Bipolar Disorder: Role of Immune-Inflammatory Cytokines, Oxidative and Nitrosative Stress and Tryptophan Catabolites

Abstract

Bipolar disorder (BD) is a complex disorder with a range of presentations. BD is defined by the presentation of symptoms of mania or depression, with classification dependent on patient/family reports and behavioural observations. Recent work has investigated the biological underpinnings of BD, highlighting the role played by increased immune-inflammatory activity, which is readily indicated by changes in pro-inflammatory cytokines or signalling, both centrally and systemically, e.g. increased interleukin-6 trans-signalling. Here, we review the recent data on immune-inflammatory pathways and cytokine changes in BD. Such changes are intimately linked to changes in oxidative and nitrosative stress (O&NS) and neuroregulatory tryptophan catabolites (TRYCATs), both centrally and peripherally. TRYCATs take tryptophan away from serotonin, N-acetylserotonin and melatonin synthesis, driving it down the TRYCAT pathway, predominantly as a result of the pro-inflammatory cytokine induction of indoleamine 2,3-dioxygenase. This has led to an emerging biological perspective on the aetiology, course and treatment of BD. Such data also better integrates the numerous comorbidities associated with BD, including addiction, cardiovascular disorders and increased reporting of pain. Immune-inflammatory, O&NS and TRYCAT pathways are also likely to be relevant biological underpinnings to the significant decrease in life expectancy in BD.

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George Anderson and Michael Maes declare that they have no conflict of interest.

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Anderson, G., Maes, M. Bipolar Disorder: Role of Immune-Inflammatory Cytokines, Oxidative and Nitrosative Stress and Tryptophan Catabolites. Curr Psychiatry Rep 17, 8 (2015). https://doi.org/10.1007/s11920-014-0541-1

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Keywords

  • Bipolar disorder
  • Depression
  • Mania
  • Oxidative and nitrosative stress
  • Inflammation
  • Melatonin
  • Tryptophan catabolites