What happens in the brain of schizophrenia patients?: An investigation from the viewpoint of neuropathology

Nagoya Journal of Medical Science

Volumn 76, Issue 1-2, 2014, Pages 11-28

  Iritani, Shuji ^a  

^a NAGOYA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

Neurodevelopmental hypothesis; Neuropathology; Postmortem brain; Schizophrenia

Indexed keywords

EID: 84897870018     PISSN: 00277622     EISSN: 21863326     Source Type: Journal    
DOI: None     Document Type: Article

References (114)

1. Alzheimer A. Beiträge zur Pathologischen Anatomie der Hirnrinde und zur anatomiscen Grundlage der Psychozen. Mschr Psychiat Neurol 1897; 2: 82-120.
2. Tatetsu S. A contribution of the morphological Background of Schizophrenia, with special reference to the findings in the telencephalon. Acta Neuropathologica 1960; 3: 558-71.
3. Shenton ME, Dickey CC, Frumin M, McCarley RW. A review of MRI findings in schizophrenia. Schizophr Res 2001; 49: 1-52.
4. Dickey CC, Salisbury DF, Nagy AI, et al. Follow-up MRI study of prefrontal volumes in first-episode psychotic patients. Schizophr Res 2004; 71: 349-51.
5. Bogerts B, Meertz E, Schonfeldt-Bausch R. Basal ganglia and limbic system pathology in schizophrenia. A morphometric study of brain volume and shrinkage. Arch Gen Psychiatry 1985; 42: 784-91.
6. Bogerts B, Falkai P, Haupts M, et al. Post-mortem volume measurements of limbic system and basal ganglia structures in chronic schizophrenics. Initial results from a new brain collection. Schizophr Res 1990; 3: 295-301.
7. Altshuler LL, Casanova MF, Goldberg TE, Kleinman JE. The hippocampus and parahippocampus in schizophrenia, suicide, and control brains. Arch Gen Psychiatry 1990; 47: 1029-34.
8. Heckers S, Heinsen H, Heinsen YC, Beckmann H. Limbic structures and lateral ventricle in schizophrenia. A quantitative postmortem study. Arch Gen Psychiatry 1990; 47: 1016-22.
9. Heckers S, Heinsen H, Heinsen Y, Beckmann H. Cortex, white matter, and basal ganglia in schizophrenia: a volumetric postmortem study. Biol Psychiatry 1991; 29: 556-66.
10. Colter N, Battal S, Crow TJ, et al. White matter reduction in the parahippocampal gyrus of patients with schizophrenia. Arch Gen Psychiatry 1987; 44: 1023.
11. Benes FM, Kwok EW, Vincent SL, Todtenkopf MS. A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives. Biol Psychiatry 1998; 44: 88-97.
12. Casanova MF, Carosella N, Kleinman JE. Neuropathological findings in a suspected case of childhood schizophrenia. J Neuropsychiatry Clin Neurosci 1990; 2: 313-9.
13. Arnold SE, Hyman BT, Van Hoesen GW, Damasio AR. Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia. Arch Gen Psychiatry 1991a; 48: 625-32.
14. Conrad AH, Clark WA, Conrad GW. Subcellular compartmentalization of myosin isoforms in embryonic chick heart ventricle myocytes during cytokinesis. Cell Motil Cytoskeleton 1991; 19: 189-206.
15. Akbarian S, Vinuela A, Kim JJ, et al. Distorted distribution of nicotinamide-adenine dinucleotide phosphatediaphorase neurons in temporal lobe of schizophrenics implies anomalous cortical development. Arch Gen Psychiatry 1993b; 50: 178-87.
16. Benes FM, Davidson J, Bird ED. Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics. Arch Gen Psychiatry 1986; 43: 31-5.
17. Arnold SE, Franz BR, Gur RC, et al. Smaller neuron size in schizophrenia in hippocampal subfields that mediate cortical-hippocampal interactions. Am J Psychiatry 1995; 152: 738-48.
18. Benes FM, McSparren J, Bird ED, et al. Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients. Arch Gen Psychiatry 1991; 48: 996-1001.
19. Benes FM, Majocha R, Bird ED, Marotta CA. Increased vertical axon numbers in cingulate cortex of schizophrenics. Arch Gen Psychiatry 1987b; 44: 1017-21.
20. Chana G, Landau S, Beasley C, et al. Two-dimensional assessment of cytoarchitecture in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia: evidence for decreased neuronal somal size and increased neuronal density. Biol Psychiatry 2003; 53: 1086-98.
