Abstract

It is known that the prevalence of depression in rheumatologic patients is higher than in the general population. Socioeconomic factors are not a sufficient explanation of mood disorder in these patients. Symptoms reported by patients with chronic inflammatory diseases resemble changes defined as “sickness behavior”. Mood disorders among somatic patients could be explained by disturbances of the immune system according to the monoaminergic theory of depression. Inflammatory factors such as IL-1 (interleukin-1), IL-2 (interleukin-2), IL-6 (interleukin-6), TNF-α (tumor necrosis factor α), and IFN-γ (interferon-γ) act within the CNS (central nervous system). They get through from peripheral tissues as well as being synthesized de novo by neurons. This cytokine activity correlates positively with depression intensity as well as with genetic polymorphism of the serotonin (5-HT) transporter. The theory of glucocorticoid resistance-mediated depression (limbic-hypothalamic-pituitary-adrenal [LHPA] axis) is also connected with gained proinflammatory cytokines activity. It might assume the form of a vicious circle. Depressed mood is probably linked with depression in immune-mediated diseases. An elevated level of proinflammatory cytokines is able to activate IDO (indoleamine 2,3-dioxygenase) – an enzyme catabolizing tryptophan (5-HT precursor). Those reactions probably play the main role at the biochemical level. IDO metabolites extensively disturb neurotransmission. 3-Hydroxykynurenine (3OH-KYN), quinolinic acid (Quin) and kynurenic acid (KYNA) are neurotoxic by releasing oxidative stress mediators. Moreover, they activate MAO (monoamine oxidase), which degrades neurotransmitters responsible for stable mood. Bidirectional communication between the neuroendocrine and immune systems is significant for depression treatment, as well as CNS protection against incremental neurodegenerationamong seemingly diverse diseases.

References

• 1. Abbott N.J., Mendonça L.L., Dolman D.E.: The blood-brain barrierin systemic lupus erythematosus. Lupus, 2003; 12: 908-915 2 Braidy N., Grant R., Adams S., Brew B.J., Guillemin G.J.: Mechanismfor quinolinic acid cytotoxicity in human astrocytes and neurons.Neurotox. Res., 2009; 16: 77-86
  Google Scholar
• 2. or interleukin-6 treatment. Neuroscience,1999; 88: 823-836
  Google Scholar
• 3. Bromet E., Andrade L.H., Hwang I., Sampson N.A., Alonso J., DeGirolamo G., De Graaf R., Demyttenaere K., Hu C., Iwata N., KaramA.N., Kaur J., Kostyuchenko S., Lépine J.P., Levinson D. i wsp.: Crossnationalepidemiology of DSM-IV major depressive episode. BMCMed., 2011; 9: 90
  Google Scholar
• 4. Bufalino C., Hepgul N., Aguglia E., Pariante C.M.: The role of immunegenes in the association between depression and inflammation:a review of recent clinical studies. Brain Behav. Immun., 2013;31: 31-47
  Google Scholar
• 5. Buras A., Waszkiewicz N., Szulc A., Sierakowski S.: Monocyticparameters in patients with rheumatologic diseases reflect intensityof depressive disorder. Pol. Merkur. Lekarski, 2012; 33: 325-329
  Google Scholar
• 6. Calogero A.E., Gallucci W.T., Chrousos G.P., Gold P.W.: Catecholamineeffects upon rat hypothalamic corticotropin-releasing hormonesecretion in vivo. J. Clin. Invest., 1988; 82: 839-846
  Google Scholar
• 7. Cervera Enguix S., Rodríguez-Rosado A., Ramos Ruiz F., SarraisOteo F., Pla Vidal J., Rodríguez-Rosado R.: Study of the evolution ofsome monocytic parameters and neuroendocrine function tests indepressed patients. Actas Luso Esp. Neurol. Psiquiatr. Cienc. Afines,1995; 23: 67-73
  Google Scholar
• 8. Cupps T.R, Fauci A.S.: Corticosteroid-mediated immunoregulationin man. Immunol. Rev., 1982; 65: 133-155
  Google Scholar
• 9. Freidin M., Bennett M.V., Kessler J.A.: Cultured sympathetic neuronssynthesize and release the cytokine interleukin 1β. Proc. Natl.Acad. Sci. USA, 1992; 89: 10440-10443
