Omics-Based Biomarkers: Application of Metabolomics in Neuropsychiatric Disorders

International Journal of Neuropsychopharmacology, Mar 2016

One of the major concerns of modern society is to identify putative biomarkers that serve as a valuable early diagnostic tool to identify a subset of patients with increased risk to develop neuropsychiatric disorders. Biomarker identification in neuropsychiatric disorders is proposed to offer a number of important benefits to patient well-being, including prediction of forthcoming disease, diagnostic precision, and a level of disease description that would guide treatment choice. Nowadays, the metabolomics approach has unlocked new possibilities in diagnostics of devastating disorders like neuropsychiatric disorders. Metabolomics-based technologies have the potential to map early biochemical changes in disease and hence provide an opportunity to develop predictive biomarkers that can be used as indicators of pathological abnormalities prior to development of clinical symptoms of neuropsychiatric disorders. This review highlights different -omics strategies for biomarker discovery in neuropsychiatric disorders. We also highlight initial outcomes from metabolomics studies in psychiatric disorders such as schizophrenia, bipolar disorder, and addictive disorders. This review will also present issues and challenges regarding the implementation of the metabolomics approach as a routine diagnostic tool in the clinical laboratory in context with neuropsychiatric disorders.

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Omics-Based Biomarkers: Application of Metabolomics in Neuropsychiatric Disorders

Advance Access Publication October Omics-Based Biomarkers: Application of Metabolomics in Neuropsychiatric Disorders Sumit?Sethi 0 1 Elisa?Brietzke 0 1 0 Interdisciplinary Laboratory for Clinical Neuroscience (LiNC), Department of Psychiatry, Universidade Federal de Sa?o Paulo - UNIFESP , Sa?o Paulo , Brazil 1 de Sa?o Paulo - UNIFESP, Research Building II, Rua Pedro de Toledo , 669-3 floor Funds - Vila Clementino - Sa?o Paulo, SP- Brazil One of the major concerns of modern society is to identify putative biomarkers that serve as a valuable early diagnostic tool to identify a subset of patients with increased risk to develop neuropsychiatric disorders. Biomarker identification in neuropsychiatric disorders is proposed to offer a number of important benefits to patient well-being, including prediction of forthcoming disease, diagnostic precision, and a level of disease description that would guide treatment choice. Nowadays, the metabolomics approach has unlocked new possibilities in diagnostics of devastating disorders like neuropsychiatric disorders. Metabolomics-based technologies have the potential to map early biochemical changes in disease and hence provide an opportunity to develop predictive biomarkers that can be used as indicators of pathological abnormalities prior to development of clinical symptoms of neuropsychiatric disorders. This review highlights different -omics strategies for biomarker discovery in neuropsychiatric disorders. We also highlight initial outcomes from metabolomics studies in psychiatric disorders such as schizophrenia, bipolar disorder, and addictive disorders. This review will also present issues and challenges regarding the implementation of the metabolomics approach as a routine diagnostic tool in the clinical laboratory in context with neuropsychiatric disorders. biomarkers; bipolar disorder; drug addiction; metabolomics; schizophrenia Introduction Millions of people undergo mental disorders such as major depressive disorder (MDD), bipolar disorder (BD), schizophrenia (SCZ), and addiction. According to the World Health Organization, the worldwide problem of neuropsychiatric disorders is 13% higher than others such as cardiovascular di-s eases and cancer (WHO, 2008). Though significant improvement has been made in the treatment of neuropsychiatric disorders, numerous patients do not respond to current therapies, had an inadequate response, or are incapable to tolerate?them. Unfortunately, our understanding of pathophysiology of these disorders remains limited. One reason for this is the fact that most of mental disorders are not unitary conditions but may be a complex of psychopathological dimensions that are yet to be identified. In addition, present knowledge is also incomplete in predicting who will and who will not respond to a certain treatment. Such doubtfulness is worrying for patients and fam-i lies who are continually involved in trial-and error selections in search of ?the right fit? and for clinicians thus resorting to extensive substituting of medications (Weiden and Buckley, 2007 ) and polypharmacy (Tranulis et? al., 2008) . So, there is a further requirement to scale up awareness in the study of psychiatric disorders in an effort to recognize at a system level the entirety of alterations that can contribute to the pathogenesis of these environments. Disease-specific molecular fingerprinting can be well-defined by integrating the use of high-throughput methodologies at the core of genomics, proteomics, metabolomics, and other -omics approaches and could aid to map dysregulated systems involved in disease pathogenesis. Furthermore, global mapping of uncharacteristic pathways in psychiatric disorders can lead to the identification of biomarkers of disease and response (Quinones and Kaddurah-Daouk, 2009) . This review summarizes general aspects of biomarker research and how metabolic abnormalities in psychiatric disorders can contribute to the identification of distinctive biomarkers. We also discuss existing challenges and the potential of metabolic approaches in the process of biomarker discovery. Biomarker Discovery Research The use of the term ?biomarker? dates back to as early as 1980 (Jeffrey, 2005) . In 1998, the National Institutes of Health Biomarkers Definitions Working Group described a biomarker as ?a characteristic that is objectively measured and evaluated as an indicator of normal biological courses, pathogenic progressions, or pharmacologic responses to a therapeutic intervention? (Aronson, 2005; Strimbu and Tavel, 2010) . In metabolomics, biomarkers can be measured in any biological sample, for example, blood, urine, or saliva (Bogdanov et?al., 2008; Holmes et?al., 2008b; Kaddurah-Daouk et? al., 2009) and can be indicators of disease traits (or risk markers), disease states, or disease rates (progression). Biomarkers could be considered to extend all the way to include our fixed genomic characters. At the level of the subcel (...truncated)


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Sethi, Sumit, Brietzke, Elisa. Omics-Based Biomarkers: Application of Metabolomics in Neuropsychiatric Disorders, International Journal of Neuropsychopharmacology, 2016, Volume 19, Issue 3, DOI: 10.1093/ijnp/pyv096