The role of cellular immunity and systemic inflammation indices in the pathogenetic mechanisms of mental disorders
https://doi.org/10.14412/2074-2711-2023-5-72-78
Abstract
To date, inflammatory mechanisms are known to be involved in neuronal damage and increased risk of associated mental disorders, but most previous work has focused primarily on cytokines and other inflammatory markers that are difficult to replicate and not economically feasible for use in routine clinical practice. Other extremely important indicators of the systemic inflammatory process are circulating blood cells and changes in their number, composition, and ratio. Hematologic indices of systemic inflammation (HISI) are already used in somatic specialties: neutrophil-lymphocyte (NLR), monocyte-lymphocyte (MLR) and platelet-lymphocyte (PLR) ratios, as well as the Systemic Immune Inflammation Index (SII) and the System Inflammation Response Index (SIRI). In the context of psychopathology, the HISI require additional investigation, which makes it necessary to pay more attention to the possible mechanisms underlying their changes. The article provides data on the contribution of each cellular element to the mechanism of neuroinflammation and neurodegeneration and on their role in the development of psychopathological processes.
Supporting agencies: The investigation has not been sponsored
About the Authors
A. P. Gorbunova
Bekhterev National Medical Research Center for Psychiatry and Neurology, Ministry of Health of Russia
Russian Federation
Competing Interests:
Russian Federation
Grigory Viktorovich Rukavishnikov
3 Bekhterev St., 192019 Saint Petersburg
Competing Interests:
There are no conflicts of interest
G. V. Rukavishnikov
Bekhterev National Medical Research Center for Psychiatry and Neurology, Ministry of Health of Russia
Russian Federation
Competing Interests:
Russian Federation
3 Bekhterev St., 192019 Saint Petersburg
Competing Interests:
There are no conflicts of interest
E. D. Kasyanov
Bekhterev National Medical Research Center for Psychiatry and Neurology, Ministry of Health of Russia
Russian Federation
Competing Interests:
Russian Federation
3 Bekhterev St., 192019 Saint Petersburg
Competing Interests:
There are no conflicts of interest
G. E. Mazo
Bekhterev National Medical Research Center for Psychiatry and Neurology, Ministry of Health of Russia
Russian Federation
Competing Interests:
Russian Federation
3 Bekhterev St., 192019 Saint Petersburg
Competing Interests:
There are no conflicts of interest
References
1. Williams JA, Burgess S, Suckling J, et al. Inflammation and Brain Structure in Schizophrenia and Other Neuropsychiatric Disorders: A Mendelian Randomization Study. JAMA Psychiatry. 2022;79(5):498-507. doi: 10.1001/jamapsychiatry.2022.0407
2. Bulut NS, Yorguner N, Carkaxhiu Bulut G. The severity of inflammation in major neuropsychiatric disorders: comparison of neutrophil-lymphocyte and platelet-lymphocyte ratios between schizophrenia, bipolar mania, bipolar depression, major depressive disorder, and obsessive compulsive disorder. Nord J Psychiatry. 2021;75(8):624-32. doi: 10.1080/08039488.2021.1919201
3. Bhattacharya A, Derecki NC, Lovenberg TW, Drevets WC. Role of neuroimmunological factors in the pathophysiology of mood disorders. Psychopharmacology (Berl). 2016;233(9):1623-36. doi: 10.1007/s00213-0164214-0
4. Inaltekin A, Yagci I. Evaluation of Simple Markers of Inflammation and Systemic Immune Inflammation Index in Schizophrenia, Bipolar Disorder Patients and Healthy Controls. Turk Psikiyatri Derg. 2023 Spring;34(1):11-5 (In Engl., Turkish). doi: 10.5080/u26248
5. Zahorec R. Ratio of neutrophil to lymphocyte counts – rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy. 2001;102(1):5-14.
