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Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research.

Maes,M, Nowak,G, Caso,JR, Leza,JC, Song,C, Kubera,M, Klein,H, Galecki,P, Noto,C, Glaab,E, Balling,R and Berk,M 2015, Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research., Mol Neurobiol, doi: 10.1007/s12035-015-9183-5.

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Title Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research.
Author(s) Maes,M
Nowak,G
Caso,JR
Leza,JC
Song,C
Kubera,M
Klein,H
Galecki,P
Noto,C
Glaab,E
Balling,R
Berk,MORCID iD for Berk,M orcid.org/0000-0002-5554-6946
Journal name Mol Neurobiol
Publisher Springer
Publication date 2015-05
ISSN 1559-1182
Keyword(s) Depression
IDO
Immune
Inflammation
Leaky gut
Neuroprogression
Oxidative and nitrosative stress
TRYCATs
Summary Meta-analyses confirm that depression is accompanied by signs of inflammation including increased levels of acute phase proteins, e.g., C-reactive protein, and pro-inflammatory cytokines, e.g., interleukin-6. Supporting the translational significance of this, a meta-analysis showed that anti-inflammatory drugs may have antidepressant effects. Here, we argue that inflammation and depression research needs to get onto a new track. Firstly, the choice of inflammatory biomarkers in depression research was often too selective and did not consider the broader pathways. Secondly, although mild inflammatory responses are present in depression, other immune-related pathways cannot be disregarded as new drug targets, e.g., activation of cell-mediated immunity, oxidative and nitrosative stress (O&NS) pathways, autoimmune responses, bacterial translocation, and activation of the toll-like receptor and neuroprogressive pathways. Thirdly, anti-inflammatory treatments are sometimes used without full understanding of their effects on the broader pathways underpinning depression. Since many of the activated immune-inflammatory pathways in depression actually confer protection against an overzealous inflammatory response, targeting these pathways may result in unpredictable and unwanted results. Furthermore, this paper discusses the required improvements in research strategy, i.e., path and drug discovery processes, omics-based techniques, and systems biomedicine methodologies. Firstly, novel methods should be employed to examine the intracellular networks that control and modulate the immune, O&NS and neuroprogressive pathways using omics-based assays, including genomics, transcriptomics, proteomics, metabolomics, epigenomics, immunoproteomics and metagenomics. Secondly, systems biomedicine analyses are essential to unravel the complex interactions between these cellular networks, pathways, and the multifactorial trigger factors and to delineate new drug targets in the cellular networks or pathways. Drug discovery processes should delineate new drugs targeting the intracellular networks and immune-related pathways.
DOI 10.1007/s12035-015-9183-5
Field of Research 110319 Psychiatry (incl Psychotherapy)
Socio Economic Objective 920410 Mental Health
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Springer Verlag
Persistent URL http://hdl.handle.net/10536/DRO/DU:30073828

Document type: Journal Article
Collection: School of Medicine
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