Skip to main content

Advertisement

SpringerLink
Log in

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

  • Bipolar Disorders (W Coryell, Section Editor)
  • Published:
Current Psychiatry Reports Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Merinkangas KR, Tohen M. Epidemiology of bipolar disorder in adults and children. In: Tsuang MT, Tohen MT, Jones PB, editors. Textbook in psychiatric epidemiology. Chichester: Wiley; 2011. p. 329–42.

    Chapter  Google Scholar 

  2. Leussis MP, Madison JM, Petryshen TL. Ankyrin 3: genetic association with bipolar disorder and relevance to disease pathophysiology. Biol Mood Anxiety Disord. 2012;2(1):18.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Seifuddin F et al. Meta-analysis of genetic association studies on bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2012;159B(5):508–18.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Frey BN et al. Biomarkers in bipolar disorder: a positional paper from the International Society for Bipolar Disorders Biomarkers Task Force. Aust N Z J Psychiatry. 2013;47(4):321–32.

    Article  PubMed  Google Scholar 

  5. Maes M et al. Interleukin-2 and interleukin-6 in schizophrenia and mania: effects of neuroleptics and mood stabilizers. J Psychiatr Res. 1995;29(2):141–52.

    Article  CAS  PubMed  Google Scholar 

  6. Maes M et al. Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. J Affect Disord. 1995;34(4):301–9.

    Article  CAS  PubMed  Google Scholar 

  7. Maes M et al. Acute phase proteins in schizophrenia, mania and major depression: modulation by psychotropic drugs. Psychiatry Res. 1997;66(1):1–11.

    Article  CAS  PubMed  Google Scholar 

  8. Wadee AA et al. Serological observations in patients suffering from acute manic episodes. Hum Psychopharmacol. 2002;17(4):175–9.

    Article  PubMed  Google Scholar 

  9. Anderson G et al. Increased IL-6 trans-signaling in depression: focus on the tryptophan catabolite pathway, melatonin and neuroprogression. Pharmacol Rep. 2013;65(6):1647–54.

    Article  CAS  PubMed  Google Scholar 

  10. Maes M et al. Targeting classical IL-6 signalling or IL-6 trans-signalling in depression? Expert Opin Ther Targets. 2014;18(5):495–512.

    Article  CAS  PubMed  Google Scholar 

  11. Moylan S et al. Oxidative & nitrosative stress in depression: why so much stress? Neurosci Biobehav Rev. 2014;45:46–62.

    Article  CAS  PubMed  Google Scholar 

  12. Berk M et al. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev. 2011;35(3):804–17.

    Article  CAS  PubMed  Google Scholar 

  13. Myint AM et al. Tryptophan breakdown pathway in bipolar mania. J Affect Disord. 2007;102(1–3):65–72.

    Article  CAS  PubMed  Google Scholar 

  14. Nievergelt CM et al. Suggestive evidence for association of the circadian genes PERIOD3 and ARNTL with bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2006;141B(3):234–41.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Duffy A et al. Biological indicators of illness risk in offspring of bipolar parents: targeting the hypothalamic-pituitary-adrenal axis and immune system. Early Interv Psychiatry. 2012;6(2):128–37.

    Article  PubMed  Google Scholar 

  16. Berk M et al. Stage managing bipolar disorder. Bipolar Disord. 2014;16(5):471–7. This is a comprehensive analysis of recent conceptualizations of the neuroprogressive nature of bipolar disorder.

    Article  PubMed  Google Scholar 

  17. Gama CS et al. Staging and neuroprogression in bipolar disorder: a systematic review of the literature. Rev Bras Psiquiatr. 2013;35(1):70–4.

    Article  PubMed  Google Scholar 

  18. Rege S, Hodgkinson SJ. Immune dysregulation and autoimmunity in bipolar disorder: synthesis of the evidence and its clinical application. Aust N Z J Psychiatry. 2013;47(12):1136–51.

    Article  PubMed  Google Scholar 

  19. Westman J et al. Cardiovascular mortality in bipolar disorder: a population-based cohort study in Sweden. BMJ Open. 2013;18:3(4).

