Shared pathological mechanisms of systemic lupus erythematosus and affective disorders

Abstract

The high prevalence and variability of neurological and psychiatric symptoms in systemic lupus erythematosus has become the basis for emphasizing the special neuropsychiatric form of the disorder. Affective disorders (pathological changes in mood and anxiety) are the second most common neuropsychiatric manifestations in patients with systemic lupus erythematosus. However, the current nomenclature primarily focuses on the general clinical manifestations of affective disorders in neuropsychiatric form systemic lupus erythematosus, without evaluating the problems of their etiopathogenesis. Thereby, the aim of this review is the integration of information on the pathological mechanisms of depression and anxiety in patients with systemic lupus erythematosus. The available data on the biological aspects of the anxiety and depression in systemic lupus erythematosus indicate that the complex pathological models may be the best approach for studying, diagnosing, and treating comorbid pathology. The latter can be based on expanding the existing clinical categories, supplementing them with data on pathological mechanisms specific to particular sub-cohorts of patients. Such an approach can provide the specific and most effective preventive, diagnostic and therapeutic measures for each category of patients.

Keywords

systemic lupus erythematosus / affective disorders / comorbidity / pathological mechanisms / neuro-inflammation

References

[1] Postal M, Lapa AT, Sinicato NA, et al. Depressive symptoms are associated with tumor necrosis factor alpha in systemic lupus erythematosus. J Neuroinflammation. 2016;13:5. DOI: 10.1186/s12974-015-0471-9

[2] Postal M., Lapa A.T., Sinicato N.A. et al. Depressive symptoms are associated with tumor necrosis factor alpha in systemic lupus erythematosus // J. Neuroinflammation. 2016. Vol. 13. P. 5. DOI: 10.1186/s12974-015-0471-9

[3] Zhang L, Fu T, Yin R, et al. Prevalence of depression and anxiety in systemic lupus erythematosus: a systematic review and meta-analysis. BMC Psychiatry. 2017;17(1):70. DOI: 10.1186/s12888-017-1234-1

[4] Zhang L., Fu T., Yin R. et al. Prevalence of depression and anxiety in systemic lupus erythematosus: a systematic review and meta-analysis // BMC Psychiatry. 2017. Vol. 17, No. 1. P. 70. DOI: 10.1186/s12888-017-1234-1

[5] Primer on the Rheumatic Diseases. J.H. Klippel, J.H. Stone, L.J. Crofford, P.H. White (eds). Springer; 2008. DOI: 10.1007/978-0-387-68566-3

[6] Ревматические заболевания: в 3 т. Том III. Заболевания мягких тканей / под ред. Дж.Х. Клиппела, Дж.Х. Стоуна, Л.Дж. Кроффорд, П.Х. Уайт; пер. с англ. Е.Л. Насонова, В.А. Насоновой, Ю.А. Олюнина. Москва, 2011.

[7] Hawro T, Krupińska-Kun M, Rabe-Jabłońska J, et al. Psychiatric disorders in patients with systemic lupus erythematosus: association of anxiety disorder with shorter disease duration. Rheumatol Int. 2011;31(10):1387–1391. DOI: 10.1007/s00296-010-1689-6

[8] Hawro T., Krupińska-Kun M., Rabe-Jabłońska J. et al. Psychiatric disorders in patients with systemic lupus erythematosus: association of anxiety disorder with shorter disease duration // Rheumatol. Int. 2011. Vol. 31, No. 10. P. 1387–1391. DOI: 10.1007/s00296-010-1689-6

[9] Kwan A, Katz P, Touma Z. The assessment of anxiety and depression and its associated factors in SLE. Curr Rheumatol Rev. 2019;15(2):90–98. DOI: 10.2174/1573397114666180926101513

[10] Kwan A., Katz P., Touma Z. The assessment of anxiety and depression and its associated factors in SLE // Curr. Rheumatol. Rev. 2019. Vol. 15, No. 2. P. 90–98. DOI: 10.2174/1573397114666180926101513

[11] Seawell AH, Danoff-Burg S. Body image and sexuality in women with and without systemic lupus erythematosus. Sex Roles. 2005;53(11):865–876. DOI: 10.1007/s11199-005-8298-y

