstract). Biol Psychiat 2000;47:120S.

    Google Scholar 

  158. Buchsbaum MS, Nenadic I, Hazlett E, Spiegel-Cohen J, Fleischman MB, Akhavan A, Silverman JM, Siever LJ. Differential metabolic rates in prefrontal and temporal Brodmann areas in schizophrenia and schizotypal personality disorder. Schizophr Res 2002;54:141–150.

    PubMed  Google Scholar 

  159. Siever LJ, Kalus O, Keefe R. The boundaries of schizophrenia. Psychiat Clin North Am 1993;16:217–244.

    CAS  Google Scholar 

  160. Raine A, Sheard C, Reynolds GP, Lencz T. Prefrontal structural and functional deficits associated with individual differences in schizotypal personality. Schizophr Res 1992;7:237–247.

    PubMed  CAS  Google Scholar 

  161. Todtenkopf MS, Vincent SL, Benes FM. A cross-study meta-analysis and three-dimensional comparison of cell counting in the anterior cingulate cortex of schizophrenic and bipolar brain. Schziophr Res 2005;73:79–89.

    Google Scholar 

  162. Goldstein JM, Seidman LJ, O'Brien LM, Horton N, Kennedy DN, Makris N, Caviness Jr VS, Faraone SV, Tsuang MT. Impact of normal sexual dimorphisms on sex differences in structural brain abnormalities in schizophrenia assessed by magnetic resonance imaging. Arch Gen Psychiat 2002;59:154–164.

    PubMed  Google Scholar 

  163. Mitelman SA, Shihabuddin L, Brickman AM, Hazlett EA, Buchsbaum MS. Volume of the cingulate and outcome in schizophrenia. Schizophr Res 2005;72:91–108.

    PubMed  Google Scholar 

  164. Crespo-Facorro B, Kim J, Andreasen NC, O'Leary DS, Magnotta V. Regional frontal abnormalities in schizophrenia: a quantitative gray matter volume and cortical surface size study. Biol Psychiat 2000;48:110–119.

    PubMed  CAS  Google Scholar 

  165. Hirayasu Y, Shenton ME, Salisbury DF, Kwon JS, Wible CG, Fischer IA, Yurgelun-Todd D, Zarate C, Kikinis R, JOlesz FA, McCarley RW. Subgenual cingulate cortex volume in first-episode psychosis. Am J Psychiat 1999;156:1091–1093.

    PubMed  CAS  Google Scholar 

  166. Ellison-Wright I, Glahn DC, Laird AR, Thelen SM, Bullmore E. The anatomy of first-episode and chronic schizophrenia: an anatomical likelihood estimation metaanalysis. Am J Psychiat 2008 Aug;165(8):1015–1023.

    PubMed  Google Scholar 

  167. Yucel M, Pantelis C, Stuart GW, Wood SJ, Maruff P, Velakoulis D, Pipingas A, Crowe SF, Tochon-Danguy HJ, Egan GF. Anterior cingulate activation during Strrop task performance: a PET to MRI coregistration study of individual patients with schizophrenia. Am J Psychiat 2002;159:251–254.

    PubMed  Google Scholar 

  168. Fornito A, Yücel M, Dean B, Wood SJ, Pantelis C. Anatomical abnormalities of the anterior cingulate cortex in schizophrenia: bridging the gap between neuroimaging and neuropathology. Schizophr Bull 2008 Apr 23 [Epub ahead of print].

    Google Scholar 

  169. Zetzsche T, Preuss U, Frodi T, Watz D, Schmitt G, Koutsouleris N, Born C, Reiser M, Moller JH, Meisenzahl EM. In-vivo topography of structural alterations of the anterior cingulate in patients with schizophrenia: new findings and comparison with the literature. Schizophr Res 2007;96:34–45.

    PubMed  Google Scholar 

  170. Yucel M, Wood SJ, Phillips LJ, Stuart GW, Smith DJ, Yung A, Velakoulis D, McGorry PD, Pantelis SC. Morphology of the anterio cingulate cortex in young men at ultra-high risk of developing a psychotic illness. Br J Psychiat 2003;182:518–524.

    Google Scholar 

  171. Marcelis M, Suckling J, Woodruff P, Hofman P, Bullmore E, van Os J. Searching for a structural endophenotypes in psychosis using computational morphometry 2003;122:153–167.

