In Situ/Histological Approaches to Neurotransmitter-Specific Postmortem Brain Studies of Schizophrenia

  • Susan E. Bachus
  • Joel E. Kleinman
Part of the Neurobiological Foundation of Aberrant Behaviors book series (NFAB, volume 4)

Abstract

To bridge the gulf between genetic vulnerability and clinical phenomenology we are obliged to understand gene expression and protein function at the cellular level of resolution. In situ postmortem methods, which merge the advantages of neurochemical specification and neuroanatomical localization, can enable this objective. Our ability to visualize and measure proteins by immunocytochemistry, neurotransmitter receptors with quantitative receptor autoradiography, and mRNA levels with in situ hybridization histochemistry, is presented, both in terms of critical methodological considerations, and according to insights these strategies have revealed into the neuropathology of schizophrenia. The greatest challenge now facing us is the synthesis of this wealth of findings into a coherent account of a dysfunctional neuroanatomically and neurochemically specified circuit subserving the pathophysiology of schizophrenia. The potential for multiple-labeling with in situ methods may aid in the reconstruction of this circuit from the connections between the microscopic elements of neuropathology.

Keywords

Prefrontal Cortex Hybridization Histochemistry Bioi Psychiatry Dopamine Hypothesis Schizophrenic Brain 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Akbarian S, Bunney WE Jr, Potkin SG, Wigal, SB, Hagman JO, Sandman CA, Jones, EG. Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development.Google Scholar
  2. Arch Gen Psychiatry 1993a;50: 169–177.Google Scholar
  3. Akbarian S, Vinuela A, Kim JJ, Potkin SG, Bunney WE Jr, Jones EG. Distorted distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in temporal lobe of schizophrenics implies anomalous cortical development. Arch Gen Psychiatry 1993b; 50: 178–187.PubMedCrossRefGoogle Scholar
  4. Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzoli A, Bunney WE Jr, Jones EG. Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatry 1995; 52: 258–266.PubMedCrossRefGoogle Scholar
  5. Akbarian S, Kim JJ, Potkin SG, Hetrick WP, Burney WE Jr, Jones EG. Maldistribution of interstitial neurons in prefrontal white matter of the brains of schizophrenic patients. Arch Gen Psychiatry 1996a; 53: 425–436.PubMedCrossRefGoogle Scholar
  6. Akbarian S, Sucher NJ, Bradley D, Tafazzoli A, Trinh D, Hetrick WP, Potkin SGGoogle Scholar
  7. Sandman CA, Bunney WE Jr, Jones EG. Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics. J Neurosci 1996b; 16: 19–30.PubMedGoogle Scholar
  8. Akil H, Watson SJ. Science and the future of psychiatry. Arch Gen Psychiatry 2000; 57: 8687.CrossRefGoogle Scholar
  9. Akil M, Pieni JN, Whitehead RE, Edgar CL, Mohila C, Sampson AR, Lewis DA. Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects. Am J Psychiatry 1999; 156: 1580–1589.PubMedGoogle Scholar
  10. Akil M, Edgar CL, Pierri JN, Casali S, Lewis DA. Decreased density of tyrosine hydroxylase-immunoreactive axons in the entorhinal cortex of schizophrenic subjects. Biol Psychiatry 2000; 47: 361–370.PubMedCrossRefGoogle Scholar
  11. Altshuler LL, Conrad A, Kovelman JA, et al. Hippocampal pyramidal cell orientation in schizophrenia. A controlled neurohistologic study of the Yakovlev Collection. Arch Gen Psychiatry 1987; 44: 1094–1098.PubMedCrossRefGoogle Scholar
  12. Alzheimer A. Beiträge zur pathologischen Anatomie der Dementia praecox. Allgemeine Zeitschrift fir Psychiatrie and Psychisch-Gerichtliche Medizin 1913; 7: 810–812.Google Scholar
  13. Andreasen NC, Arndt S, Swayze V II, Cizadlo T, Flaum M, O’Leary D, Ehrhardt JC, Yuh WT. Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging. Science 1994; 266: 294–8.PubMedCrossRefGoogle Scholar
  14. Arnold SE. Cellular and molecular neuropathology of the parahippocampal region in schizophrenia. Ann N Y Acad Sci 2000; 911: 275–292.PubMedCrossRefGoogle Scholar
  15. Arnold SE, Gur RE, Shapiro RM, Fisher KR, Moberg PJ, Gibney MR, Gur RC, Blackwell P, Trojanowski JQ. Prospective clinicopathologic studies of schizophrenia: Accrual and assessment of patients. Am J Psychiatry 1995; 152: 731–737.PubMedGoogle Scholar
  16. Bachus SE, Kleinman JE. The neuropathology of schizophrenia. J Clin Psychiatry 1996; 57 [Suppl. 1 I]: 72–83.PubMedGoogle Scholar
  17. Bachus SE, Hyde TM, Herman MM, Egan MF, Kleinman JE. Abnormal cholecystokinin mRNA levels in entorhinal cortex of schizophrenics. J Psychiatr Res 1997; 31: 233–256.PubMedCrossRefGoogle Scholar
  18. Baldino F Jr, Chesselet M-F, Lewis ME. High resolution in situ hybridization histochemistry. Methods Enzymol 1989; 168: 761–777.PubMedCrossRefGoogle Scholar
  19. Bankfalvi A, Navabi H, Bier B, Böcker W, Jasani B, Schmid KW. Wet autoclave pretreatment for antigen retrieval in diagnostic immunohistochemistry. J Pathol 1994; 174: 223–228.PubMedCrossRefGoogle Scholar
  20. Barton AJL, Pearson RCA, Najlerahim A, Harrison PJ. Pre-and postmortem influences on brain RNA. J Neurochem 1993; 61: 1–11.PubMedCrossRefGoogle Scholar
  21. Beasley CL, Reynolds GP. Parvalbumin-immunoreactive neurons are reduced in the prefrontal cortex of schizophrenics. Schizophr Res 1997; 24: 349–355.PubMedCrossRefGoogle Scholar
  22. Benes FM. What an archaeological dig can tell us about macro-and microcircuitry in brains of schizophrenia subjects. Schizophr Bull 1997; 23: 503–507.PubMedCrossRefGoogle Scholar
  23. Benes FM. Emerging principles of altered neural circuitry in schizophrenia. Brain Res Rev 2000; 31: 251–269.PubMedCrossRefGoogle Scholar
  24. Benes FM, Vincent SL, SanGiovanni SP. High resolution imaging of receptor binding in analyzing neuropsychiatric diseases. Biotechniques 1989; 7: 970–978.PubMedGoogle Scholar
  25. Benes FM, McSparren J, Bird ED, SanGiovanni JP, Vincent SL. Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients. Arch Gen Psychiatry 1991a; 48: 996–1001.PubMedCrossRefGoogle Scholar
  26. Benes FM, Sorensen I, Bird ED. Reduced neuronal size in posterior hippocampus of schizophrenic patients. Schizophr Bull 1991b; 17: 597–608.PubMedCrossRefGoogle Scholar
  27. Benes FM, Sorensen I, Vincent SL, Bird ED, Sathi M. Increased density of glutamateimmunoreactive vertical processes in superficial laminae in cingulate cortex of schizophrenic brain. Cerebr Cortex 1992a; 2: 503–512.CrossRefGoogle Scholar
  28. Benes FM, Vincent SL, Alsterberg G, Bird ED, SanGiovanni JP. Increased GABAA receptor binding in superficial layers of cingulate cortex in schizophrenics. J Neurosci 1992b; 12: 924–929.PubMedGoogle Scholar
