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Klyushnik T.P.

Mental Health Research Center

Golimbet V.E.

Mental Health Research Center

Ivanov S.V.

Mental Health Research Center

Immune mechanisms of complicity of somatic pathology in the pathogenesis of mental disorders

Authors:

Klyushnik T.P., Golimbet V.E., Ivanov S.V.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2023;123(4‑2): 20‑27

DOI: 10.17116/jnevro202312304220

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Table of contents

IMMUNE MECHANISMS OF COMPLICITY OF SOMATIC PATHOLOGY IN THE PATHOGENESIS OF MENTAL DISORDERS
IMMUNE MECHANISMS OF COMPLICITY OF SOMATIC PATHOLOGY IN THE PATHOGENESIS OF MENTAL DISORDERS

To cite this article:

Klyushnik TP, Golimbet VE, Ivanov SV. Immune mechanisms of complicity of somatic pathology in the pathogenesis of mental disorders. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;123(4‑2):20‑27. (In Russ.)
https://doi.org/10.17116/jnevro202312304220

Подписка 2025-2 (S.S. Korsakov Journal of Neurology and Psychiatry (special issues))
 
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Understanding the mechanisms of the relationship between the nervous and immune systems within the framework of the concept of the key role of inflammation, taking into account the involved genetic factors in the development of a wide range of combined forms of somatic and mental diseases, is of interest for research as well as for the development of new approaches to early diagnosis and more effective treatment of these diseases. This review analyzes the immune mechanisms of the development of mental disorders in patients with somatic diseases, in particular, the transmission of an inflammatory signal from the periphery to the CNS and the implementation of the influence of inflammatory factors on neurochemical systems that determine the characteristics of mental functioning. Particular attention is paid to the processes underlying the disruption of the blood-brain barrier caused by peripheral inflammation. Modulation of neurotransmission, changes in neuroplasticity, changes in regional activity of the brain in areas associated with the functions of threat recognition, cognitive processes and memory function, the effect of cytokines on the hypothalamic-pituitary-adrenal system are considered as mechanisms of action of inflammatory factors in the brain. The need to take into account variations in the genes of pro-inflammatory cytokines, which may be the cause of increased genetic vulnerability associated with the risk mental disorders in patients suffering from a certain somatic disease, is emphasized.

Keywords:

immune system
comorbidity of somatic and psychiatric disorders
somatic disorders
inflammatory signal transduction
variations in cytokine genes

Authors:

Klyushnik T.P.

Mental Health Research Center

Golimbet V.E.

Mental Health Research Center

Ivanov S.V.

Mental Health Research Center

Received:

21.11.2022

Accepted:

06.12.2022

List of references:

  1. Pavlov VA, Chavan SS, Tracey KJ. Molecular and Functional Neuroscience in Immunity. Annu Rev Immunol. 2018;36:783-812.  https://doi.org/10.1146/annurev-immunol-042617-053158
  2. Chu C, Artis D, Chiu IM. Neuro-immune Interactions in the Tissues. Immunity. 2020;52(3):464-474.  https://doi.org/10.1016/j.immuni.2020.02.017
  3. Korneva EA. Puti vzaimodejstviya nervnoj i immunnoj sistem: istoriya sovremennost’, klinicheskoe primenenie. Medicinskaya Immunologiya. 2020;22(3):399-602. (In Russ.).
  4. Bennett JM, Reeves G, Billman GE, et al. Inflammation-Nature’s Way to Efficiently Respond to All Types of Challenges: Implications for Understanding and Managing «the Epidemic» of Chronic Diseases. Front Med (Lausanne). 2018;5:316. eCollection 2018. https://doi.org/10.3389/fmed.2018.00316
  5. Liang CS, Gałecki P, Su KP. Unresolved Systemic Inflammation, Long COVID, and the Common Pathomechanisms of Somatic and Psychiatric Comorbidity. J Clin Med. 2022;11(17):5114. https://doi.org/10.3390/jcm11175114
  6. Perry VH. The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease. Brain Behav Immun. 2004;18(5):407-413.  https://doi.org/10.1016/j.bbi.2004.01.004
  7. Aktas O, Waiczies S, Zipp F. Neurodegeneration in autoimmune demyelination: recent mechanistic insights reveal novel therapeutic targets. J Neuroimmunol. 2007;184(1-2):17-26.  https://doi.org/10.1016/j.jneuroim.2006.11.026
  8. Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 2007;10(11):1387-1394. https://doi.org/10.1038/nn1997
  9. Hoogland IC, Houbolt C, van Westerloo DJ, et al. Systemic inflammation and microglial activation: systematic review of animal experiments. J Neuroinflammation. 2015;12:114.  https://doi.org/10.1186/s12974-015-0332-6
  10. Raison CL, Borisov AS, Majer M, et al. Activation of central nervous system inflammatory pathways by interferon-alpha: Relationship to monoamines and depression. Biol Psychiatry. 2009;65(4):296-303.  https://doi.org/10.1016/j.biopsych.2008.08.010
  11. Rankine EL, Hughes PM, Botham MS, et al. Brain cytokine synthesis induced by an intraparenchymal injection of LPS is reduced in MCP-1-deficient mice prior to leucocyte recruitment. Eur J Neurosci. 2006;24:77-86.  https://doi.org/10.1111/j.1460-9568.2006.04891.x
  12. Sun Y, Yao Z, Ye Y, et al. Ubiquitin-based pathway acts inside chloroplasts to regulate photosynthesis. Sci Adv. 2022;8(46):eabq7352. https://doi.org/10.1126/sciadv.abq7352
  13. Vidya MK, Kumar VG, Sejian V, et al. Toll-like receptors: Significance, ligands, signaling pathways, and functions in mammals. Int Rev Immunol. 2018;37(1):20-36.  https://doi.org/10.1080/08830185.2017.1380200
  14. Banks WA. Blood-Brain Barrier Transport of Cytokines: A Mechanism for Neuropathology. Curr Pharm. 2005;11(8):973-984. 
  15. Plotkin SR, Banks WA, Kastin AJ. Comparison of saturable transport and extracellular pathways in the passage of interleukin-1 alpha across the blood-brain barrier. J Neuroimmunol. 1996;67(1):41-47.  https://doi.org/10.1016/0165-5728(96)00036-7
  16. Nonaka N, Shioda S, Banks WA. Effect of lipopolysaccharide on the transport of pituitary adenylatecyclase activating polypeptide across the blood-brain barrier. Exp Neurol. 2005;191(1):137-144.  https://doi.org/10.1016/j.expneurol.2004.09.013
  17. Gotow T, Hashimoto PH. Intercellular junctions between specialized ependymal cells in the subcommissural organ of the rat. J Neurocytol. 1982;11:363-379.  https://doi.org/10.1007/BF01257983
  18. Dantzer R, O’Connor JC, Freund GG, et al. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;9:46-56.  https://doi.org/10.1038/nrn2297
