Neuroinflammation Process as a Key Etiopathogenetic Factor in the Evolution of Autism Spectrum Disorders in Child Patients
https://doi.org/10.30629/2618-6667-2023-21-5-47-55
Abstract
Background: the prevalence of autism spectrum disorders (ASD) is increasing every year, however, diagnostic and therapeutic options are still limited.
Aim: identification the patterns of the neuroinflammation process in the etiopathogenesis of ASD of child patients.
Patients and methods: clinical, anamnestic and laboratory data of 85 child patients with a confirmed ASD diagnosis. Each patient was assessed for the level of neurospecific proteins (neuron-specific enolase (NSE), S100b protein), the indices of the “Neuro-immuno-test” panel (leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) activity, autoantibodies to S100b protein and myelin basic protein) in the blood before and after a standardized three-month-course of treatment. The reference interval of the laboratory was taken as normal values. The clinical picture was assessed according to the Childhood Autism Rating Scale (CARS). The correlation calculations were carried out in the MS Excel program.
Results: in this work we describe the dynamics of the neuroinflammation process parameters in children with autism-like syndrome and psycho-speech development delay on the basis of complex anti-inflammatory therapy. The results of the research prove the increase in NSE and S100b protein quantity among 85% of patients before the treatment. More than 60% of patients had the increase of the parameters of the Neuro-test panel. The severity levels of symptoms among patients according to the scales used specified moderate and severe autism. The quantity of neurospecific proteins and immunological parameters correlated with CARS scale scores. Positive dynamics of clinical symptoms and studied parameters decrease were observed while therapy. The use of the parameters allows to evaluate objectively the severity levels of the patient’s immunomitochondrial status and shows a congruent change on the basis of etiopathogenetic therapy.
About the Authors
T. E. ObodzinskayaRussian Federation
Tatyana E. Obodzinskaya, Psychiatrist, Psychotherapist, Head of Department of Mitochondrial Medicine
Moscow
V. O. Generalov
Russian Federation
Vasily O. Generalov, Dr. of Sci. (Med.), Neurologist, Epileptologist, Head of Medical Center
Moscow
T. R. Sadykov
Russian Federation
Timur R. Sadykov, Cand. of Sci. (Med.), Neurologist, Epileptologist, Head of Inpatient Department
Moscow
A. A. Aleksandrenkova
Russian Federation
Angelina A. Aleksandrenkova, Clinical Biochemist
Moscow
G. V. Larionov
Russian Federation
Gennady V. Larionov, Clinical Biochemist
Moscow
L. V. Niculina
Russian Federation
Lyubov V. Niculina, Clinical Biochemist
Moscow
References
1. American Psychiatric Association. Diagnostic Criteria for Autistic Disorder. In: Diagnostic and Statistical Manual of Mental Disorders, 5th Edn. 2013. Washington, DC: American Psychiatric Association.
2. Boyle CA, Boulet S, Schieve LA, Cohen RA, Blumberg SJ, Yeargin-Allsopp M, Visser S, Kogan MD. Trends in the prevalence of developmental disabilities in US children, 1997–2008. Pediatrics. 2011;127(6):1034– 1042. doi: 10.1542/peds.2010-2989
3. Pardo CA, Vargas DL, Zimmerman AW. Immunity, neuroglia and neuroinflammation in autism. Int Rev Psychiatry. 2005;17(6):485–495. doi: 10.1080/02646830500381930
4. Tetreault NA, Hakeem AY, Jiang S, Williams BA, Allman E, Wold BJ, Allman JM. Microglia in the cerebral cortex in autism. J Autism Dev Disord. 2012;42(12):2569–2584. doi: 10.1007/s10803-012-1513-0 PMID: 22466688.
5. Tuchman RF. Trastornos pervasivos del desarrollo. Perspectiva neurológica [Pervasive developmental disorders: neurological perspectives]. Rev Neurol. 1996;24(135):1446–50. (Spanish). PMID: 8974753.
6. Davidovitch M, Glick L, Holtzman G, Tirosh E, Safir MP. Developmental regression in autism: maternal perception. J Autism Dev Disord. 2000;30(2):113–119. doi: 10.1023/a:1005403421141
7. Goldberg WA, Osann K, Filipek PA, Laulhere T, Jarvis K, Modahl C, Flodman P, Spence MA. Language and other regression: assessment and timing. J Autism Dev Disord. 2003;33(6):607–616. doi: 10.1023/b:-jadd.0000005998.47370.ef PMID: 14714930.
8. Werner E, Dawson G. Validation of the phenomenon of autistic regression using home videotapes. Arch Gen Psychiatry. 2005;62(8):889–895. doi: 10.1001/archpsyc.62.8.889 PMID: 16061766.
9. Hansen RL, Ozonoff S, Krakowiak P, Angkustsiri K, Jones C, Deprey LJ, Le DN, Croen LA, Hertz-Picciotto I. Regression in autism: prevalence and associated factors in the CHARGE Study. Ambul Pediatr. 2008;8(1):25–31. doi: 10.1016/j.ambp.2007.08.006 PMID: 18191778.
10. Rossignol DA, Frye RE. Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism. Front Physiol. 2014;5:150. doi: 10.3389/fphys.2014.00150 PMID: 24795645; PMCID: PMC4001006.
11. Ghaziuddin M, Al-Khouri I, Ghaziuddin N. Autistic symptoms following herpes encephalitis. Eur Child Adolesc Psychiatry. 2002;11(3):142–146. doi: 10.1007/s00787-002-0271-5 PMID: 12369775.
12. Matta SM, Hill-Yardin EL, Crack PJ. The influence of neuroinflammation in Autism Spectrum Disorder. Brain Behav Immun. 2019;79:75–90. doi: 10.1016/j.bbi.2019.04.037 Epub 2019 Apr 25.PMID: 31029798.
