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)