[12] Seawell A.H., Danoff-Burg S. Body image and sexuality in women with and without systemic lupus erythematosus // Sex. Roles. 2005. Vol. 53, No. 11. P. 865–876. DOI: 10.1007/s11199-005-8298-y

[13] Vivaldo JF, de Amorim JC, Julio PR, et al. Definition of NPSLE: Does the ACR nomenclature still hold? Front Med (Lausanne). 2018;5:138. DOI: 10.3389/fmed.2018.00138

[14] Vivaldo J.F., de Amorim J.C., Julio P.R. et al. Definition of NPSLE: Does the ACR nomenclature still hold? // Front. Med. (Lausanne). 2018. Vol. 5. P. 138. DOI: 10.3389/fmed.2018.00138

[15] Alsowaida N, Alrasheed M, Mayet A, et al. Medication adherence, depression and disease activity among patients with systemic lupus erythematosus. Lupus. 2018;27(2):327–332. DOI: 10.1177/0961203317725585

[16] Alsowaida N., Alrasheed M., Mayet A. et al. Medication adherence, depression and disease activity among patients with systemic lupus erythematosus // Lupus. 2018. Vol. 27, No. 2. P. 327–332. DOI: 10.1177/0961203317725585

[17] Palagini L, Mosca M, Tani C, et al. Depression and systemic lupus erythematosus: a systematic review. Lupus. 2013;22(5):409–416. DOI: 10.1177/0961203313477227

[18] Palagini L., Mosca M., Tani C. et al. Depression and systemic lupus erythematosus: a systematic review // Lupus. 2013. Vol. 22, No. 5. P. 409–416. DOI: 10.1177/0961203313477227

[19] Xu J, Cheng YQ, Chen B, et al. Depression in systemic lupus erythematosus patients is associated with link-polymorphism but not methylation status of the 5HTT promoter region. Lupus. 2013;22(10):1001–1010. DOI: 10.1177/0961203313498793

[20] Xu J., Cheng Y.Q., Chen B. et al. Depression in systemic lupus erythematosus patients is associated with link-polymorphism but not methylation status of the 5HTT promoter region // Lupus. 2013. Vol. 22, No. 10. P. 1001–1010. DOI: 10.1177/0961203313498793

[21] Jeltsch-David H, Muller S. Neuropsychiatric systemic lupus erythematosus: pathogenesis and biomarkers. Nat Rev Neurol. 2014;10(10):579–596. DOI: 10.1038/nrneurol.2014.148

[22] Jeltsch-David H., Muller S. Neuropsychiatric systemic lupus erythematosus: pathogenesis and biomarkers // Nat. Rev. Neurol. 2014. Vol. 10, No. 10. P. 579–596. DOI: 10.1038/nrneurol.2014.148

[23] Dantzer R. Cytokine, sickness behavior, and depression. Immunol Allergy Clin North Am. 2009;29(2):247–264. DOI: 10.1016/j.iac.2009.02.002

[24] Dantzer R. Cytokine, sickness behavior, and depression // Immunol. Allergy Clin. North Am. 2009. Vol. 29, No. 2. P. 247–264. DOI: 10.1016/j.iac.2009.02.002

[25] Khairova RA, Machado-Vieira R, Du J, Manji HK. A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder. Int J Neuropsychopharmacol. 2009;12(4):561–578. DOI: 10.1017/S1461145709009924

[26] Khairova R.A., Machado-Vieira R., Du J., Manji H.K. A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder // Int. J. Neuropsychopharmacol. 2009. Vol. 12, No. 4. P. 561–578. DOI: 10.1017/S1461145709009924

[27] Ménard C, Hodes GE, Russo SJ. Pathogenesis of depression: Insights from human and rodent studies. Neuroscience. 2016;321:138–162. DOI: 10.1016/j.neuroscience.2015.05.053

[28] Ménard C., Hodes G.E., Russo S.J. Pathogenesis of depression: Insights from human and rodent studies // Neuroscience. 2016. Vol. 321. P. 138–162. DOI: 10.1016/j.neuroscience.2015.05.053

[29] Krishnadas R, Cavanagh J. Depression: an inflammatory illness? J Neurol Neurosurg Psychiatry. 2012;83(5):495–502. DOI: 10.1136/jnnp-2011-301779

