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Evaluation of S100B, NSE, MBP and GFAP serum levels in children with attention deficit hyperactivity disorder

Year 2025, , 432 - 443, 01.04.2025
https://doi.org/10.31362/patd.1652305

Abstract

Purpose: This study aimed to investigate serum levels of S100B protein, Neuron Specific Enolase (NSE), Myelin Basic Protein (MBP) and Glial Fibrillary Acidic Protein (GFAP) that reflect glial and neural structure. To date, these proteins have been studied in neuropsychiatric diseases and relation with neuronal damage has been shown. However, there is no study that simultaneously evaluates the serum levels of these proteins in children with ADHD and compares them with healthy controls.
Materials and methods: 44 children with ADHD and 37 healthy volunteers participated in the study. They were selected from children and adolescents aged 6-18 years who had no history of other medical or psychiatric diseases and had not used psychotropic drugs for the last six months. Levels of proteins were assessed by enzyme-linked immunosorbent assay (ELISA).
Results: Serum levels of S100B, NSE and GFAP were found to be statistically significantly higher in the ADHD group than in the control group (p=0.012, p=0.000, p=0.001, respectively). No significant difference was found in the intergroup comparison for MBP (p=0.181).
Conclusion: Increased levels of S100B, NSE, GFAP may be an indicator of neuronal or glial changes in ADHD. Future studies combining serial measurements of these biochemical proteins with genetics and neuroimaging data are needed to evaluate the possible role of glial and neuronal damage in the etiopathogenesis of ADHD.

Ethical Statement

Pamukkale University Non-Interventional Clinical Research Ethics Committee in the meeting dated 29.05.2018 and numbered 11, with the number 601167787-020/40438

Supporting Institution

This study was supported by Pamukkale University Scientific Research Projects Commission with the decision numbered 2018TIPF038.

Project Number

PAÜ BAP 2018TIPF038

Thanks

The study authors would like to thank Pamukkale University Scientific Research Projects Commission