    Google Scholar 

  20. Yee HA, Loh HS, Ng CG. The prevalence and correlates of alcohol use disorder amongst bipolar patients in a hospital setting, Malaysia. Int J Psychiatry Clin Pract. 2013;17(4):292–7.

    Article  PubMed  Google Scholar 

  21. Miller C, Bauer MS. Excess mortality in bipolar disorders. Curr Psychiatry Rep. 2014;16(11):499.

    Article  PubMed  Google Scholar 

  22. Markham JA, Koenig JI. Prenatal stress: role in psychotic and depressive diseases. Psychopharmacology (Berl). 2011;214:89–106.

    Article  CAS  Google Scholar 

  23. Hamdani N et al. Relationship between Toxoplasma gondii infection and bipolar disorder in a French sample. J Affect Disord. 2013;148(2–3):444–8.

    Article  CAS  PubMed  Google Scholar 

  24. do Prado CH et al. Reduced regulatory T cells are associated with higher levels of Th1/TH17 cytokines and activated MAPK in type 1 bipolar disorder. Psychoneuroendocrinology. 2013;38(5):667–76. This is an interesting article showing significant changes in bipolar patients in regard to immune and intracellular signalling pathways.

    Article  PubMed  Google Scholar 

  25. Knijff EM et al. A relative resistance of T cells to dexamethasone in bipolar disorder. Bipolar Disord. 2006;8(6):740–50.

    Article  CAS  PubMed  Google Scholar 

  26. Drexhage RC et al. The activation of monocyte and T cell networks in patients with bipolar disorder. Brain Behav Immun. 2011;25(6):1206–13.

    Article  CAS  PubMed  Google Scholar 

  27. Torres KC et al. Expression of neuronal calcium sensor-1 (NCS-1) is decreased in leukocytes of schizophrenia and bipolar disorder patients. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(2):229–34.

    Article  CAS  PubMed  Google Scholar 

  28. Abeer El-Sayed A, Ramy HA. Immunological changes in patients with mania: changes in cell mediated immunity in a sample from Egyptian patients. Egypt J Immunol. 2006;13(1):79–85.

    Google Scholar 

  29. Munkholm K et al. Cytokines in bipolar disorder vs. healthy control subjects: a systematic review and meta-analysis. J Psychiatr Res. 2013;47(9):1119–33. This is an important meta-analysis of cytokine changes in bipolar disorder patients.

    Article  PubMed  Google Scholar 

  30. Modabbernia A et al. Cytokine alterations in bipolar disorder: a meta-analysis of 30 studies. Biol Psychiatry. 2013;74(1):15–25. An important meta-analysis of cytokine changes across a range of studies involving bipolar disorder patients.

    Article  CAS  PubMed  Google Scholar 

  31. Barbosa IG et al. Chemokines in bipolar disorder: trait or state? Eur Arch Psychiatry Clin Neurosci. 2013;263:159–65.

    Article  PubMed  Google Scholar 

  32. Barbosa IG et al. Increased levels of adipokines in bipolar disorder. J Psychiatr Res. 2012;46:389–93.

    Article  PubMed  Google Scholar 

  33. Soeiro-de-Souza MG et al. Lithium decreases plasma adiponectin levels in bipolar depression. Neurosci Lett. 2014;564:111–4.

    Article  CAS  PubMed  Google Scholar 

  34. Dickerson F et al. Elevated C-reactive protein and cognitive deficits in individuals with bipolar disorder. J Affect Disord. 2013;150(2):456–9.

    Article  CAS  PubMed  Google Scholar 

  35. Hsuchou H et al. C-reactive protein increases BBB permeability: implications for obesity and neuroinflammation. Cell Physiol Biochem. 2012;30(5):1109–19.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Hope S et al. Interleukin 1 receptor antagonist and soluble tumor necrosis factor receptor 1 are associated with general severity and psychotic symptoms in schizophrenia and bipolar disorder. Schizophr Res. 2013;145(1–3):36–42.