  29. Benes FM, Khan Y, Vincent SL, Wickramasinghe R. Differences in the subregional and cellular distribution of GABAA receptor binding in the hippocampal formation of schizophrenic brain. Synapse 1996a; 22: 338–349.PubMedCrossRefGoogle Scholar
  30. Benes FM, Vincent SL, Marie A, Khan Y. Up-regulation of GABAA receptor binding on neurons of the prefrontal cortex in schizophrenic subjects. Neuroscience 1996b; 75: 1021–1031.PubMedCrossRefGoogle Scholar
  31. Benes FM, Wickramasinghe R, Vincent SL, Khan Y, Todtenkopf M. Uncoupling of GABAA and benzodiazepine receptor binding activity in the hippocampal formation of schizophrenic brain. Brain Res 1997; 755: 121–129.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. Berger B, Gaspar P, Vemey C. Dopaminergic innervation of the cerebral cortex: Unexpected differences between rodents and primates. Trends Neurosci 1991;14: 21–27. Bernstein H-G, Stanarius A, Baumann B, Henning H, Krell D, Danos P, Falkai P, BogertsGoogle Scholar
  34. B. Nitric oxide synthase-containing neurons in the human hypothalamus: Reduced number of immunoreactive cells in the paraventricular nucleus of depressive patients and schizophrenics. Neuroscience 1998; 83: 867–875.CrossRefGoogle Scholar
  35. Bertolino A, Nawroz S, Mattay V, Barnett AS, Duyn JH, Moonen CTW, Frank JA, Tedeschi G, Weinberger DR. Regionally specific pattern of neurochemical pathology in schizophrenia as assessed by multislice proton magnetic resonance spectroscopic imaging. Am J Psychiatry 1996; 153: 1554–1563.PubMedGoogle Scholar
  36. Best CJM, Gillespie JW, Englert CR, Swalwell JI, Pfeifer J, Krizman DB, Petricoin EF, Liotta LA, Emmert-Buck MR. New approaches to molecular profiling of tissue samples. Anal Cell Pathol 2000; 20: 1–6.PubMedGoogle Scholar
  37. Bird ED, Barnes J, Iversen LL, Spokes EG, Mackay AVP, Shepherd M. Increased brain dopamine and reduced glutamic acid decarboxylase and choline acetyl transferase activity in schizophrenia and related psychoses. Lancet 1977;ii: 1157–1159.Google Scholar
  38. Bird ED, Spokes EG, Barnes J, Mackay AVP, Iversen LL. Glutamic-acid decarboxylase in schizophrenia. Lancet 1978; I: 156, 1978.Google Scholar
  39. Bogerts B, Häntsch J, Herzer M. A morphometric study of the dopamine-containing cell groups in the mesencephalon of normals, Parkinson patients, and schizophrenics. Biol Psychiatry 1983; 18: 951–960.PubMedGoogle Scholar
  40. Burke WJ, O’Malley KL, Chung HD, Harmon SK, Miller JP, Berg L. Effect of pre-and postmortem variables on specific mRNA levels in human brain. Mol Brain Res 1991; 11: 37–41.PubMedCrossRefGoogle Scholar
  41. Burnet PWJ, Harrison PJ. Substance P (NK1) receptors in the cingulate cortex in unipo-lar and bipolar mood disorder and schizophrenia. Biol Psychiatry 2000; 47: 80–83.PubMedCrossRefGoogle Scholar
  42. Burnet PWJ, Eastwood SL, Harrison PJ. Detection and quantitation of 5-HTia and 5- Htreceptor mRNAs in human hippocampus using a reverse transcriptase- polymerase chain reaction (RT-PCR) technique and their correlation with binding site densities and age. Neurosci Lett 1994; 178: 85–89.PubMedCrossRefGoogle Scholar
  43. Burnet PWJ, Eastwood SL, Harrison PJ. 5-HTia and 5-HT2 receptor mRNAs and binding site densities are differentially altered in schizophrenia. Neuropsychopharmacology 1996; 15: 442–455.PubMedCrossRefGoogle Scholar
  44. Burt DR, Creese I, Snyder SH. Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain. Science 1977; 196: 326–328.PubMedCrossRefGoogle Scholar
  45. Camps M, Cortés R, Gueye B, Probst A, Palacios JM. Dopamine receptors in human brain: Autoradiographic distribution of D2 sites. Neuroscience 1989; 28: 275–290.PubMedCrossRefGoogle Scholar
  46. Caisson A. The dopamine theory revisited. In: Hirsch SR, Weinberger DR (eds). Schizophrenia. Blackwell Science, London, 1995; pp 379–400.Google Scholar
  47. Casanova MF, Kleinman JE. The neuropathology of schizophrenia: A critical assessment of research methodologies. Biol Psychiatry 1990; 27: 353–362.PubMedCrossRefGoogle Scholar
  48. Chen RH, Fuggle SV. In situ cDNA polymerase chain reaction: A novel technique for detecting mRNA expression. Am. J. Pathol. 1993; 143: 1527–1534.Google Scholar
  49. Conti F, Fabri M, Manzoni T. Immunocytochemical evidence for glutamatergic corticocortical connections in monkeys. Brain Res 1988; 462: 148–153.PubMedCrossRefGoogle Scholar
  50. Corder R, Pralong P, Muller AF, Gaillard RC. Regional distribution of neuropeptide Y- like immunoreactivity in human hypothalamus measured by immunoradiometric assay: Possible influence of chronic respiratory failure on tissue levels. Neuroendocrinology 1990; 51: 25–30.CrossRefGoogle Scholar
  51. Cortés R, Probst A, Palacios JM. Quantitative light microscopic autoradiographic localization of cholinergic muscarinic receptors in the human brain: Forebrain. Neuroscience 1987; 20: 65–107.PubMedCrossRefGoogle Scholar
  52. Coulton G. In situ hybridization comes of age. Histochem J 1995;27:1–3.Google Scholar
  53. Court J, Spurden D, Lloyd S, McKeith I, Ballard C, Cairns N, Kerwin R, Perry R, Perry E. Neuronal nicotinic receptors in dementia with Lewy bodies and schizophrenia: a bungarotoxin and nicotine binding in the thalamus. J Neurochem 1999; 73: 1590 1597.Google Scholar
  54. Coyle JT, Draper ES. Molecules and mind: A new home for molecular research in psychiatry. Molecular Psychiatry 1996; 1: 5–6.PubMedGoogle Scholar
  55. Creese I, Burt DR, Snyder SH. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192: 481–483, 1976.PubMedCrossRefGoogle Scholar
  56. Crook JM, Dean B, Pavey G, Copolov D. The binding of [3H]AF-DX 384, is reduced in the caudate-putamen of subjects with schizophrenia. Life Sci 1999; 64: 1761–1771.PubMedCrossRefGoogle Scholar
  57. Crook JM, Tomaskovic-Crook E, Copolov DL, Dean B. Decreased muscarinic receptor binding in subjects with schizophrenia: A study of the human hippocampal formation. Biol Psychiatry 2000; 48: 381–388.Google Scholar
  58. Cross AJ, Crow TJ, Owen F. Gamma-aminobutyric acid in the brain in schizophrenia. 1979;i: 560–561.Google Scholar
  59. Crow Ti, Owen F, Cross AJ, Lofthouse R, Longden A.I. Brain biochemistry in schizophrenia. Lancet 1978a;i: 36–37.Google Scholar
  60. Crow TJ, Owen F, Cross AJ, Lofthouse R, Longden AJ, Joseph MH, Frith CD. Postmortem handling and brain biochemistry. Lancet 1978ó;i: 393–394.Google Scholar
  61. Dagerlind A, Friberg K, Bean AJ, Hökfelt T. Sensitive mRNA detection using unfixed tissue: Combined radioactive and non-radioactive in situ hybridization histochemistry. Histochemistry 1992; 98: 39–49.Google Scholar
  62. Danos P, Baumann B, Bernstein H-G, Franz M, Stauch R, Northoff G, Krell D, Falkai P, Bogerts B. Schizophrenia and anteroventral thalamic nucleus: Selective decrease of parvalbumin-immunoreactive thalamocortical projection neurons. Psychiatry Res Neuroimaging Section 1998; 82: 1–10.CrossRefGoogle Scholar
