Genetic and Proteomic Studies in Schizophrenia

  • Emmanuel Dias-Neto
  • Daniel Martins-de-Souza
  • Elida P.B. Ojopi
  • Wagner F. Gattaz


Schizophrenia (SCZ), as most other common human diseases, is a result of a complex interaction network of endogenous and exogenous factors. In SCZ, the genetic components are among the most important elements of this network: several types of DNA alterations may occur, resulting in gene expression and proteome variations that, independently or in concert, will lead to physiological imbalances that trigger the disease. Unfortunately, despite the tremendous efforts and significant contributions made by dozens of research groups around the world, most of the putative SCZ biomarkers revealed showed no consistent results when challenged with distinct sample sets.


Metachromatic Leukodystrophy Shotgun Proteomics Gyrification Index Brain Morphometry Val997Leu Polymorphism 
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.



The authors thank ABADHS (Associação Beneficente Alzira Denise Hertzog Silva), FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo – Brazil), CNPq (Conselho Nacional de Pesquisas), and DAAD (Deutscher Akademischer Austauschdienst) for their fundamental support to our research.


  1. Aberg, K., Saetre, P., Lindholm, E., Ekholm, B., Pettersson, U., Adolfsson, R. & Jazin, E. Human QKI, a new candidate gene for schizophrenia involved in myelination. Am J Med Genet B Neuropsychiatr Genet 141: 84–90, 2006a.Google Scholar
  2. Aberg, K., Saetre, P., Jareborg, N. & Jazin, E. Human QKI, a potential regulator of mRNA expression of human oligodendrocyte-related genes involved in schizophrenia. Proc Natl Acad Sci USA 103: 7482–7487, 2006b.Google Scholar
  3. Altar, C.A., Jurata, L.W., Charles, V., Lemire, A., Liu, P., Bukhman, Y., Young, T.A., Bullard, J., Yokoe, H., Webster, M.J., Knable, M.B. & Brockman, J.A. Deficient hippocampal neuron expression of proteasome, ubiquitin, and mitochondrial genes in multiple schizophrenia cohorts. Biol Psychiatry 58: 85–96, 2005.CrossRefPubMedGoogle Scholar
  4. Apelqvist, A., Li, H., Sommer, L., Beatus, P., Anderson, D.J., Honjo, T., Hrabe De Angelis, M., Lendahl, U. & Edlund, H. Notch signalling controls pancreatic cell differentiation. Nature 400: 877–881, 1999.CrossRefPubMedGoogle Scholar
  5. Arion, D., Unger, T. & Lewis, D.A. Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia. Biol Psychiatry 62: 711–721, 2007.CrossRefPubMedGoogle Scholar
  6. Aston, C., Jiang, L. & Sokolov, B.P. Microarray analysis of postmortem temporal cortex from patients with schizophrenia. J Neurosci Res 77: 858–866, 2004.CrossRefPubMedGoogle Scholar
  7. Bailer, U., Leisch, F., Meszaros, K., Lenzinger, E., Willinger, U., Strobl, R., Gebhardt, C., Gerhard, E., Fuchs, K., Sieghart, W., Kasper, S., Hornik, K. & Aschauer, H.N. Genome scan for susceptibility loci for schizophrenia. Neuropsychobiology 42: 175–182, 2000.CrossRefPubMedGoogle Scholar
  8. Beasley, C.L., Pennington, K., Behan, A., Wait, R., Dunn, M.J. & Cotter, D. Proteomic analysis of the anterior cingulate cortex in the major psychiatric disorders: Evidence for disease-associated changes. Proteomics 6: 3414–3425, 2006.CrossRefPubMedGoogle Scholar