6. Wright HL, Moots RJ, Bucknall RC, Edwards SW. Neutrophil function in inflammation and inflammatory diseases. Rheumatology (Oxford). 2010;49(9):1618-31. doi: 10.1093/rheumatology/keq045
7. Singh D, Guest PC, Dobrowolny H, et al. Changes in leukocytes and CRP in different stages of major depression. J Neuroinflammation. 2022 Apr 4;19(1):74. doi: 10.1186/s12974-022-02429-7
8. Holmes C, Cunningham C, Zotova E, et al. Proinflammatory cytokines, sickness behavior, and Alzheimer disease. Neurology. 2011;77(3):212-8. doi: 10.1212/WNL.0b013e318225ae07
9. Cowburn AS, Deighton J, Walmsley SR, Chilvers ER. The survival effect of TNF-alpha in human neutrophils is mediated via NF-kappa B-dependent IL-8 release. Eur J Immunol. 2004;34(6):1733-43. doi: 10.1002/eji.200425091
10. Pun PB, Lu J, Moochhala S. Involvement of ROS in BBB dysfunction. Free Radic Res. 2009;43(4):348-64. doi: 10.1080/10715760902751902
11. Ceylan MF, Tural Hesapcioglu S, Kanoglu Yüksekkaya S, et al. Changes in neurofilament light chain protein (NEFL) in children and adolescents with Schizophrenia and Bipolar Disorder: Early period neurodegeneration. J Psychiatr Res. 2023;161:342-7. doi: 10.1016/j.jpsychires.2023.03.027
12. Ziv Y, Schwartz M. Immune-based regulation of adult neurogenesis: implications for learning and memory. Brain Behav Immun. 2008;22(2):167-76. doi: 10.1016/j.bbi.2007.08.006
13. Moalem G, Leibowitz-Amit R, Yoles E, et al. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med. 1999;5(1):49-55. doi: 10.1038/4734
14. Yoles E, Hauben E, Palgi O, et al. Protective autoimmunity is a physiological response to CNS trauma. J Neurosci. 2001;21(11):3740-8. doi: 10.1523/JNEUROSCI.21-11-03740.2001. Erratum in: J Neurosci. 2001 Aug 1;21(15):1a.
15. Hotchkiss RS, Swanson PE, Freeman BD, et al. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med. 1999;27(7):123051. doi: 10.1097/00003246-199907000-00002
16. Szuster-Ciesielska A, Slotwinska M, Stachura A, et al. Accelerated apoptosis of blood leukocytes and oxidative stress in blood of patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(3):686-94. doi: 10.1016/j.pnpbp.2007.11.012
17. Toben C, Baune BT. An Act of Balance Between Adaptive and Maladaptive Immunity in Depression: a Role for T Lymphocytes. J Neuroimmune Pharmacol. 2015;10(4):595-609. doi: 10.1007/s11481-015-9620-2
18. Hong S, Kim EJ, Lee EJ, et al. TNF-α confers resistance to Fas-mediated apoptosis in rheumatoid arthritis through the induction of soluble Fas. Life Sci. 2015;122:37-41. doi: 10.1016/j.lfs.2014.12.008
19. Cosyns P, Maes M, Vandewoude M, et al. Impaired mitogen-induced lymphocyte responses and the hypothalamic-pituitary-adrenal axis in depressive disorders. J Affect Disord. 1989;16(1):41-8. doi: 10.1016/01650327(89)90054-2
20. Bauer ME, Papadopoulos A, Poon L, et al. Dexamethasone-induced effects on lymphocyte distribution and expression of adhesion molecules in treatment-resistant depression. Psychiatry Res. 2002;113(1-2):1-15. doi: 10.1016/s0165-1781(02)00243-3
21. Pace TW, Miller AH. Cytokines and glucocorticoid receptor signaling. Relevance to major depression. Ann N Y Acad Sci. 2009 Oct;1179:86-105. doi: 10.1111/j.17496632.2009.04984.x
22. Liu YJ, Guo DW, Tian L, et al. Peripheral T cells derived from Alzheimer's disease patients overexpress CXCR2 contributing to its transendothelial migration, which is microglial TNF-alpha-dependent. Neurobiol Aging. 2010 Feb;31(2):175-88. doi: 10.1016/j.neurobiolaging.2008.03.024
23. Sayed A, Bahbah EI, Kamel S, et al. The neutrophil-to-lymphocyte ratio in Alzheimer's disease: Current understanding and potential applications. J Neuroimmunol. 2020;349:577398. doi: 10.1016/j.jneuroim.2020.577398
24. Cardone J, Le Friec G, Vantourout P, et al. Complement regulator CD46 temporally regulates cytokine production by conventional and unconventional T cells. Nat Immunol. 2010;11(9):862-71. doi: 10.1038/ni.1917
25. Anisman H, Ravindran AV, Griffiths J, Merali Z. Endocrine and cytokine correlates of major depression and dysthymia with typical or atypical features. Mol Psychiatry. 1999;4(2):182-8. doi: 10.1038/sj.mp.4000436
26. Horstman LL, Jy W, Ahn YS, et al. Role of platelets in neuroinflammation: a wide-angle perspective. J Neuroinflammation. 2010 Feb 3;7:10. doi: 10.1186/1742-2094-7-10
27. Ziegelstein RC, Parakh K, Sakhuja A, Bhat U. Platelet function in patients with major depression. Intern Med J. 2009;39(1):38-43. doi: 10.1111/j.1445-5994.2008.01794.x
28. Palmar M, Marcano A, Castejon O. Fine structural alterations of blood platelets in depression. Biol Psychiatry. 1997;42(10):9658. doi: 10.1016/S0006-3223(97)00348-X
29. Lesch KP, Wolozin BL, Murphy DL, Reiderer P. Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem. 1993;60(6):2319-22. doi: 10.1111/j.14714159.1993.tb03522.x
30. Herr N, Bode C, Duerschmied D. The Effects of Serotonin in Immune Cells. Front Cardiovasc Med. 2017 Jul 20;4:48. doi: 10.3389/fcvm.2017.00048. eCollection 2017.