  63. Davison K. Schizophrenia-like psychoses associated with organic cerebral disorders: A review. Psychiatric Developments 1983; 1: 1–34.Google Scholar
  64. Daviss SR, Lewis DA. Local circuit neurons of the prefrontal cortex in schizophrenia: Selective increase in the density of calbindin-immunoreactive neurons. Psychiatry Res 1995; 59: 81–96.PubMedCrossRefGoogle Scholar
  65. Dean B, Crook JM, Opeskin K, Hill C, Keks N, Copolov DL. The density of muscarinic MI receptors is decreased in the caudate-putamen of subjects with schizophrenia. Molecular Psychiatry 1996; 1: 54–58.PubMedGoogle Scholar
  66. Dean B, Pavey G, Opeskin K. [3H]Raclopride binding to brain tissue from subjects with schizophrenia: Methodological aspects. Neuropharmacology 1997a; 36: 779–786.PubMedCrossRefGoogle Scholar
  67. Dean B, Opeskin K, Pavey G, Hill C, Keks N. Changes in protein kinase C and adenylate cyclase in the temporal lobe from subjects with schizophrenia. J Neural Transm 1997b; 104: 1371–1381.PubMedCrossRefGoogle Scholar
  68. Dean B, Crook JM, Pavey G, Opeskin K, Copolov DL. Muscarinic1 and 2 receptor mRNA in the human caudate-putamen: No change in ml mRNA in schizophrenia. Molecular Psychiatry 2000; 5: 203–207.PubMedCrossRefGoogle Scholar
  69. Dodd PR, Hambley JW, Cowburn RF, Hardy JA. A comparison of methodologies for the study of functional transmitter neurochemistry in human brain. J Neurochem 1988; 50: 1333–1345.PubMedCrossRefGoogle Scholar
  70. Dunlap CB. Dementia praecox. Some Preliminary observations on brains from carefully selected cases, and a consideration of certain sources of error. Am J Psychiatry 1924; 3: 403–421.Google Scholar
  71. Durrant I, Dacre B, Cunningham M. Evaluation of novel formulations of 35S- and 33Plabelled nucleotides for in situ hybridization. Histochem J 1995; 27: 89–93.PubMedCrossRefGoogle Scholar
  72. Dwork Ai. Postmortem studies of the hippocampal formation in schizophrenia.Schizophr Bull 1997; 23: 385–402.Google Scholar
  73. Eastwood SL, Harrison PJ. Detection and quantification of hippocampal synaptophysin messenger RNA in schizophrenia using autoclaved, formalin-fixed, paraffin wax-embedded sections. Neuroscience 1999; 93: 99–106.PubMedCrossRefGoogle Scholar
  74. Eastwood SL, Harrison PJ. Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: A study of complexin mRNAs. Molecular Psychiatry 2000; 5: 425–432.PubMedCrossRefGoogle Scholar
  75. Eastwood SL, McDonald B, Burnet PWJ, Beckwith JP, Kerwin RW, Harrison PJ. Decreased expression of mRNAs encoding non-NMDA glutamate receptors G1uR1 and G1uR2 in medial temporal lobe neurons in schizophrenia. Mol Brain Res 1995; 29: 21 1223.Google Scholar
  76. Eastwood SL, Kerwin RW, Harrison PJ. Immunoautoradiographic evidence for a loss of aamino-3-hydroxy-5-methyl-4-isoxazole propionate-preferring non-N-methyl-Daspartate glutamate receptors within the medial temporal lobe in schizophrenia. Biol Psychiatry 1996; 41: 636–643.CrossRefGoogle Scholar
  77. Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE, Goldman D, Weinberger DR. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA 2001; 98: 6917–6922.PubMedCrossRefGoogle Scholar
  78. Everall I, Harrison PJ. Methodological and stereological considerations in post mortem psychiatric brain research. 2001: This volume.Google Scholar
  79. Fey ET. The performance of young schizophrenics and young normals on the Wisconsin Card Test. J Consult Psychol 1951; 15: 311–319.PubMedCrossRefGoogle Scholar
  80. Fisman M. Brain stem encephalitic lesions and schizophrenia. A report of 3 cases. S Afr Med J 1974; 48: 1491–1494.PubMedGoogle Scholar
  81. Freedman R. Biological phenotypes in the genetics of schizophrenia. Biol Psychiatry 1998; 44: 939–940.PubMedCrossRefGoogle Scholar
  82. Freedman R, Hall M, Adler LE, Leonard S. Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia Biol Psychiatry 1995; 38: 22–33.Google Scholar
  83. Gall JG, Pardue ML. Formation and detection of RNA-DNA hybrid molecules in cytological preparations. Proc Natl Acad Sci USA 1969; 63: 378–383.PubMedCrossRefGoogle Scholar
  84. Gao X-M, Sakai K, Roberts RC, Conley RR, Dean B, Tamminga CA. Ionotropic glutamate receptors and expression of N-methyl-D-aspartate receptor subunits in subregions of human hippocampus: Effects of schizophrenia. Am J Psychiatry 2000; 157: 1141 1149.Google Scholar
  85. Garey LJ, Ong WY, Patel TS, Kanani M, Davis A, Mortimer AM, Barnes TRE, Hirsch SR. Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia J Neurol Neurosurg Psychiatry 1998; 65: 446–453.Google Scholar
  86. Gendelman HE, Moench TR, Narayan O, Griffin DE, Clements JE. A double labeling technique for performing immunocytochemistry and in situ hybridization in virus infected cell cultures and tissues. J Virol Methods 1985; 11: 93–103.PubMedCrossRefGoogle Scholar
  87. Glantz LA, Lewis DA. Deceased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia Arch Gen Psychiatry 2000; 57: 65–73.Google Scholar
  88. Goldberg TE, Gold JM, Braff DL. Neuropsychological functioning and time linked information processing in schizophrenia Review of Psychiatry 1991; 10: 60–78.Google Scholar
  89. Graybiel AM, Ragsdale CW Jr. Histochemically distinct compartments in the striatum of human, monkey, and cat demonstrated by acetylthiocholinesterase staining. Proc Natl Acad Sci USA 1978; 11: 5723–5726.CrossRefGoogle Scholar
  90. Gruzelier J, Seymour K, Wilson L, Jolley A, Hirsch S. Impairments on neuropsychologic tests of temporohippocampal and frontohippocampal functions and word fluency in remitting schizophrenia and affective disorders. Arch Gen Psychiatry 1988; 45: 623–629.PubMedCrossRefGoogle Scholar
  91. Guillery RW, Herrup K. Quantification without pontification: Choosing a method for counting objects in sectioned tissues. J Comp Neurol 1997; 386: 2–7.PubMedCrossRefGoogle Scholar
  92. Haase AT, Walker D, Stowring L, Ventura P, Geballe A, Blum H, Brahic M, Goldberg R, O’Brien K. Detection of two viral genomes in single cells by double-label hybridization in situ and color microradioautography. Science 1985; 227: 189–192.PubMedCrossRefGoogle Scholar
  93. Hall MD, El Mestikawy S, Emerit MB, Pichat L, Hamon M, Gozlan H. [3H]8-Hydroxy-2(di-n-propylamino)tetralin binding to pre-and postsynaptic 5-hydroxytraptamine sites in various regions of the rat brain. J Neurochem 1985; 44: 1685–1696.PubMedCrossRefGoogle Scholar
  94. Hamel E, Beaudet A. Electron microscopic autoradiographic localization of opioid receptors in rat neostriatum. Nature 1984; 312: 155–157.PubMedCrossRefGoogle Scholar
  95. Harrison PJ. The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain 1999; 122: 593–624.PubMedCrossRefGoogle Scholar