13. Hsu CJ, Wong LC, Lee WT. Immunological Dysfunction in Tourette Syndrome and Related Disorders. Int J Mol Sci. 2021;22(2):853. doi: 10.3390/ijms22020853 PMID: 33467014; PMCID: PMC7839977.
14. Bianchimano P, Britton GJ, Wallach DS, Smith EM, Cox LM, Liu S, Iwanowski K, Weiner HL, Faith JJ, Clemente JC, Tankou SK. Mining the microbiota to identify gut commensals modulating neuroinflammation in a mouse model of multiple sclerosis. Microbiome. 2022;10(1):174. doi: 10.1186/s40168-022-01364-2 PMID: 36253847; PMCID: PMC9575236.
15. Симашкова НВ, Коваль-Зайцев АА, Зверева НВ, Хромов АИ. Когнитивный дефицит в структуре расстройств аутистического спектра. Психиатрия. 2010;6(48):5–15. Simashkova NV, Koval-Zaytsev AA, Zvereva NV, Khromov AI. Cognitive Deficit in the Structure of Autistic Spectrum Disorders. Psychiatry (Moscow) (Psikhiatriya). 2010;6(48):5–15. (In Russ.).
16. Симашкова НВ, Клюшник ТП, Якупова ЛП. Клинико-биологические подходы к диагностике и обоснованию персонализированной терапии у пациентов с расстройствами аутистического спектра. Психиатрия. 2018;78(2):17–24. doi: 10.30629/2618-6667-2018-78-17-24 Simashkova NV, Klyushnik TP, Yakupova LP. Clinical and biological approaches to the diagnostics and substantiation of personalized therapy in patients with autism spectrum disorders. Psychiatry (Moscow) (Psikhiatriya). 2018;78(2):17–24. (In Russ.). doi: 10.30629/2618-6667-2018-78-17-24
17. Симашкова НВ, Клюшник ТП, Коваль-Зайцев АА, Якупова ЛП. Клинико-биологические подходы к диагностике. Аутизм и нарушения развития. 2016;14(4):51–67. doi: 10.17759/autdd.2016140408 Simashkova NV, Kljushnik TP, Koval’-Zajcev AA, Jakupova LP. Kliniko-biologicheskie podhody k diagnostike. Autizm i narushenija razvitija. 2016;14(4):51–67. doi: 10.17759/autdd.2016140408
18. Schopler E, Reichler RJ, DeVellis RF, Daly K. Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS). J Autism Dev Disord. 1980;10(1):91–103.
19. Infante JR, Martínez A, Ochoa J, Cañadillas F, Torres-Avisbal M, Vallejo JA, González FM, Pacheco C, Latre JM. Niveles de S-100 y enolasa neuroespecífica en líquido cefalorraquídeo de enfermos con patología neurológica [Level of S-100 and neuron-specific enolase in cerebrospinal fluid from subjects with neurological pathologies]. Rev Esp Med Nucl. 2003;22(4):238–243. (Spanish). doi: 10.1016/s0212-6982(03)72192-2 PMID: 12846948.
20. Langeh U, Singh S. Targeting S100B Protein as a Surrogate Biomarker and its Role in Various Neurological Disorders. Curr Neuropharmacol. 2021;19(2):265–277. doi: 10.2174/1570159X18666200729100427 PMID: 32727332; PMCID: PMC8033985.
21. Клюшник ТП. Лабораторная диагностика в мониторинге пациентов с эндогенными психозами («Ней ро-иммуно-тест»). Медицинская технология. М.: ООО «Издательство «Медицинское информационное агентство», 2016:31с. ISBN: 599860279X; ISBN-13(EAN): 9785998602795 Kljushnik TP. Laboratornaja diagnostika v monitoringe pacientov s jendogennymi psihozami (nejro-immuno-test). Medicinskaja tehnologija. M.: Medical Informational Agency, 2016:31s. (In Russ.). ISBN: 599860279X; ISBN-13(EAN): 9785998602795
22. Клименко НА, Шелест МА. Функциональная активность ней трофилов периферической крови при хроническом бронхите. Научные ведомости БелГУ. Сер. Медицина. Фармация. 2013;11(154) (22):129132. Klimenko NA, Shelest MA. Functional activity of periferal blood neutrophils in chronic bronchitis. Nauchnye vedomosti BelGU. Ser. Meditsina. Farmatsiya. 2013;11(154)(22):129–132. (In Russ.).
23. Отман ИН, Кожевникова ЕН, Зозуля СА, Петкевич НП, Иншакова ВМ, Сидякин АА, Морозов СГ, Клюшник ТП. Оценка прогностической значимости технологии «Нейро-тест» у детей с перинатальными поражениями нервной системы. Вопросы практической педиатрии. 2015;10(6):68–71. Otman IN, Kozhevnikova EN, Zozulja SA, Petkevich NP, Inshakova VM, Sidjakin AA, Morozov SG, Kljushnik TP. Ocenka prognosticheskoj znachimosti tehnologii “Nejro-test” u detej s perinatal’nymi porazhenijami nervnoj sistemy. Voprosy prakticheskoj pediatrii. 2015;10(6):68–71. (In Russ.).
Review
For citations:
Obodzinskaya T.E., Generalov V.O., Sadykov T.R., Aleksandrenkova A.A., Larionov G.V., Niculina L.V. Neuroinflammation Process as a Key Etiopathogenetic Factor in the Evolution of Autism Spectrum Disorders in Child Patients. Psychiatry (Moscow) (Psikhiatriya). 2023;21(5):47-55. (In Russ.) https://doi.org/10.30629/2618-6667-2023-21-5-47-55