References

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  • 5. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89-95. doi:10.1067/mcp.2001.113989
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  • 22. Ayaydın H, Kirmit A, Çelik H, Akaltun İ, Koyuncu İ, Bilgen Ulgar Ş. High Serum Levels of Serum 100 Beta Protein, Neuron-specific Enolase, Tau, Active Caspase-3, M30 and M65 in Children with Autism Spectrum Disorders. Clin Psychopharmacol Neurosci. 2020;18(2):270-278. doi:10.9758/cpn.2020.18.2.270
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  • 24. Demirci E, Tastepe N, Gul MK, Ozmen S, Kilic E. S100B and Neuron-Specific Enolase Levels as Brain Injury Biomarkers in Internet Addiction: Effect of Sleep. Pediatr Neurol. 2023;149:93-99. doi:10.1016/j.pediatrneurol.2023.08.029
  • 25. Whitaker JN. Myelin basic protein in cerebrospinal fluid and other body fluids. Mult Scler. 1998;4(1):16-21. doi:10.1177/135245859800400105
  • 26. Petzold A. The prognostic value of CSF neurofilaments in multiple sclerosis at 15-year follow-up. J Neurol Neurosurg Psychiatry. 2015;86(12):1388-1390. doi:10.1136/jnnp-2014-309827
  • 27. Ahlsén G, Rosengren L, Belfrage M, et al. Glial fibrillary acidic protein in the cerebrospinal fluid of children with autism and other neuropsychiatric disorders. Biol Psychiatry. 1993;33(10):734-743. doi:10.1016/0006-3223(93)90124-v
  • 28. Cetin I, Bulut H, Simsek S. Examination of the Neuroplastic Biomarker Levels in Attention Deficit Hyperactivity Disorder. Asian J Biochem. 2017;12:1-8. doi:10.3923/ajb.2017.1.8
  • 29. Turgay A. Disruptive behavior disorders: child and adolescent screening and rating scales for children, adolescents, parents and teachers. West Bloomfield (Michigan): Integrative Therapy Institute Publication; 1994.
  • 30. Ercan ES, Amado S, Somer O, Çıkoğlu S. Development of a test battery for the assessment of attention deficit hyperactivity disorder. Turkish J of Child and Adolesc Mental Health. 2001;8:132-144.
  • 31. Grant DA, Berg EA. Wisconsin Card Sorting Test [Database record]. APA PsycTests. 1948. doi:10.1037/t31298-000
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  • 34. Stroop, J. R. (1935). Studies of interference in serial verbal reactions. Journal of experimental psychology, 1935;18(6):643-662. doi:0.1037/h0054651
  • 35. Kilic G, İlden Kockar A, Irak M, Şener S, Karakaş S. The standardizatıon study of the stroop test TBAG form in chıldren between 6-11 years of age. Turkish J of Child and Adolesc Mental Health. 2002;9(2):86-99.
  • 36. Janigro D, Mondello S, Posti JP, Unden J. GFAP and S100B: What You Always Wanted to Know and Never Dared to Ask. Front Neurol. 2022;13:835597. Published 2022 Mar 21. doi:10.3389/fneur.2022.835597
  • 37. Kozlowski T, Bargiel W, Grabarczyk M, Skibinska M. Peripheral S100B Protein Levels in Five Major Psychiatric Disorders: A Systematic Review. Brain Sci. 2023;13(9):1334. Published 2023 Sep 16. doi:10.3390/brainsci13091334
  • 38. Oades RD, Dauvermann MR, Schimmelmann BG, Schwarz MJ, Myint AM. Attention-deficit hyperactivity disorder (ADHD) and glial integrity: S100B, cytokines and kynurenine metabolism--effects of medication. Behav Brain Funct. 2010;6:32. Published 2010 Jun 9. doi:10.1186/1744-9081-6-32.
  • 39. Ouadih Moran M, Muñoz Hoyos A, D'Marco L, Molina Carballo A, Seiquer I, Checa Ros A. Is S100B Involved in Attention-Deficit/Hyperactivity Disorder (ADHD)? Comparisons with Controls and Changes Following a Triple Therapy Containing Methylphenidate, Melatonin and ω-3 PUFAs. Nutrients. 2023;15(3):712. Published 2023 Jan 31. doi:10.3390/nu15030712
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  • 41. Wilkinson AA, Dennis M, Simic N, et al. Brain biomarkers and pre-injury cognition are associated with long-term cognitive outcome in children with traumatic brain injury. BMC Pediatr. 2017;17(1):173. Published 2017 Jul 24. doi:10.1186/s12887-017-0925-6
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Dikkat eksikliği hiperaktivite bozukluğu olan çocuklarda serum S100B, NSE, MBP ve GFAP düzeylerinin değerlendirilmesi

Year 2025, , 432 - 443, 01.04.2025
https://doi.org/10.31362/patd.1652305

Abstract

Amaç: Bu çalışmanın amacı glial ve nöral yapıyı yansıtan S100B proteini, Nöron Spesifik Enolaz (NSE), Miyelin Bazik Protein (MBP) ve Glial Fibriller Asidik Protein (GFAP) serum düzeylerini araştırmaktır. Bugüne kadar bu proteinler nöropsikiyatrik hastalıklarda çalışılmış ve nöronal hasarla ilişkisi gösterilmiştir. Ancak bu proteinlerin serum düzeylerini DEHB'li çocuklarda eş zamanlı olarak değerlendirerek sağlıklı kontroller ile karşılaştıran bir çalışma mevcut değildir.
Gereç ve yöntem: Çalışmaya 44 DEHB’li ve 37 sağlıklı gönüllü katımıştır. Katılımcılar, başka tıbbi veya psikiyatrik hastalık öyküsü olmayan ve son altı aydır psikotropik ilaç kullanmayan 6-18 yaş arası çocuk ve gençler arasından seçilmiştir. Serum protein seviyeleri enzim-bağlı immünosorbent yöntemi (ELISA) ile değerlendirilmiştir.
Bulgular: S100B, NSE ve GFAP serum düzeyleri, DEHB grubunda kontrol grubundan istatistiksel olarak anlamlı düzeyde yüksek bulunmuştur (sırasıyla p=0,012, p=0,000, p=0,001). MBP için gruplar arası karşılaştırmada anlamlılık düzeyinde bir farklılık saptanmamıştır (p=0,181).
Sonuç: S100B, NSE, GFAP'nin yükselmiş düzeyleri DEHB'deki nöronal veya glial değişikliklerin bir göstergesi olabilir. DEHB etiyopatogenezinde glial ve nöronal hasarın olası rolünü değerlendirmek için bu biyokimyasal proteinlerin seri ölçümlerini genetik ve nörogörüntüleme verileriyle birleştiren gelecek çalışmalara ihtiyaç vardır.

