The role of oxidative stress levels and S100B levels in children with functional neurological disorder

Pediatric functional neurological disorder

Authors

Keywords:

pediatric, functional neurological disorder, oxidative stress, S100B

Abstract

Background/Aim: Although stressors and traumatic life events are known to be predisposing factors for developing functional neurological disorder (FND), the etiology of the disorder has not been fully elucidated. In this study, oxidative stress parameters and serum levels of S100B protein were investigated in pediatric patients with functional neurological disorder. The association of these parameters with stress factors and traumatic life events was investigated.

Methods: This case-control study included a control group of 35 patients aged 8-18 years and 32 healthy subjects diagnosed with functional neurological disorder. The Childhood Trauma Scale and Dissociative Experiences Scale were applied to both groups. Serum levels of the patient and control groups were compared by blood sampling: total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and S100B.

Results: It was found that the Childhood Trauma Scale total score, emotional neglect, emotional abuse, physical neglect and the Dissociative Experiences Scale were statistically significantly higher in the FND group than in the control group (P˂0.001, 0.001, P=0.013, P=0.017, 0.001). Stressors were found to be statistically significantly higher in the FND group than in the control group (P=0.020). There was no statistical difference between the FND group and control groups regarding the TAS, TOS, OSI, and S100B levels (P=0.965, P=0.228, P=0.268, P=0.517, respectively).

Conclusion: Our study is the first to investigate TOS, TAS, OSI and S100B in children with FND. In our study, although stressors and traumatic experiences were significantly higher in the functional neurological disorder group compared to the control group according to the stress susceptibility model, contrary to expectations, there was no significant difference in oxidative stress parameters and serum S100B levels. It was thought that the interaction between FND, which is characterized by biopsychosocial interaction and can manifest itself with various clinical symptoms, and stress may not be linear as initially thought, and the interaction between genetic predisposition and environmental factors may play a more complex role. The absence of significant differences observed in oxidative stress parameters and serum S100B levels may suggest that we should focus on different pathways and different potential biomarkers that need to be investigated in the future to understand the etiology and diagnosis of FND. However, the limitations noted above may affect the generalizability of the study findings.

Downloads

Download data is not yet available.

References

American Psychiatric Association, DSM-5 Task Force. (2013). Diagnostic and statistical manual of mental disorders: DSM-5™ (5th ed.). American Psychiatric Publishing, Inc., 2013 doi: 10.1176/appi.books.9780890425596. DOI: https://doi.org/10.1176/appi.books.9780890425596

Sadock B, Sadock V, Ruiz PK. Sadocks synopsis of psychiatry: Behavioral sciences/clinical psychiatry. Philadelphia: Wolter Kluwer, Lippincott Williams & Watkins; 2015.

Roelofs K, Keijsers GPJ, Hoogduin KAL, Näring GWB, Moene FC. Childhood abuse in patients with functional neurological disorder . Am J Psychiatry. 2002;159:1908-13. doi: 10.1176/appi.ajp.159.11.1908. DOI: https://doi.org/10.1176/appi.ajp.159.11.1908

Maqsood N, Akram B, Luqman N, Amin R. Functional neurological disorder: Psycho-Social Stressors And Life Events In Children. Professional. 2014;21:489-94. doi: 10.21649/akemu.v23i2.1584 DOI: https://doi.org/10.29309/TPMJ/2014.21.03.2003

Chung J, Mukerji S, Kozlowska K. Cortisol and α-amylase awakening response in children and adolescents with functional neurological (conversion) disorder. Aust N Z J Psychiatry. 2023;57(1):115-29. doi: 10.1177/00048674221082520. DOI: https://doi.org/10.1177/00048674221082520

Weber S, Bühler J, Vanini G, Loukas S, Bruckmaier R, Aybek S. Identification of biopsychological trait markers in functional neurological disorders. Brain. 2023;146(6):2627-41. doi: 10.1093/brain/awac442. DOI: https://doi.org/10.1093/brain/awac442

Spiers JG, Chen HJ, Sernia C, Lavidis NA. Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress. Front Neurosci. 2014;8:456. doi: 10.3389/fnins.2014.00456. DOI: https://doi.org/10.3389/fnins.2014.00456

Halliwell B. The antioxidant paradox: less paradoxical now? Br J Clin Pharmacol. 2013;75:637-44. doi: 10.1111/j.1365-2125.2012.04272.x. DOI: https://doi.org/10.1111/j.1365-2125.2012.04272.x

Sies H, Cadenas E. Oxidative stress: damage to intact cells and organs. Philos Trans R Soc Lond B Biol Sci. 1985;311:617-31. doi: 10.1098/rstb.1985.0168 DOI: https://doi.org/10.1098/rstb.1985.0168

Nunomura A, Tamaoki T, Motohashi N. Role of oxidative stress in the pathophysiology of neuropsychiatric disorders. Seishin Shinkeigaku Zasshi. 2014;116:842-58.

