Advertisement

Are mental diseases brain diseases? The contribution of neuropathology to understanding of schizophrenic psychoses

  • Michael B. Knable
  • Daniel R. Weinberger
Article

Abstract

Nearly a century after the seminal contributions of Emil Kraepelin, the search for neuropathologic correlates of schizophrenic psychoses continues. A multitude of neuroanatomic and neurochemical findings has emerged in recent years, but many of these findings are not replicated or are difficult to interpret in light of methodologic problems. In this review replicated neuropathologic and neuroimaging studies are discussed. The hypothesis that emerges from these studies is that schizophrenia is a developmental abnormality affecting the connectivity of the prefrontal and medial temporal cortices.

Key words

Schizophrenia Psychosis Neuropathology Neuroimaging 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Akbarian S, Bunney WE, Potkin S, et al (1993a) Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbance of cortical development. Arch Gen Psychiatry 50: 169–177PubMedGoogle Scholar
  2. Akbarian S, Vinuela A, Kim JJ, et al (1993b) Distorted distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in temporal lobe of schizophrenics implies anomalous cortical development. Arch Gen Psychiatry 50:178–187PubMedGoogle Scholar
  3. Altshuler L, Conrad A, Kovelman JA, Scheibel A (1987) Hippocampal cell disorientation in schizophrenia: a controlled neurohistologic study of the Yakovlev collection. Arch Gen Psychiatry 44:1094–1098PubMedGoogle Scholar
  4. Arnold SE, Hyman BT, Van Hoese GW, Damasio AR (1991) Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia. Arch Gen Psychiatry 48:625–632PubMedGoogle Scholar
  5. Asano N (1967) Pneumoencephalographic study of schizophrenia. In: Mitsuda H et al (eds) Clinical genetics in psychiatry: problems in nosological classification. Igaku Shoin, Tokyo, pp 209–217Google Scholar
  6. Barta PE, Pearlson GD, Powers RE et al (1990) Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia. Am J Psychiatry 147:1457–1462PubMedGoogle Scholar
  7. Benes FM, Davidson J, Bird ED (1986) Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics. Arch Gen Psychiatry 43:31–35PubMedGoogle Scholar
  8. Benes FM, Sorenson I, Bird E (1991) Reduced neuronal size in posterior hippocampus of schizophrenic patients. Schizophr Bull 17:597–608PubMedGoogle Scholar
  9. Berman KF, Illowsky BP, Weinberger DR (1988) Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. IV Further evidence for regional and behavioral specificity. Arch Gen Psychiatry 45:616–622PubMedGoogle Scholar
  10. Berman KF, Weinberger DR (1991) Functional localization in the brain in schizophrenia. In: Tasman A, Goldfinger S (eds) American Psychiatric Press Review of Psychiatry, vol 10. American Psychiatric Association Press, Washington, DC, pp 24–59Google Scholar
  11. Berman KF, Torrey EF, Daniel DG, Weinberger DR (1992) Regional cerebral blood flow in monozygotic twins discordant and concordant for schizophrenia. Arch Gen Psychiatry 49: 927–934PubMedGoogle Scholar
  12. Bogerts B, Meertz E, Schonfeldt-Bausch R (1985) Basal ganglia and limbic system pathology in schizophrenia. Arch Gen Psychiatry 42:784–791PubMedGoogle Scholar
  13. Bogerts B, Falkai P, Haupts M, et al (1990a) Post-mortem volume measurements of limbic system and basal ganglia structures in chronic schizophrenics. Schizophr Res 3:295–301CrossRefPubMedGoogle Scholar
  14. Bogerts B, Ashtari M, Degreef G, et al (1990b) Reduced temporal limbic structure volume on magnetic resonance images in first episode schizophrenia. Psychiatry Res 35:1–13PubMedGoogle Scholar