    Article  PubMed  Google Scholar 

  37. Remlinger-Molenda A et al. Activity of selected cytokines in bipolar patients during manic and depressive episodes. Psychiatr Pol. 2012;46(4):599–611.

    PubMed  Google Scholar 

  38. Hsu JW et al. Association of thalamic serotonin transporter and interleukin-10 in bipolar I disorder: a SPECT study. Bipolar Disord. 2014;16(3):241–8.

    Article  CAS  PubMed  Google Scholar 

  39. Cetin T et al. Plasma concentrations of soluble cytokine receptors in euthymic bipolar patients with and without subsyndromal symptoms. BMC Psychiatry. 2012;12:158.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Brietzke E et al. Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder. J Affect Disord. 2009;116(3):214–7.

    Article  CAS  PubMed  Google Scholar 

  41. Ortiz-Domínguez A et al. Immune variations in bipolar disorder: phasic differences. Bipolar Disord. 2007;9(6):596–602.

    Article  PubMed  Google Scholar 

  42. Becking K et al. The association between immune activation and manic symptoms in patients with a depressive disorder. Transl Psychiatry. 2013;3:e314.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Bai YM et al. Comparison of inflammatory cytokine levels among type I/type II and manic/hypomanic/euthymic/depressive states of bipolar disorder. J Affect Disord. 2014;166:187–92.

    Article  CAS  PubMed  Google Scholar 

  44. Wieck A et al. Pro-inflammatory cytokines and soluble receptors in response to acute psychosocial stress: differential reactivity in bipolar disorder. Neurosci Lett. 2014;580:17–21.

    Article  CAS  PubMed  Google Scholar 

  45. Barbosa IG et al. A preliminary report of increased plasma levels of IL-33 in bipolar disorder: further evidence of pro-inflammatory status. J Affect Disord. 2014;157:41–4.

    Article  CAS  PubMed  Google Scholar 

  46. Knijff EM et al. An imbalance in the production of IL-1beta and IL-6 by monocytes of bipolar patients: restoration by lithium treatment. Bipolar Disord. 2007;9(7):743–53.

    Article  CAS  PubMed  Google Scholar 

  47. Kim YK et al. Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder. J Affect Disord. 2007;104(1–3):91–5.

    Article  CAS  PubMed  Google Scholar 

  48. Nassar A, Azab AN. Effects of lithium on inflammation. ACS Chem Neurosci. In press.

  49. Goldstein BI et al. Preliminary findings regarding proinflammatory markers and brain-derived neurotrophic factor among adolescents with bipolar spectrum disorders. J Ch Adol Psychopharmacol. 2011;21:479–84.

    Article  CAS  Google Scholar 

  50. Brambilla P et al. Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia. Transl Psychiatry. 2014;4:e406. Important data on changes in monocyte and T cell-associated cytokines in bipolar disorder patients.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Muxel SM et al. NF-kB drives the synthesis of melatonin in RAW 264.7 macrophages by inducing the transcription of the arylalkylamine-nacetyltransferase (AA-NAT) gene. PLoS ONE. 2012;7(12):e52010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Barbosa IG et al. Altered intracellular signaling cascades in peripheral blood mononuclear cells from BD patients. J Psychiatr Res. 2013;47(12):1949–54.

    Article  PubMed  Google Scholar 

  53. Bartels M et al. Valproic acid treatment is associated with altered leukocyte subset development. J Clin Psychopharmacol. 2012;32(6):832–4.

    Article  CAS  PubMed  Google Scholar 

  54. Himmerich H et al. Modulation of cytokine production by drugs with antiepileptic or mood stabilizer properties in anti-CD3- and anti-Cd40-stimulated blood in vitro. Oxid Med Cell Longev. 2014;2014:806162.

    Article  PubMed Central  PubMed  Google Scholar 

  55. Niles LP et al. Valproic acid up-regulates melatonin MT1 and MT2 receptors and neurotrophic factors CDNF and MANF in the rat brain. Int J Neuropsychopharmacol. 2012;15(9):1343–50.