21. Benes FM, Bird ED. An analysis of the arrangement of neurons in the cingulate cortex of schizophrenic patients. Arch Gen Psychiatry 1987a; 44: 608-16.
22. Akbarian S, Bunney WE, Jr., Potkin SG, et al. Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development. Arch Gen Psychiatry 1993a; 50: 169-77.
23. Harrison PJ. The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain 1999; 122 (Pt 4): 593-624.
24. Mathalon DH, Sullivan EV, Lim KO, Pfefferbaum A. Progressive brain volume changes and the clinical course of schizophrenia in men: a longitudinal magnetic resonance imaging study. Arch Gen Psychiatry 2001; 58: 148-57.
25. Honea R, Crow TJ, Passingham D, Mackay CE. Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies. Am J Psychiatry 2005; 162: 2233-45.
26. Keilhoff G, Bernstein HG, Becker A, et al. Increased neurogenesis in a rat ketamine model of schizophrenia. Biol Psychiatry 2004; 56: 317-22.
27. van Haren NE, Hulshoff Pol HE, Schnack HG, et al. Focal gray matter changes in schizophrenia across the course of the illness: a 5-year follow-up study. Neuropsychopharmacology 2007; 32: 2057-66.
28. Iritani S, Kuroki N, Ikeda K, Kazamatsuri H. Calbindin immunoreactivity in the hippocampal formation and neocortex of schizophrenics. Prog Neuropsychopharmacol Biol Psychiatry 1999; 23: 409-21.
29. Iritani S, Kuroki N, Niizato K, Ikeda K. Morphological changes in neuropeptide Y-positive fiber in the hippocampal formation of schizophrenics. Prog Neuropsychopharmacol Biol Psychiatry 2000; 24: 241-9.
30. Arnold SE, Trojanowski JQ. Recent advances in defining the neuropathology of schizophrenia. Acta Neuropathol 1996; 92: 217-31.
31. Olin SC, Mednick SA, Cannon T, et al. School teacher ratings predictive of psychiatric outcome 25 years later. Br J Psychiatry Suppl 1998; 172: 7-13.
32. Davidson M, Chen W, Wilce PA. Behavioral analysis of PTZ-kindled rats after acute and chronic ethanol treatments. Pharmacol Biochem Behav 1999; 64: 7-13.
33. Niemi LT, Suvisaari JM, Tuulio-Henriksson A, Lonnqvist JK. Childhood developmental abnormalities in schizophrenia: evidence from high-risk studies. Schizophr Res 2003; 60: 239-58.
34. Gourion D, Goldberger C, Bourdel MC, et al. Minor physical anomalies in patients with schizophrenia and their parents: prevalence and pattern of craniofacial abnormalities. Psychiatry Res 2004; 125: 21-8.
35. Lewis DA, Levitt P. Schizophrenia as a disorder of neurodevelopment. Annu Rev Neurosci 2002; 25: 409-32.
36. Kunugi H, Vallada HP, Sham PC, et al. Catechol-O-methyltransferase polymorphisms and schizophrenia: a transmission disequilibrium study in multiply affected families. Psychiatr Genet 1997; 7: 97-101.
37. Price G, Cercignani M, Bagary MS, et al. A volumetric MRI and magnetization transfer imaging follow-up study of patients with first-episode schizophrenia. Schizophr Res 2006; 87: 100-8.
38. Tsuang DW, Faraone SV, Tsuang MT. Genetic counseling for psychiatric disorders. Curr Psychiatry Rep 2001; 3: 138-43.
39. Huttunen MO, Machon RA, Mednick SA. Prenatal factors in the pathogenesis of schizophrenia. Br J Psychiatry Suppl 199415-9.
40. Benes FM. Neurobiological investigations in cingulate cortex of schizophrenic brain. Schizophr Bull 1993; 19: 537-49.
41. Hong CJ, Yu YW, Lin CH, Tsai SJ. An association study of a brain-derived neurotrophic factor Val66Met polymorphism and clozapine response of schizophrenic patients. Neurosci Lett 2003; 349: 206-8.
42. Agartz I, Sedvall GC, Terenius L, et al. BDNF gene variants and brain morphology in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2006; 141B: 513-23.
43. Selemon LD, Rajkowska G, Goldman-Rakic PS. Abnormally high neuronal density in the schizophrenic cortex. A morphometric analysis of prefrontal area 9 and occipital area 17. Arch Gen Psychiatry 1995; 52: 805-18; discussion 19-20.
44. Glantz LA, Lewis DA. Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry 2000; 57: 65-73.