  9. Behan, A., Byrne, C., Dunn, M.J., Cagney, G. & Cotter, D.R. Proteomic analysis of membrane microdomain-associated proteins in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder reveals alterations in LAMP, STXBP1 and BASP1 protein expression. Mol Psychiatry 2008 Feb 12. [Epub ahead of print]Google Scholar
  10. Ben-Shachar, D. & Laifenfeld, D. Mitochondria, synaptic plasticity, and schizophrenia. Int Rev Neurobiol 59: 273–296, 2004.CrossRefPubMedGoogle Scholar
  11. Ben-Shachar, D., Zuk, R., Gazawi, H. & Ljubuncic, P. Dopamine toxicity involves mitochondrial complex I inhibition: Implications to dopamine-related neuropsychiatric disorders. Biochem Pharmacol 67: 1965–1974, 2004.CrossRefPubMedGoogle Scholar
  12. Bergson, C., Levenson, R., Goldman-Rakic, P.S. & Lidow, M.S. Dopamine receptor-interacting proteins: The Ca(2+) connection in dopamine signaling. Trends Pharmacol Sci 24: 486–492, 2003.CrossRefPubMedGoogle Scholar
  13. Bowden, N.A., Scott, R.J. & Tooney, P.A. Altered expression of regulator of G-protein signalling 4 (RGS4) mRNA in the superior temporal gyrus in schizophrenia. Schizophr Res 89: 165–168, 2007.CrossRefPubMedGoogle Scholar
  14. Carlsson, A., Waters, N., Holm-Waters, S., Tedroff, J., Nilsson, M. & Carlsson, M.L. Interactions between monoamines, glutamate, and GABA in schizophrenia: New evidence. Annu Rev Pharmacol Toxicol 41: 237–260, 2001.CrossRefPubMedGoogle Scholar
  15. Chiu, Y.F., Mcgrath, J.A., Thornquist, M.H., Wolyniec, P.S., Nestadt, G., Swartz, K.L., Lasseter, V.K., Liang, K.Y. & Pulver, A.E. Genetic heterogeneity in schizophrenia II: Conditional analyses of affected schizophrenia sibling pairs provide evidence for an interaction between markers on chromosome 8p and 14q. Mol Psychiatry 7: 658–664, 2002.CrossRefPubMedGoogle Scholar
  16. Clark, D., Dedova, I., Cordwell, S. & Matsumoto, I. A proteome analysis of the anterior cingulate cortex gray matter in schizophrenia. Mol Psychiatry 11: 459–470, 2006.CrossRefPubMedGoogle Scholar
  17. Costa, R.M., Drew, C. & Silva, A.J. Notch to remember. Trends Neurosci 28: 429–435, 2005.CrossRefPubMedGoogle Scholar
  18. Covault, J., Lee, J., Jensen, K. & Kranzler, H. Nogo 3’-untranslated region CAA insertion: Failure to replicate association with schizophrenia and demonstration of marked population difference in frequency of the insertion. Brain Res Mol Brain Res 120: 197–200, 2004.CrossRefPubMedGoogle Scholar
  19. De Bellard, M.E., Ching, W., Gossler, A. & Bronner-Fraser, M. Disruption of segmental neural crest migration and ephrin expression in delta-1 null mice. Dev Biol 249: 121–130, 2002.CrossRefPubMedGoogle Scholar
  20. Delisi, L.E., Mesen, A., Rodriguez, C., Bertheau, A., Laprade, B., Llach, M., Riondet, S., Razi, K., Relja, M., Byerley, W. & Sherrington, R. Genome-wide scan for linkage to schizophrenia in a Spanish-origin cohort from Costa Rica. Am J Med Genet 114: 497–508, 2002.CrossRefPubMedGoogle Scholar