    Google Scholar 

  172. Haznedar MM, Buchsbaum MS, Hazlett EA, Shihabuddin L, New A, Siever LJ. Cingulate gyrus volume and metabolism in the schizophrenia spectrum. Schizophr Res 2004;71:249–262.

    PubMed  Google Scholar 

  173. Takahashi T, Suzuki M, Kawasaki Y, Kurokawa K, Hagino H, Yamashita I, Zhou SY, Nohara S, Nakamura K, Seto H, Kurachi M. Volumetric magnetic resonance imaging study of the anterior cingulate gyrus in schizotypal disorder. Eur Arch Psychiat Clin Neurosci 2002;252:268–277.

    Google Scholar 

  174. Pearlson GD, Petty RG, Ross CA, Tien AY. Schizophrenia: a disease of heteromodal association cortex? Neuropsychopharmacology 1996;14:1–17.

    PubMed  CAS  Google Scholar 

  175. Lawrie SM, Abukmeil SS. Brain abnormality in schizophrenia: a systematic and quantitative review of volumetric magnetic resonance imaging studies. Br J Psychiat 1998;172: 110–120.

    CAS  Google Scholar 

  176. Ho BC. MRI brain volume abnormalities in young, nonpsy-chotic relatives of schizophrenia probands are associated with subsequent prodromal symptoms. Schizophr Res 2007;96:1–13.

    PubMed  Google Scholar 

  177. Gogtay N, Greenstein D, Lenane M, Clasen L, Sharp W, Gochman P, Butler P, Evans A. Cortical brain development in nonpsychotic siblings of patients with childhood-onset schizophrenia. Rapoport J Arch Gen Psychiat 2007;64: 772–780.

    Google Scholar 

  178. Shihabuddin L, Silverman JM, Buchsbaum MS, Siever LJ, Luu C, Germans MK, Metzger M, Mohs RC, Smith CJ, Spiegel-Cohen J, Davis KL. Ventricular enlargement associated with linkage marker for schizophrenia-related disorders in one pedigree. Mol Psychiat 1996;1:215–222.

    CAS  Google Scholar 

  179. Ture U, Yasargil DC, Al-Mefty O, Yasargil MG. Topographic anatomy of the insular region. J Neurosurg 1999;90:720–733.

    PubMed  CAS  Google Scholar 

  180. Augustine JR. Circuitry and functional aspects of the insular lobe in primates including humans. Brain Res Brain Res Rev 1996;22:229–244.

    PubMed  CAS  Google Scholar 

  181. Kim JJ, Youn T, Lee JM, Kim IY, Kim SI, Kwon JS. Morphometric abnormality of the insula in schizophrenia: a comparison with obsessive-compulsive disorder and normal control using MRI. Schizophr Res 2003;60:191–198.

    PubMed  Google Scholar 

  182. Wright IC, Ellison ZRK, Sharma T, Friston KJ, Murray RM, McGuire PK. Mapping of grey matter changes in schizophrenia. Schizophr Res 1999;35:1–14.

    PubMed  CAS  Google Scholar 

  183. Honea RA, Meyer-Lindenberg A, Hobbs KB, Pezawas L, Mattay VS, Egan MF, Verchinski B, Passingham RE, Weinberger DR, Callicott JH. Is gray matter volume an intermediate phenotype for schizophrenia? A voxel-based morphometry study of patients with schizophrenia and their healthy siblings. Biol Psychiat 2008;63:465–474.

    PubMed  Google Scholar 

  184. Takahashi T, Suzuki M, Zhou SY, Hagino H, Tanino R, Kawasaki Y, Nohara S, Yamashita I, Seto H, Kurachi M. Volumetric MRI study of the short and long insular cortices in schizophrenia spectrum disorders. Psychiat Res 2005;138:209–220.

    Google Scholar 

  185. Yoneyama E, Matsui M, Kawasaki Y, Nohara S, Takahashi T, Hagino H, Suzuki M, Seto H, Kurachi M. Acta Psychiat Scand 2003;108:333–340.

    PubMed  CAS  Google Scholar 

  186. Nelson MD, Saykin AJ, Flashman LA et al. Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging: a meta-analytic study. Arch Gen Psychiat 1998;55:443–440.

    Google Scholar 

  187. Breier A, Buchanan RW, Elkashef A et al. Brain morphology and schizophrenia: a magnetic resonance imaging study of limbic, prefrontal cortex and caudate structure. Arch Gen Psychiat 1992;49:921–926.