    Article  CAS  PubMed  Google Scholar 

  56. Söderlund J et al. Elevation of cerebrospinal fluid interleukin-1β in bipolar disorder. J Psychiatry Neurosci. 2011;36(2):114–8.

    Article  PubMed Central  PubMed  Google Scholar 

  57. Shelton RC et al. Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression. Mol Psychiatry. 2011;16(7):751–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Bahna SG et al. Regional upregulation of hippocampal melatonin MT2 receptors by valproic acid: therapeutic implications for Alzheimer’s disease. Neurosci Lett. 2014;576:84–7.

    Article  CAS  PubMed  Google Scholar 

  59. Anderson G, Maes M. Local melatonin regulates inflammation resolution: a common factor in neurodegenerative, psychiatric and systemic inflammatory disorders. CNS Neurol Disord Drug Targets. 2014;13(5):817–27. An important summary of the potential roles of local melatonin across a host of conditions, including bipolar disorder.

    Article  CAS  PubMed  Google Scholar 

  60. Lotrich FE et al. The relationship between interleukin-1 receptor antagonist and cognitive function in older adults with bipolar disorder. Int J Geriatr Psychiatry. 2014;29(6):635–44.

    Article  PubMed  Google Scholar 

  61. Doganavsargil-Baysal O et al. Levels of TNF-α, soluble TNF receptors (sTNFR1, sTNFR2), and cognition in bipolar disorder. Hum Psychopharmacol. 2013;28(2):160–7.

    Article  CAS  PubMed  Google Scholar 

  62. Volkert J, et al. Evidence for cognitive subgroups in bipolar disorder and the influence of subclinical depression and sleep disturbances. Eur Neuropsychopharmacol. In press.

  63. Buoli M et al. The impact of mood episodes and duration of illness on cognition in bipolar disorder. Compr Psychiatry. 2014;55(7):1561–6.

    Article  PubMed  Google Scholar 

  64. Rosa AR et al. Clinical staging in bipolar disorder: focus on cognition and functioning. J Clin Psychiatry. 2014;75(5):e450–6.

    Article  PubMed  Google Scholar 

  65. Soczynska JK et al. Mood disorders and obesity: understanding inflammation as a pathophysiological nexus. Neuromol Med. 2011;13(2):93–116.

    Article  CAS  Google Scholar 

  66. Mesman E, et al. Monocyte activation, brain-derived neurotrophic factor (BDNF), and S100B in bipolar offspring: a follow-up study from adolescence into adulthood. Bipolar Disord. In press.

  67. Anderson G, Maes M. Oxidative/nitrosative stress and immuno-inflammatory pathways in depression: treatment implications. Curr Pharm Des. 2014;20(23):3812–47. A comprehensive review on the biological changes, and their interconnectedness, occurring in depression.

    Article  CAS  PubMed  Google Scholar 

  68. Aydemir O, et al. Oxidative stress markers, cognitive functions, and psychosocial functioning in bipolar disorder: an empirical cross-sectional study. Rev Bras Psiquiatr. In press.

  69. Versace A et al. Elevated serum measures of lipid peroxidation and abnormal prefrontal white matter in euthymic bipolar adults: toward peripheral biomarkers of bipolar disorder. Mol Psychiatry. 2014;19(2):200–8. Important data showing an association of oxidative stress with changes in central white matter.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Andreazza AC et al. Specific subcellular changes in oxidative stress in prefrontal cortex from patients with bipolar disorder. J Neurochem. 2013;127(4):552–61.

    Article  CAS  PubMed  Google Scholar 

  71. Bortolasci CC et al. Lowered plasma paraoxonase (PON)1 activity is a trait marker of major depression and PON1 Q192R gene polymorphism-smoking interactions differentially predict the odds of major depression and bipolar disorder. J Affect Disord. 2014;159:23–30. Important data that contributes to the biological differentiation of unipolar and bipolar depression.

