CNS Drugs

, Volume 28, Issue 1, pp 1–10 | Cite as

Role of Immune-Inflammatory and Oxidative and Nitrosative Stress Pathways in the Etiology of Depression: Therapeutic Implications

  • George Anderson
  • Michael Berk
  • Olivia Dean
  • Steven Moylan
  • Michael Maes
Leading Article


Accumulating data have led to a re-conceptualization of depression that emphasizes the role of immune-inflammatory processes, coupled to oxidative and nitrosative stress (O&NS). These in turn drive the production of neuroregulatory tryptophan catabolites (TRYCATs), driving tryptophan away from serotonin, melatonin, and N-acetylserotonin production, and contributing to central dysregulation. This revised perspective better encompasses the diverse range of biological changes occurring in depression and in doing so provides novel and readily attainable treatment targets, as well as potential screening investigations prior to treatment initiation. We briefly review the role that immune-inflammatory, O&NS, and TRYCAT pathways play in the etiology, course, and treatment of depression. We then discuss the pharmacological treatment implications arising from this, including the potentiation of currently available antidepressants by the adjunctive use of immune- and O&NS-targeted therapies. The use of such a frame of reference and the treatment benefits attained are likely to have wider implications and utility for depression-associated conditions, including the neuroinflammatory and (neuro)degenerative disorders.


Melatonin CoQ10 Neopterin Quinolinic Acid Treatment Resistance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Authors’ contributions:

GA and MM participated in the design of this review, while all authors helped to draft the paper. All authors contributed equally to this paper. All authors read and approved the final version.

Conflict of interest

No specific funding was obtained for this specific review.

MBk has received grant/research support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Organon, Novartis, Mayne Pharma, and Servier, has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay, and Wyeth, and served as a consultant to Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, and Servier. OMD has received grant support from the Brain and Behavior Foundation, Simons Autism Foundation, Cooperative Research Centre-Mental Health, Stanley Medical Research Institute, Lilly, and NHMRC, and received an ASBD/Servier grant.

The other authors, GA, MM, OD, and SM, declare that they have no competing interests.


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Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • George Anderson
    • 1
  • Michael Berk
    • 2
    • 3
    • 4
    • 5
  • Olivia Dean
    • 2
    • 3
    • 5
  • Steven Moylan
    • 2
  • Michael Maes
    • 2
    • 6
  1. 1.CRCGlasgowScotland
  2. 2.IMPACT Strategic Research Centre and School of MedicineDeakin UniversityGeelongAustralia
  3. 3.Department of PsychiatryThe University of MelbourneParkvilleAustralia
  4. 4.Orygen Youth Health Research CentreParkvilleAustralia
  5. 5.Florey Institute for Neuroscience and Mental HealthParkvilleAustralia
  6. 6.Department of PsychiatryChulalongkorn UniversityBangkokThailand

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