31. Kusumi I, Koyama T, Yamashita I. Serotonin-induced platelet intracellular calcium mobilization in depressed patients. Psychopharmacology (Berl). 1994;113(3-4):3227. doi: 10.1007/BF02245204
32. Ellis PM, Salmond C. Is platelet imipramine binding reduced in depression? A meta-analysis. Biol Psychiatry. 1994;36(5):2929. doi: 10.1016/0006-3223(94)90626-2
33. D'haenen H, De Waele M, Leysen JE. Platelet 3H-paroxetine binding in depressed patients. Psychiatry Res. 1988;26(1):11-7. doi: 10.1016/0165-1781(88)90082-0
34. Garcia-Sevilla JA, Zis AP, Hollingsworth PJ, et al. Platelet alpha 2-adrenergic receptors in major depressive disorder. Binding of tritiated clonidine before and after tricyclic antidepressant drug treatment. Arch Gen Psychiatry. 1981;38(12):132733. doi: 10.1001/archpsyc.1981.01780370029003
35. Garcia-Sevilla JA, Padro D, Giralt MT, et al. Alpha 2-adrenoceptor-mediated inhibition of platelet adenylate cyclase and induction of aggregation in major depression. Effect of long-term cyclic antidepressant drug treatment. Arch Gen Psychiatry. 1990;47(2):125-32. doi: 10.1001/archpsyc.1990.01810140025005
36. Takahashi Y, Yu Z, Sakai M, Tomita H. Linking Activation of Microglia and Peripheral Monocytic Cells to the Pathophysiology of Psychiatric Disorders. Front Cell Neurosci. 2016 Jun 3;10:144. doi: 10.3389/fncel.2016.00144
37. Simon MS, Schiweck C, Arteaga-Henriquez G, et al. Monocyte mitochondrial dysfunction, inflammaging, and inflammatory pyroptosis in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2021;111:110391. doi: 10.1016/j.pnpbp.2021.110391
38. Italiani P, Boraschi D. From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation. Front Immunol. 2014 Oct 17;5:514. doi: 10.3389/fimmu.2014.00514. eCollection 2014.