    Article  CAS  PubMed  Google Scholar 

  72. Banerjee U et al. Effects of lithium therapy on Na+-K+-ATPase activity and lipid peroxidation in bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2012;37(1):56–61.

    Article  CAS  PubMed  Google Scholar 

  73. Khairova R et al. Effects of lithium on oxidative stress parameters in healthy subjects. Mol Med Rep. 2012;5(3):680–2.

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Tan DX et al. Mitochondria and chloroplasts as the original sites of melatonin synthesis: a hypothesis related to melatonin’s primary function and evolution in eukaryotes. J Pineal Res. 2013;54(2):127–38.

    Article  CAS  PubMed  Google Scholar 

  75. Wilson CB et al. Valproic acid effects in the hippocampus and prefrontal cortex in an animal model of post-traumatic stress disorder. Behav Brain Res. 2014;268:72–80.

    Article  CAS  PubMed  Google Scholar 

  76. Soeiro-de-Souza MG et al. Number of manic episodes is associated with elevated DNA oxidation in bipolar I disorder. Int J Neuropsychopharmacol. 2013;16(7):1505–12. An important article highlighting the changes occurring in neuroprogression in bipolar patients.

    Article  CAS  PubMed  Google Scholar 

  77. Abe N et al. Altered sirtuin deacetylase gene expression in patients with a mood disorder. J Psychiatr Res. 2011;45(8):1106–12.

    Article  PubMed  Google Scholar 

  78. Fernandes BS et al. Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: a systematic review and meta-regression analysis. J Psychiatr Res. 2011;45(8):995–1004.

    Article  PubMed  Google Scholar 

  79. Iuvone PM et al. N-acetylserotonin: circadian activation of the BDNF receptor and neuroprotection in the retina and brain. Adv Exp Med Biol. 2014;801:765–71.

    Article  PubMed Central  PubMed  Google Scholar 

  80. Anderson G, Maes M. Metabolic syndrome, Alzheimer’s, schizophrenia and depression: role for leptin, melatonin, kynurenine pathways and neuropeptides. Chap 13. In: Farooqui T, Farooqui AA, editors. Metabolic syndrome and neurological disorders. Chichester, UK: Wiley; 2013.

    Google Scholar 

  81. Johansson AS et al. Activation of kynurenine pathway in ex vivo fibroblasts from patients with bipolar disorder or schizophrenia: cytokine challenge increases production of 3-hydroxykynurenine. J Psychiatr Res. 2013;47(11):1815–23.

    Article  PubMed  Google Scholar 

  82. Lavebratt C et al. The KMO allele encoding Arg452 is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression. Mol Psychiatry. 2014;19(3):334–41.

    Article  CAS  PubMed  Google Scholar 

  83. Reininghaus EZ et al. Tryptophan breakdown is increased in euthymic overweight individuals with bipolar disorder: a preliminary report. Bipolar Disord. 2014;16(4):432–40. Preliminary data, but potentially of great importance, as the article highlights changes in tryptophan catabolites in bipolar patients.

    Article  CAS  PubMed  Google Scholar 

  84. Anderson G. Neuronal-immune interactions in mediating stress effects in the etiology and course of schizophrenia: role of the amygdala in developmental co-ordination. Med Hypotheses. 2011;76:54–60.

    Article  PubMed  Google Scholar 

  85. Stubbs B, et al. The prevalence of pain in bipolar disorder: a systematic review and large-scale meta-analysis. Acta Psychiatr Scand. In press.

  86. Maes M, Rief W. Diagnostic classifications in depression and somatization should include biomarkers, such as disorders in the tryptophan catabolite (TRYCAT) pathway. Psychiatry Res. 2012;196(2–3):243–9.

    Article  CAS  PubMed  Google Scholar 

  87. Anderson G, Berk M, Maes M. Biological phenotypes underpin the physio-somatic symptoms of somatization, depression, and chronic fatigue syndrome. Acta Psychiatr Scand. 2014;129(2):83–97.