45. Glantz LA, Gilmore JH, Lieberman JA, Jarskog LF. Apoptotic mechanisms and the synaptic pathology of schizophrenia. Schizophr Res 2006; 81: 47-63.
46. Arnold SE, Lee VM, Gur RE, Trojanowski JQ. Abnormal expression of two microtubule-associated proteins (MAP2 and MAP5) in specific subfields of the hippocampal formation in schizophrenia. Proc Natl Acad Sci U S A 1991b; 88: 10850-4.
47. Browning MD, Dudek EM, Rapier JL, et al. Significant reductions in synapsin but not synaptophysin specific activity in the brains of some schizophrenics. Biol Psychiatry 1993; 34: 529-35.
48. Eastwood SL, Harrison PJ. Decreased synaptophysin in the medial temporal lobe in schizophrenia demonstrated using immunoautoradiography. Neuroscience 1995; 69: 339-43.
49. Harrison PJ, Eastwood SL. Preferential involvement of excitatory neurons in medial temporal lobe in schizophrenia. Lancet 1998; 352: 1669-73.
50. Young CE, Arima K, Xie J, et al. SNAP-25 deficit and hippocampal connectivity in schizophrenia. Cereb Cortex 1998; 8: 261-8.
51. Eastwood SL, Harrison PJ. Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs. Mol Psychiatry 2000; 5: 425-32.
52. Talbot K, Eidem WL, Tinsley CL, et al. Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia. J Clin Invest 2004; 113: 1353-63.
53. Eastwood SL, Harrison PJ. Decreased expression of vesicular glutamate transporter 1 and complexin II mRNAs in schizophrenia: further evidence for a synaptic pathology affecting glutamate neurons. Schizophr Res 2005; 73: 159-72.
54. Sawada K, Barr AM, Nakamura M, et al. Hippocampal complexin proteins and cognitive dysfunction in schizophrenia. Arch Gen Psychiatry 2005; 62: 263-72.
55. Kolomeets NS, Orlovskaya DD, Rachmanova VI, Uranova NA. Ultrastructural alterations in hippocampal mossy fiber synapses in schizophrenia: a postmortem morphometric study. Synapse 2005; 57: 47-55.
56. Aganova EA, Uranova NA. Morphometric analysis of synaptic contacts in the anterior limbic cortex in the endogenous psychoses. Neurosci Behav Physiol 1992; 22: 59-65.
57. Perrone-Bizzozero NI, Sower AC, Bird ED, et al. Levels of the growth-associated protein GAP-43 are selectively increased in association cortices in schizophrenia. Proc Natl Acad Sci U S A 1996; 93: 14182-7.
58. Benes FM, Todtenkopf MS, Taylor JB. Differential distribution of tyrosine hydroxylase fibers on small and large neurons in layer II of anterior cingulate cortex of schizophrenic brain. Synapse 1997; 25: 80-92.
59. Gabriel SM, Haroutunian V, Powchik P, et al. Increased concentrations of presynaptic proteins in the cingulate cortex of subjects with schizophrenia. Arch Gen Psychiatry 1997; 54: 559-66.
60. Honer WG, Falkai P, Young C, et al. Cingulate cortex synaptic terminal proteins and neural cell adhesion molecule in schizophrenia. Neuroscience 1997; 78: 99-110.
61. Glantz LA, Lewis DA. Reduction of synaptophysin immunoreactivity in the prefrontal cortex of subjects with schizophrenia. Regional and diagnostic specificity. Arch Gen Psychiatry 1997; 54: 660-9.
62. Garey LJ, Ong WY, Patel TS, et al. Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. J Neurol Neurosurg Psychiatry 1998; 65: 446-53.
63. Thompson PM, Sower AC, Perrone-Bizzozero NI. Altered levels of the synaptosomal associated protein SNAP-25 in schizophrenia. Biol Psychiatry 1998; 43: 239-43.
64. Woo TU, Whitehead RE, Melchitzky DS, Lewis DA. A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia. Proc Natl Acad Sci U S A 1998; 95: 5341-6.
65. Karson CN, Mrak RE, Schluterman KO, et al. Alterations in synaptic proteins and their encoding mRNAs in prefrontal cortex in schizophrenia: a possible neurochemical basis for 'hypofrontality'. Mol Psychiatry 1999; 4: 39-45.
66. Honer WG, Falkai P, Chen C, et al. Synaptic and plasticity-associated proteins in anterior frontal cortex in severe mental illness. Neuroscience 1999; 91: 1247-55.