39. Lampiasi N, Bonaventura R, Deidda I, et al. Inflammation and the Potential Implication of Macrophage-Microglia Polarization in Human ASD: An Overview. Int J Mol Sci. 2023 Jan 31;24(3):2703. doi: 10.3390/ijms24032703
40. Duman RS, Sanacora G, Krystal JH. Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments. Neuron. 2019 Apr 3;102(1):75-90. doi: 10.1016/j.neuron.2019.03.013
41. Kartal O, Kartal AT. Value of neutrophil to lymphocyte and platelet to lymphocyte ratios in pneumonia. Bratisl Lek Listy. 2017;118(9):513-6. doi: 10.4149/BLL_2017_099
42. Zheng HH, Xiang Y, Wang Y, et al. Clinical value of blood related indexes in the diagnosis of bacterial infectious pneumonia in children. Transl Pediatr. 2022;11(1):114-9. doi: 10.21037/tp-21-568
43. Guthrie GJ, Charles KA, Roxburgh CS, et al. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol. 2013;88(1):218-30. doi: 10.1016/j.critrevonc.2013.03.010
44. Zhao CN, Mao YM, Wang P, et al. Lack of association between mean platelet volume and disease activity in systemic lupus erythematosus patients: a systematic review and metaanalysis. Rheumatol Int. 2018;38(9):1635-41. doi: 10.1007/s00296-018-4065-6
45. Gasparyan AY, Ayvazyan L, Mikhailidis DP, Kitas GD. Mean platelet volume: a link between thrombosis and inflammation? Curr Pharm Des. 2011;17(1):47-58. doi: 10.2174/138161211795049804
46. Mazza MG, Lucchi S, Tringali AGM, et al. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: A meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2018;84(Pt A):229-36. doi: 10.1016/j.pnpbp.2018.03.012
47. Inanli I, Aydin M, Caliskan AM, Eren I. Neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and mean platelet volume as systemic inflammatory markers in different states of bipolar disorder. Nord J Psychiatry. 2019;73(6):372-9. doi: 10.1080/08039488.2019.1640789
48. Medawar PB. Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br J Exp Pathol. 1948;29(1):58-69.
49. Andersson PB, Perry VH, Gordon S. The acute inflammatory response to lipopolysaccharide in CNS parenchyma differs from that in other body tissues. Neuroscience. 1992;48(1):169-86. doi: 10.1016/0306-4522(92)90347-5
50. Engelhardt B, Ransohoff RM. The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol. 2005;26(9):48595. doi: 10.1016/j.it.2005.07.004
51. Cserr HF, Knopf PM. Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: a new view. Immunol Today. 1992;13(12):507-12. doi: 10.1016/01675699(92)90027-5
52. Baruch K, Schwartz M. CNS-specific T cells shape brain function via the choroid plexus. Brain Behav Immun. 2013;34:11-6. doi: 10.1016/j.bbi.2013.04.002
53. Castro Dias M, Mapunda JA, Vladymyrov M, Engelhardt B. Structure and Junctional Complexes of Endothelial, Epithelial and Glial Brain Barriers. Int J Mol Sci. 2019 Oct 29;20(21):5372. doi: 10.3390/ijms20215372
54. Cugurra A, Mamuladze T, Rustenhoven J, et al. Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma. Science. 2021;373(6553):eabf7844. doi: 10.1126/science.abf7844
55. Degraff Z, Souza GS, Santos NA, et al. Brain atrophy and cognitive decline in bipolar disorder: Influence of medication use, symptomatology and illness duration. J Psychiatr Res. 2023;163:421-9. doi: 10.1016/j.jpsychires.2023.05.074
56. Leite Dantas R, Freff J, Ambree O, et al. Dendritic Cells: Neglected Modulators of Peripheral Immune Responses and Neuroinflammation in Mood Disorders? Cells. 2021 Apr 19;10(4):941. doi: 10.3390/cells10040941
57. Tan EYL, Köhler S, Hamel REG, et al. Depressive Symptoms in Mild Cognitive Impairment and the Risk of Dementia: A Systematic Review and Comparative MetaAnalysis of Clinical and Community-Based Studies. J Alzheimers Dis. 2019;67(4):1319-29. doi: 10.3233/JAD-180513
58. Wang S, Mao S, Xiang D, Fang C. Association between depression and the subsequent risk of Parkinson's disease: A meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2018;86:186-92. doi: 10.1016/j.pnpbp.2018.05.025
59. Hamelin L, Lagarde J, Dorothee G, et al. Distinct dynamic profiles of microglial activation are associated with progression of Alzheimer's disease. Brain. 2018;141(6):1855-70. doi: 10.1093/brain/awy079
60. Ghadery C, Koshimori Y, Christopher L, et al. The Interaction Between Neuroinflammation and β-Amyloid in Cognitive Decline in Parkinson's Disease. Mol Neurobiol. 2020;57(1):492-501. doi: 10.1007/s12035-019-01714-6
Review
For citations:
Gorbunova AP, Rukavishnikov GV, Kasyanov ED, Mazo GE. The role of cellular immunity and systemic inflammation indices in the pathogenetic mechanisms of mental disorders. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2023;15(5):72-78. (In Russ.) https://doi.org/10.14412/2074-2711-2023-5-72-78
Views:
431
Email this article 