  15. Breier A, Buchanan RW, Elkashef A, et al (1992) Brain morphology and schizophrenia. A magnetic resonance imaging study of limbic, prefrontal cortex, and caudate structures. Arch Gen Psychiatry 49:921–926PubMedGoogle Scholar
  16. Broca P (1863) Localisation des fonctions cérébrales: Siège du langage articulé. Bulletin de la Société d'Anthropologie 4:200–203Google Scholar
  17. Brown R, Colter N, Corsellis JAN, et al (1986) Postmortem evidence of structural brain changes in schizophrenia. Arch Gen Psychiatry 43:36–42PubMedGoogle Scholar
  18. Christison GW, Casanova MF, Weinberger DR, et al (1989) A quantitative investigation of hippocampal pyramidal cell size, shape, and variability of orientation in schizophrenia. Arch Gen Psychiatry 46:1027–1032PubMedGoogle Scholar
  19. Cleghorn JM, Zipursky RB, List SJ (1991) Structural and functional brain imaging in schizophrenia. J Psychiatr Neurosci 1653–1674Google Scholar
  20. Colter N, Battal S, Crow TJ et al (1987) White matter reduction in the parahippocampal gyrus of patients with schizophrenia. Arch Gen Psychiatry 44:1023Google Scholar
  21. Conrad AS, Abebe T, Austin R et al (1991) Hippocampal pyramidal cell disarray in schizophrenia as a bilateral phenomenon. Arch Gen Psychiatry 48:413–417PubMedGoogle Scholar
  22. Davison K, Bagley CR (1969) Schizophrenia—like psychoses associated with organic disorders of the central nervous system. Br J Psychiatry 113 (Suppl 1):18–69Google Scholar
  23. Degreef G, Ashtari M, Bogerts B, et al (1992) Volumes of ventricular system subdivisions measured from magnetic resonance images in first episode schizophrenic patients. Arch Gen Psychiatry 49:531–537PubMedGoogle Scholar
  24. DeLisi LE, Goldin LR, Hamovit JR, et al (1986) A family study of the association of increased ventricular size with schizophrenia. Arch Gen Psychiatry 43:148–153PubMedGoogle Scholar
  25. DeLisi LE, Dauphinais ID, Gershon ES (1988) Perinatal complications and reduced size of brain limbic structures in familial schizophrenia. Schizophr Bull 14:185–191PubMedGoogle Scholar
  26. DeLisi LE, Buchsbaum MS, Holcomb HH, et al (1989) Increased temporal lobe glucose use in chronic schizophrenic patients. Biol Psychiatry 25:835–851CrossRefPubMedGoogle Scholar
  27. DeLisi L, Hoff AL, Schwartz JE, et al (1991) Brain morphology in first-episode schizophrenic-like psychotic patients: a quantitative magnetic resonance imaging study. Biol Psychiatry 29: 159–175PubMedGoogle Scholar
  28. Falkai P, Bogerts B, Rozumek M (1988) Limbic pathology in schizophrenia: the entorhinal region. Biol Psychiatry 24: 515–521CrossRefPubMedGoogle Scholar
  29. Goldberg TE, Gold JM, Braff DL (1991) Neuropsychological functioning and time-linked information processing in schizophrenia. In: Tasman A, Goldfinger S (eds) American Psychiatric Press Review of Psychiatry, vol 10. American Psychiatric Association Press, Washington, DC, pp 60–78Google Scholar
  30. Gur RE, Mozley D, Resnick SM, et al (1991) Magnetic resonance imaging in schizophrenia. I. Volumetric analysis of brain and cerebrospinal fluid. Arch Gen Psychiatry 48:407–412PubMedGoogle Scholar
  31. Haug JO (1962) Pneumoencephalographic studies in mental disease. Acta Psychiatr Scand 38 (Suppl) 165:1–114Google Scholar
  32. Hecker E (1871) Die Hebephrenia. Arch Pathol Anat Physiol Klin Med 52:394Google Scholar
  33. Heckers S, Heinsen H, Beckmann H (1991) Hippocampal neuron number in schizophrenia. A stereologic study. Arch Gen Psychiatry 48:1002–1008PubMedGoogle Scholar
  34. Huber G (1957) Pneumoencephalographische und psychopathologische Bilder bei endogenen Psychosen. Springer, Berlin Heidelberg New YorkGoogle Scholar
