Asthenic disorder in children and adolescents: Aspects of diagnosis and pathogenesis

Asthenic disorder in children and adolescents is a polyetiological condition characterized by a varied clinical picture with the dominant complaint of increased fatigue and rapid exhaustion, both mental and physical, which are persistent and last for a long period of time. It is reported that medical aid appealability rates due to asthenic symptoms achieve up to 64%. The prevalence of asthenic disorder in children and adolescents is extremely difficult to determine, as the numerous clinical symptoms are often viewed within the context of other diseases rather than as a single, hallmark pathology. The development of this condition is driven by challenging-to-differentiate functional and organic disorders that arise secondary to other, diverse pathologies. Dysfunction of the reticular activating system (RAS) is one of the primary mechanisms underlying asthenic syndrome. Severe manifestations of asthenic disorder which result in the significant impairment of daily activities and considerable deterioration of the patient's quality of life for more than 6 months are considered as a separate nosological entity — chronic fatigue syndrome (CFS). Genes regulating the hypothalamic-pituitary-adrenal (HPA) axis that is the body's main way of responding to stress are believed to be involved in the development of CFS. A single component failure can disrupt the entire system and contribute to the development of increased fatigue. Asthenic disorders are one of the common symptoms in patients who have suffered a traumatic brain injury (TBI). N-acetylaspartate (NAA) is seen as one of the markers of nerve tissue damage and repair in traumatic brain injury. Research on the role of NAA in the development of asthenic disorders is of great interest. Brain magnetic resonance spectroscopy (MRS) has found specific neurochemical abnormalities that can potentially be treated with agents targeting metabolic disturbances identified in the central nervous system. The search for new physiological and biochemical markers of asthenic syndrome will expand our understanding of the pathogenesis and treatment options for these disorders.

1. Zakharova IN, Tvorogova TM, Pshenichnikova II, Sgibneva AI. Asthenic syndrome in schoolchildren: From the risk of development to diagnosis and treatment. Pediatrics. Consilium Medicum. 2021;(1):76–83. (In Russ.) Available at: https://www.elibrary.ru/cdvusl.

2. Potupchik TV, Evert LS, Veselova OF, Krysenko LV, Kostyuchenko YuR. Pharmacotherapy of Asthenic Syndrome in Children. Doctor.Ru. 2022;21(3):66–71. (In Russ.) Available at: https://journaldoctor.ru/catalog/nevrologiya/farmakoterapiya-i-komplementarnoe-lechenie-astenicheskogo-sindroma-u-detey.

3. Krol A, Wimmer RD, Halassa MM, Feng G. Thalamic Reticular Dysfunction as a Circuit Endophenotype in Neurodevelopmental Disorders. Neuron. 2018;98(2):282–295. https://doi.org/10.1016/j.neuron.2018.03.021.

4. Puri BK. The effects of stress on the dorsal raphe nucleus of the reticular formation and its role in the aetiology of disparate medical and neuropsychiatric disorders. Med Hypotheses. 2016;96:A4–A5. https://doi.org/10.1016/j.mehy.2016.09.006.

5. Nizovtseva OA. Asthenic syndrome in children. Trudnyj Pacient. 2022;20(1):39–43. (In Russ.) Available at: https://www.elibrary.ru/qbwabw.

6. Duffy FH, Shankardass A, McAnulty GB, Als H. A unique pattern of cortical connectivity characterizes patients with attention deficit disorders: a large electroencephalographic coherence study. BMC Med. 2017;15(1):51. https://doi.org/10.1186/s12916-017-0805-9.

7. Kulikova TG, Baulina ME. Neurophysiological and neuroanatomical correlates of children’s attention deficit hyperactivity disorder. Psychology, Sociology and Pedagogy. 2017;(4):56–61. (In Russ.) Available at: https://psychology.snauka.ru/en/2017/04/8078.

8. Bereskin D, Gorbunov JA. Features of Bioelectric Activity of the Cerebral Cortex and Thinking Disorders in Children with Various Borderline Disorders of Residual Organic Genesis. Experimental Psychology (Russia). 2021;14(1):151–171. (In Russ.) https://doi.org/10.17759/exppsy.2021140107.

9. Lavrik SIu, Domitrak SV, Shprakh VV. Correction of central nervous system energy processes in children with the minimal cerebral dysfunction. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2011;111(4):37–41. (In Russ.) Available at: https://www.mediasphera.ru/issues/zhurnal-nevrologii-i-psikhiatrii-im-s-s-korsakova/2011/4/031997-7298201146.

10. Chutko LS, Surushkina SYu, Yakovenko EA, Cherednichenko DV. Chronic fatigue syndrome in children. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2024;124(9):28–33. (In Russ.) https://doi.org/10.17116/jnevro202412409128.