  Google Scholar
• 10. Gallagher P., Reid K.S., Ferrier I.N.: Neuropsychological functioningin health and mood disorder: modulation by glucocorticoidsand their receptors. Psychoneuroendocrinology, 2009; 34 (Suppl.1): S196-S207
  Google Scholar
• 11. Gardoni F., Boraso M., Zianni E., Corsini E., Galli C.L., Cattabeni F.,Marinovich M., Di Luca M., Viviani B.: Distribution of interleukin-1receptor complex at the synaptic membrane driven by interleukin-1b and NMDA stimulation. J. Neuroinflammation, 2011; 8: 14
  Google Scholar
• 12. Hepgul N., Mondelli V., Pariante C.M.: Psychological and biologicalmechanisms of cytokine induced depression. Epidemiol. Psichiatr.Soc., 2010; 19: 98-102
  Google Scholar
• 13. Het S., Ramlow G., Wolf O.T.: A meta-analytic review of the effectsof acute cortisol administration on human memory. Psychoneuroendocrinology,2005; 30: 771-784
  Google Scholar
• 14. Katon W., Lin E.H., Kroenke K.: The association of depressionand anxiety with medical symptom burden in patients with chronicmedical illness. Gen. Hosp. Psychiatry, 2007; 29: 147-155
  Google Scholar
• 15. Kessler R.C., Chiu W.T., Demler O., Merikangas K.R., Walters E.E.:Prevalence, severity, and comorbidity of 12-month DSM-IV disordersin the National Comorbidity Survey Replication. Arch. Gen.Psychiatry, 2005; 62: 617-627
  Google Scholar
• 16. Koo J.W., Duman R.S.: IL-1β is an essential mediator of the antineurogenicand anhedonic effects of stress. Proc. Natl. Acad. Sci.USA, 2008; 105: 751-756
  Google Scholar
• 17. Kronfol Z., Remick D.G.: Cytokines and the brain: implicationsfor clinical psychiatry. Am. J. Psychiatry, 2000; 157: 683-694
  Google Scholar
• 18. Laidmäe V., Tulva T.: Negative outcomes of the chronic disease:people with rheumatism in Estonia. Internet J. Rheumatol.,2008; 4: 1-11
  Google Scholar
• 19. Lee Y.H., Ji J.D., Song G.G.: Tumor necrosis factor-alpha promoter– 308 A/G polymorphism and rheumatoid arthritis susceptibility:a metaanalysis. J. Rheumatol., 2007; 34: 43-49
  Google Scholar
• 20. Leonard B., Maes M.: Mechanistic explanations how cell-mediatedimmune activation, inflammation and oxidative and nitrosativestress pathways and their sequels and concomitants play a rolein the pathophysiology of unipolar depression. Neurosci. Biobehav.Rev, 2012; 36: 764-785
  Google Scholar
• 21. Linthorst A.C., Flachskamm C., Müller-Preuss P., Holsboer F.,Reul J.M.: Effect of bacterial endotoxin and interleukin-1β on hippocampalserotonergic neurotransmission, behavioral activity, andfree corticosterone levels: an in vivo microdialysis study. J Neurosci,1995; 15: 2920-2934
  Google Scholar
• 22. Liu Y., Ho R.C., Mak A.: The role of interleukin (IL)-17 in anxietyand depression of patients with rheumatoid arthritis. Int. J. Rheum.Dis., 2012; 15: 183-187
  Google Scholar
• 23. Maes M.: Depression is an inflammatory disease, but cell-mediatedimmune activation is the key component of depression. Prog.Neuropsychopharmacol. Biol. Psychiatry, 2011; 35: 664-675
  Google Scholar
• 24. Maes M., Leonard B.E., Myint A.M., Kubera M., Verkerk R.: Thenew ‘5-HT’ hypothesis of depression: cell-mediated immune activationinduces indoleamine 2,3-dioxygenase, which leads to lowerplasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onsetof depression. Prog. Neuropsychopharmacol. Biol. Psychiatry,2011; 35: 702-721
  Google Scholar
• 25. Margaretten M., Julian L., Katz P., Yelin E.: Depression in patientswith rheumatoid arthritis: description, causes and mechanisms. Int.J. Clin. Rheumtol., 2011; 6: 617-623
  Google Scholar
• 26. Merali Z., Brennan K., Brau P., Anisman H.: Dissociating anorexiaand anhedonia elicited by interleukin-1b: antidepressant and gendereffects on responding for „free chow” and „earned” sucrose intake.Psychopharmacology, 2003; 165: 413-418
