title: Molecular profiles of schizophrenia in the CNS at different stages of illness.
abstract: Results from clinical and imaging studies provide evidence for changes in schizophrenia with disease progression, however, the underlying molecular differences that may occur at different stages of illness have not been investigated. To test the hypothesis that the molecular basis for schizophrenia changes from early to chronic illness, we profiled genome-wide expression patterns in prefrontal cortex of schizophrenic subjects at different stages of illness, along with their age- and sex-matched controls. Results show that gene expression profiles change dramatically depending on the stage of illness, whereby the greatest number and magnitude of gene expression differences were detected in subjects with short-term illness (<or=4 years from diagnosis). Comprehensive pathways analyses revealed that each defined stage of illness was associated with dysfunction in both distinct, as well as overlapping systems. Short-term illness was particularly associated with disruptions in gene transcription, metal ion binding, RNA processing and vesicle-mediated transport. In contrast, long-term illness was associated with inflammation, stimulus-response and immune functions. We validated expression differences of 12 transcripts associated with these various functions by real-time PCR analysis. While only four genes, SAMSN1, CDC42BPB, DSC2 and PTPRE, were consistently expressed across all groups, there was dysfunction in overlapping systems among all stages, including cellular signal transduction, lipid metabolism and protein localization. Our results demonstrate that the molecular basis for schizophrenia changes from early to chronic stages, providing evidence for a changing nature of schizophrenia with disease progression.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Narayan
authors.forename: Bin
authors.initials: B
authors.lastname: Tang
authors.forename: Steven R
authors.initials: SR
authors.lastname: Head
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Gilmartin
authors.forename: J Gregor
authors.initials: JG
authors.lastname: Sutcliffe
authors.forename: Brian
authors.initials: B
authors.lastname: Dean
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Thomas
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008297:Male; D008670:Metals / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012559:Schizophrenia / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D008670:Metals
references.citation: OMICS. 2006 Winter;10(4):444-54
references.pmid: 17233556
references.citation: Mol Psychiatry. 2008 Feb;13(2):147-61
references.pmid: 17471287
references.citation: Schizophr Bull. 1988;14(4):515-42
references.pmid: 3064280
references.citation: Aust N Z J Psychiatry. 2007 Apr;41(4):308-20
references.pmid: 17464717
references.citation: Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9873-8
references.pmid: 10449787
references.citation: Stem Cells. 2007 Feb;25(2):354-63
references.pmid: 17082226
references.citation: Arch Gen Psychiatry. 2002 Jul;59(7):631-40
references.pmid: 12090816
references.citation: Schizophr Res. 2001 Oct 1;52(1-2):37-46
references.pmid: 11595390
references.citation: Brain Res Bull. 2001 Jul 15;55(5):641-50
references.pmid: 11576761
references.citation: Psychiatry Clin Neurosci. 2001 Feb;55(1):41-7
references.pmid: 11235857
references.citation: J Neurosci. 2002 Apr 1;22(7):2718-29
references.pmid: 11923437
references.citation: Am J Geriatr Psychiatry. 2003 Nov-Dec;11(6):610-9
references.pmid: 14609801
references.citation: Am J Psychiatry. 1996 Apr;153(4):533-7
references.pmid: 8599402
references.citation: N Engl J Med. 2005 Sep 22;353(12):1209-23
references.pmid: 16172203
references.citation: Am J Psychiatry. 2003 Dec;160(12):2181-9
references.pmid: 14638588
references.citation: Int Rev Neurobiol. 2005;63:41-82
references.pmid: 15797465
references.citation: Mol Psychiatry. 2005 Mar;10(3):309-22