  19. Blatteis CM, Li S. Pyrogenic signaling via vagal afferents: what stimulates their receptors? Auton Neurosci. 2000;85(1-3):66-71.  https://doi.org/10.1016/S1566-0702(00)00221-6
  20. Schnydrig S, Korner L, Landweer S, et al. Peripheral lipopolysaccharide administration transiently affects expression of brain-derived neurotrophic factor, corticotropin and proopiomelanocortin in mouse brain. Neurosci Lett. 2007;429(1):69-73.  https://doi.org/10.1016/j.neulet.2007.09.067
  21. Salvador AF, de Lima KA, Kipnis J. Neuromodulation by the immune system: a focus on cytokines. Nat Rev Immunol. 2021;21(8):526-541.  https://doi.org/10.1038/s41577-021-00508-z
  22. Fleshner M, Goehler LE, Hermann J, et al. Interleukin-1beta induced corticosterone elevation and hypothalamic NE depletion is vagally mediated. Brain Res Bull. 1995;37:6:605-610.  https://doi.org/10.1016/0361-9230(95)00051-f
  23. Berthoud HR, Neuhuber WL. Functional and chemical anatomy of the afferent vagal system. Auton Neurosci. 2000;85:1-3:1-17.  https://doi.org/10.1016/S1566-0702(00)00215-0
  24. Goehler LE, Gaykema RP, Hansen MK, et al. Vagal immune-to-brain communication: a visceral chemosensory pathway. Auton Neurosci. 2000;85:1-3:49-59.  https://doi.org/10.1016/S1566-0702(00)00219-8
  25. Day HE, Curran EJ, Watson SJ Jr, et al. Distinct neurochemical populations in the rat central nucleus of the amygdala and bed nucleus of the stria terminalis: evidence for their selective activation by interleukin-1beta. J Comp Neurol. 1999;413:1:113-128. 
  26. Korneva EA, Shekoyan VA. Regulation of protective functions of the body. L.: Nauka; 1982. (In Russ.).
  27. Steinberg BE, Tracey KJ, Slutsky AS. Bacteria and the neural code. N Engl J Med. 2014;371:22:2131-2133. https://doi.org/10.1056/NEJMcibr1412003
  28. Banks WA. The blood-brain barrier in neuroimmunology: Tales of separation and assimilation. Brain Behav Immun. 2015;44:1-8.  https://doi.org/10.1016/j.bbi.2014.08.007
  29. Abbott NJ, Patabendige AA, Dolman DE, et al. Structure and function of the blood-brain barrier. Neurobiol. Dis. 2010;37:13-25.  https://doi.org/10.1016/j.nbd.2009.07.030
  30. Huang X, Hussain B, Chang J. Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms. CNS Neurosci Ther. 2021;27(1):36-47.  https://doi.org/10.1111/cns.13569
  31. Anisman H, Merali Z, Hayley S. Neurotransmitter, peptide and cytokine processes in relation to depressive disorder: Comorbidity between depression and neurodegenerative disorders. Prog Neurobiol. 2008;85:1-74.  https://doi.org/10.1016/j.pneurobio.2008.01.004
  32. Yirmiya R, Pollak Y, Barak O, et al. Effects of antidepressant drugs on the behavioral and physiological responses to lipopolysaccharide (LPS) in rodents. Neuropsychopharmacology. 2001;24(5):531-544.  https://doi.org/10.1016/S0893-133X(00)00226-8
  33. Musselman DL, Lawson DH, Gumnick JF, et al. Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med. 2001;344(13):961-966.  https://doi.org/10.1056/NEJM200103293441303
  34. Fujigaki H, Saito K, Fujigaki S, et al. The signal transducer and activator of transcription 1 alpha and interferon regulatory factor 1 are not essential for the induction of indoleamine 2,3-dioxygenase by lipopolysaccharide: Involvement of p38 mitogen-activated protein kinase and nuclear factor-kappaB pathways, and synergistic effect of several proinflammatory cytokines. J Biochem. 2006;139:655-662.  https://doi.org/10.1093/jb/mvj072
  35. Schwarcz R, Pellicciari R. Manipulation of brain kynurenines: Glial targets, neuronal effects, and clinical opportunities. J Pharmacol Exp Ther. 2002;303:1-10.  https://doi.org/10.1124/jpet.102.034439