[30] Krishnadas R., Cavanagh J. Depression: an inflammatory illness? // J. Neurol. Neurosurg. Psychiatry. 2012. Vol. 83, No. 5. P. 495–502. DOI: 10.1136/jnnp-2011-301779

[31] Himmerich H, Fulda S, Linseisen J, et al. Depression, comorbidities and the TNF-alpha system. Eur Psychiatry. 2008;23(6):421–429. DOI: 10.1016/j.eurpsy.2008.03.013

[32] Himmerich H., Fulda S., Linseisen J. et al. Depression, comorbidities and the TNF-alpha system // Eur. Psychiatry. 2008. Vol. 23, No. 6. P. 421–429. DOI: 10.1016/j.eurpsy.2008.03.013

[33] Berthold-Losleben M, Himmerich H. The TNF-alpha system: functional aspects in depression, narcolepsy and psychopharmacology. Curr Neuropharmacol. 2008;6(3):193–202. DOI: 10.2174/157015908785777238

[34] Berthold-Losleben M., Himmerich H. The TNF-alpha system: functional aspects in depression, narcolepsy and psychopharmacology // Curr. Neuropharmacol. 2008. Vol. 6, No. 3. P. 193–202. DOI: 10.2174/157015908785777238

[35] Doczy EJ, Seroogy K, Harrison CR, Herman JP. Hypothalamo-pituitary-adrenocortical axis, glucocorticoids, and neurologic disease. Immunol Allergy Clin North Am. 2009;29(2):265–284. DOI: 10.1016/j.iac.2009.02.003

[36] Doczy E.J., Seroogy K., Harrison C.R., Herman J.P. Hypothalamo-pituitary-adrenocortical axis, glucocorticoids, and neurologic disease // Immunol. Allergy Clin. North Am. 2009. Vol. 29, No. 2. P. 265–284.DOI: 10.1016/j.iac.2009.02.003

[37] Black PH. Immune system-central nervous system interactions: effect and immunomodulatory consequences of immune system mediators on the brain. Antimicrob Agents Chemother. 1994;38(1):7–12. DOI: 10.1128/AAC.38.1.7

[38] Black P.H. Immune system-central nervous system interactions: effect and immunomodulatory consequences of immune system mediators on the brain // Antimicrob. Agents Chemother. 1994. Vol. 38, No. 1. P. 7–12. DOI: 10.1128/AAC.38.1.7

[39] Vallieres L, Rivest S. Interleukin-6 is a needed proinflammatory cytokine in the prolonged neural activity and transcriptional activation of corticotropinreleasing factor during endotoxemia. Endocrinology. 1999;140(9):3890–3903. DOI: 10.1210/endo.140.9.6983

[40] Vallieres L., Rivest S. Interleukin-6 is a needed proinflammatory cytokine in the prolonged neural activity and transcriptional activation of corticotropinreleasing factor during endotoxemia // Endocrinology. 1999. Vol. 140, No. 9. P. 3890–3903. DOI: 10.1210/endo.140.9.6983

[41] Chrousos GP. The hypothalamic-pituitary-adrenal axis and immunemediated inflammation. N Engl J Med. 1995;332(20):1351–1362. DOI: 10.1056/NEJM199505183322008

[42] Chrousos G.P. The hypothalamic-pituitary-adrenal axis and immunemediated inflammation // N. Engl. J. Med. 1995. Vol. 332, No. 20. P. 1351–1362. DOI: 10.1056/NEJM199505183322008

[43] McCann SM, Lyson K, Karanth S, et al. Mechanism of action of cytokines to induce the pattern of pituitary hormone secretion in infection. Ann N Y Acad Sci. 1995;771:386–395. DOI: 10.1111/j.1749-6632.1995.tb44697.x

[44] McCann S.M., Lyson K., Karanth S. et al. Mechanism of action of cytokines to induce the pattern of pituitary hormone secretion in infection // Ann. N Y Acad. Sci. 1995. Vol. 771. P. 386–395. DOI: 10.1111/j.1749-6632.1995.tb44697.x

[45] Dantzer R, Wollman E, Vitkovic L, Yirmiya R. Cytokines and depression: fortuitous or causative association? Mol Psychiatry. 1999;4(4):328–332. DOI: 10.1038/sj.mp.4000572