  35. Hyde TM, Casanova MF, Kleinman JE, et al (1991) Neuroanatomical and neurochemical pathology in schizophrenia. In: Tasman A, Goldfinger S (eds) American Psychiatric Press Review of Psychiatry, vol 10. American Psychiatric Association Press, Washington, DC, pp 7–23Google Scholar
  36. Iacono WG, Smith GN, Moreau M, et al (1988) Ventricular and sulcal size at the onset of psychosis. Am J Psychiatry 145: 820–824PubMedGoogle Scholar
  37. Ingvar DH, Franzen G (1974a) Abnormalities of cerebral blood flow distribution in patients with chronic schizophrenia. Acta Psychiatr Scand 50:425–462PubMedGoogle Scholar
  38. Ingvar DH, Franzen G (1974b) Distribution of cerebral activity in chronic schizophrenia. Lancet 2:1484–1486CrossRefPubMedGoogle Scholar
  39. Illowsky BP, Juliano DM, Bigelow LB, Weinberger DR (1988) Stability of CT scan findings in schizophrenia: results of an 8-year follow-up study. J Neurol Neurosurg Psychiatry 51:209–213PubMedGoogle Scholar
  40. Jacobi W, Winkler H (1927) Encephalographische studien an chronisch schizophrenen. Arch Psychiatr Nervenkr 81: 299–332CrossRefGoogle Scholar
  41. Jakob H, Beckmann H (1986) Prenatal developmental disturbances in the limbic allocortex in schizophrenics. J Neural Transm 65:303–326CrossRefPubMedGoogle Scholar
  42. Jeste DV, Lohr JB (1989) Hippocampal pathologic findings in schizophrenia. Arch Gen Psychiatry 46:1019–1024PubMedGoogle Scholar
  43. Johnstone EC, Crow TJ, Frith CD, et al (1976) Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet 2:924–926CrossRefPubMedGoogle Scholar
  44. Kelsoe JR, Cadet JL, Pickar D, et al (1988) Quantitative neuroanatomy in schizophrenia. Arch Gen Psychiatry 45:533–541PubMedGoogle Scholar
  45. Kovelman JA, Scheibel AB (1984) A neurohistological correlate of schizophrenia. Biol Psychiatry 19:1601–1621PubMedGoogle Scholar
  46. Kraepelin E (1919) Dementia Praecox and paraphrenia (transl by Barclay RM; edited by Robertson GM). Facsimile Edition, Krieger, Huntington, NY, 1971Google Scholar
  47. Lemke R (1935) Untersuchung über die soziale Prognose der Schizophrenie unter besonderer Berücksichtigung des encephalographischen Befundes. Arch Psychiatr Nervenkr 104: 89–136CrossRefGoogle Scholar
  48. Lichtheim L (1885) On aphasia. Brain 7:433–484Google Scholar
  49. Liddle PF, Friston KJ, Frith CD, et al (1992) Patterns of cerebral blood flow in schizophrenia. Br J Psychiatry 160:179–186PubMedGoogle Scholar
  50. Marsh L, Suddath RL, Higgins N, Weinberger DR (1993) Medial temporal lobe structures in schizophrenia: lack of correlation between size reduction and normal age-related changes. Schizophr ResGoogle Scholar
  51. Nauta WJH, Domesick VB (1982) Neuronal associations of the limbic system. Neural Basis Behav 10:175–206Google Scholar
  52. Nyback H, Wiesel FA, Berggren BM (1982) Computed tomography of the brain in patients with acute psychosis and in healthy volunteers. Acta Psychiatr Scand 65:403–414PubMedGoogle Scholar
  53. Pakkenberg B (1987) Post-mortem study of chronic schizophrenic brains. Br J Psychiatry 151:744–752PubMedGoogle Scholar
  54. Penfield W, Rasmussen T (1950) The cerebral cortex of man. MacMillan, New YorkGoogle Scholar
  55. Rakic P (1988) Specification of cerebral cortical areas. Science 241:170–176PubMedGoogle Scholar
  56. Reveley AM, Reveley MA, Clifford CA, et al (1982) Cerebral ventricular size in twins discordant for schizophrenia. Lancet 2: 540–541CrossRefPubMedGoogle Scholar
  57. Roberts GW, Colter N, Lofthouse R, et al (1986) Gliosis in schizophrenia. Biol Psychiatry 21:1043–1050CrossRefPubMedGoogle Scholar
  58. Scheibel AB, Kovelman JA (1981) Disorientation of the hippocampal pyramidal cell and its processes in the schizophrenic patient. Biol Psychiatry 16:101–102Google Scholar
  59. Schulz SC, Koller MM, Kishore PR, et al 81983) Ventricular enlargement in teenage patients with schizophrenia spectrum disorders. Am J Psychiatry 140:1592–1595Google Scholar