  21. Dracheva, S., Davis, K.L., Chin, B. Woo, D.A., Schmeidler, J. & Haroutunian, V. Myelin-associated mRNA and protein expression deficits in the anterior cingulate cortex and hippocampus in elderly schizophrenia patients. Neurobiol Dis 21 :531–540, 2006.CrossRefPubMedGoogle Scholar
  22. Duan, X., Chang, J.H., Ge, S., Faulkner, R.L., et al. Disrupted-in-schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Cell 130: 1146–1158, 2007.CrossRefPubMedGoogle Scholar
  23. Erdely, H.A., Tamminga, C.A., Roberts, R.C. & Vogel, M.W. Regional alterations in RGS4 protein in schizophrenia. Synapse 59: 472–479, 2006.CrossRefPubMedGoogle Scholar
  24. Fournier, A.E., Grandpre, T. & Strittmatter, S.M. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 409: 341–346, 2001.CrossRefPubMedGoogle Scholar
  25. Gattaz, W.F. & Brunner, J. Phospholipase A2 and the hypofrontality hypothesis of schizophrenia. Prostaglandins Leukot Essent Fatty Acids 55: 109–113, 1996.CrossRefPubMedGoogle Scholar
  26. Gattaz, W.F., Hubner, C.V., Nevalainen, T.J., Thuren, T. & Kinnunen, P.K. Increased serum phospholipase A2 activity in schizophrenia: A replication study. Biol Psychiatry 28: 495–501, 1990.PubMedGoogle Scholar
  27. Goodlett, D.R., Keller, A., Watts, J.D., Newitt, R., Yi, E.C., Purvine, S., Eng, J.K., Von Haller, P., Aebersold, R., & Kolker, E. Differential stable isotope labeling of peptides for quantitation and de novo sequence derivation. Rapid Commun Mass Spectrom 15: 1214–1221, 2001.CrossRefPubMedGoogle Scholar
  28. Greengard, P. The neurobiology of slow synaptic transmission. Science 294: 1024–1030, 2001.CrossRefPubMedGoogle Scholar
  29. Gregório, S.P., Gattaz, W.F., Tavares, H., Kieling, C., Timm, S., Wang, A.G., Rasmussen, H.B., Werge, T. & Dias-Neto, E. Analysis of coding-polymorphisms in NOTCH-related genes reveals NUMBL poly-glutamine repeat to be associated with schizophrenia in Brazilian and Danish subjects. Schizophr Res 88: 275–282, 2006.CrossRefGoogle Scholar
  30. Gregório, S.P., Mury, F.B., Ojopi, E.B., Sallet, P.C., Moreno, D.H., Yacubian, J., Tavares, H., Santos, F.R., Gattaz, W.F. & Dias-Neto, E. Nogo CAA 3´UTR Insertion polymorphism is not associated with Schizophrenia nor with Bipolar Disorder. Schizophr Res 75: 5–9, 2005.CrossRefPubMedGoogle Scholar
  31. Gregório, S.P., Sallet, P.C., Do, K.A., Lin, E., Gattaz, W.F. & Dias-Neto, E. Polymorphisms in genes involved in neurodevelopment may be associated with altered brain morphology in schizophrenia: Preliminary evidence. Psychiatry Res 165: 1–9, 2009.CrossRefPubMedGoogle Scholar
  32. Gruhler, A., Olsen, J.V., Mohammed, S., Mortensen, P., Faergeman, N.J., Mann, M. & Jensen, O.N. Quantitative phosphoproteomics applied to the yeast pheromone signaling pathway. Mol Cell Proteomics 4: 310–327, 2005.CrossRefPubMedGoogle Scholar
  33. Gygi, S.P., Rist, B., Gerber, S.A., Turecek, F., Gelb, M.H. & Aebersold, R. Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol 17: 994–999, 1999.CrossRefPubMedGoogle Scholar
  34. Haas, W., Faherty, B.K., Gerber, S.A., Elias, J.E., Beausoleil, S.A., Bakalarski, C.E., LI, X., Villen, J. & Gygi S.P. Optimization and use of peptide mass measurement accuracy in shotgun proteomics. Mol Cell Proteomics 5: 1326–1337, 2006.CrossRefPubMedGoogle Scholar