Jellinger KA. Recent advances in our understanding of neurodegeneration. J Neural Transm. 2009;116(9):1111-62. doi: 10.1007/s00702-009-0240-y DOI: https://doi.org/10.1007/s00702-009-0240-y

Selek S, Altindag A, Saracoglu G, Celik H, Aksoy N.Prolidase activity and its diagnostic performance in bipolar disorder. J Affect Disord. 2011;129:84-6. doi: 10.1016/j.jad.2010.09.003 DOI: https://doi.org/10.1016/j.jad.2010.09.003

Kul M, Unal F, Kandemir H, Sarkarati B, Kilinc K, Kandemir SB.Evaluation of oxidative metabolism in child and adolescent patients with attention deficit hyperactivity disorder. Psychiatry Investig. 2015;12:361. doi: 10.4306/pi.2015.12.3.361 DOI: https://doi.org/10.4306/pi.2015.12.3.361

Bal N, Acar ŞT, Tamer L. Altered Levels of Malondialdehyde and Vitamin E in Major Depressive Disorder and Generalized Anxiety Disorder. Dusunen Adam. 2012;25:206-11. doi: 10.5350/dajpn2012250302 DOI: https://doi.org/10.5350/DAJPN2012250302

Qin B, Panickar KS, Anderson RA. Cinnamon polyphenols attenuate the hydrogen peroxide-induced down regulation of S100β secretion by regulating sirtuin 1 in C6 rat glioma cells. Life Sci. 2014;102:72-9. doi: 10.1016/j.lfs.2014.02.038 DOI: https://doi.org/10.1016/j.lfs.2014.02.038

L Schroeter M, Sacher J, Steiner J, Schoenknecht P, Mueller K. Serum S100B represents a new biomarker for mood disorders. Curr Drug Targets. 2013;14:1237-48. doi: 10.2174/13894501113149990014 DOI: https://doi.org/10.2174/13894501113149990014

Huttunen HJ, Kuja-Panula J, Sorci G, Agneletti AL, Donato R, Rauvala H. Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through receptor for advanced glycation end products (RAGE) activation. J Biol Chem. 2000;275:40096-105. doi: 10.1074/jbc.M006993200 DOI: https://doi.org/10.1074/jbc.M006993200

Carlton E, Falcone T, Batra A, Fazio V, Franco K, Janigro D. Do systemic inflammation and blood-brain barrier failure play a role in pediatric psychosis? Cleve Clin J Med. 2009;76:93.

Rothermundt M, Missler U, Arolt V, Peters M, Leadbeater J, Wiesmann M, et al. Increased S100B blood levels in unmedicated and treated schizophrenic patients are correlated with negative symptomatology. Mol Psychiatry. 2001;6:445-9. doi: 10.1038/sj.mp.4000889 DOI: https://doi.org/10.1038/sj.mp.4000889

Schroeter ML, Abdul-Khaliq H, Diefenbacher A, Blasig IE. S100B is increased in mood disorders and may be reduced by antidepressive treatment. Neuroreport. 2002;13:1675-8. doi: 10.1097/00001756-200209160-00021 DOI: https://doi.org/10.1097/00001756-200209160-00021

Machado-Vieira R, Lara DR, Portela LV, Gonçalves CA, Soares JC, Kapczinski F, et al. Elevated serum S100B protein in drug-free bipolar patients during first manic episode: a pilot study. Eur Neuropsychopharmacol. 2002;12:269-72. doi: 10.1016/s0924-977x(02)00029-9 DOI: https://doi.org/10.1016/S0924-977X(02)00029-9

von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Int J Surg. 2014;12:1495-9. DOI: https://doi.org/10.1016/j.ijsu.2014.07.013

Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004;37:277-85. doi: 10.1016/j.clinbiochem.2003.11.015 DOI: https://doi.org/10.1016/j.clinbiochem.2003.11.015

Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical biochemistry. 2005;38:1103-11. doi: 10.1016/j.clinbiochem.2005.08.008 DOI: https://doi.org/10.1016/j.clinbiochem.2005.08.008

Bernstein D, Fink L. Manual for the childhood trauma questionnaire. New York: The Psychological Corporation; 1998.