    PubMed  CAS  Google Scholar 

  188. Yeo RA, Hodde-Vargas J, Hendren RL et al. Brain abnormalities in schizophrenia-spectrum children: implications for a neurodevelopmental perspective. Psychiat Res Neuroimaging 1997;76:1–13.

    CAS  Google Scholar 

  189. Seidman LJ, Faraone SV, Goldstein JM, Goodman JM, Kremen WS, Matsuda G, Hoge EA, Kennedy D, Makris N, Caviness VS, Tsuang MT. Reduced subcortical brain volumes in nonpsychotic siblings of schizophrenic patients: a pilot magnetic resonance imaging study. Am J Med Genet 1997;74:507–514.

    PubMed  CAS  Google Scholar 

  190. Keshavan MS, Montrose DM, Pierri JN, Dick EL, Rosenberg D, Talagala L, Sweeney JA. Magnetic resonance imaging and spectroscopy in offspring at risk for schizophrenia: preliminary studies. Prog Neuro-Psychopharmacol Biol Psychiat 1997;21:1285–1295.

    CAS  Google Scholar 

  191. Faraone SV, Seidman LJ, Kremen WS, Kennedy D, Makris N, Caviness VS, Goldstein J, Tsuang MT. Structural brain abnormalities among relatives of patients with schizophrenia: implications for linkage studies. Schizophr Res 2003;6:125–140.

    Google Scholar 

  192. Goldman AL, Pezawas L, Mattay VS, Fischl B, Verchinski BA, Zoltick B, Weinberger DR, Meyer-Lindenberg A. Heritability of brain morphology related to schizophrenia: a large-scale automated magnetic resonance imaging segmentation study. Biol Psychiat 2008;63:475–483.

    PubMed  Google Scholar 

  193. Staal WG, Hulshoff Pol HE, Schnack HG, Hoogendoorn MLC, Jellema K, Kahn RS. Structural brain abnormalities in patients with schizophrenia and their healthy siblings. Am J Psychiat 2000;157:416–421.

    PubMed  CAS  Google Scholar 

  194. Lehéricy S, Ducros M, Van de Moortele PF, Francois C, Thivard L, Poupon C, Swindale N, Ugurbil K, Kim DS. Diffusion tensor fiber tracking shows distinct corticostriatal circuits in humans. Ann Neurol 2004 Apr;55(4):522–529.

    PubMed  Google Scholar 

  195. Chakos MH, Lieberman JA, Bilder RM, Borenstein M, Lerner G, Bogerts B, Wu H, Kinon B, Ashtari M. Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs. Am J Psychiat 1994;151:1430–1436.

    PubMed  CAS  Google Scholar 

  196. Chakos MH, Lieberman JA, Alvir J, Bilder R, Ashtari M. Caudate nuclei volumes in schizophrenic patients treated with typical antipsychotics or clozapine. Lancet 1995;345:456–457.

    PubMed  CAS  Google Scholar 

  197. Keshavan MS, Bagwell WW, Haas GL, Sweeney JA, Schooler NR, Pettegrew JW. Changes in caudate volume with neuroleptic treatment. Lancet 1994;344:1434.

    PubMed  CAS  Google Scholar 

  198. Shihabuddin L, Buchsbaum MS, Hazlett EA, Silverman J, New A, Brickman AM, Mitropoulou V, Nunn M, Fleishman MB, Tang C, Siever LJ. Striatal size and glucose metabolic rate in schizotypal personality disorder and schizophrenia. Arch Gen Psychiat 2001;58:877–884.

    PubMed  CAS  Google Scholar 

  199. Berman KF. Functional neuroimaging in schizophrenia. In: Davis KL, Charney DC, Coyle JT, and Nemeroff C (eds.), Neuropsychopharmacology: The Fifth Generation of Progress, Lippincott Williams and Wilkins Publishers, Philadelphia, pp 745–756, 2002.

    Google Scholar 

  200. Lang DJ, Kopala LC, Vandorpe RA, Rui Q, Smith GN, Goghari VM, Lapointe JS, Honer WG. Reduced basal ganglia volumes after switching to olanzapine in chronically treated patients with schizophrenia. Am J Psychiat 2004;161:1829–1836.