  36. Capuron L, Neurauter G, Musselman DL, et al. Interferon-alpha-induced changes in tryptophan metabolism. relationship to depression and paroxetine treatment. Biol Psychiatry. 2003;54(9):906-914.  https://doi.org/10.1016/s0006-3223(03)00173-2
  37. O’Connor JC, Lawson MA, André C, et al. Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol Psychiatry. 2009;14(5):511-522.  https://doi.org/10.1038/sj.mp.4002148
  38. Wu HQ, Rassoulpour A, Schwarcz R. Kynurenic acid leads, dopamine follows: A new case of volume transmission in the brain? J Neural Transmission. 2007;114:33-41.  https://doi.org/10.1007/s00702-006-0562-y
  39. Kitagami T, Yamada K, Miura H, et al. Mechanism of systemically injected interferon-alpha impeding monoamine biosynthesis in rats: Role of nitric oxide as a signal crossing the blood-brain barrier. Brain Res. 2003;978:104-115.  https://doi.org/10.1016/s0006-8993(03)02776-8
  40. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009;65(9):732-741.  https://doi.org/10.1016/j.biopsych.2008.11.029
  41. Barrientos RM, Sprunger DB, Campeau S, et al. BDNF mRNA expression in rat hippocampus following contextual learning is blocked by intrahippocampal IL-1beta administration. J Neuroimmunol. 2004;155(1-2):119-126.  https://doi.org/10.1016/j.jneuroim.2004.06.009
  42. Gavillet M, Allaman I, Magistretti PJ. Modulation of astrocytic metabolic phenotype by proinflammatory cytokines. Glia. 2008;56(9):975-989.  https://doi.org/10.1002/glia.20671
  43. Rajkowska G, Miguel-Hidalgo JJ. Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets. 2007;6(3):219-233.  https://doi.org/10.2174/187152707780619326
  44. McTigue DM. The life, death, and replacement of oligodendrocytes in the adult CNS. J Neurochem. 2008;107:1-19.  https://doi.org/10.1111/j.1471-4159.2008.05570.x
  45. Thornton P, Pinteaux E, Gibson RM, et al. Interleukin-1-induced neurotoxicity is mediated by glia and requires caspase activation and free radical release. J Neurochem. 2006;98(1):258-266.  https://doi.org/10.1111/j.1471-4159.2006.03872.x
  46. Volterra A, Meldolesi J. Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci. 2005;6(8):626-640.  https://doi.org/10.1038/nrn1722
  47. Bezzi P, Domercq M, Brambilla L, et al. CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity. Nat Neurosci. 2001;4(7):702-710.  https://doi.org/10.1038/89490
  48. Steiner J, Bielau H, Brisch R, et al. Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. J Psychiatr Res. 2008;42(2):151-157.  https://doi.org/10.1016/j.jpsychires.2006.10.013
  49. Miller AH, Ancoli-Israel S, Bower JE, et al. Neuroendocrine-immune mechanisms of behavioral comorbidities in patients with cancer. J Clin Oncol. 2008;26(6):971-982.  https://doi.org/10.1200/JCO.2007.10.7805
  50. Capuron L, Ravaud ADantzer R. Timing and specificity of the cognitive changes induced by interleukin-2 and interferon-alpha treatments in cancer patients. Psychosom Med. 2001;63(3):376-386.  https://doi.org/10.1097/00006842-200105000-00007
  51. Maier SF. Bi-directional immune-brain communication: Implications for understanding stress, pain, and cognition. Brain Behav Immun. 2003;17(2):69-85.  https://doi.org/10.1016/s0889-1591(03)00032-1
  52. Besedovsky HO, del Rey A. Immune-neuro-endocrine interactions: facts and hypotheses. Endocr Rev. 1996;17(1):64-102.  https://doi.org/10.1210/edrv-17-1-64
  53. Raison CL, Borisov AS, Woolwine BJ, et al. Interferon-alpha effects on diurnal hypothalamic-pituitary-adrenal axis activity: relationship with proinflammatory cytokines and behavior. Mol Psychiatry. 2010;15(5):535-547.  https://doi.org/10.1038/mp.2008.58
