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Evaluation of Serum S100B Levels in Male Children Younger than 6 Years Old with Autism Spectrum Disorder: A Psychiatric and Biochemical Perspective

Year 2021, Volume: 23 Issue: 3, 263 - 269, 30.12.2021
https://doi.org/10.18678/dtfd.976021

Abstract

Aim: Autism spectrum disorder is a neurodevelopmental disorder. The S100 calcium binding protein B (S100B) is among the markers of astrocyte activation as well as brain damage. Herein, it was aimed to evaluate S100B levels to determine whether there is a relation with the severity of autism spectrum disorder and establish possible causes of different results among the studies in the literature from a psychiatric and biochemical perspective.
Material and Methods: Twenty-five male children with autism spectrum disorder were included as the study group along with twenty-seven male children as the control group. The childhood autism rating scale and the autism behavior checklist were applied. Serum S100B protein levels were measured by enzyme-linked immunosorbent assay (ELISA).
Results: The mean serum S100B level was 1008.61±171.34 pg/mL in the study group and 1060.14±182.83 pg/mL in the control group, and no statistically significant difference was found between the groups (p=0.300). Based on the childhood autism rating scale scores, 60% (n=15) of the children with autism spectrum disorder had severe autism, whereas 40% (n=10) had mild-to-moderate autism. There was no significant difference in terms of the serum S100B levels between the groups of autism spectrum disorder severity (p=0.935) or according to the autistic regression status (p=0.667).
Conclusion: For S100B to be accepted as a reliable biomarker for autism spectrum disorder, more studies considering some factors with larger samples should be performed. Moreover, to understand the effect of biochemical methodology on the results, further studies are suggested on this subject.

References

  • American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington DC: American Psychiatric Association; 2013.
  • Esnafoglu E, Ayyıldız SN, Cırrık S, Erturk EY, Erdil A, Daglı A, 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.
  • Kleindienst A, Hesse F, Bullock MR, Buchfelder M. The neurotrophic protein S100B: value as a marker of brain damage and possible therapeutic implications. Prog Brain Res. 2007;161:317-25.
  • Michetti F, D'Ambrosi N, Toesca A, Puglisi MA, Serrano A, Marchese E, et al. The S100B story: from biomarker to active factor in neural injury. J Neurochem. 2019;148(2):168-87.
  • Tomova A, Keményová P, Filčíková D, Szapuová Ž, Kováč A, Babinská K, et al. Plasma levels of glial cell marker S100B in children with autism. Physiol Res. 2019;68(Suppl 3):S315-23.
  • Morera-Fumero AL, Abreu-Gonzalez P, Henry-Benitez M, Yelmo-Cruz S, Diaz-Mesa E. Summer/winter changes in serum S100B protein concentration as a source of research variance. J Psychiatr Res. 2013;47(6):791-5.
  • 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.
  • 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):270-8.
  • Golubova TF, Tsukurova L, Korsunskaya LL, Osipyan RR, Vlasenko SV, Savchuk EA. [S100B protein in the blood of children with autism spectrum disorders]. Zh Nevrol Psikhiatr Im S S Korsakova. 2019;119(12):76-83. Russian.
  • Guloksuz SA, Abali O, Aktas Cetin E, Bilgic Gazioglu S, Deniz G, Yildirim A, et al. Elevated plasma concentrations of S100 calcium-binding protein B and tumor necrosis factor alpha in children with autism spectrum disorders. Braz J Psychiatry. 2017;39(3):195-200.
  • Schopler E, Reichler RJ, DeVellis RF, Daly K. Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS). J Autism Dev Disord. 1980;10:91-103.
  • İncekaş Gassaloğlu S, Baykara B, Avcil S, Demiral Y. [Validity and reliability analysis of Turkish version of childhood autism rating scale]. Turk Psikiyatri Derg. 2016;27(4):266-74. Turkish.
  • Sucuoğlu B, Öktem F, Akkök F, Gökler B. A study about childhood autism scales. Psikiyatri Psikol Psikofarmakol Derg. 1996;4(2):116-21. Turkish.
  • Krug DA, Arick JR, Almond PA. ASIEP-2: autism screening instrument for educational planning. 2nd ed. Austin, Texas: Pro-ed Inc.; 1993.
  • Yılmaz Irmak T, Tekinsav Sütçü S, Aydın A, Sorias O. An investigation of validity and reliability of autism behavior checklist (ABC). Turk J Child Adolesc Ment Health 2007;14(1):13-23. Turkish.
  • Zheng Z, Zheng P, Zou X. Peripheral blood S100B levels in autism spectrum disorder: A systematic review and meta-analysis. J Autism Dev Disord. 2021;51(8):2569-77.
  • Astrand R, Romner B, Lanke J, Undén J. Reference values for venous and capillary S100B in children. Clin Chim Acta. 2011;412(23-24):2190-3.
  • Castellani C, Stojakovic T, Cichocki M, Scharnagl H, Erwa W, Gutmann A, et al. Reference ranges for neuroprotein S-100B: from infants to adolescents. Clin Chem Lab Med. 2008;46(9):1296-9.
  • Bouvier D, Castellani C, Fournier M, Dauphin JB, Ughetto S, Breton M, et al. Reference ranges for serum S100B protein during the first three years of life. Clin Biochem. 2011;44(10-11):927-9.
  • Vedin T, Karlsson M, Edelhamre M, Bergenheim M, Larsson PA. Prospective comparison of capillary and venous brain biomarker S100B: capillary samples have large inter-sample variation and poor correlation with venous samples. Int J Emerg Med. 2019;12(1):26.
  • Sedaghat F, Notopoulos A. S100 protein family and its application in clinical practice. Hippokratia. 2008;12(4):198-204.
  • Müller K, Elverland A, Romner B, Waterloo K, Langbakk B, Undén J, et al. Analysis of protein S-100B in serum: a methodological study. Clin Chem Lab Med. 2006;44(9):1111-4.
  • Skogstrand K, Hagen CM, Borbye-Lorenzen N, Christiansen M, Bybjerg-Grauholm J, Bækvad-Hansen M, et al. Reduced neonatal brain-derived neurotrophic factor is associated with autism spectrum disorders. Transl Psychiatry. 2019;9(1):252.
  • Ikeda Y, Umemura K. [Analysis of reference values of serum S100B concentrations of Japanese adults]. Rinsho Byori. 2005 May;53(5):395-9. Japanese.
  • Raabe A, Grolms C, Keller M, Döhnert J, Sorge O, Seifert V. Correlation of computed tomography findings and serum brain damage markers following severe head injury. Acta Neurochir (Wien). 1998;140(8):787-91; discussion 791-2.
  • Henriksson AE. S100B and the influence of seasonal variation. Scand J Clin Lab Invest. 2016;76(4):338-40.
  • Morera-Fumero AL, Díaz-Mesa E, Abreu-Gonzalez P, Fernandez-Lopez L, Cejas-Mendez MDR. Day/night changes in serum S100B protein concentrations in acute paranoid schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2017;75:207-12.
  • Fernández-López L, Molina-Carballo A, Cubero-Millán I, Checa-Ros A, Machado-Casas I, Blanca-Jover E, et al. Indole tryptophan metabolism and cytokine S100B in children with attention-deficit/hyperactivity disorder: daily fluctuations, responses to methylphenidate, and interrelationship with depressive symptomatology. J Child Adolesc Psychopharmacol. 2020;30(3):177-88.
  • Shaker NM, Taha GRA, 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(5):191.
  • Barger BD, Campbell JM, McDonough JD. Prevalence and onset of regression within autism spectrum disorders: a meta-analytic review. J Autism Dev Disord. 2013;43(4):817-28.