  96. Harrison PJ, Eastwood SL. Preferential involvement of excitatory neurons in medial temporal lobe in schizophrenia. Lancet 1998; 352: 1669–1673.PubMedCrossRefGoogle Scholar
  97. Harrison PJ, Kleinman JE. Methodological issues. In: Harris PJ, Roberts GW (eds). The Neuropathology of Schizophrenia: Progress and Interpretation. Oxford Univ Press, New York, NY, 2000; pp 339–350.Google Scholar
  98. Harrison PJ, Pearson RCA. In situ hybridization histochemistry and the study of gene expression in the human brain. Prog Neurobiol 1990; 34; 271–312.PubMedCrossRefGoogle Scholar
  99. Harrison PJ, McLaughlin D, Kerwin RW. Decreased hippocampal expression of a glutamate receptor gene in schizophrenia. Lancet 1991a; 337: 450–452.PubMedCrossRefGoogle Scholar
  100. Harrison PJ, Procter AW, Barton AJL, Lowe SL, Najlerahim A, Bertolucci PHF, Bowen DM, Pearson RCA. Terminal coma affects messenger RNA detection in post mortem human temporal cortex. Mol Brain Res 1991b; 9: 161–164.PubMedCrossRefGoogle Scholar
  101. Harrison PJ, Barton AJL, Procter AW, Bowen DM, Pearson RCA. The effects of Alzheimer’s disease, other dementias, and premortem course on f3-amyloid precursor protein messenger RNA in frontal cortex. J Neurochem 1994; 62: 635–644.PubMedCrossRefGoogle Scholar
  102. Harrison PJ, Heath PR, Eastwood SL, Burnet PWJ, McDonald B, Pearson RCA. The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: Selective mRNA vulnerability and comparison with their encoded proteins. Neurosci Lett 1995; 200: 151–154.PubMedCrossRefGoogle Scholar
  103. Healy DJ, Sima AAF, Tapp A, Watson SJ, Meador-Woodruff JH. Frequency of neuropathology in a brain bank from a long-term, domiciliary population. J Psychiatr Res 1996; 30: 45–49.PubMedCrossRefGoogle Scholar
  104. Heath RG, Krupp IM. Schizophrenia as an immunologic disorder. I. Démonstration of antibrain globulins by fluorescent antibody techniques. Arch Gen Psychiatry 1967; 16: 1–9.PubMedCrossRefGoogle Scholar
  105. Herkenham M. Receptor autoradiography: Optimizing anatomical resolution. In: Leslie FM, Altar CA (eds). Receptor Localization: Ligand Autoradiography. Alan R Liss, New York, NY, 1988; pp 37–47.Google Scholar
  106. Hill C, Keks N, Roberts S, Opeskin K, Dean B, MacKinnon A, Copolov D. Problem of diagnosis in postmortem brain studies of schizophrenia. Am J Psychiatry 996;153: 533537.Google Scholar
  107. Hirsch SR, Das I, Garey LJ, de Belleroche J. A pivotal role for glutamate in the pathogenesis of schizophrenia, and its cognitive dysfunction. Pharmacol Biochem Behav 1997; 56: 797–802.PubMedCrossRefGoogle Scholar
  108. Hökfelt T, Fuxe K, Goldstein M, Joh TH. Immunohistochemical localization of three catecholamine synthesizing enzymes: Aspects on methodology. Histochemie 1973; 33: 231–254.PubMedGoogle Scholar
  109. Hökfelt T, Ljungdahl A, Fuxe K, Johansson O. Dopamine nerve terminals in the rat limbic cortex: Aspects of the dopamine hypothesis of schizophrenia. Science 1974; 184, 177–179.Google Scholar
  110. Honer WG, Young C, Falkai P. Synaptic pathology. In: Harrison PJ, Roberts GW (eds). Oxford Univ Press, New York, NY, 2000; pp 105–136.Google Scholar
  111. Huntley GW, Morrison JH, Prikhozhan A, Sealfon SC. Localization of multiple dopamine receptor subtype mRNAs in human and monkey motor cortex and striatum. Mol Brain Res 1992; 15: 181–188.PubMedCrossRefGoogle Scholar
  112. Huntsman MM, Tran B-V, Potkin SG, Bunney WE Jr, Jones EG. Altered ratios of alternatively spliced long and short y2 subunit mRNAs of the y-amino butyrate type Areceptor in prefrontal cortex of schizophrenics. Proc Natl Acad Sci USA 1998; 95: 15066–15071.PubMedCrossRefGoogle Scholar
  113. Hurd, Y.L. Herman MM, Hyde TM, Bigelow LB, Weinberger DR, Kleinman JE.Google Scholar
  114. Prodynorphin mRNA expression is increased in the patch vs matrix compartment of theGoogle Scholar
  115. caudate nucleus in suicide subjects. Molecular Psychiatry 1997; 2: 495–500.CrossRefGoogle Scholar
  116. Hyman SE. Genes, gene expression, and behavior. Neurobiology of Disease 2000; 7: 528–532.PubMedCrossRefGoogle Scholar
  117. Ibrahim HM, Hogg AJ, Healy DJ, Haroutunian V, Davis KL, Meador-Woodruff JH. Ionotropic glutamate receptor binding and subunit mRNA expression in thalamic nuclei in schizophrenia. Am J Psychiatry 2000; 157: 1811–1823.PubMedCrossRefGoogle Scholar
  118. Ichimiya Y, Emson PC, Christodoulou C, Gait MJ, Ruth JL. Simultaneous visualization of vasopressin and oxytocin mRNA-containing neurons in the hypothalamus using non- radioactive in situ hybridization histochemistry. J Neuroendocrinol 1989; 2: 73–75.CrossRefGoogle Scholar
  119. Impagnatiello F, Guidotti AR, Resold C, Dwivedi Y, Caruncho H, Pisu MG, Uzunov DP, Smalheiser NR, Davis JM, Pandey GN, Pappas GD, Tueting P, Sharma RP, Costa E. A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Proc Natl Acad Sci 1998; 95: 15718–15723.PubMedCrossRefGoogle Scholar
  120. Johnston NL, Cerevnak J, Shore AD, Torrey EF, Yolken RH, The Stanley Neuropathology Consortium. Multivariate analysis of RNA levels from postmortem human brains as measured by three different methods of RT-PCR. J Neurosci Methods 1997; 77: 83–92.PubMedCrossRefGoogle Scholar
  121. Johnston-Wilson NL, Sims CD, Hofmann J-P, Anderson L, Shore AD, Torrey EF, Yolken RH, The Stanley Neuropathology Consortium. Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. Molecular Psychiatry 2000; 5: 142–149.PubMedCrossRefGoogle Scholar
  122. Jones EG, Hendry SHC, Liu X-B, Hodgins S, Potkin SG, Tourtellotte WW. A method for fixation of previously fresh-frozen human adult and fetal brains that preserves histological quality and immunoreactivity. J Neurosci Methods 1992; 44: 133–144.PubMedCrossRefGoogle Scholar
  123. Joyce JN, Lexow N, Kim SJ, Artymyshyn R, Senzon S, Lawerence D, Cassanova MF, Kleinman JE, Bird ED, Winokur A. Distribution of beta-adrenergic receptor subtypes in human postmortem brain: Alterations in limbic regions of schizophrenics. Synapse 1992; 10: 228–246.Google Scholar
  124. Joyce JN, Shane A, Lexow N, Winokur A, Casanova MF, Kleinman JE. Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenics. Neuropsychopharmacology 1993; 8: 315–336.PubMedGoogle Scholar
  125. Kaiya H. Neuromelanin, neuroleptics and schizophrenia. Hypothesis of an interaction between noradrenergic and dopaminergic system. Neuropsychobiology 1980; 6: 241–248.CrossRefGoogle Scholar
  126. Kalus P, Senitz D, Beckmann H. Altered distribution of parvalbumin-immunoreactive local circuit neurons in the anterior cingulate cortex of schizophrenic patients. Psychiatry Res Neuroimaging Section 1997; 75: 49–59.CrossRefGoogle Scholar
  127. Kendell RE. The choice of diagnostic criteria for biological research. Arch Gen Psychiatry 1982; 39: 1334–1339.PubMedCrossRefGoogle Scholar