67. Pierri JN, Chaudry AS, Woo TU, Lewis DA. Alterations in chandelier neuron axon terminals in the prefrontal cortex of schizophrenic subjects. Am J Psychiatry 1999; 156: 1709-19.
68. Ohnuma T, Kato H, Arai H, et al. Gene expression of PSD95 in prefrontal cortex and hippocampus in schizophrenia. Neuroreport 2000; 11: 3133-7.
69. Benes FM, Todtenkopf MS, Logiotatos P, Williams M. Glutamate decarboxylase(65)-immunoreactive terminals in cingulate and prefrontal cortices of schizophrenic and bipolar brain. J Chem Neuroanat 2000; 20: 259-69.
70. Volk DW, Pierri JN, Fritschy JM, et al. Reciprocal alterations in pre-and postsynaptic inhibitory markers at chandelier cell inputs to pyramidal neurons in schizophrenia. Cereb Cortex 2002; 12: 1063-70.
71. Toyooka K, Iritani S, Makifuchi T, et al. Selective reduction of a PDZ protein, SAP-97, in the prefrontal cortex of patients with chronic schizophrenia. J Neurochem 2002; 83: 797-806.
72. Halim ND, Weickert CS, McClintock BW, et al. Presynaptic proteins in the prefrontal cortex of patients with schizophrenia and rats with abnormal prefrontal development. Mol Psychiatry 2003; 8: 797-810.
73. Konopaske GT, Sweet RA, Wu Q, et al. Regional specificity of chandelier neuron axon terminal alterations in schizophrenia. Neuroscience 2006; 138: 189-96.
74. Roberts RC, Roche JK, Conley RR. Synaptic differences in the patch matrix compartments of subjects with schizophrenia: a postmortem ultrastructural study of the striatum. Neurobiol Dis 2005; 20: 324-35.
75. Okabe S, Collin C, Auerbach JM, et al. Hippocampal synaptic plasticity in mice overexpressing an embryonic subunit of the NMDA receptor. J Neurosci 1998; 18: 4177-88.
76. Grant SG. Synapse signalling complexes and networks: machines underlying cognition. Bioessays 2003; 25: 1229-35.
77. Owens DF, Kriegstein AR. Developmental neurotransmitters?. Neuron 2002; 36: 989-91.
78. Zakzanis KK, Hansen KT. Dopamine D2 densities and the schizophrenic brain. Schizophr Res 1998; 32: 201-6.
79. Harrison PJ, Burnet PW. The 5-HT2A (serotonin2A) receptor gene in the aetiology, pathophysiology and pharmacotherapy of schizophrenia. J Psychopharmacol 1997; 11: 18-20.
80. Burnet PW, Eastwood SL, Harrison PJ. 5-HT1A and 5-HT2A receptor mRNAs and binding site densities are differentially altered in schizophrenia. Neuropsychopharmacology 1996; 15: 442-55.
81. Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 1991; 148: 1301-8.
82. Kerwin R, Patel S, Meldrum B. Quantitative autoradiographic analysis of glutamate binding sites in the hippocampal formation in normal and schizophrenic brain post mortem. Neuroscience 1990; 39: 25-32.
83. Porter RH, Eastwood SL, Harrison PJ. Distribution of kainate receptor subunit mRNAs in human hip pocampus, neocortex and cerebellum, and bilateral reduction of hippocampal GluR6 and KA2 transcripts in schizophrenia. Brain Res 1997; 751: 217-31.
84. Harrison PJ, Weinberger DR. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 2005; 10: 40-68; image 5.
85. Ozeki Y, Tomoda T, Kleiderlein J, et al. Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth. Proc Natl Acad Sci U S A 2003; 100: 289-94.
86. Kamiya A, Kubo K, Tomoda T, et al. A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development. Nat Cell Biol 2005; 7: 1167-78.
87. Numakawa T, Yagasaki Y, Ishimoto T, et al. Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia. Hum Mol Genet 2004; 13: 2699-708.
88. Hashimoto R, Straub RE, Weickert CS, et al. Expression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in schizophrenia. Mol Psychiatry 2004; 9: 299-307.
89. Ohnishi T, Hashimoto R, Mori T, et al. The association between the Val158Met polymorphism of the catechol-O-methyl transferase gene and morphological abnormalities of the brain in chronic schizophrenia. Brain 2006; 129: 399-410.
90. Mirnics K, Middleton FA, Stanwood GD, et al. Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia. Mol Psychiatry 2001; 6: 293-301.