Otizm Spektrum Bozukluğu Olan 6 Yaşından Küçük Erkekler Çocuklarda Serum S100B Düzeylerinin Değerlendirilmesi: Psikiyatrik ve Biyokimyasal Perspektif

Year 2021, Volume: 23 Issue: 3, 263 - 269, 30.12.2021
https://doi.org/10.18678/dtfd.976021

Abstract

Amaç: Otizm spektrum bozukluğu nörogelişimsel bir bozukluktur. S100 kalsiyum bağlayıcı protein B (S100B), beyin hasarının yanı sıra astrosit aktivasyonunun da belirteçleri arasındadır. Bu çalışmada, otizm spektrum bozukluğunun şiddeti ile ilişkisi olup olmadığını belirlemek için S100B düzeylerinin değerlendirilmesi ve literatürdeki çalışmalar arasında farklı sonuçların olası nedenlerinin psikiyatrik ve biyokimyasal açıdan değerlendirilmesi amaçlanmıştır.
Gereç ve Yöntemler: Çalışma grubu olarak yirmi beş otizm spektrum bozukluğu olan erkek çocuk ve kontrol grubu olarak ise yirmi yedi erkek çocuk çalışmaya dahil edildi. Çocukluk otizm derecelendirme ölçeği ve otizm davranış kontrol listesi uygulandı. Serum S100B protein seviyeleri, enzyme-linked immunosorbent assay (ELISA) ile ölçüldü.
Bulgular: Ortalama S100B serum düzeyleri çalışma grubunda 1008,61±171,34 pg/mL ve kontrol grubunda 1060,14±182,83 pg/mL idi ve gruplar arasında istatistiksel olarak anlamlı bir fark yoktu (p=0,300). Çocukluk otizm derecelendirme ölçeği puanlarına göre, otizm spektrum bozukluğu tanılı çocukların %60’ı (n=15) şiddetli otizme sahipken, %40’ı (n=10) hafif-orta otizme sahipti. S100B serum seviyeleri bakımından, otizm spektrum bozukluğu şiddet grupları arasında (p=0,935) veya otistik regresyon durumuna göre (p=0,667) anlamlı bir fark yoktu.
Sonuç: S100B’nin otizm spektrum bozukluğu için güvenilir bir biyobelirteç olarak kabul edilebilmesi için daha geniş örneklem olan ve bazı faktörleri de dikkate alan daha fazla çalışma yapılmalıdır. Ayrıca biyokimyasal metodolojinin sonuçlara etkisini anlamak için bu konuda daha fazla çalışma yapılması da önerilmektedir.