  35. Hakak, Y., Walker, J.R., Li, C., Wong, W.H., Davis, K.L., Buxbaum, J.D., Haroutunian, V. & Fienberg, A.A. Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc Natl Acad Sci USA 98: 4746–4751, 2001.CrossRefPubMedGoogle Scholar
  36. Harrison, P.J. The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain 122: 593–624, 1999.CrossRefPubMedGoogle Scholar
  37. Hashimoto, R., Straub, R.E., Weickert, C.S., Hyde, T.M., Kleinman, J.E. & Weinberger, D.R. Expression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in schizophrenia. Mol Psychiatry 9: 299–307, 2004.CrossRefPubMedGoogle Scholar
  38. Hemby, S.E., Ginsberg, S.D., Brunk, B., Arnold, S.E., Trojanowski, J.Q. & Eberwine, J.H. Gene expression profile for schizophrenia: Discrete neuron transcription patterns in the entorhinal cortex. Arch Gen Psychiatry 59: 631–640, 2002.CrossRefPubMedGoogle Scholar
  39. Hrabe De Angelis, M., Mcintyre, J. & Gossler, A. Maintenance of somite borders in mice requires the Delta homologue DII1. Nature 386: 717–721, 1997.CrossRefGoogle Scholar
  40. Hyde, T.M., Ziegler, J.C. & Weinberger, D.R. Psychiatric disturbances in metachromatic leukodystrophy. Insights into the neurobiology of psychosis. Arch Neurol 49: 401–406, 1992.PubMedGoogle Scholar
  41. Johnston-Wilson, N.L., Sims, C.D., Hofmann, J.P., Anderson, L., Shore, A.D., Torrey, E.F. & Yolken, R.H. Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. The Stanley Neuropathology Consortium. Mol Psychiatry 5: 142–149, 2000.CrossRefPubMedGoogle Scholar
  42. Katsel, P., Davis, K.L. & Haroutunian, V. Variations in myelin and oligodendrocyte-related gene expression across multiple brain regions in schizophrenia: A gene ontology study. Schizophr Res 79: 157–173, 2005.CrossRefPubMedGoogle Scholar
  43. Kiernan, A.E., Ahituv, N., Fuchs, H., Balling, R., Avraham, K.B., Steel, K.P. & Hrabe De Angelis, M. The Notch ligand Jagged1 is required for inner ear sensory development. Proc Natl Acad Sci USA 98: 3873–3878, 2001.CrossRefPubMedGoogle Scholar
  44. Kim, S.K. & Hebrok, M. Intercellular signals regulating pancreas development and function. Genes Dev 15: 111–127, 2001.CrossRefPubMedGoogle Scholar
  45. Kirov, G., Grozeva, D., Norton, N., Ivanov, D., Mantripragada, K.K., Holmans, P. International Schizophrenia Consortium; The Wellcome Trust Case Control Consortium, Craddock, N., Owen, M.J. & O’donovan, M.C. Support for the involvement of large CNVs in the pathogenesis of schizophrenia. Hum Mol Genet 2009 [Epub ahead of print]Google Scholar
  46. Kopan, R. & Turner, D.L. The Notch pathway: Democracy and aristocracy in the selection of cell fate. Curr Opin Neurobiol 6: 594–601, 1996.CrossRefPubMedGoogle Scholar
  47. Korostishevsky, M., Kaganovich, M., Cholostoy, A., Ashkenazi, M., Ratner, Y., Dahary, D., Bernstein, J., Bening-Abu-Shach, U., Ben-Asher, E., Lancet, D., Ritsner, M. & Navon, R. Is the G72/G30 locus associated with schizophrenia? Single nucleotide polymorphisms, haplotypes, and gene expression analysis. Biol Psychiatry 56: 169–176, 2004.CrossRefPubMedGoogle Scholar
