Schizophrenia Research
Volume 119, Issue 1 , Pages 210-218 , June 2010

Diagnostic classification of schizophrenia by neural network analysis of blood-based gene expression signatures

  • Makoto Takahashi

      Affiliations

    • Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori 1-757, Niigata 951-8510, Japan
    • These authors contributed equally to this work.
    • ,
  • Hiroshi Hayashi

      Affiliations

    • R&D Department, SRL Inc., Tokyo 191-0031, Japan
    • These authors contributed equally to this work.
    • ,
  • Yuichiro Watanabe

      Affiliations

    • Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori 1-757, Niigata 951-8510, Japan
    • ,
  • Kazushi Sawamura

      Affiliations

    • Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori 1-757, Niigata 951-8510, Japan
    • ,
  • Naoki Fukui

      Affiliations

    • Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori 1-757, Niigata 951-8510, Japan
    • ,
  • Junzo Watanabe

      Affiliations

    • Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori 1-757, Niigata 951-8510, Japan
    • ,
  • Tsuyoshi Kitajima

      Affiliations

    • Department of Psychiatry, Fujita Health University School of Medicine, Aichi 470-1192, Japan
    • CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan
    • ,
  • Yoshio Yamanouchi

      Affiliations

    • Department of Psychiatry, Fujita Health University School of Medicine, Aichi 470-1192, Japan
    • CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan
    • ,
  • Nakao Iwata

      Affiliations

    • Department of Psychiatry, Fujita Health University School of Medicine, Aichi 470-1192, Japan
    • CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan
    • ,
  • Katsuyoshi Mizukami

      Affiliations

    • Department of Psychiatry, Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8575, Japan
    • ,
  • Takafumi Hori

      Affiliations

    • Department of Psychiatry, Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8575, Japan
    • ,
  • Kazutaka Shimoda

      Affiliations

    • Department of Psychiatry, Dokkyo Medical University School of Medicine, Tochigi 321-0293, Japan
    • ,
  • Hiroshi Ujike

      Affiliations

    • Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
    • ,
  • Norio Ozaki

      Affiliations

    • CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan
    • Department of Psychiatry, Nagoya University Graduate School of Medicine, Aichi 466-8550, Japan
    • ,
  • Kentarou Iijima

      Affiliations

    • R&D Department, SRL Inc., Tokyo 191-0031, Japan
    • ,
  • Kazuo Takemura

      Affiliations

    • R&D Department, SRL Inc., Tokyo 191-0031, Japan
    • ,
  • Hideyuki Aoshima

      Affiliations

    • R&D Department, SRL Inc., Tokyo 191-0031, Japan
    • ,
  • Toshiyuki Someya

      Affiliations

    • Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori 1-757, Niigata 951-8510, Japan
    • Corresponding Author InformationCorresponding author. Tel.: +81 25 227 2210; fax: +81 25 227 0777.

Received 3 July 2009 ,Revised 12 December 2009 ,Accepted 20 December 2009.

