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Schizophrenia as a progressive developmental disorder: the evidence and its implications

  • Bryan T. Woods

Abstract

I would like to propose that there are certain limiting characteristics of the in vivo structural brain changes observed in schizophrenia that must be explained by any postulated pathogenetic hypothesis. These characteristics are not so specific as to be diagnostically useful in individuals in the absence of behavioral data, but they are useful in the search for the genetic defect(s) that most observers now agree are the necessary if not sufficient cause(s) of the illness. This potential utility comes about at two stages in this genetic search; first, because brain volume loss is a quantitative trait, it is possible to use it to separate out a sub-set of schizophrenic patients who are more likely to share a common genetic defect, even if the illness is heterogeneic in an unselected patient group. Second, even if a gene region is shown to be associated with schizophrenia with high probability, it will still be necessary to screen as many as a hundred or more genes in the region to find the specific cause. In this search a genetic defect that measurably affects brain growth and development is much more amenable to isolation in an animal model than one that affects only behavior; it’s hard to be sure what a schizophrenic mouse would look like.

Keywords

Brain Volume Gray Matter Volume Brain Morphology Quantitative Magnetic Resonance Imaging Brain Volume Loss 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Andreasen NC, Flashman L, Flaum M, Arndt SV, Swayze V, O’Leary DS, Ehrhardt JC, Yuh WTC (1994) Regional brain abnormalities in schizophrenia measured with magnetic resonance imaging. JAMA 272:1763–1769PubMedCrossRefGoogle Scholar
  2. Blatter DD, Bigler ED, Gale SD, Johnson SC, Anderson CV, Burnett, BM, Parker N, Kurth S, Horn SD (1995) Quantitative volumetric analysis of brain MR: normative database spanning 5 decades of life. Am J Neuroradiol 16:241–251PubMedGoogle Scholar
  3. Cannon TD, Van Erp TGM, Huttunen M, Lonqvist J, Salonen O, Valanne L, Veli-Pekka P, Standertskjold-Nordenstam C-G, Gur RC, Yan M (1998) Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls. Arch Gen Psychiat 55:1084–1091PubMedCrossRefGoogle Scholar
  4. Cahn W, Pol HE, Lems EB, Van Haren, Schnack HG, Van der Linden, Schothorst PF, Van Engeland, Kahn RS (2002) Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Archives of General Psychiatry 59:1002–1011PubMedCrossRefGoogle Scholar
  5. Dickey CC, Shenton ME, Hirayasu Y, Fischer I, Voglmaier MM, Niznikiewicz MA, Seidman LJ, Fraone S, McCarley RW (2000) Large CSF volume not attributable to ventricular volume in schizotypal personality disorder. Am J Psychiatry 157:48–54PubMedGoogle Scholar
  6. Flaum M, Swayze VW, O’Leary DS, Yuh WTC, Erhardt JC, Arndt SV, Andreasen NC (1995) Effects of diagnosis, laterality, and gender on brain morphology in schizophrenia. Am J Psychiatry 152:704–714PubMedGoogle Scholar
  7. Giedd JN, Snell JW, Lange N, Rajapakse JC, Casey BJ, Kozuch PL, Vaituzis AC, Vauss YC, Hamburger SD, Kaysen D, Rapoport JL (1996) Quantitative magnetic resonance imaging of human brain development: Ages 4–18. Cerebral Cortex 6:551–560PubMedCrossRefGoogle Scholar
  8. Gur RE, Moony V, Mozley D, Swanson C, Bilker W, Gur RC (1998) Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia. Am J Psychiatry 155:1711–1717PubMedGoogle Scholar
  9. Gur RE, Mozley D, Resnick SM, Shtasel D, Kohn M, Zimmerman R, Herman G, Atlas S, Grossman R, Erwin R, Gur RC (1991) Magnetic resonance imaging in schizophrenia. Arch Gen Psychiatry 48:407–412PubMedCrossRefGoogle Scholar