  48. Law, A.J., Lipska, B.K., Weickert, C.S., Hyde, T.M., Straub, R.E., Hashimoto, R., Harrison, P.J., Kleinman, J.E. & Weinberger, D.R. Neuregulin 1 transcripts are differentially expressed in schizophrenia and regulated by 5’ SNPs associated with the disease. Proc Natl Acad Sci USA 103: 6747–6752, 2006.CrossRefPubMedGoogle Scholar
  49. Lewis, C.M., Levinson, D.F., Wise, L.H., Delisi, L.E., Straub, R.E., Hovatta, I., Williams, N.M., Schwab, S.G., Pulver, A.E., Faraone, S.V., Brzustowicz, L.M., Kaufmann, C.A., Garver, D.L., Gurling, H.M., Lindholm, E., Coon, H., Moises, H.W., Byerley, W., Shaw, S.H., Mesen, A., Sherrington, R., O’neill, F.A., Walsh, D., Kendler, K.S., Ekelund, J., Paunio, T., Lönnqvist, J., Peltonen, L., et al. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. Am J Human Genetics 73: 34–48, 2003.CrossRefGoogle Scholar
  50. Link, A.J., Eng, J., Schieltz, D.M., Carmack, E., Mize, G.J., Morris, D.R., Garvik, B.M. & Yates, J.R. III Direct analysis of protein complexes using mass spectrometry. Nat Biotechnol 17: 676–682, 1999.CrossRefPubMedGoogle Scholar
  51. Liu, J.P., Sim, A.T. & Robinson, P.J. Calcineurin inhibition of dynamin I GTPase activity coupled to nerve terminal depolarization. Science 265: 970–973, 1994.CrossRefPubMedGoogle Scholar
  52. Macgregor, S., Visscher, P.M., Knott, S.A., Thomson, P., Porteous, D.J., Millar, J.K. Devon, R.S., Blackwood, D. & Muir, W.J. A genome scan and follow-up study identify a bipolar disorder susceptibility locus on chromosome 1q42. Mol Psychiatry 9: 1083–1090, 2004.CrossRefPubMedGoogle Scholar
  53. Malenka, R.C. Synaptic plasticity in the hippocampus: LTP and LTD. Cell 78: 535–538, 1994.CrossRefPubMedGoogle Scholar
  54. Martins-De-Souza, D., Gattaz, W.F., Schmitt, A., Maccarrone, G., Hunyadi-Gulyás, E., Eberlin, M.N., Souza, G.H., Marangoni, S., Novello, J.C., Turck, C.W. & Dias-Neto, E. Proteomic analysis of dorsolateral prefrontal cortex indicates the involvement of cytoskeleton, oligodendrocyte, energy metabolism and new potential markers in schizophrenia. J Psychiatr Res [Epub ahead of print], 2008a.Google Scholar
  55. Martins-De-Souza, D., Gattaz, W.F., Schmitt, A, Rewerts, C., Maccarrone, G., Dias-Neto, E. & Turck, C.W. Proteome analysis of human dorsolateral prefrontal cortex using shotgun mass spectrometry. J Sep Sci 31: 3122–3126, 2008b.Google Scholar
  56. Martins-De-Souza, D., Gattaz, W.F., Schmitt, A., Rewerts, C., Maccarrone, G., Dias-Neto, E. & Turck, C.W. Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia. Eur Arch Psychiatry Clin Neurosci 2009 Jan 22. [Epub ahead of print], 2009a.Google Scholar
  57. Martins-De-Souza, D., Gattaz, W.F., Schmitt, A., Rewerts, C., Marangoni, S., Novello, J.C., Maccarrone, G., Turck, C.W. & Dias-Neto, E. Alterations in oligodendrocyte proteins, calcium homeostasis and new potential markers in schizophrenia anterior temporal lobe are revealed by shotgun proteome analysis. J Neural Transm 116: 275–289, 2009b.Google Scholar
  58. Martins-De-Souza, D., Gattaz, W.F., Schmitt, A., Novello, J.C., Turck, C.W., Marangoni, S. & Dias-Neto, E. Proteome analysis of schizophrenia patients Wernicke’s area reveals an energy metabolism dysregulation. BMC Psychiatry 9:17, 2009c.Google Scholar