[46] Dantzer R., Wollman E., Vitkovic L., Yirmiya R. Cytokines and depression: fortuitous or causative association? // Mol. Psychiatry. 1999. Vol. 4, No. 4. P. 328–332. DOI: 10.1038/sj.mp.4000572

[47] Dowlati Y, Herrmann N, Swardfager W, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010;67(5):446–457. DOI: 10.1016/j.biopsych.2009.09.033

[48] Dowlati Y., Herrmann N., Swardfager W. et al. A meta-analysis of cytokines in major depression // Biol. Psychiatry. 2010. Vol. 67, No. 5. P. 446–457. DOI: 10.1016/j.biopsych.2009.09.033

[49] Zhu CB, Blakely RD, Hewlett WA. The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters. Neuropsychopharmacology. 2006;31(10):2121–2131. DOI: 10.1038/sj.npp.1301029

[50] Zhu C.B., Blakely R.D., Hewlett W.A. The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters // Neuropsychopharmacology. 2006. Vol. 31, No. 10. P. 2121–2131. DOI: 10.1038/sj.npp.1301029

[51] Müller N, Schwarz MJ. Immunologische Aspekte bei depressiven Störungen [Immunological aspects of depressive disorders]. Nervenarzt. 2007;78(11):1261–1273. (In German). DOI: 10.1007/s00115-007-2311-3

[52] Müller N., Schwarz M.J. Immunologische Aspekte bei depressiven Störungen [Immunological aspects of depressive disorders] // Nervenarzt. 2007. Vol. 78, No. 11. P. 1261–1273. (In German). DOI: 10.1007/s00115-007-2311-3

[53] Wichers M, Maes M. The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans. Int J Neuropsychopharmacol. 2002;5(4):375–388. DOI: 10.1017/S1461145702003103

[54] Wichers M., Maes M. The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans // Int. J. Neuropsychopharmacol. 2002. Vol. 5, No. 4. P. 375–388. DOI: 10.1017/S1461145702003103

[55] Himmerich H, Fulda S, Linseisen J, et al. Depression, comorbidities and the TNF-alpha system. Eur Psychiatry. 2008;23(6):421–429. DOI: 10.1016/j.eurpsy.2008.03.013

[56] Himmerich H., Fulda S., Linseisen J. et al. Depression, comorbidities and the TNF-alpha system // Eur. Psychiatry. 2008. Vol. 23, No. 6. P. 421–429. DOI: 10.1016/j.eurpsy.2008.03.013

[57] Lang UE, Borgwardt S. Molecular mechanisms of depression: perspectives on new treatment strategies. Cell Physiol Biochem. 2013;31(6):761–777. DOI: 10.1159/000350094

[58] Lang U.E., Borgwardt S. Molecular mechanisms of depression: perspectives on new treatment strategies // Cell. Physiol. Biochem. 2013. Vol. 31, No. 6. P. 761–777. DOI: 10.1159/000350094

[59] Tisseverasinghe A, Peschken C, Hitchon C. Anxiety and mood disorders in systemic lupus erythematosus: current insights and future directions. Curr Rheumatol Rep. 2018;20(12):85. DOI: 10.1007/s11926-018-0797-2

[60] Tisseverasinghe A., Peschken C., Hitchon C. Anxiety and mood disorders in systemic lupus erythematosus: current insights and future directions // Curr. Rheumatol. Rep. 2018. Vol. 20, No. 12. P. 85. DOI: 10.1007/s11926-018-0797-2

[61] Seth G, Sundaresh A, Mariaselvam CM, et al. Immunological biomarkers in neuropsychiatric systemic lupus erythematosus: a comparative cross-sectional study from a tertiary care center in South India. Lupus. 2020;29(4):413–420. DOI: 10.1177/0961203320908940

[62] Seth G., Sundaresh A., Mariaselvam C.M. et al. Immunological biomarkers in neuropsychiatric systemic lupus erythematosus: a comparative cross-sectional study from a tertiary care center in South India // Lupus. 2020. Vol. 29, No. 4. P. 413–420. DOI: 10.1177/0961203320908940