Ethical Statement

601167787-020/40438 numara ile etik kurul onayı alınmıştır.

Supporting Institution

PAÜ BAP

Project Number

PAÜ BAP 2018TIPF038

Thanks

Pamukkale Üniversitesi BAP'a teşekkürlerimizle.

References

  • 1. Biederman J. Attention-deficit/hyperactivity disorder: a selective overview. Biol Psychiatry. 2005;57(11):1215-1220. doi:10.1016/j.biopsych.2004.10.020
  • 2. Faraone SV, Asherson P, Banaschewski T, et al. Attention-deficit/hyperactivity disorder. Nat Rev Dis Primers. 2015;1:15020. Published 2015 Aug 6. doi:10.1038/nrdp.2015.20
  • 3. Polanczyk GV, Casella EB, Miguel EC, Reed UC. Attention deficit disorder/hyperactivity: a scientific overview. Clinics (Sao Paulo). 2012;67(10):1125-1126. doi:10.6061/clinics/2012(10)01
  • 4. Faraone SV, Bonvicini C, Scassellati C. Biomarkers in the diagnosis of ADHD--promising directions. Curr Psychiatry Rep. 2014;16(11):497. doi:10.1007/s11920-014-0497-1
  • 5. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89-95. doi:10.1067/mcp.2001.113989
  • 6. Mehta T, Mannem N, Yarasi NK, Pradeep C, Bollu PC. Biomarkers for ADHD: the Present and Future Directions. Curr Dev Disord Rep. 2020;7:85-92. doi:10.1007/s40474-020-00196-9
  • 7. Lamers KJ, Vos P, Verbeek MM, Rosmalen F, van Geel WJ, van Engelen BG. Protein S-100B, neuron-specific enolase (NSE), myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF) and blood of neurological patients. Brain Res Bull. 2003;61(3):261-264. doi:10.1016/s0361-9230(03)00089-3
  • 8. Donato R. Intracellular and extracellular roles of S100 proteins. Microsc Res Tech. 2003;60(6):540-551. doi:10.1002/jemt.10296
  • 9. Sen J, Belli A. S100B in neuropathologic states: the CRP of the brain?. J Neurosci Res. 2007;85(7):1373-1380. doi:10.1002/jnr.21211
  • 10. Park ES, Park CI, Choi KS, Choi IH, Shin JS. Over-expression of S100B protein in children with cerebral palsy or delayed development. Brain Dev. 2004;26(3):190-196. doi:10.1016/S0387-7604(03)00126-8
  • 11. Manev H, Manev R. S100B: an old neurotrophic factor with putative new roles in psychiatric illnesses. J Psychiatr Res. 2001;35(6):347-350. doi:10.1016/s0022-3956(01)00039-5
  • 12. Al Ayadhi LY, Mostafa GA. A lack of association between elevated serum levels of S100B protein and autoimmunity in autistic children. J Neuroinflammation. 2012;9:54. Published 2012 Mar 16. doi:10.1186/1742-2094-9-54
  • 13. Shaker NM, Taha GR, Kholeif H, Sayed NM, El Sheikh MM, Abulmagd ML. Serum levels of S100b, interleukin-6 and anti-transglutaminase Ii IgA as immune markers in a sample of egyptian children with autistic spectrum disorders. Autism Open Access. 2016;6:1-8. doi:10.4172/2165-7890.1000191
  • 14. Smith TF, Anastopoulos AD, Garrett ME, et al. Angiogenic, neurotrophic, and inflammatory system SNPs moderate the association between birth weight and ADHD symptom severity. Am J Med Genet B Neuropsychiatr Genet. 2014;165B(8):691-704. doi:10.1002/ajmg.b.32275
  • 15. Oades RD. An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD). Atten Defic Hyperact Disord. 2011;3(4):301-318. doi:10.1007/s12402-011-0062-2
