Molecular Neurobiology

, Volume 53, Issue 5, pp 2927–2935 | Cite as

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

  • Michael Maes
  • Gabriel Nowak
  • Javier R. Caso
  • Juan Carlos Leza
  • Cai Song
  • Marta Kubera
  • Hans Klein
  • Piotr Galecki
  • Cristiano Noto
  • Enrico Glaab
  • Rudi Balling
  • Michael Berk


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.


Depression Immune Inflammation Neuroprogression Oxidative and nitrosative stress Leaky gut IDO TRYCATs 



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.


All authors contributed equally to the paper.


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.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Michael Maes
    • 1
    • 2
    • 3
    • 15
  • Gabriel Nowak
    • 4
    • 5
  • Javier R. Caso
    • 6
  • Juan Carlos Leza
    • 6
  • Cai Song
    • 7
    • 8
  • Marta Kubera
    • 9
  • Hans Klein
    • 10
  • Piotr Galecki
    • 11
  • Cristiano Noto
    • 12
  • Enrico Glaab
    • 13
  • Rudi Balling
    • 13
  • Michael Berk
    • 1
    • 14
  1. 1.IMPACT Research CenterDeakin UniversityGeelongAustralia
  2. 2.Department of Psychiatry, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  3. 3.Health Sciences Graduate Program, Health Sciences CenterState University of LondrinaLondrinaBrazil
  4. 4.Department of PharmacobiologyJagiellonian University Medical CollegeKrakówPoland
  5. 5.Department of Neurobiology, Institute of PharmacologyPolish Academy of SciencesKrakówPoland
  6. 6.Department of Pharmacology, Faculty of MedicineUniversity Complutense, Centro de Investigación Biomédica en Salud Mental (CIBERSAM) & Instituto de Investigación Sanitaria Hospital 12 de OctubreMadridSpain
  7. 7.Department of Psychology and NeuroscienceDalhousie UniversityHalifaxCanada
  8. 8.Research Institute for Marine Nutrition and DrugsGuangdong Ocean UniversityZhanjiangChina
  9. 9.Department of Experimental Neuroendocrinology, Institute of PharmacologyPolish Academy of ScienceKrakowPoland
  10. 10.Department of PsychiatryUniversity of GroningenGroningenThe Netherlands
  11. 11.Department of Adult PsychiatryMedial University of ŁódźŁódźPoland
  12. 12.Department of PsychiatryUniversidade Federal de São Paulo (UNIFESP)Sao PauloBrazil
  13. 13.Luxembourg Centre for Systems BiomedicineUniversity of LuxemburgEsch-sur-AlzetteLuxembourg
  14. 14.Orygen, The National Centre of Excellence in Youth Mental Health, Department of Psychiatry and The Florey Institute of Neuroscience and Mental HealthThe University of MelbourneParkvilleAustralia
  15. 15.IMPACT Strategic Research Center, Barwon HealthDeakin UniversityGeelongAustralia

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