Psychiatric Disorders Biomarker Identification: from Proteomics to Systems Biology

Abstract

The pathobiology of psychiatric disorders remains mostly obscure. Diagnosis is often imprecise and current treatments are empirical and at best symptomatic. The identification of biomarkers can help with developing improved drugs and establishing more precise disease diagnoses. Proteins are prime biomarker candidates, because of the central role they play in both, disease etiology and treatment. Today's high throughput methods are capable to detect potential biomarkers by screening complex proteome mixtures of different disease states. A meaningful interpretation of the candidates is indispensable for deeper insights into affective disorders and requires investigation on multiple levels of the cellular system. Thus a systems biology approach is critical to understand and explain the behavior of biomarker candidates and to make use of them in psychiatry.

References

• 1 Anderson NL, Anderson NG. Proteome and proteomics: New technologies, new concepts, and new words.  Electrophoresis. 1998;  19 ((11)) 1853-1861
• 2 Bender W, Albus M, Möller HJ, Tretter F. Towards systemic theories in biological psychiatry.  Pharmacopsychiatry. 2006;  39 ((Suppl 1)) S4-S9
• 3 Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: Meta-analysis of clinical studies.  Acta Neurol Scand Suppl. 1994;  154 7-14
• 4 Chen F, Wollmer MA, Hoerndli F, Munch G, Kuhla B, Rogaev EI. et al . Role for glyoxalase I in Alzheimer's disease.  Proc Natl Acad Sci USA. 2004;  101 ((20)) 7687-7692
• 5 Carlsson A. The neurochemical circuitry of schizophrenia.  Pharmacopsychiatry. 2006;  39 ((Suppl 1)) S10-S14
• 6 Ditzen C, Jastorff AM, Kessler MS, Bunck M, Teplytska L, Erhardt A. et al . Protein biomarkers in a mouse model of extremes in trait anxiety.  Mol Cell Proteomics. 2006;  5 ((10)) 1914-1920
• 7 Gross C, Hen R. The developmental origins of anxiety.  Nat Rev Neurosci. 2004;  5 ((7)) 545-552
• 8 Hegde AN, DiAntonio A. Ubiquitin and the synapse.  Nat Rev Neurosci. 2002;  3 ((11)) 854-861
• 9 Holland JH. Adaptation in natural and artificial systems. 1st ed. Ann Arbor (MI): The University of Michigan Press 1975
• 10 Hyman SE. Can neuroscience be integrated into the DSM-V?.  Nat Rev Neurosci. 2007;  8 ((9)) 725-732
• 11 Insel TR. From animal models to model animals.  Biol Psychiatry. 2007;  62 ((12)) 1337-1339
• 12 Junaid MA, Kowal D, Barua M, Pullarkat PS, Sklower Brooks S, Pullarkat RK. Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor.  Am J Med Genet A. 2004;  131 ((1)) 11-17
• 13 Kanehisa M. KEGG: From genes to biochemical pathways. In: Letovsky SI, editor. Bioinfomatics: Databases and Systems. Norwell (MA): Kluwer Academic Publishers 1999: 63-76
• 14 Kim SY, Volsky DJ. PAGE: parametric analysis of gene set enrichment.  BMC Bioinformatics. 2005;  6 144
• 15 Kitano H. Computational systems biology.  Nature. 2002;  420 ((6912)) 206-210
• 16 Krömer SA, Kesser MS, Milfay D, Birg IN, Bunck M, Czibere L. et al . Identification of glyoxalase-I as a protein marker in a mouse model of extremes in trait anxiety.  J Neurosci. 2005;  25 ((17)) 4375-4384
• 17 Ma Y, Peng Y. Co-expression Gene Discovery from Microarray for Integrative Systems Biology. In: Li X, Zaiane OR, Li Z editors. Advanced Data Mining and Applications 2006: 2nd International Conference. ADMA; 2006 August 14–16; Xian, China. Heidelberg: Springer-Verlag 2006: 809-818
• 18 MacCoss MJ, Wu CC, Matthews DE, Yates  3rd  JR. Measurement of the isotope enrichment of stable isotope-labeled proteins using high-resolution mass spectra of peptides.  Anal Chem. 2005;  77 ((23)) 7646-7653
• 19 Mill J, Petronis A. Molecular studies of major depressive disorder: the epigenetic perspective.  Mol Psychiatry. 2007;  12 ((9)) 799-814
• 20 Mootha VK, Lepage P, Miller K, Bunkenborg J, Reich M, Hjerrild M. et al . Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics.  Proc Natl Acad Sci USA. 2003;  100 ((2)) 605-610
• 21 Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J. et al . PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes.  Nat Genet. 2003;  34 ((3)) 267-273
• 22 Ong SE, Mann M. Mass spectrometry-based proteomics turns quantitative.  Nat Chem Biol. 2005;  1 ((5)) 252-262
• 23 Saxena V, Orgill D, Kohane I. Absolute enrichment: gene set enrichment analysis for homeostatic systems.  Nucleic Acids Res. 2006;  34 ((22)) e151
• 24 Schlösser RGM, Koch K, Wagner G. Assessing the state space of the brain with fMRI: an integrative view of current methods.  Pharmacopsychiatry. 2007;  40 ((Suppl 1)) S85-S92
• 25 Sheeley DM, Breen JJ, Old SE. Building integrated approaches for the proteomics of complex, dynamic systems: NIH programs in technology and infrastructure development.  J Proteome Res. 2005;  4 ((4)) 1114-1122
• 26 Silveri MM, Parow AM, Villafuerte RA, Damico KE, Goren J, Stoll AL. et al . S-adenosyl-L-methionine: effects on brain bioenergetic status and transverse relaxation time in healthy subjects.  Biol Psychiatry. 2003;  54 ((8)) 833-839
• 27 Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA. et al . Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles.  Proc Natl Acad Sci USA. 2005;  102 ((43)) 15545-15550
• 28 Tanna VL, Wilson AF, Winokur G, Elston RC. Linkage analysis of pure depressive disease.  J Psychiatr Res. 1989;  23 ((2)) 99-107
• 29 The Gene Ontology Consortium . The Gene Ontology project in 2008.  Nucleic Acids Res. 2008;  36 ((Database issue)) D440-D444
• 30 Tiffin N, Kelso JF, Powell AR, Pan H, Bajic VB, Hide WA. Integration of text- and data-mining using ontologies successfully selects disease gene candidates.  Nucleic Acids Res. 2005;  33 ((5)) 1544-1552

1 both authors contributed equally to this work.

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