  59. Mata, I., Perez-Iglesias, R., Roiz-Santiañez, R., Tordesillas-Gutierrez, D., Gonzalez-Mandly, A., Vazquez-Barquero, J.L. & Crespo-Facorro, B. A neuregulin 1 variant is associated with increased lateral ventricle volume in patients with first-episode schizophrenia. Biol Psychiatry 65: 535–540, 2009.CrossRefPubMedGoogle Scholar
  60. McCarley, R.W., Wible, C.G., Frumin, M., Hirayasu, Y., Levitt, J.J., Fischer, I.A. & Shenton, M.E. MRI anatomy of schizophrenia. Biol Psychiatry 45: 1099–1119, 1999.CrossRefPubMedGoogle Scholar
  61. McCullumsmith, R.E., Gupta, D., Beneyto, M., Kreger, E., Haroutunian, V., Davis, K.L., Meador-Woodruff, J.H. Expression of transcripts for myelination -related genes in the anterior cingulated cortex in schizophrenia Schizophr Res 90: 15-27, 2007.Google Scholar
  62. Meier, S., Brauer, A.U., Heimrich, B., Schwab, M.E., Nitsch, R. & Savaskan, N.E. Molecular analysis of Nogo expression in the hippocampus during development and following lesion and seizure. FASEB J 17: 1153–1155, 2003.PubMedGoogle Scholar
  63. Middleton, F.A., Mirnics, K., Pierri, J.N., Lewis, D.A. & Levitt, P. Gene expression profiling reveals alterations of specific metabolic pathways in schizophrenia. J Neurosci 22: 2718–2729, 2002.PubMedGoogle Scholar
  64. Mimmack, M.L., Ryan, M., Baba, H., Navarro-Ruiz, J., Iritani, S., Faull, R.L., Mckenna, P.J., Jones, P.B., Arai, H., Starkey, M., Emson, P.C. & Bahn, S. Gene expression analysis in schizophrenia: Reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22. Proc Natl Acad Sci USA 99: 4680–4685, 2002.CrossRefPubMedGoogle Scholar
  65. Mirnics, K., Middleton, F.A., Marquez, A., Lewis, D.A. & Levitt, P. Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex. Neuron 28: 53–67, 2000.CrossRefPubMedGoogle Scholar
  66. Miyakawa, T., Leiter, L.M., Gerber, D.J., Gainetdinov, R.R., Sotnikova, T.D., Zeng, H., Caron, M.G. & Tonegawa, S. Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia. Proc Natl Acad Sci USA 100: 8987–8992, 2003.CrossRefPubMedGoogle Scholar
  67. Novak, G., Kim, D., Seeman, P. & Tallerico, T. Schizophrenia and Nogo: Elevated mRNA in cortex, and high prevalence of a homozygous CAA insert. Brain Res Mol Brain Res 107: 183–189, 2002.CrossRefPubMedGoogle Scholar
  68. Ong, S.E., Blagoev, B., Kratchmarova, I., Kristensen, D.B., Steen, H., Pandey, A. & Mann, M. Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1: 376–386, 2002.CrossRefPubMedGoogle Scholar
  69. Pennington, K., Beasley, C.L., Dicker, P., Fagan, A., English, J., Pariante, C.M., Wait, R., Dunn, M.J. & Cotter, D.R. Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder. Mol Psychiatry 13: 1102–1117, 2008.CrossRefPubMedGoogle Scholar
  70. Polak, M., Haymaker, W., Johnson, J.E. & D’amelio, F. (1982) Neuroglia and their reactions. In: Haymaker W, Adams RD (Eds.) Histology and Histopathology of the Nervous System. Springfield: Charles C. Thomas, 1982.Google Scholar
