The role of systemic inflammation in the pathogenesis of hyperkinetic disorder
https://doi.org/10.31363/2313-7053-2025-3-1088
Abstract
Hyperkinetic disorder (HD) is a common mental disorder in children and affects 5% of the population. In recent years, the important role of systemic inflammation in the pathogenesis of HD has been discussed. It is believed that the level of neutrophils, lymphocytes, platelets and monocytes, as well as their ratios, can serve as markers of systemic inflammation in HD. However, the question of the specificity of the data obtained remains open due to insufficient data. The specificity of markers of neuroinflammation and systemic inflammation, levels of hyperkinetic disorder remains insufficiently studied, which requires clarification in future studies with the exclusion of background residual organic pathology of the brain, inflammatory and autoimmune diseases in comparison not only with a group of healthy controls, but also with a group of patients with other mental disorders.
Keywords
hyperkinetic disorder,
systemic inflammation,
interleukins,
cellular ratio,
depression,
inflammation,
biomarker
Supporting agencies: The article was performed within the framework of the state assignment of the «V.M. Bekhterev National Research Medical Center for Psychiatry and Neurology of the Ministry of Health of Russia» 2024-2026 (XSOZ 2024 0012).
About the Authors
Rauf F. Gasanov
V.M. Bekhterev National research medical center for psychiatry and neurology
Russian Federation
Russian Federation
Saint-Petersburg
Igor V. Makarov
V.M. Bekhterev National research medical center for psychiatry and neurology
Russian Federation
Russian Federation
Saint-Petersburg
Daria A. Emelina
V.M. Bekhterev National research medical center for psychiatry and neurology
Russian Federation
Russian Federation
Saint-Petersburg
Ilya V. Kravchenko
V.M. Bekhterev National research medical center for psychiatry and neurology
Russian Federation
Russian Federation
Saint-Petersburg
Ekaterina S. Prokhorenko
V.M. Bekhterev National research medical center for psychiatry and neurology
Russian Federation
Russian Federation
Saint-Petersburg
References
1. Andryukov BG, Bogdanova VD, Lyapun IN. Phenotypic heterogeneity of neutrophils: new antimicrobial characteristics and diagnostic technologies. Gematologiya i transfuziologiya. 2019;64(2):211-221. (In Russ.). https://doi.org/10.35754/0234-5730-2019-64-2-211-221.
2. Gasanov RF, Makarov IV, Emelina DA, Avtenuk AS. Neuroinflammation and its role in the pathogenesis of attention deficit hyperactivity disorder (literature review). Obozrenie psihiatrii i medicinskoj psihologii im. V.M. Bekhtereva. 2023;57(1):8-22. (In Russ.). https://doi.org/10.31363/2313-7053-2023-699.
3. Devojno LV, Idova GV, Al'perina EL, Chejdo MA, Gevorgyan MM, Davydova SM. Systemic brain mechanisms of neuroimmunomodulation: psychoemotional contribution. Sibirskij nauchnyj medicinskij zhurnal. 2004;2:90–97. (In Russ.).
4. Emelina DA, Kravchenko IV, Makarov IV., Gasanov RF., Prokhorenko E.S. The Role of Systemic Inflammation in Psychiatric Disorders Development in Children: Literature Review. Voprosy sovremennoj pediatrii. 2024;23(4):204-212. (In Russ.). https://doi.org/10.15690/vsp.v23i4.2780.
5. Zheleznikova GF, Skripchenko NV. Immunopathogenesis of infectious and inflammatory diseases of the central nervous system. Zhurnal infektologii. 2011;2:28–32. (In Russ.).
6. Karchevskaya AE, Payushina OV, Sharova EV, Oknina LB, Titov OY. Neuroinflammation as secondary damage in head injury. Annaly klinicheskoj i eksperimental'noj nevrologii. 2023;17(1):55-68. (In Russ.). https://doi.org/10.54101/ACEN.2023.1.7.
7. Selyanina NV, Karakulova YUV. Interaction of serotonin and cytokines in the pathogenesis of brain contusion. Fundamental'nye issledovaniya. 2013;7:638–641. (In Russ.).
8. Stavinskaya OA. Serotonin deprivation as a factor in the regulation of immunological reactivity. Ekologiya cheloveka. 2008;1:22–25. (In Russ.).