  Google Scholar
• 27. Newcomer J.W., Selke G., Melson A.K., Hershey T., Craft S., RichardsK., Alderson A.L.: Decreased memory performance in healthyhumans induced by stress-level cortisol treatment. Arch. Gen. Psychiatry,1999; 56: 527-533
  Google Scholar
• 28. O’Connor T.M., O’Halloran D.J., Shanahan F.: The stress responseand the hypothalamic–pituitary–adrenal axis: from molecule tomelancholia. QJM, 2000; 93: 323-333
  Google Scholar
• 29. Pawlik A., Kurzawski M., Florczak M., Gawronska Szklarz B.,Herczyńska M.: IL1β+3953 exon 5 and IL-2 – 330 promoter polymorphismsin patients with rheumatoid arthritis. Clin. Exp. Rheumatol.,2005; 23: 159-164
  Google Scholar
• 30. Qin H., Benveniste E.N.: ELISA methodology to quantify astrocyteproduction of cytokines/chemokines in vitro. Methods Mol.Biol., 2012; 814: 235-249
  Google Scholar
• 31. Raison C.L., Dantzer R., Kelley K.W., Lawson M.A., Woolwine B.J.,Vogt G., Spivey J.R., Saito K., Miller A.H.: CSF concentrations of braintryptophan and kynurenines during immune stimulation with IFNalpha:relationship to CNS immune responses and depression. Mol.Psychiatry, 2010; 15: 393-403
  Google Scholar
• 32. Schiepers O.J., Wichers M.C., Maes M.: Cytokines and majordepression. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2005;29: 201-217
  Google Scholar
• 33. Sirivelu M.P., Mohankumar P.S., Mohankumar S.M.: Differentialeffects of systemic interleukin-1β on gene expression in brainstemnoradrenergic nuclei. Life Sci., 2012; 90: 77-81
  Google Scholar
• 34. Smith J.A., Das A., Ray S.K.,Banik N.L.: Role of pro-inflammatorycytokines released from microglia in neurodegenerative diseases.Brain Res. Bull., 2012; 87: 10-20
  Google Scholar
• 35. Song C.: The effect of thymectomy and IL-1 on memory: implicationsfor the relationship between immunity and depression. BrainBehav. Immun., 2002; 16: 557-568
  Google Scholar
• 36. Song C., Manku M.S., Horrobin D.F.: Long-chain polyunsaturatedfatty acids modulate interleukin-1β-induced changes in behavior,monoaminergic neurotransmitters, and brain inflammation in rats.J. Nutr., 2008; 138: 954-963
  Google Scholar
• 37. Song C., Merali Z., Anisman H.: Variations of nucleus accumbensdopamine and serotonin following systemic interleukin-1, interleukin-
  Google Scholar
• 38. Stuart M.J., Baune B.T.: Depression and type 2 diabetes: inflammatorymechanisms of a psychoneuroendocrine co-morbidity. Neurosci.Biobehav. Rev., 2012; 36: 658-676
  Google Scholar
• 39. Sudom K., Turrin N.P., Hayley S., Anisman H.: Influence of chronicinterleukin-2 infusion and stressors on sickness behaviors andneurochemical change in mice. Neuroimmunomodulation, 2004;11: 341-350
  Google Scholar
• 40. Tkacs N.C., Li J.: Immune stimulation induces Fos expressionin brainstem amygdala afferents. Brain Res. Bull., 1999; 48: 223-231
  Google Scholar
• 41. Tracey K.J.: Reflex control of immunity. Nat. Rev. Immunol.,2009; 9: 418-428
  Google Scholar
• 42. Tynan R.J., Weidenhofer J., Hinwood M., Cairns M.J., Day T.A.,Walker F.R.: A comparative examination of the anti-inflammatoryeffects of SSRI and SNRI antidepressants on LPS stimulated microglia.Brain Behav. Immun., 2012; 26: 469-479
  Google Scholar
• 43. Utsuyama M., Hirokawa K.: Differential expression of variouscytokine receptors in the brain after stimulation with LPS in youngand old mice. Exp. Gerontol., 2002; 37: 411-420
  Google Scholar
• 44. Wichers M.C., Maes M.: The role of indoleamine 2,3 dioxygenase(IDO) in the pathophysiology of interferon-α-induced depression. J.Psychiatry Neurosci., 2004; 29: 11-17
  Google Scholar
• 45. Yukioka M., Komatsubara Y., Maeda A., Shichikawa K., YukiokaK., Furumitsu Y.: Depressive tendency in patients with RA. Ryumachi,2002; 42: 584-590
  Google Scholar

Full text