    PubMed  Google Scholar 

  201. Andersson C, Hamer RM, Lawler CP, Mailman RB, Lieberman JA. Striatal volume changes in the rat following long-term administration of typical and atypical antipsychotic drugs. Neuropsychopharmacology 2002;27:143–151.

    PubMed  CAS  Google Scholar 

  202. Corson PW, Nopoulos P, Andreasen NC, Heckel D, Arndt S. Caudate size in first-episode neuroleptic-naïve schizophrenic patients measured using an artificial neural network. Biol Psychiat 1999;46:712–720.

    PubMed  CAS  Google Scholar 

  203. Keshavan MS, Rosenberg D, Sweeney JA, Pettegrew JW. Decreased caudate volume in neuroleptic-naïve psychotic patients. Am J Psychiat 1998;155:774–778.

    PubMed  CAS  Google Scholar 

  204. Andreasen NC. The role of the thalamus in schizophrenia. Can J Psychiat 1997;42:27–33.

    CAS  Google Scholar 

  205. Konick LC, Friedman L. Meta-analysis of thalamic size in schizophrenia. Biol Psychiat 2001;49:28–38.

    PubMed  CAS  Google Scholar 

  206. Byne W, Buchsbaum MS, Kemether E, Hazlett E, Shinwari A, Siever LJ. MRI assessment of medial and dorsal pulvinar nuclei of the thalamus in schizophrenia and schizotypal personality disorder. Arch Gen Psychiat 2001;58:133–140.

    PubMed  CAS  Google Scholar 

  207. Portas CM, Goldstein JM, Shenton ME, Hokama HH, Wible CG, Fischer I, Kikinis R, Donnino R, Jolesz FA, McCarley RW. Volumetric evaluation of the thalamus in schizophrenic male patients using magnetic resonance imaging. Biol Psychiat 1998;43:649–659.

    PubMed  CAS  Google Scholar 

  208. Hazlett EA, Buchsbaum MS, Byne W, Wei TC, Spiegel-Cohen J, Geneve C, Kinderlehrer R, Haznedar MM, Shihabuddin L, Sievel LJ. Three-dimensional analysis with MRI and PET of the size, shape and function of the thalamus in the schizophrenia spectrum. Am J Psychiat 1999;156:1190–1199.

    PubMed  CAS  Google Scholar 

  209. Byne W, Buchsbaum MS, Mattiace LA et al. Postmortem assessment of thalamic nuclear volumes in subjects with schizophrenia. Am J Psychiat 2002;159:59–65.

    PubMed  Google Scholar 

  210. Manaye K, German D, Liang C-L, Hicks P, Young K. Reduced number of mediodorsalthalamic neurons in schizophrenics. Soc Neurosci Abst 1997;23:2200.

    Google Scholar 

  211. Pakkenberg B. Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. Arch Gen Psychiat 1990;47:1023–1028.

    PubMed  CAS  Google Scholar 

  212. Young KA, Manaye KF, Liang C, Hicks PB, German DC. Reduced number of mediodorsal and anterior thalamic neurons in schizophrenia. Biol Psychiat 2000;47:944–953.

    PubMed  CAS  Google Scholar 

  213. Lawrie SM. Premorbid structural abnormalities in schizophrenia. In: Keshavan M, Kennedy J, Murray R (Eds.), Neurodevelopment and Schizophrenia. Cambridge: Cambridge University Press, 2004; pp. 347–372.

    Google Scholar 

  214. Staal WG, Hulshoff Pol HE, Schnack H, van der Schot AC, Kahn RS. Partial volume decrease of the thalamus in relatives of patients with schizophrenia. Am J Psychiat 1998;155:1784–1786.

    PubMed  CAS  Google Scholar 

  215. Steel R, Whalley H, Miller P, Best JJK, Johnstone EC, Lawrie SM. Structural MRI of the brain in presumed carriers of genes for schizophrenia, their affected and unaffected siblings. J Neurol Neurosurg Psychiat 2002;72:455–458.

    PubMed  CAS  Google Scholar 

  216. Schmahmann JD, Caplan D. Cognition, emotion and the cerebellum. Brain 2006 Feb;129(Pt 2):290–292.

    PubMed  Google Scholar 

  217. Wassink TH, Andreasen NC, Nopoulos P, Flaum M. Cerebellar morphology as a predictor of symptom and psychosocial outcome in schizophrenia. Biol Psychiat 1999;45:41–48.