9. Sumlivaya ON. Correlation between serotonin and cytokine changes in patients with tick-borne encephalitis. Permskij medicinskij zhurnal. 2015;32(4):68-73. (In Russ.).
10. Banks WA. Blood-brain barrier transport of cytokines: a mechanism for neuropathology. Curr. Pharm. Des. 2005;8:973–984.
11. Bonilla FC, Oettgen HC. Adaptive immunity. J Allergy Clin Immunol. 2010;125:33-40. https://doi.org/10.1016/j.jaci.2009.09.017.
12. Cheng Y, Wang Y, Wang X, Jiang Z, Zhu L, Fang S. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio in depression: an updated systematic review and meta-analysis. Front Psychiatry. 2022;13:893097. https://doi.org/10.3389/fpsyt.2022.893097.
13. Corominas-Roso M, Armario A, Palomar G, Corrales M, Carrasco J, Richarte V, et al. IL-6 and TNF-α in unmedicated adults with ADHD: relationship to cortisol awakening response. Psychoneuroendocrinology. 2017;79:67–73. https://doi.org/10.1016/j.psyneuen.2017.02.017.
14. Darwish A, Elgohary T, Nosair N. Serum Interleukin-6 level in children with Attention-Deficit Hyperactivity Disorder (ADHD). J Child Neurol. 2019;34:61–7. https://doi.org/10.1177/0883073818809831.
15. Donfrancesco R, Nativio P, Borrelli E, Giua E, Andriola E, Villa MP, et al. Serum cytokines in pediatric neuropsychiatric syndromes: focus on Attention deficit hyperactivity disorder. Minerva Pediatr. 2021;73:398–404. https://doi.org/10.23736/S2724-5276.16.04642-9.
16. Dunn G, Nigg J, Sullivan E. Neuroinflammation as a risk factor for attention deficit hyperactivity disorder. Pharmacol Biochem Behav. 2019;182:22–34.
17. Erre GL, Paliogiannis P, Castagna F, Mangoni AA, Carru C, Passiu G, et al. Meta-analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio in rheumatoid arthritis. Eur J Clin Invest. 2019;49:e13037. https://doi.org/10.1111/eci.13037.
18. Gędek A, Modrzejewski S, Gędek M, Antosik AZ, Mierzejewski P and Dominiak M. Neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and monocyte to lymphocyte ratio in ADHD: a systematic review and meta-analysis. Front. Psychiatry. 2023;14:1258868. https://doi.org/10.3389/fpsyt.2023.1258868.
19. Germic N, Frangez Z, Yousefi S, Simon H-U. Regulation of the innate immune system by autophagy: monocytes, macrophages, dendritic cells and antigen presentation. Cell Death Differ. 2019;26:715–27. https://doi.org/10.1038/s41418-019-0297-6.
20. Instanes J, Halmøy A, Engeland A, Haavik J, Furu K, Klungsøyr K. Attention-deficit/hyperactivity disorder in offspring of mothers with inflammatory and immune system diseases. Biol Psychiatry. 2017;81:452–9. https://doi.org/10.1016/j.biopsych.2015.11.024.
21. Koupenova M, Clancy L, Corkrey HA, Freedman JE. Circulating platelets as mediators of immunity, inflammation, and thrombosis. Circ Res. 2018;122:337–51. https://doi.org/10.1161/CIRCRESAHA.117.310795.
22. Li B, Concepcion K, Meng X, Zhang L. Brain-immune interactions in perinatal hypoxic-ischemic brain injury. Prog Neurobiol. 2017;159:50-68. https://doi.org/10.1016/j.pneurobio.2017.10.006.
23. Liew PX, Kubes P. The neutrophil’s role during health and disease. Physiol Rev. 2019;99:1223–48. https://doi.org/10.1152/physrev.00012.2018.
24. Lin Y, Chen Y, Gau S, Yeh T, Fan H, Hwang Y, et al. Associations between allergic diseases and attention deficit hyperactivity/oppositional defiant disorders in children. Pediatr Res. 2016;80:480–5. https://doi.org/10.1038/pr.2016.111.
25. Mayadas TN, Cullere X, Lowell CA. The multifaceted functions of neutrophils. Annu Rev Pathol. 2014; 9:181–218. https://doi.org/10.1146/annurev-pathol-020712-164023.