  128. Kerwin RW, Beats BC. Increased forskolin binding in the left parahippocampal gyrus and CA1 region in post mortem schizophrenic brain determined by quantitative autoradiography. Neurosci Lett 1990; 118: 164–168.PubMedCrossRefGoogle Scholar
  129. 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.PubMedCrossRefGoogle Scholar
  130. Kerwin R, Robinson P, Stephenson J. Distribution of CCK binding sites in the human hippocampal formation and their alteration in schizophrenia: A postmortem autoradiographic study. Psychol Med 1992; 22: 37–43.Google Scholar
  131. Kingsbury AE, Foster OJF, Nisbet AP, Cairns N, Bray L, Eve DJ, Lees AJ, Marsden CD. Tissue pH as an indicator of mRNA preservation in human postmortem brain. Mol Brain Res 1995; 28: 311–318.PubMedCrossRefGoogle Scholar
  132. Kitteil DA, Hyde TM, Herman MM, Kleinman JE. The collection of tissue at autopsy: Practical and ethical issues. In: Dean B, Kleinman JE, Hyde TM (eds). Using CNS Tissue in Psychiatric Research: A Practical Guide. Harwood Acad Pub, Amsterdam, 1999; pp 1–18.Google Scholar
  133. Kleinman JE, Hyde TM, Herman MM. Methodological issues in the neuropathology of mental illness. In: Bloom FE, Kupfer DJ (eds). Psychopharmacology: The Fourth Generation of Progress. Raven Press, New York, NY, 1995; pp 859–864.Google Scholar
  134. Kornhuber J, Retz W, Riederer P, Heinsen H, Fritze J. Effect of antemortem and postmortem factors on [3H]glutamate binding in the human brain. Neurosci Lett 1988; 93: 312–317.PubMedCrossRefGoogle Scholar
  135. Kuhar MJ, Unnerstall JR. Quantitative receptor mapping by autoradiography: Some current technical problems. Trends Neurosci 1985; 8: 49–53.CrossRefGoogle Scholar
  136. Kuhar MJ, DeSouza EB, Unnerstall JR. Neurotransmitter receptor mapping by autoradiography and other methods. Ann Rev Neurosci 1986; 9: 27–59.PubMedCrossRefGoogle Scholar
  137. Lahti RA, Roberts RC, Cochrane EV, Primus RJ, Gallager DW, Conley RR, Tamminga CA. Direct determination of dopamine D4 receptors in normal and schizophrenic postmortem brain tissue: A [3H]NGD-94–1 study. Molecular Psychiatry 1998; 3: 528–533.PubMedCrossRefGoogle Scholar
  138. Larsson L-I. Methods for immunocytochemistry of neurohormonal peptides. In: Björklund A, Hökfelt T (eds). Handbook of Chemical Neuroanatomy. Vol 1. Methods in Chemical Neuroanatomy. Elsevier Science Pub BV, New York, NY, 1983; pp 147–209.Google Scholar
  139. Laruelle M, Abi-Dargham A, vanDyck CH, Gil R, D’Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci USA 1996; 93: 9235–9240.PubMedCrossRefGoogle Scholar
  140. LeCorre S, Harper CG, Lopez P, Ward P, Catts S. Increased levels of expression of an NMDAR I splice variant in the superior temporal gyrus in schizophrenia. Neuroreport 2000; 11: 983–986.CrossRefGoogle Scholar
  141. Leonard S, Logel J, Luthman D, Casanova M, Kirch D, Freedman R. Biological stability of mRNA isolated from human postmortem brain collections. Biol Psychiatry 1993; 33: 456–466.PubMedCrossRefGoogle Scholar
  142. Lewis DA. Schizophrenia and disordered neural circuitry. Schizophr Bull 1997; 23: 529–531.PubMedCrossRefGoogle Scholar
  143. Lewis DA, Akil M. Cortical dopamine in schizophrenia: Strategies for postmortem studies. J Psychiatr Res 1997; 31: 175–195.PubMedCrossRefGoogle Scholar
  144. Lewis ME, Sherman TG, Watson SJ. In situ hybridization histochemistry with synthetic oligonucleotides: Strategies and methods. Peptides 1985; 6: 75–87.PubMedCrossRefGoogle Scholar
  145. Lewis ME, Khachaturian H, Schäfer MK-H, Watson SJ. Anatomical approaches to the study of neuropeptides and related mRNA in the central nervous system. In: Martin JB, Barchas JD (eds). Neuropeptides in Neurologic and Psychiatric Disease. Raven Press, New York, NY, 1986; pp 79–109.Google Scholar
  146. Lewis ME, Rogers WT, Krause RG II, Schwaber JS. Quantitation and digital representation of in situ hybridization histochemistry. Methods Enzymol 1989; 168: 808–821.PubMedCrossRefGoogle Scholar
  147. Lewis ME, Robbins E, Baldino F Jr. In situ hybridization histochemistry with radioactive and non-radioactive cRNA and DNA probes. In: Sharif NA (ed). Molecular Imaging inGoogle Scholar
  148. Neuroscience. IRL Press, Oxford, 1993, pp 1–22.Google Scholar
  149. Lexow N, Joyce JN, Kim SJ, Phillips J, Casanova MF, Bird ED, Kleinman JE. Alterations in TRH receptors in temporal lobe of schizophrenics: A quantitative autoradiographic study. Synapse 1994; 18: 315–327.PubMedCrossRefGoogle Scholar
  150. Leysen J. Problems in in vitro receptor binding studies and identification and role of serotonin receptor sites. Neuropharmacology 1984; 23: 247–254.PubMedCrossRefGoogle Scholar
  151. Lidow MS, Goldman-Rakic PS, Rakic P, Gallager DW. Differential quenching and limits of resolution in autoradiograms of brain tissue labeled with 3H-, 125I- and 14C-compounds. Brain Res 1988; 459: 105–119.PubMedCrossRefGoogle Scholar
  152. Linares-Cruz G, Millot G, DeCremoux P, Vassy J, Olofsson B, Rigaut JP, Calvo F. Combined analysis of in situ hybridization, cell cycle and structural markers using reflectance and immunofluorescence confocal microscopy. Histochem J 1995; 27: 1523.CrossRefGoogle Scholar
  153. Loewi O. Über humorale Übertragbarkeit der Herznervenwirkung. I. Mitteilung. Pflügers Arch 1921; 189: 239–242.CrossRefGoogle Scholar
  154. Loiacono RE, Gundlach AL. In situ hybridisation histochemistry: Application to human brain tissue. In: Dean B, Kleinman JE, Hyde TM (eds). Using CNS Tissue in Psychiatric Research: A Practical Guide. Harwood Acad Pub, Amsterdam, 1999; pp 85–105.Google Scholar
  155. Longson D, Deakin JFW, Benes FM. Increased density of entorhinal glutamate-immunoreactive vertical fibers in schizophrenia. J Neural Transm 1996; 103: 503–507.PubMedCrossRefGoogle Scholar
  156. Lu W, Haber SN. In situ hybridization histochemistry: A new method for processing material stored for several years. Brain Res 1992; 578: 155–160.Google Scholar
  157. Marcusson J, Oreland L, Winblad B. Effect of age on human brain serotonin (S-1) binding sites. J Neurochem 1984; 43: 1699–1705.PubMedCrossRefGoogle Scholar
  158. Meador-Woodruff JH, Haroutunian V, Powchik P, Davidson M, Davis KL, Watson SJ. Dopamine receptor transcript expression in striatum and prefrontal and occipital cortex. Focal abnormalities in orbitofrontal cortex in schizophrenia. Arch Gen Psychiatry 1997; 54: 1089–1095.PubMedCrossRefGoogle Scholar
  159. Meador-WoodruffJH, Davis KL, Haroutunian V. Abnormal kainate receptor expression in prefrontal cortex in schizophrenia. Neuropsychopharmacology 2001;24: 545–552.Google Scholar
  160. Mengod G, Charli J-L, Palacios JM. The use of in situ hybridization histochemistry for the study of neuropeptide gene expression in the human brain. Cell Mol NeurobiolGoogle Scholar
  161. 1990;.