References 

  1. Aston C, Jiang L, Sokolov BP. Microarray analysis of postmortem temporal cortex from patients with schizophrenia. J. Neurosci. Res. 2004;77(6):858–866
  2. Cheung VG, Conlin LK, Weber TM, Arcaro M, Jen KY, Morley M, et al. Natural variation in human gene expression assessed in lymphoblastoid cells. Nat. Genet. 2003;33(3):422–425
  3. Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M, Abderrahim H, et al. Genetic and physiological data implicating the new human gene G72 and the gene for d-amino acid oxidase in schizophrenia. Proc. Natl. Acad. Sci. U. S. A. 2002;99(21):13,675–13,680
  4. De Bruyne V, Al-Mulla F, Pot B. Methods for microarray data analysis. Methods Mol. Biol. 2007;382:373–391
  5. Debey S, Schoenbeck U, Hellmich M, Gathof BS, Pillai R, Zander T, et al. Comparison of different isolation techniques prior gene expression profiling of blood derived cells: impact on physiological responses, on overall expression and the role of different cell types. Pharmacogenomics J. 2004;4(3):193–207
  6. Eady JJ, Wortley GM, Wormstone YM, Hughes JC, Astley SB, Foxall RJ, et al. Variation in gene expression profiles of peripheral blood mononuclear cells from healthy volunteers. Physiol. Genomics. 2005;22(3):402–411
  7. Hakak Y, Walker JR, Li C, Wong WH, Davis KL, Buxbaum JD, et al. Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc. Natl. Acad. Sci. U. S. A. 2001;98(8):4746–4751
  8. Hashimoto K, Fukushima T, Shimizu E, Komatsu N, Watanabe H, Shinoda N, et al. Decreased serum levels of d-serine in patients with schizophrenia: evidence in support of the N-methyl-d-aspartate receptor hypofunction hypothesis of schizophrenia. Arch. Gen. Psychiatry. 2003;60(6):572–576
  9. Hemby SE, Ginsberg SD, Brunk B, Arnold SE, Trojanowski JQ, Eberwine JH. Gene expression profile for schizophrenia: discrete neuron transcription patterns in the entorhinal cortex. Arch. Gen. Psychiatry. 2002;59(7):631–640
  10. Huang da W, Sherman BT, Tan Q, Kir J, Liu D, Bryant D, et al. DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res. 2007;35:W169–W175Web Server issue
  11. Iwamoto K, Kato T. Gene expression profiling in schizophrenia and related mental disorders. Neuroscientist. 2006;12(4):349–361
  12. Iwamoto K, Kakiuchi C, Bundo M, Ikeda K, Kato T. Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders. Mol. Psychiatry. 2004;9(4):406–416
  13. Iwamoto K, Bundo M, Kato T. Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis. Hum. Mol. Genet. 2005;14(2):241–253
  14. Jaeger J, Sengupta R, Ruzzo WL. Improved gene selection for classification of microarrays. Pac. Symp. Biocomput. 2003;53–64
  15. Khan J, Wei JS, Ringner M, Saal LH, Ladanyi M, Westermann F, et al. Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks. Nat. Med. 2001;7(6):673–679
  16. Lancashire LJ, Rees RC, Ball GR. Identification of gene transcript signatures predictive for estrogen receptor and lymph node status using a stepwise forward selection artificial neural network modelling approach. Artif. Intell. Med. 2008;43(2):99–111
  17. Li Q. Improvement of bias and generalizability for computer-aided diagnostic schemes. Comput. Med. Imaging Graph. 2007;31(4–5):338–345
  18. Li J, Liu H, Ng SK, Wong L. Discovery of significant rules for classifying cancer diagnosis data. Bioinformatics. 2003;19(Suppl 2):ii93–ii102
  19. Lin YH, Friederichs J, Black MA, Mages J, Rosenberg R, Guilford PJ, et al. Multiple gene expression classifiers from different array platforms predict poor prognosis of colorectal cancer. Clin. Cancer Res. 2007;13(2):498–507
  20. Liu B, Cui Q, Jiang T, Ma S. A combinational feature selection and ensemble neural network method for classification of gene expression data. BMC Bioinformatics. 2004;5(136):1–12
  21. Middleton FA, Pato CN, Gentile KL, McGann L, Brown AM, Trauzzi M, et al. Gene expression analysis of peripheral blood leukocytes from discordant sib-pairs with schizophrenia and bipolar disorder reveals points of convergence between genetic and functional genomic approaches. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2005;136B(1):12–25
  22. Mirnics 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(1):53–67
  23. Mirnics K, Middleton FA, Stanwood GD, Lewis DA, Levitt P. Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia. Mol. Psychiatry. 2001;6(3):293–301
  24. Mothet JP, Parent AT, Wolosker H, Brady RO, Linden DJ, Ferris CD, et al. d-serine is an endogenous ligand for the glycine site of the N-methyl-d-aspartate receptor. Proc. Natl. Acad. Sci. U. S. A. 2000;97(9):4926–4931
  25. Ohmori T, Morita K, Saito T, Ohta M, Ueno S, Rokutan K. Assessment of human stress and depression by DNA microarray analysis. J. Med. Invest. 2005;52:266–271Suppl
  26. Vawter MP, Ferran E, Galke B, Cooper K, Bunney WE, Byerley W. Microarray screening of lymphocyte gene expression differences in a multiplex schizophrenia pedigree. Schizophr. Res. 2004;67(1):41–52
  27. O'Neill MC, Song L. Neural network analysis of lymphoma microarray data: prognosis and diagnosis near-perfect. BMC Bioinformatics. 2003;4(13):1–12
  28. Radich JP, Mao M, Stepaniants S, Biery M, Castle J, Ward T, et al. Individual-specific variation of gene expression in peripheral blood leukocytes. Genomics. 2004;83(6):980–988
  29. Rainen L, Oelmueller U, Jurgensen S, Wyrich R, Ballas C, Schram J, et al. Stabilization of mRNA expression in whole blood samples. Clin. Chem. 2002;48(11):1883–1890
  30. Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, et al. Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression. Proc. Natl. Acad. Sci. U. S. A. 2004;101(25):9309–9314
  31. Schwarz E, Bahn S. The utility of biomarker discovery approaches for the detection of disease mechanisms in psychiatric disorders. Br. J. Pharmacol. 2008;153(Suppl 1):S133–S136
  32. Storey JD, Tibshirani R. Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. U. S. A. 2003;100(16):9440–9445
  33. Sugai T, Kawamura M, Iritani S, Araki K, Makifuchi T, Imai C, et al. Prefrontal abnormality of schizophrenia revealed by DNA microarray: impact on glial and neurotrophic gene expression. Ann. N.Y. Acad. Sci. 2004;1025:84–91
  34. Sullivan PF, Fan C, Perou CM. Evaluating the comparability of gene expression in blood and brain. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2006;141B(3):261–268
  35. Tkachev D, Mimmack ML, Ryan MM, Wayland M, Freeman T, Jones PB, et al. Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet. 2003;362(9386):798–805
  36. Tsuang MT, Nossova N, Yager T, Tsuang MM, Guo SC, Shyu KG, et al. Assessing the validity of blood-based gene expression profiles for the classification of schizophrenia and bipolar disorder: a preliminary report. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2005;133B(1):1–5
  37. Whitney AR, Diehn M, Popper SJ, Alizadeh AA, Boldrick JC, Relman DA, et al. Individuality and variation in gene expression patterns in human blood. Proc. Natl. Acad. Sci. U. S. A. 2003;100(4):1896–1901
  38. Xu Y, Selaru FM, Yin J, Zou TT, Shustova V, Mori Y, et al. Artificial neural networks and gene filtering distinguish between global gene expression profiles of Barrett's esophagus and esophageal cancer. Cancer Res. 2002;62(12):3493–3497
  39. Zvara A, Szekeres G, Janka Z, Kelemen JZ, Cimmer C, Santha M, et al. Over-expression of dopamine D2 receptor and inwardly rectifying potassium channel genes in drug-naive schizophrenic peripheral blood lymphocytes as potential diagnostic markers. Dis. Markers. 2005;21(2):61–69

PII: S0920-9964(09)00615-X

doi: 10.1016/j.schres.2009.12.024

Schizophrenia Research
Volume 119, Issue 1 , Pages 210-218 , June 2010

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