Sar V, Ozturk E, Ikikardes E. Validity and reliability of the Turkish version of Childhood Trauma Questionnaire. Turkiye Klinikleri Tip Bilimleri Dergisi. 2012;32(4):1054-63. DOI: https://doi.org/10.5336/medsci.2011-26947

Carlson EB, Putnam FW, Ross CA, et al. Validity of the Dissociative Experiences Scale in screening for multiple personality disorder: a multicenter study. Am J Psychiatry. 1993;150(7):1030-6. doi: 10.1176/ajp.150.7.1030. DOI: https://doi.org/10.1176/ajp.150.7.1030

Sar V, Kundakci T, Kiziltan E, Bakim B, Yargic LI, Tutkun H. The reliability and validity of the Turkish version of the Dissociative Experiences Scale (DES-II). Proceedings of the 33rd National Congress of Psychiatry. Antalya: Psychiatric Association of Turkey; 1997.

Gu HF, Tang CK, Yang YZ. Psychological stress, immune response, and atherosclerosis. Atherosclerosis. 2012;223(1):69-77. doi: 10.1016/j.atherosclerosis. DOI: https://doi.org/10.1016/j.atherosclerosis.2012.01.021

Biswas SK. Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox? Oxid Med Cell Longev. 2016;2016:5698931. doi: 10.1155/2016/5698931. DOI: https://doi.org/10.1155/2016/5698931

Keynejad RC, Frodl T, Kanaan R, Pariante C, Reuber M, Nicholson TR. Stress and functional neurological disorders: mechanistic insights. J Neurol Neurosurg Psychiatry. 2019;90:813-21. doi: 10.1136/jnnp-2018-318297. DOI: https://doi.org/10.1136/jnnp-2018-318297

Shalev H, Serlin Y, Friedman A. Breaching the blood-brain barrier as a gate to psychiatric disorder. Cardiovasc Psychiatry Neurol. 2009;2009:278531. doi: 10.1155/2009/278531. DOI: https://doi.org/10.1155/2009/278531

Falcone T, Janigro D, Lovell R, et al. S100B blood levels and childhood trauma in adolescent inpatients. J Psychiatr Res. 2015;62:14-22. doi: 10.1016/j.jpsychires.2014.12.002. DOI: https://doi.org/10.1016/j.jpsychires.2014.12.002

Büyükaslan H, Kandemir SB, Asoğlu M, et al. Evaluation of oxidant, antioxidant, and S100B levels in patients with functional neurological disorder. Neuropsychiatr Dis Treat. 2016;12:1725. doi: 10.2147/NDT.S109174. DOI: https://doi.org/10.2147/NDT.S109174

Schiavone S, Colaianna M, Curtis L. Impact of early life stress on the pathogenesis of mental disorders: relation to brain oxidative stress. Curr Pharm Des. 2015;21:1404-12. doi: 10.2174/1381612821666150105143358. DOI: https://doi.org/10.2174/1381612821666150105143358

Schiavone S, Jaquet V, Trabace L, Krause KH. Severe life stress and oxidative stress in the brain: from animal models to human pathology. Antioxid Redox Signal. 2013;18:1475-90. doi: 10.1089/ars.2012.4720. DOI: https://doi.org/10.1089/ars.2012.4720

von Bernhardi R, Eugenín-von Bernhardi J, Flores B, Eugenín León J.Glial cells and integrity of the nervous system. Adv Exp Med Biol. 2016:1-24. doi: 10.1007/978-3-319-40764-7_1. DOI: https://doi.org/10.1007/978-3-319-40764-7_1

Stephenson CP, Baguley IJ. Functional neurological disorder (functional neurological disorder): a role for microglial-based plasticity mechanisms? Med Hypotheses. 2018;111:41-8. doi: 10.1016/j.mehy.2017.12.010. DOI: https://doi.org/10.1016/j.mehy.2017.12.010