    : 113–126.Google Scholar
  162. Mengod G, Vivanco MM, Christnacher A, Probst, Palacios JM. Study of proopiomelanocortin mRNA expression in human postmortem pituitaries. Mol Brain Res 1991; 10: 129–137.PubMedCrossRefGoogle Scholar
  163. Miller JA. The calibration of 35S or 32P with 14C-labeled brain paste or 14C-plastic standards for quantitative autoradiography using LKB Ultrofilm or Amersham Hyperfilm. Neurosci Lett 1991; 121: 211–214.PubMedCrossRefGoogle Scholar
  164. Milner B. Effects of different brain lesions on card sorting. Arch Neurol 1963;9: 90–100. Mimics K, Middleton FA, Marquez A, Lewis DA, Levitt P. Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex. Neuron 2000; 28: 53–67.CrossRefGoogle Scholar
  165. Moench TR, Gendelman HE, Clements JE, Narayan O, Griffin DE. Efficiency of in situ hybridization as a function of probe size and fixation technique. J Virol Methods 1985; 11: 119–130.PubMedCrossRefGoogle Scholar
  166. Morrison-Bogorad M, Zimmerman AL, Pardue S. Heat-shock 70 messenger RNA levels in human brain: correlation with agonal fever. J Neurochem. 1995; 64: 235–246.PubMedCrossRefGoogle Scholar
  167. Murakami H, Liotta L, Star RA. IF-LCM: Laser capture microdissection of immunofluorescently defined cells for mRNA analysis. Kidney Int 2000; 58: 1346–1353.PubMedCrossRefGoogle Scholar
  168. Nauta WJH: The problem of the frontal lobe: A reinterpretation. J Psychiatr Res 1971; 8: 167–187.Google Scholar
  169. Noga JT, Hyde TM, Bachus SE, Herman MM, Kleinman JE. AMPA receptor binding in the dorsolateral prefrontal cortex of schizophrenics and controls. Schizophr Res 2001; 48: 361–370.PubMedCrossRefGoogle Scholar
  170. Nunez DJ, Davenport AP, Emson PC, Brown MJ. A quantitative `in-situ’ hybridization method using computer-assisted image analysis. Validation and measurement of atrial-natriuretic-factor mRNA in the rat heart. Biochem J 1989; 263: 121–127.PubMedGoogle Scholar
  171. Ohnuma T, Augood SJ, Arai H, McKenna PJ, Emson PC. Expression of the human excitatory amino acid transporter 2 and metabotropic glutamate receptors 3 and 5 in the prefrontal cortex from normal individuals and patients with schizophrenia. Mol Brain Res 1998; 56: 207–217.PubMedCrossRefGoogle Scholar
  172. Ohnuma T, Augood SJ, Arai H, McKenna PJ, Emson PC. Measurement of GABAergic parameters in the prefrontal cortex in schizophrenia: Focus on GABA content, GABAA receptor a-1 subunit messenger RNA and human GABA transporter-1 (HGAT-1) subunit messenger RNA expression. Neuroscience 1999; 93: 441.PubMedCrossRefGoogle Scholar
  173. Ohnuma T, Tessler S, Arai H, Faull RLM, McKenna PJ, Emson PC. Gene expression of metabotropic glutamate receptor 5 and excitatory amino acid transporter 2 in the schizophrenic hippocampus. Mol Brain Res 2000a; 85: 24–31.PubMedCrossRefGoogle Scholar
  174. Ohnuma T, Kato H, Arai H, Faull RLM, McKenna PJ, Emson PC. Gene expression of PSD95 in prefrontal cortex and hippocampus in schizophrenia. Neuroreport 2000b; 11: 3133–3137.PubMedCrossRefGoogle Scholar
  175. Oliver KR, Wainwright A, Heavens RP, Sirinathsinghji DJS. Retrieval of cellular mRNA in paraffin-embedded human brain using hydrated autoclaving. J Neurosci Methods 1997; 77: 169–174.PubMedCrossRefGoogle Scholar
  176. Olson L. Postmortem fluorescence histochemistry of monoamine neuron systems in the human brain: A new approach in the search for a neuropathology of schizophrenia. J Psychiatr Res 1974; 11: 199–203.PubMedCrossRefGoogle Scholar
  177. Ong WY, Garey LJ. Ultrastructural features of biopsied temporopolar cortex (area 38) in a case of schizophrenia. Schizophr Res 1993; 10: 15–27.PubMedCrossRefGoogle Scholar
  178. Opeskin K, Dean B, Pavey G, Hill C, Keks N, Copolov D. Neither protein kinase C nor adenylate cyclase are altered in the striatum from subjects with schizophrenia. Schizophr Res 1996; 22: 159–164.PubMedCrossRefGoogle Scholar
  179. Pakkenberg B. Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. Arch Gen Psychiatry 1990; 47: 1023–1028.PubMedCrossRefGoogle Scholar
  180. Palacios JM, Mengod G. Visualization of neurotransmitter receptors and their mRNAs in the human brain. Arzneimittelforschung 1992; 42: 189–195.PubMedGoogle Scholar
  181. Perrett CW, Marchbanks RM, Whatley SA. Characterisation of messenger RNA extracted postmortem from the brains of schizophrenic, depressed and control subjects. J Neurol Neurosurg Psychiatry 1988; 51: 325–331.PubMedCrossRefGoogle Scholar
  182. Perry EK, Blessed G, Perry RH, Tomlinson BE. Brain biochemistry in schizophrenia. Lancet 1978;i: 35–36.Google Scholar
  183. Perry EK, Perry RH, Tomlinson BE. The influence of agonal status on some neurochemi- cal activities of postmortem human brain tissue. Neurosci Lett 1982; 29: 303–308.PubMedCrossRefGoogle Scholar
  184. Pieni JN, Chaudry AS, Woo T-UW, Lewis DA. Alterations in chandelier neuron axon terminals in the prefrontal cortex of schizophrenic subjects. Am J Psychiatry 1999; 156: 1709–1719.Google Scholar
  185. Pieni JN, Volk CL, Auh S, Sampson A, Lewis DA. Decreased somal size of deep layer 3 pyramidal neurons in the prefrontal cortex of subjects with schizophrenia. Arch Gen Psychiatry 2001; 58: 466–473.CrossRefGoogle Scholar
  186. Piggott MA, Perry EK, Sahgal A, Perry RH. Examination of parameters influencing [3H]Google Scholar
  187. MK-801 binding in postmortem human cortex. J Neurochem 1992: 58: 1001–1008.CrossRefGoogle Scholar
  188. Plum, F. 1972. Prospects for research on schizophrenia. III. Neurophysiology.Google Scholar
  189. Neuropathological findings. Neurosci. Res. Prog. Bull. 10: 384–388.Google Scholar
  190. Porter RHP, Eastwood SL, Harrison PJ. Distribution of kainate receptor subunit mRNAs in human hippocampus, neocortex and cerebellum, and bilateral reduction of hippocampal GluR6 and KA2 transcripts in schizophrenia. Brain Res 1997; 751: 217–231.PubMedCrossRefGoogle Scholar
  191. Pralong D, Tomaskovic-Crook E, Opeskin K, Copolov D, Dean B. Serotonin2A receptors are reduced in the planum temporale from subjects with schizophrenia. Schizophr Res 2000; 44: 35–45.PubMedCrossRefGoogle Scholar
