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Metabolomics: A Global Biochemical Approach to the Discovery of Biomarkers for Psychiatric Disorders

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Biomarkers for Psychiatric Disorders

Abstract

A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal or pathogenic processes, as well as responses to therapeutic interventions. The discovery of biomarkers for psychiatric disorders and their incorporation into clinical decision-making could dramatically change the future delivery of health care. Thus, there is great need for the discovery, evaluation, and clinical validation of biomarkers. Abnormalities present in psychiatric illness might be related to changes in cellular metabolism leading to measurable differences in the composition and levels of the universe of all plasma metabolites known as the metabolome. Characterizing these biochemical changes could be very useful in the identification of disease biomarkers. Metabolomics is the study of metabolism at the global level. The concept that a metabolic state is representative of the overall physiologic status of the organism lies at the heart of metabolomics. Metabolomic studies capture global biochemical events by assaying thousands of small molecules in cells, tissues, organs, or biological fluids, followed by the application of informatic techniques to define metabolomic signatures. Metabolomic studies can lead to enhanced understanding of disease mechanisms in psychiatric illnesses, as demonstrated by early work in schizophrenia and mood disorders. This chapter begins with an overview of the principles underlying biomarker research and changes in metabolism associated with psychiatric disorders. Then, it describes the conceptual basis for metabolomics, the analytical and informatic techniques used to define metabolomic signatures, and how to use this information to identify biomarkers for psychiatric disorders.

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Abbreviations

5-HIAA:

5-hydroxyindoleacetic acid

5HT:

Serotonin

ACH:

Acetylcholine

AODS:

Antioxidant defense system

BD:

Bipolar Disorder

CSF:

Cerebrospinal fluid

DA:

Dopamine

DFA:

Discriminant function analysis

GABA:

Gamma-aminobutyric acid

GC:

Gas chromatography

Glu:

Glutamate

HVA:

Homovanillic acid

LC:

Liquid chromatography

LCECA:

Liquid chromatography coupled with electrochemical array detection

LC-MS:

Liquid chromatography coupled with mass spectroscopy

Li:

Lithium

MDD:

Major Depressive Disorder

MHPG:

3-methoxy-4-hydroxyphenylglycol

MS:

Mass spectrometry

NE (or NA):

Norepinephrine

NMR:

Nuclear magnetic resonance spectroscopy

NT:

Neurotransmitter pathways

PC:

Phosphotidylcholine

PCA:

Principal components analysis

PDBs:

Psychiatric disorders biomarkers

PE:

Phosphotidylethanolamine

PLS:

Partial least squares

SQZ:

Schizophrenia

SSRI:

Selective serotonin reuptake inhibitors

Vlp:

Valproate

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Acknowledgments

Supported in part by National Institutes of Health grants R24 GM078233, “The Metabolomics Research Network” (R.K.D., B.S.K., R.M.W.); SMRI (R.K.-D.), NARSAD (R.K.-D.), Stanley Medical Research Institute (M.P.Q. and J.C.S.); MH 68766 (J.C.S.), MH 69774 (J.C.S.), MH 068662 (J.C.S.), RR 20571 (J.C.S.), UTHSCSA's GCRC (M01-RR-01346) (J.C.S.) and Department of Psychiatry Friends of Psychiatry Grant (M.P.Q. and J.C.S.), NARSAD (J.C.S.), Veterans Administration (Merit Review) (J.C.S.), and the Krus Endowed Chair in Psychiatry (J.C.S.).

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  1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA

    Rima Kaddurah-Daouk

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  1. Rima Kaddurah-Daouk
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    Kaddurah-Daouk, R., Soares, J.C., Quinones, M.P. (2008). Metabolomics: A Global Biochemical Approach to the Discovery of Biomarkers for Psychiatric Disorders. In: Turck, C. (eds) Biomarkers for Psychiatric Disorders. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-79251-4_6

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