  54. Bower JE, Ganz PA, Dickerson SS, et al. Diurnal cortisol rhythm and fatigue in breast cancer survivors. Psychoneuroendocrinology. 2005;30(1):92-100.  https://doi.org/10.1016/j.psyneuen.2004.06.003
  55. Pace TW, Hu F, Miller AH. Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav Immun. 2007;21(1):9-19.  https://doi.org/10.1016/j.bbi.2006.08.009
  56. Watanabe K, Stringer S, Frei O, et al. A global overview of pleiotropy and genetic architecture in complex traits. Nat Genet. 2019;51(9):1339-1348. https://doi.org/10.1038/s41588-019-0481-0
  57. Abraham LJ, Kroeger KM. Impact of the -308 TNF promoter polymorphism on the transcriptional regulation of the TNF gene: relevance to disease. J Leukoc Biol. 1999;66(4):562-566.  https://doi.org/10.1002/jlb.66.4.562
  58. McCusker SM, Curran MD, Dynan KB, et al. Association between polymorphism in regulatory region of gene encoding tumour necrosis factor alpha and risk of Alzheimer’s disease and vascular dementia: a case-control study. Lancet 2001;357:436-439.  https://doi.org/10.1016/s0140-6736(00)04008-3
  59. Laddha NC, Dwivedi M, Mansuri MS, et al. Association of neuropeptide Y (NPY), interleukin-1B (IL1B) genetic variants and correlation of IL1B transcript levels with vitiligo susceptibility. PLoS One. 2014;9(9):e107020. eCollection 2014. https://doi.org/10.1371/journal.pone.0107020
  60. Fishman D, Faulds G, Jeffery R, et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systematic-onset juvenile chronic arthritis. J Clin Invest. 1998;102(7):1369-1376. https://doi.org/10.1172/JCI2629
  61. Kim JM, Stewart R, Kim SW, et al. Associations of cytokine gene polymorphisms with post-stroke depression. World J Biol Psychiatry. 2012;12(8):579-587.  https://doi.org/10.3109/15622975.2011.588247
  62. Kim JM, Kang HJ, Kim JW, et al. Associations of Tumor Necrosis Factor-α and Interleukin-1β Levels and Polymorphisms with Post-Stroke Depression. Am J Geriatr Psychiatry. 2017;25(12):1300-1308. https://doi.org/10.1016/j.jagp.2017.07.012
  63. Yang GS, Kumar S, Dorsey SG, et al. Support Care Cancer. 2019;27(2):351-371.  https://doi.org/10.1007/s00520-018-4508-3
  64. JanBower JE, Ganz PA, Irwin MR, et al. Cytokine genetic variations and fatigue among patients with breast cancer. J Clin Oncol. 2013;31(13):1656-1661. https://doi.org/10.1200/JCO.2012.46.2143
  65. Cameron B, Webber K, Li H, et al. Genetic associations of fatigue and other symptoms following breast cancer treatment: A prospective study. Brain Behav Immun Health. 2020;10:100189. eCollection 2021. https://doi.org/10.1016/j.bbih.2020.100189
  66. Kober KM, Smoot B, Paul SM, et al. Polymorphisms in Cytokine Genes Are Associated With Higher Levels of Fatigue and Lower Levels of Energy in Women After Breast Cancer Surgery. Pain Symptom Manage. 2016;52(5):695-708.e4.  https://doi.org/10.1016/j.jpainsymman.2016.04.014
  67. Bull SJ, Huezo-Diaz P, Binder EB, et al. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment. Mol Psychiatry. 2009;4(12):1095-1104. https://doi.org/10.1038/mp.2008.48
  68. Udina M, Moreno-España J, Navinés R, et al. Serotonin and interleukin-6: the role of genetic polymorphisms in IFN-induced neuropsychiatric symptoms. Psychoneuroendocrinology. 2013;38(9):1803-1813. https://doi.org/10.1016/j.psyneuen.2013.03.007
  69. Nikkheslat N, Zunszain PA, Horowitz MA, et al. Insufficient glucocorticoid signaling and elevated inflammation in coronary heart disease patients with comorbid depression. Brain Behav Immun. 2015;48:8-18.  https://doi.org/10.1016/j.bbi.2015.02.002

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