    Article  CAS  PubMed  Google Scholar 

  88. Hackel D et al. The connection of monocytes and reactive oxygen species in pain. PLoS One. 2013;8(5):e63564.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  89. Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuroendocrinol Lett. 2008;29(1):117–24. An article of considerable importance that highlights the role of the gut in driving inflammatory changes in mood disorders.

    PubMed  Google Scholar 

  90. Cox AJ, West NP, Cripps AW. Obesity, inflammation, and the gut microbiota. Lancet Diabetes Endocrinol. In press.

  91. Elamin E et al. Ethanol impairs intestinal barrier function in humans through mitogen activated protein kinase signaling: a combined in vivo and in vitro approach. PLoS One. 2014;9(9):e107421.

    Article  PubMed Central  PubMed  Google Scholar 

  92. Konturek PC, Brzozowski T, Konturek SJ. Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. J Physiol Pharmacol. 2011;62(6):591–9.

    CAS  PubMed  Google Scholar 

  93. Sommansson A et al. Melatonin inhibits alcohol-induced increases in duodenal mucosal permeability in rats in vivo. Am J Physiol Gastrointest Liver Physiol. 2013;305(1):G95–G105.

    Article  CAS  PubMed  Google Scholar 

  94. Bala S et al. Acute binge drinking increases serum endotoxin and bacterial DNA levels in healthy individuals. PLoS One. 2014;9(5):e96864.

    Article  PubMed Central  PubMed  Google Scholar 

  95. Etain B et al. Genetic and functional abnormalities of the melatonin biosynthesis pathway in patients with bipolar disorder. Hum Mol Genet. 2012;21(18):4030–7.

    Article  CAS  PubMed  Google Scholar 

  96. Yu HN et al. Effects of fish oil with a high content of n-3 polyunsaturated fatty acids on mouse gut microbiota. Arch Med Res. 2014;45(3):195–20.

    Article  CAS  PubMed  Google Scholar 

  97. Anderson G, Maes M. Melatonin: an overlooked factor in schizophrenia and in the inhibition of anti-psychotic side effects. Metab Brain Dis. 2012;27(2):113–9.

    Article  CAS  PubMed  Google Scholar 

  98. Robillard R et al. Sleep-wake cycle and melatonin rhythms in adolescents and young adults with mood disorders: comparison of unipolar and bipolar phenotypes. Eur Psychiatry. 2013;28(7):412–6.

    Article  CAS  PubMed  Google Scholar 

  99. Markus RP, Cecon E, Pires-Lapa MA. Immune-pineal axis: nuclear factor κB (NF-kB) mediates the shift in the melatonin source from pinealocytes to immune competent cells. Int J Mol Sci. 2013;14(6):10979–97.

    Article  PubMed Central  PubMed  Google Scholar 

  100. Romo-Nava F et al. Melatonin attenuates antipsychotic metabolic effects: an eight-week randomized, double-blind, parallel-group, placebo-controlled clinical trial. Bipolar Disord. 2014;16(4):410–21. A very important article showing that melatonin can prevent the inflammatory and metabolic dysregulation associated with antipsychotic treatment of bipolar disorder.

    Article  CAS  PubMed  Google Scholar 

  101. Redlich R, et al. Brain morphometric biomarkers distinguishing unipolar and bipolar depression: a voxel-based morphometry-pattern classification approach. JAMA Psychiatry. 2014;71(11):1222–30.

  102. Pinato L, et al. Selective protection of the cerebellum against intracerebroventricular LPS is mediated by local melatonin synthesis. Brain Struct Funct. In press.

Download references

Compliance with Ethics Guidelines

Conflict of Interest

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

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. CRC Scotland & London, Eccleston Square, London, UK

    George Anderson

  2. Impact Strategic Treatment Center, Deakin University, Geelong, Australia

    Michael Maes

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

    Michael Maes

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

    Michael Maes

Authors
  1. George Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Maes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George Anderson.

Additional information

This article is part of the Topical Collection on Bipolar Disorders

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11920-014-0541-1

Keywords

Search

Navigation