[63] Figueiredo-Braga M, Cornaby C, Cortez A, et al. Depression and anxiety in systemic lupus erythematosus: The crosstalk between immunological, clinical, and psychosocial factors. Medicine (Baltimore). 2018;97(28):e11376. DOI: 10.1097/MD.0000000000011376

[64] Figueiredo-Braga M., Cornaby C., Cortez A. et al. Depression and anxiety in systemic lupus erythematosus: The crosstalk between immunological, clinical, and psychosocial factors // Medicine (Baltimore). 2018. Vol. 97, No. 28. P. e11376. DOI: 10.1097/MD.0000000000011376

[65] Zheng Q, Xu MJ, Cheng J, et al. Serum levels of brain-derived neurotrophic factor are associated with depressive symptoms in patients with systemic lupus erythematosus. Psychoneuroendocrinology. 2017;78:246–252. DOI: 10.1016/j.psyneuen.2016.12.001

[66] Zheng Q., Xu M.J., Cheng J. et al. Serum levels of brain-derived neurotrophic factor are associated with depressive symptoms in patients with systemic lupus erythematosus // Psychoneuroendocrinology. 2017. Vol. 78. P. 246–252. DOI: 10.1016/j.psyneuen.2016.12.001

[67] Ikenouchi-Sugita A, Yoshimura R, Okamoto T, et al. Serum brain-derived neurotrophic factor levels as a novel biological marker for the activities of psychiatric symptoms in systemic lupus erythematosus. World J Biol Psychiatry. 2010;11(2):121–128. DOI: 10.3109/15622970903521131

[68] Ikenouchi-Sugita A., Yoshimura R., Okamoto T. et al. Serum brain-derived neurotrophic factor levels as a novel biological marker for the activities of psychiatric symptoms in systemic lupus erythematosus // World J. Biol. Psychiatry. 2010. Vol. 11, No. 2. P. 121–128. DOI: 10.3109/15622970903521131

[69] Lahita RG, Bradlow HL, Kunkel HG, Fishman J. Alterations of estrogen metabolism in systemic lupus erythematosus. Arthritis Rheum. 1979;22(11):1195–1198. DOI: 10.1002/art.1780221106

[70] Lahita R.G., Bradlow H.L., Kunkel H.G., Fishman J. Alterations of estrogen metabolism in systemic lupus erythematosus // Arthritis Rheum. 1979. Vol. 22, No. 11. P. 1195–1198. DOI: 10.1002/art.1780221106

[71] Khan WA, Zaman GS, Alouffi S, Khan MWA. Depression and its related parameters increased the production of autoantibodies against 16α-hydroxyestrone-albumin complex in systemic lupus erythematosus. Int Immunopharmacol. 2019;71:215–223. DOI: 10.1016/j.intimp.2019.03.036

[72] Khan W.A., Zaman G.S., Alouffi S., Khan M.W.A. Depression and its related parameters increased the production of autoantibodies against 16α-hydroxyestrone-albumin complex in systemic lupus erythematosus // Int. Immunopharmacol. 2019. Vol. 71. P. 215–223. DOI: 10.1016/j.intimp.2019.03.036

[73] Weidler C, Härle P, Schedel J, et al. Patients with rheumatoid arthritis and systemic lupus erythematosus have increased renal excretion of mitogenic estrogens in relation to endogenous antiestrogens. J Rheumatol. 2004;31(3):489–494.

[74] Weidler C., Härle P., Schedel J. et al. Patients with rheumatoid arthritis and systemic lupus erythematosus have increased renal excretion of mitogenic estrogens in relation to endogenous antiestrogens // J. Rheumatol. 2004. Vol. 31, No. 3. P. 489–494.

