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

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Abstract

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.

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Acknowledgments

MB is supported by a NHMRC Senior Principal Research Fellowship (GNT1059660).

Conflict of Interest

MB has received Grant/Research Support from the National Institute of Health (USA), Simons Foundation, CRC for Mental Health, Stanley Medical Research Institute, Medical Benefits Fund, National Health and Medical Research Council (NHMRC of Australia), Beyond Blue, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Organon, Novartis, Mayne Pharma, Servier, and Astra Zeneca. He has been a paid consultant for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, and Pfizer and a paid speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Organon, Pfizer, Sanofi Synthelabo, Solvay, and Wyeth.

Other authors do not report any conflict of interest.

Contributions

All authors contributed equally to the paper.

Funding

There was no specific funding for this specific study.

We confirm that we have read the journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Author information

Authors and Affiliations

  1. IMPACT Research Center, Deakin University, Geelong, Australia

    Michael Maes & Michael Berk

  2. Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Michael Maes

  3. Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, Brazil

    Michael Maes

  4. Department of Pharmacobiology, Jagiellonian University Medical College, Medyczna 9, 30-688, Kraków, Poland

    Gabriel Nowak

  5. Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland

    Gabriel Nowak

  6. Department of Pharmacology, Faculty of Medicine, University Complutense, Centro de Investigación Biomédica en Salud Mental (CIBERSAM) & Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain

    Javier R. Caso & Juan Carlos Leza

  7. Department of Psychology and Neuroscience, Dalhousie University, Halifax, Canada

    Cai Song

  8. Research Institute for Marine Nutrition and Drugs, Guangdong Ocean University, Zhanjiang, China

    Cai Song

  9. Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Science, Krakow, Poland

    Marta Kubera

  10. Department of Psychiatry, University of Groningen, Groningen, The Netherlands

    Hans Klein

  11. Department of Adult Psychiatry, Medial University of Łódź, Łódź, Poland

    Piotr Galecki

  12. Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), Sao Paulo, Brazil

    Cristiano Noto

  13. Luxembourg Centre for Systems Biomedicine, University of Luxemburg, Esch-sur-Alzette, Luxembourg

    Enrico Glaab & Rudi Balling

  14. Orygen, The National Centre of Excellence in Youth Mental Health, Department of Psychiatry and The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia

    Michael Berk

  15. IMPACT Strategic Research Center, Barwon Health, Deakin University, Geelong, Vic, Australia

    Michael Maes

Authors
  1. Michael Maes
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  2. Gabriel Nowak
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  3. Javier R. Caso
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  4. Juan Carlos Leza
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  5. Cai Song
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  6. Marta Kubera
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  7. Hans Klein
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  8. Piotr Galecki
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  9. Cristiano Noto
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  10. Enrico Glaab
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  11. Rudi Balling
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  12. Michael Berk
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Corresponding author

Correspondence to Michael Maes.

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Maes, M., Nowak, G., Caso, J.R. et al. Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research. Mol Neurobiol 53, 2927–2935 (2016). https://doi.org/10.1007/s12035-015-9183-5

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  • DOI: https://doi.org/10.1007/s12035-015-9183-5

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