  192. Quester R, Schröder R. The shrinkage of the human brain stem during formalin fixation and embedding in paraffin. J Neurosci Methods 1997; 75: 81–89.PubMedCrossRefGoogle Scholar
  193. Ragsdale DS, Miledi R. Expressional potency of mRNAs encoding receptors and voltage-activated channels in the postmortem rat brain. Proc Natl Acad Sci USA 1991; 88: 1854–1858.PubMedCrossRefGoogle Scholar
  194. Ravid R, VanZweiten EJ, Swaab DF. Brain banking and the human hypothalamus—factors to match for, pitfalls and potentials. Prog Brain Res 1992; 93: 83–95.PubMedCrossRefGoogle Scholar
  195. Riederer P, Gsell W, Calza L, Franzek E, Jungkunz G, Jellinger K, Reynolds GP, Crow T, Cruz-Sànchez FF, Beckmann H. Consensus on minimal criteria of clinical and neuropathological diagnosis of schizophrenia and affective disorders for post mortem research. Report from the European Dementia and Schizophrenia Network (BIOMED I). J Neural Transm [Gen Sect] 1995; 102: 255–264.CrossRefGoogle Scholar
  196. Ross BN, Knowler JT, McCulloch J. On the stability of messenger RNA and ribosomal RNA in the brains of control human subjects and patients with Alzheimer’s disease. JNeurochem 1992; 58: 1810–1819.CrossRefGoogle Scholar
  197. Roth U, Diab IM, Watanabe M, Dinerstein RJ. A correlative radioautographic, fluorescent, and histochemical technique for cytopharmacology. Mol Pharmacol 1974; 10: 986–998.PubMedGoogle Scholar
  198. Roth M. Interaction of genetic and environmental factors in the causation of schizophrenia. In: Richter D (ed). Schizophrenia: Somatic Aspects. MacMillan, New York, NY, 1957; pp 15–31.Google Scholar
  199. Royston MC, Slater P, Simpson MDC, Deakin JFW. Analysis of laminar distribution of kappa opiate receptor in human cortex: Comparison between schizophrenia and normal. J Neurosci Methods 1991; 36: 145–153.PubMedCrossRefGoogle Scholar
  200. Saykin AJ, Gur RC, Gur RE, Mozley PD, Mozley LH, Resnick SM, Kester B, Stafiniak P. Neuropsychological function in schizophrenia. Arch Gen Psychiatry 1991; 48: 618–624.PubMedCrossRefGoogle Scholar
  201. Schalling M, Friberg K, Bird E, Goldstein M, Schiffinann SN, Mailleux P, Vanderhaeghen J-J, Hökfelt T. Presence of cholecystokinin mRNA in dopamine cells in the ventral mesencephalon of a human with schizophrenia. Acta Physiol Scand 1989; 137: 467–468.PubMedCrossRefGoogle Scholar
  202. Schramm M, Falkai P, Tepest R, Schneider-Axmann T, Przkora R, Waha A, Pietsch T, Bonte W, Bayer TA. Stability of RNA transcripts in postmortem psychiatric brains. J Neural Transm 1999; 106: 329–335.PubMedCrossRefGoogle Scholar
  203. Seeman P, Lee T, Chau-Wong M, Wong K. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 1976; 261: 717–719.PubMedCrossRefGoogle Scholar
  204. 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: 805–818.PubMedCrossRefGoogle Scholar
  205. Shi S-R, Key ME, Kalra KL. Antigen retrieval in formalin-fixed, paraffin-embedded tissues: An enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 1991; 39: 741–748.PubMedCrossRefGoogle Scholar
  206. Simone NL, Remaley AT, Charboneau L, Petricoin EF III, Glickman JW, Emmert-Buck MR, Fleisher TA, Liotta LA. Sensitive immunoassay of tissue cell proteins procured by laser capture microdissection. Am J Pathol 2000a; 156: 445–452.PubMedCrossRefGoogle Scholar
  207. Simone NL, Paweletz CP, Charboneau L, Petricoin EF III, Liotta LA. Laser capture microdissection: Beyond functional genomics to proteomics. Molecular Diagnosis 2000b; 5: 301–307.PubMedGoogle Scholar
  208. Simpson MDC, Lubman DI, Slater P, Deakin JFW. Autoradiography with [3H]8-OHDPAT reveals increases in 5-HTIA receptors in ventral prefrontal cortex in schizophrenia. Biol Psychiatry 1996; 39: 919–928.PubMedCrossRefGoogle Scholar
  209. Singer RH, Lawrence JB, Silva F, Langevin GL, Pomeroy M, Billings–Gagliardi S. Strategies of ultrastructural visualization of biotinated probes hybridized to messenger RNA in situ. Curr Top Microbiol Immunol 1989;143: 55–55–69.Google Scholar
  210. Smiley JF, Williams SM, Szigeti K, Goldman-Rakic PS. Light and electron microscopic characterization of dopamine-immunoreactive axons in human cerebral cortex. J Comp Neurol 1992; 321: 325–335.PubMedCrossRefGoogle Scholar
  211. Snyder SH, Ferris CD. Novel neurotransmitters and their neuropsychiatric relevance. Am J Psychiatry 2000; 157: 1738–1751.PubMedCrossRefGoogle Scholar
  212. Southard EE. On the topographical distribution of cortex lesions and anomalies in dementia praecox, with some account of their functional significance. Am J Insanity 1914; 71: 383–403.Google Scholar
  213. Stevens JR. An anatomy of schizophrenia? Arch Gen Psychiat 29: 177, 1973.PubMedCrossRefGoogle Scholar
  214. Stevens JR. Enough of pooled averages: Been there, done that. Biol Psychiat 1997; 41: 633–635.PubMedCrossRefGoogle Scholar
  215. Steward O. mRNA localization in neurons: A multipurpose mechanism? Neuron 1997; 18: 9–12.PubMedCrossRefGoogle Scholar
  216. Sulzer D, Joyce MP, Lin L, Geldwert D, Haber SN, Hattori T, Rayport S. Dopamine neurons make glutamatergic synapses in vitro. J Neurosci 1998; 18: 4588–4602.PubMedGoogle Scholar
  217. Sun Y, Zhang L, Johnston NL, Torrey EF, Yolken RH. Serial analysis of gene expression in the frontal cortex of patients with bipolar disorder. Br J Psychiatry 2001; 178: 5137 - S141.CrossRefGoogle Scholar
  218. Tallerico T, Novak G, Liu ISC, Ulpian C, Seeman P. Schizophrenia: Elevated mRNA for dopamine D2Longer receptors in frontal cortex. Mol Brain Res 2001; 87: 160–165.PubMedCrossRefGoogle Scholar
  219. Tang SW, Helmeste D, Fang H, Li M, Vu R, Bunney W Jr, Potkin S, Jones EG. Differential labeling of dopamine and sigma sites by [3H]nemonapride. and [3H]raclopride in postmortem human brains. Brain Res 1997; 765: 7–12.PubMedCrossRefGoogle Scholar
  220. Tecott LH, Eberwine JH, Barchas JD, Valentino KL. Methodological considerations in the utilization of in situ hybridization. In: Eberwine JH, Valentino KL, Barchas JD (eds). In Situ Hybridization In Neurobiology: Advances in Methodology. Oxford Univ Press, New York, NY, 1994; pp 3–23.Google Scholar
  221. Torrey EF, Peterson MR. Schizophrenia and the limbic system. Lancet 1974;ii: 942–946.Google Scholar