    PubMed  CAS  Google Scholar 

  218. Andreasen NC, Pierson R. The role of the cerebellum in schizophrenia. Biol Psychiat 2008;64:81–88.

    PubMed  Google Scholar 

  219. Jacobsen LK, Giedd JN, Rajapakse JC, Hamburger SD, Vaituzis AC, Frazier JA, Lenane MC, Rapoport JL. Quantitative magnetic resonance imaging of the corpus callosum in childhood onset schizophrenia. Psychiat Res Neuroimaging 1997;68:77–86.

    CAS  Google Scholar 

  220. James AC, James S, Smith DM, Javaloyes A. Cerebellar, prefrontal cortex, and thalamic volumes over two time points in adolescent-onset schizophrenia. Am J Psychiat 2004;161:1023–1029.

    PubMed  Google Scholar 

  221. Levitt JJ, McCarley RW, Nestor PG, Petrescu C, Donnino R, Hirayasu Y et al. Quantitative volumetric MRI study of the cerebellum and vermis in schizophrenia: clinical and cognitive correlates. Am J Psychiat 1999;156:1105–1107.

    PubMed  CAS  Google Scholar 

  222. Loeber RT, Cintron CM, Yurgelun-Todd DA. Morphometry of individual cerebellar lobules in schizophrenia. Am J Psychiat 2001;158:952–954.

    PubMed  CAS  Google Scholar 

  223. McDonald C, Grech A, Toulopoulou T, Schulze K, Chapple B, Sham P, Walshe M, Sharma T, Sigmundsson T, Chitnis X, Murray RM. Brain volumes in familial and non-familial schizophrenic probands and their unaffected relatives. Am J Med Genet 2002;114:616–625.

    PubMed  Google Scholar 

  224. David AS. Schizophrenia and the corpus callosum: developmental, structural and functional relationships. Behav Brain Res 1994;64:203–211.

    PubMed  CAS  Google Scholar 

  225. Coger RW, Serafetinides EA. Schizophrenia, corpus callosum and interhemispheric communication: a review. Psychiat Res 1990;34:163–184.

    CAS  Google Scholar 

  226. Pandya D, Seltzer B. The topography of commissural fibers. In: Lepore F, Petito M, Jasper H (Eds.), Two Hemispheres — One Brain: Functions of the Corpus Callosum. New York: Alan R. Lis, 1986.

    Google Scholar 

  227. Rotarska-Jagiela A, Schonmeyer R, Oertel V, Haenschel C, Vogeley K, Linden DEJ. The corpus callosum in schizophrenia-volume and connectivity changes affect specific regions. Neuroimage 2008;39:1522–1532.

    PubMed  Google Scholar 

  228. Chua SE, Sharma T, Takei N, Murray RM, Woodruff PW. A magnetic resonance imaging study of corpus callosum size in familial schizophrenic subjects, their relatives, and normal controls. Schizophr Res 2000;41:397–403.

    PubMed  CAS  Google Scholar 

  229. Woodruff PW, McManus IC, David AS. Meta-analysis of corpus callosum size in schizophrenia. J Neurol Neurosurg Psychiat 1995 Apr;58(4):457–461.

    PubMed  CAS  Google Scholar 

  230. Narr KL, Thompson PM, Sharma T, Moussai J, Cannestra AF, Toga AW. Mapping morphology of the corpus callosum in schizophrenia. Cereb Cortex 2000;10:40–49.

    PubMed  CAS  Google Scholar 

  231. Casanova MF, Sanders RD, Goldberg TE, Bigelow LB, Christison G, Torrey EF, Weinberger DR. J Neurol Neurosurg Psychiat 1990;53:416–421.

    PubMed  CAS  Google Scholar 

  232. Tibbo P, Nopoulos P, Arndt S, Andreasen NC. Corpus callosum shape and size in male patients with schizophrenia. Biol Psychiat 1998;44:405–412.

    PubMed  CAS  Google Scholar 

  233. Narr KL, Cannon TD, Woods RP, Thompson PM, Kim S, Asunction D, van Erp TG, Poutanen VP, Huttunen M, Lönnqvist J, Standerksjöld-Nordenstam CG, Kaprio J, Mazziotta JC, Toga AW. Genetic contributions to altered callosal morphology in schizophrenia. J Neurosci 2002 May 1;22(9):3720–3729.