[75] Reichlin S. Prolactin and growth hormone secretion in stress. Adv Exp Med Biol. 1988;245:353–376. DOI: 10.1007/978-1-4899-2064-5_28

[76] Reichlin S. Prolactin and growth hormone secretion in stress // Adv. Exp. Med. Biol. 1988. Vol. 245. P. 353–376. DOI: 10.1007/978-1-4899-2064-5_28

[77] Dorshkind K, Horseman ND. The roles of prolactin, growth hormone, insulin-like growth factor-I, and thyroid hormones in lymphocyte development and function: insights from genetic models of hormone and hormone receptor deficiency. Endocr Rev. 2000;21(3):292–312. DOI: 10.1210/edrv.21.3.0397

[78] Dorshkind K., Horseman N.D. The roles of prolactin, growth hormone, insulin-like growth factor-I, and thyroid hormones in lymphocyte development and function: insights from genetic models of hormone and hormone receptor deficiency // Endocr. Rev. 2000. Vol. 21, No. 3. P. 292–312. DOI: 10.1210/edrv.21.3.0397

[79] Torner L, Toschi N, Pohlinger A, et al. Anxiolytic and anti-stress effects of brain prolactin: improved efficacy of antisense targeting of the prolactin receptor by molecular modeling. J Neurosci. 2001;21(9):3207–3214. DOI: 10.1523/JNEUROSCI.21-09-03207.2001

[80] Torner L., Toschi N., Pohlinger A. et al. Anxiolytic and anti-stress effects of brain prolactin: improved efficacy of antisense targeting of the prolactin receptor by molecular modeling // J. Neurosci. 2001. Vol. 21, No. 9. P. 3207–3214. DOI: 10.1523/JNEUROSCI.21-09-03207.2001

[81] Torner L, Neumann ID. The brain prolactin system: involvement in stress response adaptations in lactation. Stress. 2002;5(4):249–257. DOI: 10.1080/1025389021000048638

[82] Torner L., Neumann I.D. The brain prolactin system: involvement in stress response adaptations in lactation // Stress. 2002. Vol. 5, No. 4. P. 249–257. DOI: 10.1080/1025389021000048638

[83] Yu-Lee LY. Prolactin modulation of immune and inflammatory responses. Recent Prog Horm Res. 2002;57:435–455. DOI: 10.1210/rp.57.1.435

[84] Yu-Lee L.Y. Prolactin modulation of immune and inflammatory responses // Recent Prog. Horm. Res. 2002. Vol. 57. P. 435–455. DOI: 10.1210/rp.57.1.435

[85] Cook CJ. Oxytocin and prolactin suppress cortisol responses to acute stress in both lactating and non-lactating sheep. J Dairy Res. 1997;64(3):327–339. DOI: 10.1017/s0022029997002240

[86] Cook C.J. Oxytocin and prolactin suppress cortisol responses to acute stress in both lactating and non-lactating sheep // J. Dairy Res. 1997. Vol. 64, No. 3. P. 327–339. DOI: 10.1017/s0022029997002240

[87] Jara LJ, Medina G, Saavedra MA, et al. Prolactin has a pathogenic role in systemic lupus erythematosus. Immunol Res. 2017;65(2):512–523. DOI: 10.1007/s12026-016-8891-x

[88] Jara L.J., Medina G., Saavedra M.A. et al. Prolactin has a pathogenic role in systemic lupus erythematosus // Immunol. Res. 2017. Vol. 65, No. 2. P. 512–523. DOI: 10.1007/s12026-016-8891-x

[89] Gholamrezaei A, Bonakdar ZS, Mirbagher L, Hosseini N. Sleep disorders in systemic lupus erythematosus. Does vitamin D play a role? Lupus. 2014;23(10):1054–1058. DOI: 10.1177/0961203314532563

[90] Gholamrezaei A., Bonakdar Z.S., Mirbagher L., Hosseini N. Sleep disorders in systemic lupus erythematosus. Does vitamin D play a role? // Lupus. 2014. Vol. 23, No. 10. P. 1054–1058. DOI: 10.1177/0961203314532563

[91] Katzav A, Solodeev I, Brodsky O, et al. Induction of autoimmune depression in mice by anti-ribosomal P antibodies via the limbic system. Arthritis Rheum. 2007;56(3):938–948. DOI: 10.1002/art.22419

[92] Katzav A., Solodeev I., Brodsky O. et al. Induction of autoimmune depression in mice by anti-ribosomal P antibodies via the limbic system // Arthritis Rheum. 2007. Vol. 56, No. 3. P. 938–948. DOI: 10.1002/art.22419

RIGHTS & PERMISSIONS

Rukavishnikov G.V., Smirnova A.A., Neznanov N.G., Mazurov V.I., Mazo G.E.