  222. Torrey EF, Webster M, Knable M, Johnston N, Yolken RH. The Stanley Foundation brain collection and neuropathology consortium. Schizophr Res 2000;44: 151–155. Tsuang M. Schizophrenia: Genes and environment. Biol Psychiatry 2000; 47: 210–220.Google Scholar
  223. Uhl GR. In situ hybridization: Quantitation using radiolabeled hybridization probes.Methods Enzymol 1989;168: 741–752.Google Scholar
  224. Van der Loos CM, Volkers HH, Rook R, Van den Berg FM, Houthoff H-J. Simultaneous application of in situ DNA hybridization and immunohistochemistry on one tissue section. Histochem J 1989; 21: 279–284.PubMedCrossRefGoogle Scholar
  225. Virgo L, Humphries C, Mortimer A, Barnes T, Hirsch, S, de Belleroche J. Chólecystokinin messenger RNA deficit in frontal and temporal cerebral cortex in schizophrenia. Biol Psychiatry 1995; 37: 694–701.PubMedCrossRefGoogle Scholar
  226. Volk DW, Austin MC, Pierri JN, Sampson AR, Lewis DA. Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical yaminobutyric acid neurons in subjects with schizophrenia. Arch Gen Psychiatry 2000; 57: 237–245.PubMedCrossRefGoogle Scholar
  227. Volk DW, Austin MC, Pierri JN, Sampson AR, Lewis DA. GABA transporter-1 mRNA in the prefrontal cortex in schizophrenia: Decreased expression in a subset of neurons. Am J Psychiatry 2001; 158: 256–265.PubMedCrossRefGoogle Scholar
  228. Vonsattel JPG, Aizawa H, Ge P, DiFiglia M, McKee AC, MacDonald M, Gusella JF. Landwehrmeyer GB, Bird ED, Richardson EP Jr, Hedley-Whyte ET. An improved approach to prepare human brains for research. J Neuropath Exp Neurol 1995; 54: 4256.Google Scholar
  229. Wagman AMI. Report of a workshop on issues in brain tissue acquisition. Schizophr Bull 1992; 18: 149–153.PubMedCrossRefGoogle Scholar
  230. Weinberger DR. Anteromedial temporal-prefrontal connectivity: A functional neuro-anatomical system implicated in schizophrenia. In: Carroll BJ, Barrett JE, (eds). Psychopathology and the Brain. Raven Press, New York, NY, 1991; pp 25–43.Google Scholar
  231. Weinberger DR. Cell biology of the hippocampal formation in schizophrenia. 1999; 45: 395–402.Google Scholar
  232. West MJ. New stereological methods for counting neurons. Neurobiol Aging 1993; 14: 275–285.PubMedCrossRefGoogle Scholar
  233. Whitehouse PJ. Receptor autoradiography: Applications in neuropathology. Trends Neurosci 1985; 8: 434–437.Google Scholar
  234. Wiesner RJ, Zak R. Quantitative approaches for studying gene expression. Am J Physiol 1991; 260: L179 - L188.PubMedGoogle Scholar
  235. Willner P. The dopamine hypothesis of schizophrenia: Current status, future prospects. Int Clin Psychopharmacol 1997; 12: 297–308.PubMedCrossRefGoogle Scholar
  236. Witter MP, Amaral DG. Entorhinal cortex of the monkey: V. Projections to the dentate gyrus, hippocampus, and subicular complex. J Comp Neurol 1991; 307: 437–459.PubMedCrossRefGoogle Scholar
  237. Wolf SS, Hyde TM, Saunders RC, Herman MM, Weinberger DR, Kleinman JE. Autoradio-graphic characterization of neurotensin receptors in the entorhinal cortex of schizophrenic patients and control subjects. J Neural Transm [Gen Sect] 1995; 102: 55–65.CrossRefGoogle Scholar
  238. Woo T-U, Miller JD, Lewis DA. Schizophrenia and the parvalbumin-containing class of cortical local circuit neurons. Am J Psychiatry 1997; 154: 1013–1015.PubMedGoogle Scholar
  239. Woo T-U, Whitehead RE, Melchitzky DS, Lewis DA. A subclass of prefrontal yaminobutyric acid axon terminals are selectively altered in schizophrenia. Proc Natl Acad Sci USA 1998; 95: 5341–5346.PubMedCrossRefGoogle Scholar
  240. Wyatt RJ, Erdelyi E, Schwartz M, Herman M, Barchas JD. Difficulties in comparing catecholamine-related enzymes from the brains of schizophrenics and controls. Biol Psychiatry 1978; 13: 317–334.PubMedGoogle Scholar
  241. Yee F, Yolken RH. Identification of differentially expressed RNA transcripts in neuropsychiatric disorders. Biol Psychiatry 1997; 41: 759–761.PubMedCrossRefGoogle Scholar
  242. Young WS III. In situ hybridization histochemical detection of neuropeptide mRNA using DNA and RNA probes. Methods Enzymol 1989a: 168: 702–710.PubMedCrossRefGoogle Scholar
  243. Young WS III. Simultaneous use of digoxigenin-and radiolabeled probes for hybridization histochemistry. Neuropeptides 1989b; 13: 271–275.PubMedCrossRefGoogle Scholar
  244. Young WS III. In situ hybridization histochemistry. In: Björklund A, Hökfelt T, Wouterlood F, van den Pol AN. (eds). Handbook of Chemical Neuroanatomy. Vol 8: Methods for the Analysis of Neuronal Microcircuits and Synaptic Interactions. 1990, Elsevier Science Pub BV, New York, NY; pp 481–511.Google Scholar
  245. Young WS III. In situ hybridization with oligodeoxyribonucleotide probes. In:Google Scholar
  246. Wilkinson DG (ed). In Situ Hybridization. A Practical Approach. Oxford Univ Press, New York, NY, 1992; pp. 33–44.Google Scholar
  247. Young WS III, Kuhar MJ. Opiate receptor autoradiography: In vitro labeling of tissue slices. In: van Ree JM, Terenius L (eds). Characteristics and Function of Opioids. Elsevier/North-Holland Biomedical Press, Amsterdam; pp 451–452.Google Scholar
  248. Young WS III, Kuhar MJ. Autoradiographic localisation of benzodiazepine receptors in the brains of humans and animals. Nature 1979; 280: 393–395.CrossRefGoogle Scholar
  249. Zachrisson O, de Belleroche J, Wendt KR, Hirsch S, Lindefors N. Cholecystokinin CCKB receptor mRNA isoforms: expression in schizophrenic brains. Neuroreport 1999; 10: 3265–3268.PubMedCrossRefGoogle Scholar
  250. Zaidel DW, Esiri MM, Harrison PJ. Size, shape, and orientation of neurons in the left and right hippocampus: Investigation of normal asymmetries and alterations in schizophrenia. Am J Psychiatry 1997a; 154: 812–818.PubMedGoogle Scholar
  251. Zaidel DW, Esiri MM, Harrison PJ. The hippocampus in schizophrenia: Lateralized increase in neuronal density and altered cytoarchitectural asymmetry. Psychol Med 1997b; 27: 703–713.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Susan E. Bachus
  • Joel E. Kleinman

There are no affiliations available

Personalised recommendations