  71. Polesskaya, O.O., Haroutunian, V., Davis, K.L., Hernandez, I. & Sokolov, B.P. Novel putative nonprotein-coding RNA gene from 11q14 displays decreased expression in brains of patients with schizophrenia. J Neurosci Res 74: 111–122, 2003.CrossRefPubMedGoogle Scholar
  72. Prabakaran, S., Swatton, J.E., Ryan, M.M., Huffaker, S.J., Huang, J.T., Griffin, J.L., Wayland, M., Freeman, T., Dudbridge, F., Lilley, K.S., Karp, N.A., Hester, S., Tkachev, D., Mimmack, M.L., Yolken, R.H., Webster, M.J., Torrey, E.F. & Bahn, S. Mitochondrial dysfunction in schizophrenia: Evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry 9: 684–697, 2004.CrossRefPubMedGoogle Scholar
  73. Przemeck, G.K., Heinzmann, U., Beckers, J. & Hrabe De Angelis, M. Node and midline defects are associated with left-right development in Delta1 mutant embryos. Development 130: 3–13, 2003.CrossRefPubMedGoogle Scholar
  74. Pulver, A.E. Search for schizophrenia susceptibility genes. Biol Psychiatry 47: 221–230, 2000.CrossRefPubMedGoogle Scholar
  75. Ross, P.L., Huang, Y.N., Marchese, J.N., Williamson, B., Parker, K., Hattan, S., Khainovski, N., Pillai, S., Dey, S., Daniels, S., Purkayastha, S., Juhasz, P., Martin, S., Bartlet-Jones, M., He, F., Jacobson, A. & Pappin, D.J. Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics 3: 1154–1169, 2004.CrossRefPubMedGoogle Scholar
  76. Schmidt, A., Kellermann, J. & Lottspeich, F. A novel strategy for quantitative proteomics using isotope-coded protein labels. Proteomics 5: 4–15, 2005.CrossRefPubMedGoogle Scholar
  77. Seeman, P. Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse 1: 133–152, 1987.CrossRefPubMedGoogle Scholar
  78. Segal, D., Koschnick, J.R., Slegers, L.H. & Hof, P.R. Oligodendrocyte pathophysiology: A new view of schizophrenia. Int J Neuropsychopharmacol 10: 503–511, 2007.CrossRefPubMedGoogle Scholar
  79. Shenton, M.E., Dickey, C.C., Frumin, M. & McCarley, R.W. A review of MRI findings in schizophrenia. Schizophr Res 49: 1–52, 2001.CrossRefPubMedGoogle Scholar
  80. Shimizu, K., Chiba, S., Saito, T., Kumano, K., Hamada, Y. & Hirai, H. Functional diversity among Notch1, Notch2, and Notch3 receptors. Biochem Biophys Res Commun 291: 775–779, 2002.CrossRefPubMedGoogle Scholar
  81. Sivagnanasundaram, S., Crossett, B., Dedova, I., Cordwell, S. & Matsumoto, I. Abnormal pathways in the genu of the corpus callosum in schizophrenia pathogenesis: A proteome study. Proteomics Clin Appl 1: 1291–1305, 2007.CrossRefGoogle Scholar
  82. Sobell, J.L., Mikesell, M.J. & Mcmurray, C.T. Genetics and etiopathophysiology of schizophrenia. Mayo Clin Proc 77: 1068–1082, 2002.CrossRefPubMedGoogle Scholar
  83. Stefansson, H., Rujescu, D., Cichon, S., Pietiläinen, O.P., Ingason, A., Steinberg, S. et al., Large recurrent microdeletions associated with schizophrenia. Nature 455: 232–236, 2009.CrossRefGoogle Scholar
  84. Sugai, T., Kawamura, M., Iritani, S., Araki, K., Makifuchi, T., Imai, C., Nakamura, R., Kakita, A., Takahashi, H. & Nawa, H. Prefrontal abnormality of schizophrenia revealed by DNA microarray: Impact on glial and neurotrophic gene expression. Ann N Y Acad Sci 1025: 84–91, 2004.CrossRefPubMedGoogle Scholar