  10. Gur RE, Mozley D, Shtasel DL, Cannon TD, Gallacher F, Turetsky B, Grossman R, Gur RC (1994) Clinical subtypes of schizophrenia: differences in brain and CSF volume. Am J Psychiatry 151:343–350PubMedGoogle Scholar
  11. Gur RE, Turetsky BJ, Bilker WB, Gur RC (1999) Reduced gray matter volume in schizophrenia. Arch Gen Psychiatry 56:905–911PubMedCrossRefGoogle Scholar
  12. Huppe PS, Warfield S, Kikinis R, Barnes PD, Zientara GP, Jolesz FA, Tsuji MK, Volpe JJ (1998) Quantitative magnetic resonce imaging of brain development in premature and mature newborns. Ann Neurol 43:224–235CrossRefGoogle Scholar
  13. Jernigan TL, Press GA, Hesselink JR (1990) Methods of measuring brain morphologic features on magnetic resonance images. Arch Neurol 47:27–32PubMedCrossRefGoogle Scholar
  14. Nopoulos P, Flaum M, Andreasen NC (1997) Sex differences in brain morphology in schizophrenia. Am J Psychiatry 154:1648–1654PubMedGoogle Scholar
  15. Nopoulos P, Torres I, Flaum M, Andreasen NC, Ehrhardt JC, Yuh WTC (1995) Brain morphology in first-episode schizophrenia. Am J Psychiatry 152:1721–1723PubMedGoogle Scholar
  16. Paillere-Martinot M-L, Cacin A, Aretiges E, Poline J-B, Joliot M, Maller L, Recasens C, Attar-Levy D, Martinot J-L (2001) Cerebral gray and white matter reductions and clinical correlates in patients with early onset schizophrenia. Schizophrenia Research 50:19–26PubMedCrossRefGoogle Scholar
  17. Pearlson GD, Barta PE, Powers RE, Menon RR, Richards SS, Aylward EH, Federman EB, Chase GA, Petty RG, Tien AY (1997) Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder. Biol Psychiatry 41:1–14PubMedCrossRefGoogle Scholar
  18. Pfefferbaum A, Mathalon DH, Sullivan EV, Rawles JM, Zipursky RB, Lim KO (1994) A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Arch Neurol 51:874–887PubMedCrossRefGoogle Scholar
  19. Pol HEH, Hoek HW, Susser E, Brown AS, Dingemans A, Schnack HA, Van Haren NEM, Ramos LMP, Gispen-de Wied CC, Kahn RS (2000) Prenatal exposure to famine and brain morphology in schizophrenia. Am J Psychiatry 157:1170–1172CrossRefGoogle Scholar
  20. Shenton ME, Kikinis R, Jolesz FA, Pollak SD, LeMay M, Wible CG, Hokama H, Martin J, Metcalf B, Coleman M, McCarley RW (1992) Abnormalities of left temporal lobe and thought disorder in schizophrenia. NEJM 327:604–612PubMedCrossRefGoogle Scholar
  21. Sigmundsson T, Suckling J, Maier M, Williams SCR, Bullmore ET, Greenwood KE, Fukuda R, Ron MA, Toone BK (2001) Structural abnormalities in frontal, temporal, and limbic regions and interconnecting white matter tracts in schizophrenic patients with prominent negative symptoms. Am J Psychiatry 158:234–243PubMedCrossRefGoogle Scholar
  22. Staal WG, Pol HEH, Schnack HG, Hoogendoorn MLC, Jellema K, Kahn RS (2000) Structural brain abnormalities in patients with schizophrenia and their healthy siblings. Am J Psychiatry 157:416–421PubMedCrossRefGoogle Scholar
  23. Staal WG, Pol HEH, Schnack HG, Neeltje EM, Van Haren NEM, Seifert M, Kahn RS (2001) Structural brain abnormalities in chronic schizophrenia at the extremes of the outcome spectrum. Am J Psychiatry 158:1140–1142PubMedCrossRefGoogle Scholar
  24. Woods BT, Yurgelun-Todd D (1991) Brain volume loss in schizophrenia: when does it occur and is it progressive? Schizophrenia Res 5:202–204CrossRefGoogle Scholar
  25. Woods BT (1998) Is schizophrenia a progressive neurodevelopmental disorder? To-ward a unitary pathogenetic mechanism. Am J Psychiatry 155:1661–1670PubMedGoogle Scholar
  26. Zipursky RB, Lamb EK, Kapur S, Mikulis DJ (1998) Cerebral gray matter volume def-icits in first episode psychosis. Arch Gen Psychiatry 55:540–546PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • Bryan T. Woods
    • 1
  1. 1.University of Texas Health Science CenterHoustonUSA

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