references.pmid: 15303102
references.citation: Neuron. 2001 Aug 16;31(3):353-65
references.pmid: 11516394
references.citation: Biol Psychiatry. 1999 Sep 15;46(6):729-39
references.pmid: 10494440
references.citation: Acta Psychiatr Scand. 1975 Jul;52(1):49-57
references.pmid: 1155202
references.citation: Biol Psychiatry. 2008 Jan 1;63(1):106-13
references.pmid: 17599810
references.citation: Biostatistics. 2007 Jan;8(1):118-27
references.pmid: 16632515
references.citation: Arch Gen Psychiatry. 1991 Nov;48(11):969-77
references.pmid: 1747020
references.citation: Arch Gen Psychiatry. 2003 Jun;60(6):585-94
references.pmid: 12796222
references.citation: Eur Arch Psychiatry Neurol Sci. 1989;238(3):126-34
references.pmid: 2785921
references.citation: Psychiatry Res. 2004 Jan 15;130(1):57-70
references.pmid: 14972368
references.citation: Arch Gen Psychiatry. 2001 Feb;58(2):148-57
references.pmid: 11177116
references.citation: Neuroscientist. 2006 Aug;12(4):349-61
references.pmid: 16840711
references.citation: Biol Psychiatry. 2007 Oct 1;62(7):711-21
references.pmid: 17568569
references.citation: Int J Neuropsychopharmacol. 2007 Aug;10(4):557-63
references.pmid: 17291371
references.citation: Neurobiol Aging. 1992 Nov-Dec;13(6):641-8
references.pmid: 1362796
references.citation: Neuron. 2000 Oct;28(1):53-67
references.pmid: 11086983
references.citation: Psychiatry Res. 2007 Feb 28;154(2):133-45
references.pmid: 17276660
references.citation: Biol Psychiatry. 2006 Jul 15;60(2):163-76
references.pmid: 16616896
references.citation: J Neurochem. 2006 Feb;96(3):743-57
references.pmid: 16405510
references.citation: Mol Psychiatry. 2006 Mar;11(3):241-51
references.pmid: 16288314
references.citation: Neuropsychopharmacology. 2007 Oct;32(10):2057-66
references.pmid: 17327887
references.citation: Int J Neuropsychopharmacol. 2007 Aug;10(4):565-73
references.pmid: 17291370
references.citation: Bioinformatics. 2005 May 15;21(10):2548-9
references.pmid: 15734774
references.citation: J Clin Psychiatry. 2006 Oct;67(10):e14
references.pmid: 17107237
references.citation: Br J Psychiatry. 1995 Sep;167(3):338-42
references.pmid: 7496642
references.citation: Biol Psychiatry. 2001 Dec 1;50(11):884-97
references.pmid: 11743943
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4746-51
references.pmid: 11296301
references.citation: Genome Biol. 2001;2(8):RESEARCH0032
references.pmid: 11532216
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
references.pmid: 9843981
references.citation: J Nerv Ment Dis. 1997 Dec;185(12):715-21
references.pmid: 9442182
references.citation: J Psychiatr Res. 1998 May-Aug;32(3-4):133-41
references.pmid: 9793866
references.citation: Am J Psychiatry. 2007 Jul;164(7):1082-9
references.pmid: 17606660
references.citation: Biol Psychiatry. 1999 Jan 1;45(1):32-40
references.pmid: 9894573
references.citation: Bioinformatics. 2004 Jan 1;20(1):93-9
references.pmid: 14693814
references.citation: Brain Res Bull. 2001 Jul 15;55(5):651-9
references.pmid: 11576762
references.citation: Schizophr Res. 2005 Nov 15;79(2-3):157-73
references.pmid: 16139990
references.citation: Mol Psychiatry. 2002;7(6):571-8
references.pmid: 12140780
references.citation: Lancet. 2003 Sep 6;362(9386):798-805
references.pmid: 13678875
references.citation: Ann N Y Acad Sci. 2004 Oct;1025:84-91
references.pmid: 15542704
references.citation: Nat Rev Neurosci. 2005 Apr;6(4):312-24
references.pmid: 15803162
references.citation: CNS Spectr. 2005 Apr;10(4):277-80
references.pmid: 15788955
references.citation: Mol Neurobiol. 2006 Oct;34(2):109-28
references.pmid: 17220533
references.citation: Schizophr Res. 2005 Apr 1;74(1):15-26
references.pmid: 15694750
references.citation: Schizophr Res. 2002 Nov 1;58(1):11-20
references.pmid: 12363385
references.citation: Am J Psychiatry. 2001 Sep;158(9):1441-8
references.pmid: 11532729
references.citation: Dialogues Clin Neurosci. 2006;8(1):71-8
references.pmid: 16640116