  85. Talbot, K., Eidem, W.L., Tinsley, C.L., Benson, M.A., Thompson, E.W., Smith, R.J., Hahn, C.G., Siegel, S.J., Trojanowski, J.Q., Gur, R.E., Blake, D.J. & Arnold, S.E. Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia. J Clin Invest 113: 1353–1363, 2004.PubMedGoogle Scholar
  86. Tkachev, D., Mimmack, M.L., Ryan, M.M., Wayland, M., Freeman, T., Jones, P.B., Starkey, M., Webster, M.J., Yolken, R.H. & Bahn, S. Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet 362: 798–805, 2003.CrossRefPubMedGoogle Scholar
  87. Uranova, N., Orlovskaya, D., Vikhreva, O. Zimina, I., Kolomeets, N., Vostrikov, V. & Rachmanova, V. Electron microscopy of oligodendroglia in severe mental illness. Brain Res Bull 55: 597–610, 2001.CrossRefPubMedGoogle Scholar
  88. Vawter, M.P., Barret, T., Cheadle, C., Sokolov, B.P., Wood, W.H., Donovan, D.M., Webster, M., Freed, W.J. & Becker, K.G. Application of cDNA microarrays to examine gene expression differences in schizophrenia. Brain Res Bull 55: 641–650, 2001.CrossRefPubMedGoogle Scholar
  89. Vawter, M.P., Crook, J.M., Hyde, T.M., Kleinman, J.E., Weinberger, D.R., Becker, K.G. & Freed, W.J. Microarray analysis of gene expression in the prefrontal cortex in schizophrenia: A preliminary study. Schizophr Res. 58: 11–20, 2002.CrossRefPubMedGoogle Scholar
  90. Velculescu, E., Zhang, L., Volgelstein, B., & Kinzler, W. Serial analysis of gene expression. Science 270: 484–487, 1995.CrossRefPubMedGoogle Scholar
  91. Volk, D.W., Austin, M.C., Pierri, J.N., Sampson, A.R. & Lewis, D.A. Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia. Arch Gen Psychiatry 57: 237–245, 2000.CrossRefPubMedGoogle Scholar
  92. Weickert, C.S., Rothmond, D.A., Hyde, T.M., Kleinman, J.E. & Straub, R.E. Reduced DTNBP1 (dysbindin-1) mRNA in the hippocampal formation of schizophrenia patients. Schizophr Res 98: 105–110, 2008.CrossRefPubMedGoogle Scholar
  93. Weickert, C.S., Straub, R.E., Mcclintock, B.W., Matsumoto, M., Hashimoto, R., Hyde, T.M., Herman, M.M., Weinberger, D.R. & Kleinman, J.E. Human dysbindin (DTNBP1) gene expression in normal brain and in schizophrenic prefrontal cortex and midbrain. Arch Gen Psychiatry 61: 544–555, 2004.CrossRefPubMedGoogle Scholar
  94. Yao, J.K., Reddy, R.D. & Van Kammen, D.P. Oxidative damage and schizophrenia: An overview of the evidence and its therapeutic implications. CNS Drugs 15: 287–310, 2001.CrossRefPubMedGoogle Scholar
  95. Zeng, H., Chattarji, S., Barbarosie, M., Rondi-Reig, L., Philpot, B.D., Miyakawa, T., Bear, M.F. & Tonegawa, S. Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory. Cell 107: 617–629, 2001.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Emmanuel Dias-Neto
    • 1
  • Daniel Martins-de-Souza
    • 2
  • Elida P.B. Ojopi
    • 2
  • Wagner F. Gattaz
    • 3
  1. 1.Laboratory of Neuroscience (LIM-27) Institute of Psychiatry, Faculty of MedicineUniversity of São PauloSão PauloBrazil
  2. 2.Laboratory of Neuroscience, Department and Institute of Psychiatry, Faculty of MedicineUniversity of São PauloSão PauloBrazil
  3. 3.Department and Institute of Psychiatry, Faculty of MedicineUniversity of São PauloSão PauloBrazil

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