91. Varnas K, Lawyer G, Jonsson EG, et al. Brain-derived neurotrophic factor polymorphisms and frontal cortex morphology in schizophrenia. Psychiatr Genet 2008; 18: 177-83.
92. Wassink TH, Nopoulos P, Pietila J, et al. NOTCH4 and the frontal lobe in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2003; 118B: 1-7.
93. Corfas G, Roy K, Buxbaum JD. Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia. Nat Neurosci 2004; 7: 575-80.
94. Lemke G. Neuregulin-1 and myelination. Sci STKE 2006; 2006: pe11.
95. McInnes LA, Lauriat TL. RNA metabolism and dysmyelination in schizophrenia. Neurosci Biobehav Rev 2006; 30: 551-61.
96. Chowdari KV, Mirnics K, Semwal P, et al. Association and linkage analyses of RGS4 polymorphisms in schizophrenia. Hum Mol Genet 2002; 11: 1373-80.
97. Ashe PC, Berry MD, Boulton AA. Schizophrenia, a neurodegenerative disorder with neurodevelopmental antecedents. Prog Neuropsychopharmacol Biol Psychiatry 2001; 25: 691-707.
98. Jonsson EG, Edman-Ahlbom B, Sillen A, et al. Brain-derived neurotrophic factor gene (BDNF) variants and schizophrenia: an association study. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 924-33.
99. Pezawas L, Verchinski BA, Mattay VS, et al. The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology. J Neurosci 2004; 24: 10099-102.
100. Iritani S, Niizato K, Nawa H, et al. Immunohistochemical study of brain-derived neurotrophic factor and its receptor, TrkB, in the hippocampal formation of schizophrenic brains. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27: 801-7.
101. Ikeda M, Hikita T, Taya S, et al. Identification of YWHAE, a gene encoding 14-3-3epsilon, as a possible susceptibility gene for schizophrenia. Hum Mol Genet 2008; 17: 3212-22.
102. Taya S, Shinoda T, Tsuboi D, et al. DISC1 regulates the transport of the NUDEL/LIS1/14-3-3epsilon complex through kinesin-1. J Neurosci 2007; 27: 15-26.
103. Sekiguchi H, Iritani S, Habuchi C, et al. Impairment of the tyrosine hydroxylase neuronal network in the orbitofrontal cortex of a genetically modified mouse model of schizophrenia. Brain Res 2011; 1392: 47-53.
104. Carter CS, Barch DM, Buchanan RW, et al. Identifying cognitive mechanisms targeted for treatment development in schizophrenia: an overview of the first meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia Initiative. Biol Psychiatry 2008; 64: 4-10.
105. Kerns JG, Nuechterlein KH, Braver TS, Barch DM. Executive functioning component mechanisms and schizophrenia. Biol Psychiatry 2008; 64: 26-33.
106. Jellinger KA, Gabriel E. No increased incidence of Alzheimer's disease in elderly schizophrenics. Acta Neuropathol 1999; 97: 165-9.
107. Mirra SS, Heyman A, McKeel D, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 1991; 41: 479-86.
108. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991; 82: 239-59.
109. Powchik P, Davidson M, Haroutunian V, et al. Postmortem studies in schizophrenia. Schizophr Bull 1998; 24: 325-41.
110. Purohit DP, Perl DP, Haroutunian V, et al. Alzheimer disease and related neurodegenerative diseases in elderly patients with schizophrenia: a postmortem neuropathologic study of 100 cases. Arch Gen Psychiatry 1998; 55: 205-11.
111. Wisniewski HM, Constantinidis J, Wegiel J, et al. Neurofibrillary pathology in brains of elderly schizophrenics treated with neuroleptics. Alzheimer Dis Assoc Disord 1994; 8: 211-27.
112. Gong CX, Shaikh S, Grundke-Iqbal I, Iqbal K. Inhibition of protein phosphatase-2B (calcineurin) activity towards Alzheimer abnormally phosphorylated tau by neuroleptics. Brain Res 1996; 741: 95-102.
113. Wischik CM, Edwards PC, Lai RY, et al. Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines. Proc Natl Acad Sci U S A 1996; 93: 11213-8.
114. Higaki J, Murphy GM, Jr., Cordell B. Inhibition of beta-amyloid formation by haloperidol: a possible mechanism for reduced frequency of Alzheimer's disease pathology in schizophrenia. J Neurochem 1997; 68: 333-6.