  • 16. Liu W, Huo X, Liu D, Zeng X, Zhang Y, Xu X. S100β in heavy metal-related child attention-deficit hyperactivity disorder in an informal e-waste recycling area. Neurotoxicology. 2014;45:185-191. doi:10.1016/j.neuro.2014.10.013
  • 17. Marangos PJ, Schmechel DE. Neuron specific enolase, a clinically useful marker for neurons and neuroendocrine cells. Annu Rev Neurosci. 1987;10:269-295. doi:10.1146/annurev.ne.10.030187.001413
  • 18. Kawata K, Liu CY, Merkel SF, Ramirez SH, Tierney RT, Langford D. Blood biomarkers for brain injury: What are we measuring?. Neurosci Biobehav Rev. 2016;68:460-473. doi:10.1016/j.neubiorev.2016.05.009
  • 19. Isgrò MA, Bottoni P, Scatena R. Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects. Adv Exp Med Biol. 2015;867:125-143. doi:10.1007/978-94-017-7215-0_9
  • 20. Wiener CD, Jansen K, Ghisleni G, et al. Reduced serum levels of neuron specific enolase (NSE) in drug-naïve subjects with major depression and bipolar disorder. Neurochem Res. 2013;38(7):1394-1398. doi:10.1007/s11064-013-1036-x
  • 21. Stancioiu F, Bogdan R, Dumitrescu R. Neuron-Specific Enolase (NSE) as a Biomarker for Autistic Spectrum Disease (ASD). Life (Basel). 2023;13(8):1736. Published 2023 Aug 13. doi:10.3390/life13081736
  • 22. Ayaydın H, Kirmit A, Çelik H, Akaltun İ, Koyuncu İ, Bilgen Ulgar Ş. High Serum Levels of Serum 100 Beta Protein, Neuron-specific Enolase, Tau, Active Caspase-3, M30 and M65 in Children with Autism Spectrum Disorders. Clin Psychopharmacol Neurosci. 2020;18(2):270-278. doi:10.9758/cpn.2020.18.2.270
  • 23. Esnafoglu E, Ayyıldız SN, Cırrık S, et al. Evaluation of serum Neuron-specific enolase, S100B, myelin basic protein and glial fibrilliary acidic protein as brain specific proteins in children with autism spectrum disorder. Int J Dev Neurosci. 2017;61:86-91. doi:10.1016/j.ijdevneu.2017.06.011
  • 24. Demirci E, Tastepe N, Gul MK, Ozmen S, Kilic E. S100B and Neuron-Specific Enolase Levels as Brain Injury Biomarkers in Internet Addiction: Effect of Sleep. Pediatr Neurol. 2023;149:93-99. doi:10.1016/j.pediatrneurol.2023.08.029
  • 25. Whitaker JN. Myelin basic protein in cerebrospinal fluid and other body fluids. Mult Scler. 1998;4(1):16-21. doi:10.1177/135245859800400105
  • 26. Petzold A. The prognostic value of CSF neurofilaments in multiple sclerosis at 15-year follow-up. J Neurol Neurosurg Psychiatry. 2015;86(12):1388-1390. doi:10.1136/jnnp-2014-309827
  • 27. Ahlsén G, Rosengren L, Belfrage M, et al. Glial fibrillary acidic protein in the cerebrospinal fluid of children with autism and other neuropsychiatric disorders. Biol Psychiatry. 1993;33(10):734-743. doi:10.1016/0006-3223(93)90124-v
  • 28. Cetin I, Bulut H, Simsek S. Examination of the Neuroplastic Biomarker Levels in Attention Deficit Hyperactivity Disorder. Asian J Biochem. 2017;12:1-8. doi:10.3923/ajb.2017.1.8
  • 29. Turgay A. Disruptive behavior disorders: child and adolescent screening and rating scales for children, adolescents, parents and teachers. West Bloomfield (Michigan): Integrative Therapy Institute Publication; 1994.