11. Crawley E. The epidemiology of chronic fatigue syndrome/myalgic encephalitis in children. Arch Dis Child. 2014;99(2):171–174. https://doi.org/10.1136/archdischild-2012-302156.

12. Knight S, Elders S, Rodda J, Harvey A, Lubitz L, Rowe K et al. Epidemiology of paediatric chronic fatigue syndrome in Australia. Arch Dis Child. 2019;104(8):733–738. https://doi.org/10.1136/archdischild-2018-316450.

13. Clery P, Royston A, Driver K, Bailey J, Crawley E, Loades M. What treatments work for anxiety and depression in children and adolescents with chronic fatigue syndrome? An updated systematic review. BMJ Open. 2022;12(1):e051358. https://doi.org/10.1136/bmjopen-2021-051358.

14. Royston AP, Burge S, Idini I, Brigden A, Pike KC. Management of severe ME/CFS in children and young people in the UK: a British Paediatric Surveillance Unit study. BMJ Paediatr Open. 2024;8(1):e002436. https://doi.org/10.1136/bmjpo-2023-002436.

15. Kamyshnikova LA, Zherdeva AA. Chronic fatigue syndrome in the practice of a general practitioner: prevalence, diagnosis, and management of patients (literature review). Lechaschi Vrach. 2025;(9):61–64. (In Russ.) https://doi.org/10.51793/OS.2025.28.9.009

16. Vorobyova YuD, Danilov AB. Chronic fatigue syndrom: modern aspects of diagnosis and treatment. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2021;121(4):113–120. (In Russ.) https://doi.org/10.17116/jnevro2021121402113.

17. Sady MD, Vaughan CG, Gioia GA. Psychometric characteristics of the post-concussion symptom inventory in children and adolescents. Arch Clin Neuropsychol. 2014;29(4):348–363. https://doi.org/10.1093/arclin/acu014.

18. Govindaraju V, Young K, Maudsley AA. Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed. 2000;13(3):129–153. https://doi.org/10.1002/1099-1492(200005)13:3<129::aid-nbm619>3.0.co;2-v.

19. Lin AP, Liao HJ, Merugumala SK, Prabhu SP, Meehan WP 3rd, Ross BD. Metabolic imaging of mild traumatic brain injury. Brain Imaging Behav. 2012;6(2):208–223. https://doi.org/10.1007/s11682-012-9181-4.

20. Signoretti S, Marmarou A, Tavazzi B, Lazzarino G, Beaumont A, Vagnozzi R. N-Acetylaspartate reduction as a measure of injury severity and mitochondrial dysfunction following diffuse traumatic brain injury. J Neurotrauma. 2001;18(10):977–991. https://doi.org/10.1089/08977150152693683.

21. Widerström-Noga E, Govind V, Adcock JP, Levin BE, Maudsley AA. Subacute Pain after Traumatic Brain Injury Is Associated with Lower Insular N-Acetylaspartate Concentrations. J Neurotrauma. 2016;33(14):1380–1389. https://doi.org/10.1089/neu.2015.4098.

22. Moffett JR, Ross B, Arun P, Madhavarao CN, Namboodiri AM. N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol. 2007;81(2):89–131. https://doi.org/10.1016/j.pneurobio.2006.12.003.

23. De Stefano N, Matthews PM, Arnold DL. Reversible decreases in N-acetylaspartate after acute brain injury. Magn Reson Med. 1995;34(5):721–727. https://doi.org/10.1002/mrm.1910340511.

24. Godlewska BR, Williams S, Emir UE, Chen C, Sharpley AL, Goncalves AJ et al. Neurochemical abnormalities in chronic fatigue syndrome: a pilot magnetic resonance spectroscopy study at 7 Tesla. Psychopharmacology. 2022;239(1):163–171. https://doi.org/10.1007/s00213-021-05986-6.

25. Shchederkina IO, Ovsyannikov DYu, Glazyrina AA, Ivin NO, Bronina NV, Kuznetsova AA, Gorev VV. Asthenic syndrome in children and adolescents: Choice of treatment. Nervous Diseases. 2021;(2):34–39. (In Russ.) https://doi.org/10.24412/2226-0757-2021-12322.

26. Milovanova OA, Astanina SYu. Treatment of asthenoneurotic disorders in children. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2016;116(12):112–113. (In Russ.) https://doi.org/10.17116/jnevro2016116121112-113.

27. Esin RG, Khayrullin IKh, Esin OR, Fatykhova AF, Gismatullina EI, Isaeva YuN. Efficacy of potassium N-acetylaminosuccinate (Cogitum) in the treatment of asthenic syndrome: results of double-blind placebo-controlled trial. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2023;123(6):52–56. (In Russ.) https://doi.org/10.17116/jnevro202312306152.