  60. Shenton ME, Kikinis R, Jolesz FA, et al (1992) Abnormalities of the left temporal lobe and thought disorder in schizophrenia: a quantitative magnetic resonance imaging study. N Engl J Med 327:604–612PubMedGoogle Scholar
  61. Sponheim SR, Iacono WG, Beiser M (1991) Stability of ventricular size after the onset of psychosis in schizophrenia. Psychiatr Res 40:21–29CrossRefGoogle Scholar
  62. Stevens JR (1982) The neuropathology of schizophrenia. Arch Gen Psychiatry 39:1131–1139PubMedGoogle Scholar
  63. Storey PB (1966) Lumbar air encephalography in chronic schizophrenia: a controlled experiment. Br J Psychiatry 112:135–144PubMedGoogle Scholar
  64. Suddath R, Casanova MF, Goldberg TE, et al (1989) Temporal lobe pathology in schizophrenia: a quantitative magnetic resonance imaging study. Am J Psychiatry 146:464–472PubMedGoogle Scholar
  65. Suddath R, Christison GW, Torrey EF, et al (1990) Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. N Engl J Med 322:789–794PubMedGoogle Scholar
  66. Tamminga CA, Burrows GH, Chase TN, Alphs LD, Thaker GK (1988) Dopamine neuronal tracts in schizophrenia: their pharmacology and in vivo metabolism. In: Kalivas PW, Nemeroff CB (eds) The Mesocortical Dopamine System, vol 537. Ann NY Acad Sci, New YorkGoogle Scholar
  67. Weinberger DR (1993) A connectionist approach to the prefrontal cortex. J Neuropsychiatry Clin Neurosci 5:241–253PubMedGoogle Scholar
  68. Weinberger DR (1995) Neurodevelopmental perspectives on schizophrenia. In: Bloom F, Kupfer D (eds) Psychopharmacology: a fourth generation of progress. Raven Press, New York, pp 1171–1183Google Scholar
  69. Weinberger DR, DeLisi LE, Neophytides AN, Wyatt RJ (1981) Familial aspects of CT scan abnormalities in chronic schizophrenia patients. Psychiatry Res 4:65–71CrossRefPubMedGoogle Scholar
  70. Weinberger DR, DeLisi L, Perman GP, et al (1982) Computed tomography in schizophreniform disorder and other acute psychiatric disorders. Arch Gen Psychiatry 39:778–793PubMedGoogle Scholar
  71. Weinberger DR, Wagner RL, Wyatt RJ (1983) Neuropathologic studies of schizophrenia: a selective review. Schizophr Bull 9: 193–212PubMedGoogle Scholar
  72. Weinberger DR, Berman KF, Zec RF (1986) Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. regional cerebral blood flow evidence. Arch Gen Psychiatry 43: 114–124PubMedGoogle Scholar
  73. Weinberger DR, Berman KF, Suddath R, Torrey EF (1992) Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins. Am J Psychiatry 149:890–897PubMedGoogle Scholar
  74. Wernicke C (1874) Der aphasische Symptomencomplex. Cohn and Weigert, BreslauGoogle Scholar
  75. Wiesel FA, Wik G, Sjogren I, et al (1987) Regional brain glucose metabolism in drug-free schizophrenic patients and clinical correlates. Acta Psychiatr Scand 76:628–641PubMedGoogle Scholar
  76. Young AH, Blackwood DHR, Roxborough H, et al (1991) A magnetic resonance imaging study of schizophrenia: brain structure and clinical symptoms. Br J Psychiatry 158:158–164PubMedGoogle Scholar
  77. Zigun JR, Weinberger DR (1992) In vivo studies of brain morphology in schizophrenia. In: Lindemayer JP, Kay SR (eds) New biological vistas on schizophrenia. Brunner/Mazel, New York, pp 57–81Google Scholar
  78. Zipursky RB, Lim KO, Sullivan EV, et al (1992) Widespread cerebral gray matter volume deficits in schizophrenia. Arch Gen Psychiatry 49:195–205PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Michael B. Knable
    • 1
  • Daniel R. Weinberger
    • 1
  1. 1.National Institute of Mental HealthNational Institutes of Health, Intramural Research Program, Clinical Brain Disorders BranchWashington, D.C.USA

Personalised recommendations