  • 30. Ercan ES, Amado S, Somer O, Çıkoğlu S. Development of a test battery for the assessment of attention deficit hyperactivity disorder. Turkish J of Child and Adolesc Mental Health. 2001;8:132-144.
  • 31. Grant DA, Berg EA. Wisconsin Card Sorting Test [Database record]. APA PsycTests. 1948. doi:10.1037/t31298-000
  • 32. Heaton RK. A manual for the Wisconsin Card Sorting Test. Odessa, FL: Psychological Assessment Resources;1981.
  • 33. Karakaş S. BİLNOT Bataryası El Kitabı: Nöropsikolojik Testler için Araştırma ve Geliştirme Çalışmaları (1. Ed.). Ankara: Dizayn Ofset;2004.
  • 34. Stroop, J. R. (1935). Studies of interference in serial verbal reactions. Journal of experimental psychology, 1935;18(6):643-662. doi:0.1037/h0054651
  • 35. Kilic G, İlden Kockar A, Irak M, Şener S, Karakaş S. The standardizatıon study of the stroop test TBAG form in chıldren between 6-11 years of age. Turkish J of Child and Adolesc Mental Health. 2002;9(2):86-99.
  • 36. Janigro D, Mondello S, Posti JP, Unden J. GFAP and S100B: What You Always Wanted to Know and Never Dared to Ask. Front Neurol. 2022;13:835597. Published 2022 Mar 21. doi:10.3389/fneur.2022.835597
  • 37. Kozlowski T, Bargiel W, Grabarczyk M, Skibinska M. Peripheral S100B Protein Levels in Five Major Psychiatric Disorders: A Systematic Review. Brain Sci. 2023;13(9):1334. Published 2023 Sep 16. doi:10.3390/brainsci13091334
  • 38. Oades RD, Dauvermann MR, Schimmelmann BG, Schwarz MJ, Myint AM. Attention-deficit hyperactivity disorder (ADHD) and glial integrity: S100B, cytokines and kynurenine metabolism--effects of medication. Behav Brain Funct. 2010;6:32. Published 2010 Jun 9. doi:10.1186/1744-9081-6-32.
  • 39. Ouadih Moran M, Muñoz Hoyos A, D'Marco L, Molina Carballo A, Seiquer I, Checa Ros A. Is S100B Involved in Attention-Deficit/Hyperactivity Disorder (ADHD)? Comparisons with Controls and Changes Following a Triple Therapy Containing Methylphenidate, Melatonin and ω-3 PUFAs. Nutrients. 2023;15(3):712. Published 2023 Jan 31. doi:10.3390/nu15030712
  • 40. Royds JA, Timperley WR, Taylor CB. Levels of enolase and other enzymes in the cerebrospinal fluid as indices of pathological change. J Neurol Neurosurg Psychiatry. 1981;44(12):1129-1135. doi:10.1136/jnnp.44.12.1129
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Details

Primary Language English
Subjects Child and Adolescent Psychiatry
Journal Section Research Article
Authors

Hatice Çelik Yıldırım 0009-0009-6151-7242

Bürge Kabukçu Başay 0000-0003-4124-2340

Egem Burcu Ünal 0000-0002-9499-2316

Project Number PAÜ BAP 2018TIPF038
Early Pub Date March 28, 2025
Publication Date April 1, 2025
Submission Date March 7, 2025
Acceptance Date March 27, 2025
Published in Issue Year 2025

Cite

AMA Çelik Yıldırım H, Kabukçu Başay B, Ünal EB. Evaluation of S100B, NSE, MBP and GFAP serum levels in children with attention deficit hyperactivity disorder. Pam Tıp Derg. April 2025;18(2):432-443. doi:10.31362/patd.1652305
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