Kozlowska K, Spooner CJ, Palmer DM, et al. “Motoring in idle”: The default mode and somatomotor networks are overactive in children and adolescents with functional neurological symptoms. Neuroimage Clin. 2018;18:730-43. doi: 10.1016/j.nicl.2018.02.003. DOI: https://doi.org/10.1016/j.nicl.2018.02.003

Kozlowska K, Griffiths KR, Foster SL, Linton J, Williams LM, Korgaonkar MS. Grey matter abnormalities in children and adolescents with functional neurological symptom disorder. Neuroimage Clin. 2017;15:306-14. doi: 10.1016/j.nicl.2017.04.028. DOI: https://doi.org/10.1016/j.nicl.2017.04.028

Aybek S, Nicholson TR, Draganski B, et al. Grey matter changes in motor functional neurological disorder. J Neurol Neurosurg Psychiatry. 2014;85:236-8. doi: 10.1136/jnnp-2012-304158. DOI: https://doi.org/10.1136/jnnp-2012-304158

Perez DL, Williams B, Matin N, et al. Corticolimbic structural alterations linked to health status and trait anxiety in functional neurological disorder. J Neurol Neurosurg. Psychiatry 2017;88:1052-9. doi: 10.1136/jnnp-2017-316359. DOI: https://doi.org/10.1136/jnnp-2017-316359

Ozdemir PG, Kaplan I, Uysal C, et al. Serum total oxidant and antioxidant status in earthquake survivors with post-traumatic stress disorder. Acta Neuropsychiatr. 2015;27:153-8. doi: 10.1017/neu.2014.47. DOI: https://doi.org/10.1017/neu.2014.47

Demir S, Bulut M, Atli A, et al. Decreased prolidase activity in patients with posttraumatic stress disorder. Psychiatry Investig. 2016;13:420. doi: 10.4306/pi.2016.13.4.420. DOI: https://doi.org/10.4306/pi.2016.13.4.420

Atli A, Bulut M, Bez Y, et al. Altered lipid peroxidation markers are related to post-traumatic stress disorder (PTSD) and not trauma itself in earthquake survivors. Eur Arch Psychiatry Clin Neurosci. 2016;266:329-36. doi: 10.1007/s00406-015-0638-5. DOI: https://doi.org/10.1007/s00406-015-0638-5

Gonçalves CA, Leite MC, Guerra MC. Adipocytes as an important source of serum S100B and possible roles of this protein in adipose tissue. Cardiovasc Psychiatry Neurol. 2010:790431. doi: 10.1155/2010/790431. DOI: https://doi.org/10.1155/2010/790431

Tubaro C, Arcuri C, Giambanco I, Donato R.100B protein in myoblasts modulates myogenic differentiation via NF-kappaB dependent inhibition of MyoD expression J Cell Physiol. 2010;223:270-82. doi: 10.1002/jcp.22035. DOI: https://doi.org/10.1002/jcp.22035

Rothermundt M, Peters M, Prehn JHM, Arolt V. S100B in brain damage and neurodegeneration. Microsc Res Tech. 2003;60:614-32. doi: 10.1002/jemt.10303. DOI: https://doi.org/10.1002/jemt.10303

Kozlowska K, Nunn KP, Rose D, Morris A, Ouvrier RA, Varghese J. Conversion disorder in Australian pediatric practice. J Am Acad Child Adolesc Psychiatry. 2007;46(1):68-75. doi: 10.1097/01.chi.0000242235.83140.1f. DOI: https://doi.org/10.1097/01.chi.0000242235.83140.1f

Bègue I, Adams C, Stone J, Perez DL. Structural alterations in functional neurological disorder and related conditions: a software and hardware problem? Neuroimage Clin. 2019;22:101798. doi: 10.1016/j.nicl.2019.101798. DOI: https://doi.org/10.1016/j.nicl.2019.101798

Downloads

Published

2023-12-07

Issue

Section

Research Article

How to Cite

1.
Sizer E, Çobanoğlu T, Kaplan İbrahim. The role of oxidative stress levels and S100B levels in children with functional neurological disorder: Pediatric functional neurological disorder. J Surg Med [Internet]. 2023 Dec. 7 [cited 2024 Dec. 13];7(12):748-53. Available from: https://jsurgmed.com/article/view/7856