    PubMed  CAS  Google Scholar 

  234. Woodruff PW, Phillips ML, Rushe T, Wright IC, Murray RM, David AS. Corpus callosum size and inter-hemispheric function in schizophrenia. Schizophr Res. 1997 Feb 28;23(3):189–196.

    PubMed  CAS  Google Scholar 

  235. Woodruff PW, Pearlson GD, Geer MJ, Barta PE, Childcoat HD. A computerized magnetic resonance imaging study of corpus callosum morphology in schizophrenia. Psychol Med 1993;23:45–56.

    PubMed  CAS  Google Scholar 

  236. Kwon JS, Shenton ME, Hirayasu Y, Salisbury DF, Fischer IA, Dickey CC, Yurgelun-Todd D, Tohen M, Kikinis R, Jolesz FA, McCarley RW. MRI study of cavum septi pellucid in schizophrenia, affective disorder and schizotypal personality disorder. Am J Psychiat 1998;155:509–515.

    PubMed  CAS  Google Scholar 

  237. Nopoulos P, Swayze V, Andreasen NC. Pattern of brain morphology in patients with schizophrenia and large cavum septi pellucid. J Neuropsychiat Clin Neurosci 1996;8:147–152.

    CAS  Google Scholar 

  238. Nopoulos P, Swayze V, Flaum M, Erhardt JC, Yuh WT, Andreasen NC. Cavum septum pellucid and patients with schizophrenia as detected by magnetic resonance imaging. Biol Psychiat 1997;41:1102–1108.

    PubMed  CAS  Google Scholar 

  239. Rajarethinam R, Sohi J, Arfken C, Keshavan MS. No difference in the prevalence of cavum septum pellucidum (CSP) between first-episode schizophrenia patients, offspring of schizophrenia patients and healthy controls. Schizophr Res. 2008 Aug;103(1–3):22–25.

    PubMed  Google Scholar 

  240. Choi JS, Kang DH, Park JY, Jung WH, Choi CH, Chon MW, Jung MH, Lee JM, Kwon JS. Cavum septum pellucidum in subjects at ultra-high risk for psychosis: compared with first-degree relatives of patients with schizophrenia and healthy volunteers. Prog Neuropsychopharmacol Biol Psychiat 2008;32:1326–1330.

    Google Scholar 

  241. Shelton RC, Weinberger DR. X-ray computerized tomography studies in schizophrenia: a review and synthesis. In: Nasrallah HA, Weinberger DR (Eds.), The Handbook of Schizophrneia, Vol I: The Neurology of Schziophrenia. New York: Elsevier, 1986; pp. 207–250.

    Google Scholar 

  242. Dauphinais ID, DeLisi LE, Crow TJ et al. Reduction in temporal lobe size in siblings with schizophrenia: a mag-netic resonance imaging study. Psychiat Res 1990;35:137–147.

    CAS  Google Scholar 

  243. Degreef G, Bogerts B, Ashtari M et al. Ventricular system morphology in first episode schizophrenia: a volumetric study of ventricular subdivisions on MRI (abstract). Schizophr Res 1990;3:18.

    Google Scholar 

  244. Johnstone EC, Owens DG, Crow TJ et al. Temporal lobe structure as determined by nuclear magnetic resonance in schizophrenia and bipolar affective disorder. J Neurol Neurosurg Psychiat 1989;52:736–741.

    PubMed  CAS  Google Scholar 

  245. Shenton ME, Kikinis R, McCarley RW et al. Application of automated MRI volumetric measurement techniques to the ventricular system in schizophrenics and normal controls. Schizophr Res 1991;5:103–113.

    PubMed  CAS  Google Scholar 

  246. Lieberman J, Chakos M, Wu H, Alvir J, Hoffman E, Robinson D et al. Longitudinal study of brain morphology in first episode schizophrenia. Biol Psychiat 2001;49:487–499.

    PubMed  CAS  Google Scholar 

  247. Buckley PF, Dean D, Bookstein FL, Friedman L, Kwon D, Lewis JS, Kamath J, Lys C. Three-dimensional magnetic resonance-based morphometrics and ventricular dysmorphology in schizophrenia. Biol Psychiat 1999;45:62–67.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Mamah, D., Barch, D.M., Csernansky, J.G. (2009). Neuromorphometric Measures as Endophenotypes of Schizophrenia Spectrum Disorders. In: Ritsner, M.S. (eds) The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9831-4_5

Download citation

Publish with us

Policies and ethics