26. Mazza MG, Lucchi S, Rossetti A, Clerici M. Neutrophil-lymphocyte ratio, monocytelymphocyte ratio and platelet-lymphocyte ratio in non-affective psychosis: a meta-analysis and systematic review. World J Biol Psychiatry. 2020;21:326–38. https://doi.org/10.1080/15622975.2019.1583371.
27. Mazza MG, Lucchi S, Tringali AGM, Rossetti A, Botti ER, Clerici M. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2018;84:229–36. https://doi.org/10.1016/j.pnpbp.2018.03.012.
28. Mihai A, Caruntu A, Opris-Belinski D, Jurcut C, Dima A, Caruntu C, et al. The predictive role of Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Monocytes-to-Lymphocyte Ratio (MLR) and gammaglobulins for the development of cutaneous vasculitis lesions in Primary Sjögren’s syndrome. J Clin Med. 2022;11:5525. https://doi.org/10.3390/jcm11195525.
29. Molina-Carballo A, Naranjo-Gómez A, Uberos J, Justicia-Martínez F, Ruiz-Ramos MJ, Cubero-Millán I, Contreras-Chova F, Augustin-Morales MD, Khaldy-Belkadi H, Muñoz-Hoyos A. Methylphenidate effects on blood serotonin and melatonin levels may help to synchronise biological rhythms in children with ADHD. J Psychiatr Res. 2013;47(3):377-83. https://doi.org/10.1016/j.jpsychires.2012.09.020.
30. Oades RD, Dauvermann MR, Schimmelmann BG, Schwarz MJ, Myint A-M. Attention-deficit hyperactivity disorder (ADHD) and glial integrity: S100B, cytokines and kynurenine metabolism–effects of medication. Behav Brain Funct. 2010;6:29. https://doi.org/10.1186/1744-9081-6-29.
31. Qun S, Tang Y, Sun J, Liu Z, Wu J, Zhang J, et al. Neutrophil-to-lymphocyte ratio predicts 3-month outcome of acute ischemic stroke. Neurotox Res. 2017;31:444–52. https://doi.org/10.1007/s12640-017-9707-z.
32. Ramos-Quiroga JA, Corominas-Roso M, Palomar G, Ferrer R, Valero S, Corrales M, et al. Cortisol awakening response in adults with attention deficit hyperactivity disorder: subtype differences and association with the emotional lability. Eur Neuropsychopharmacol. 2016;26:1140–9. https://doi.org/10.1016/j.euroneuro.2016.03.014.
33. Saccaro L, Schilliger Z, Perroud N, Piguet C. Inflammation, anxiety, and stress in attention-deficit/hyperactivity disorder. Biomedicines. 2021;9:1313. https://doi.org/10.3390/biomedicines9101313.
34. Su M, Ouyang X, Song Y. Neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and monocyte to lymphocyte ratio in depression: {A} meta-analysis. J Affect Disord. 2022;308:375–83. https://doi.org/10.1016/j.jad.2022.04.038.
35. Urbanowicz T, Olasińska-Wiśniewska A, Michalak M, Rodzki M, Witkowska A, Straburzyńska-Migaj E, et al. The prognostic significance of neutrophil to Lymphocyte Ratio (NLR), Monocyte to Lymphocyte Ratio (MLR) and Platelet to Lymphocyte Ratio (PLR) on Long-Term Survival in Off-Pump Coronary Artery Bypass Grafting (OPCAB) procedures. Biology. 2021;11:34. https://doi.org/10.3390/biology11010034.
36. Wohleb ES, Fenn AM, Pacenta AM, Powell ND, Sheridan JF, Godbout JP. Peripheral innate immune challenge exaggerated microglia activation, increased the number of inflammatory CNS macrophages, and prolonged social withdrawal in socially defeated mice. Psychoneuroendocrinology. 2012;37:1491–505. https://doi.org/10.1016/j.psyneuen.2012.02.003.
Review
For citations:
Gasanov R.F., Makarov I.V., Emelina D.A., Kravchenko I.V., Prokhorenko E.S. The role of systemic inflammation in the pathogenesis of hyperkinetic disorder. V.M. BEKHTEREV REVIEW OF PSYCHIATRY AND MEDICAL PSYCHOLOGY. (In Russ.) https://doi.org/10.31363/2313-7053-2025-3-1088
Views:
24
Email this article 