References

  • American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington DC: American Psychiatric Association; 2013.
  • Esnafoglu E, Ayyıldız SN, Cırrık S, Erturk EY, Erdil A, Daglı A, 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.
  • Kleindienst A, Hesse F, Bullock MR, Buchfelder M. The neurotrophic protein S100B: value as a marker of brain damage and possible therapeutic implications. Prog Brain Res. 2007;161:317-25.
  • Michetti F, D'Ambrosi N, Toesca A, Puglisi MA, Serrano A, Marchese E, et al. The S100B story: from biomarker to active factor in neural injury. J Neurochem. 2019;148(2):168-87.
  • Tomova A, Keményová P, Filčíková D, Szapuová Ž, Kováč A, Babinská K, et al. Plasma levels of glial cell marker S100B in children with autism. Physiol Res. 2019;68(Suppl 3):S315-23.
  • Morera-Fumero AL, Abreu-Gonzalez P, Henry-Benitez M, Yelmo-Cruz S, Diaz-Mesa E. Summer/winter changes in serum S100B protein concentration as a source of research variance. J Psychiatr Res. 2013;47(6):791-5.
  • 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.
  • 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):270-8.
  • Golubova TF, Tsukurova L, Korsunskaya LL, Osipyan RR, Vlasenko SV, Savchuk EA. [S100B protein in the blood of children with autism spectrum disorders]. Zh Nevrol Psikhiatr Im S S Korsakova. 2019;119(12):76-83. Russian.
  • Guloksuz SA, Abali O, Aktas Cetin E, Bilgic Gazioglu S, Deniz G, Yildirim A, et al. Elevated plasma concentrations of S100 calcium-binding protein B and tumor necrosis factor alpha in children with autism spectrum disorders. Braz J Psychiatry. 2017;39(3):195-200.
  • Schopler E, Reichler RJ, DeVellis RF, Daly K. Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS). J Autism Dev Disord. 1980;10:91-103.
  • İncekaş Gassaloğlu S, Baykara B, Avcil S, Demiral Y. [Validity and reliability analysis of Turkish version of childhood autism rating scale]. Turk Psikiyatri Derg. 2016;27(4):266-74. Turkish.
  • Sucuoğlu B, Öktem F, Akkök F, Gökler B. A study about childhood autism scales. Psikiyatri Psikol Psikofarmakol Derg. 1996;4(2):116-21. Turkish.
  • Krug DA, Arick JR, Almond PA. ASIEP-2: autism screening instrument for educational planning. 2nd ed. Austin, Texas: Pro-ed Inc.; 1993.
  • Yılmaz Irmak T, Tekinsav Sütçü S, Aydın A, Sorias O. An investigation of validity and reliability of autism behavior checklist (ABC). Turk J Child Adolesc Ment Health 2007;14(1):13-23. Turkish.
  • Zheng Z, Zheng P, Zou X. Peripheral blood S100B levels in autism spectrum disorder: A systematic review and meta-analysis. J Autism Dev Disord. 2021;51(8):2569-77.
  • Astrand R, Romner B, Lanke J, Undén J. Reference values for venous and capillary S100B in children. Clin Chim Acta. 2011;412(23-24):2190-3.
  • Castellani C, Stojakovic T, Cichocki M, Scharnagl H, Erwa W, Gutmann A, et al. Reference ranges for neuroprotein S-100B: from infants to adolescents. Clin Chem Lab Med. 2008;46(9):1296-9.
  • Bouvier D, Castellani C, Fournier M, Dauphin JB, Ughetto S, Breton M, et al. Reference ranges for serum S100B protein during the first three years of life. Clin Biochem. 2011;44(10-11):927-9.
  • Vedin T, Karlsson M, Edelhamre M, Bergenheim M, Larsson PA. Prospective comparison of capillary and venous brain biomarker S100B: capillary samples have large inter-sample variation and poor correlation with venous samples. Int J Emerg Med. 2019;12(1):26.
  • Sedaghat F, Notopoulos A. S100 protein family and its application in clinical practice. Hippokratia. 2008;12(4):198-204.
  • Müller K, Elverland A, Romner B, Waterloo K, Langbakk B, Undén J, et al. Analysis of protein S-100B in serum: a methodological study. Clin Chem Lab Med. 2006;44(9):1111-4.
  • Skogstrand K, Hagen CM, Borbye-Lorenzen N, Christiansen M, Bybjerg-Grauholm J, Bækvad-Hansen M, et al. Reduced neonatal brain-derived neurotrophic factor is associated with autism spectrum disorders. Transl Psychiatry. 2019;9(1):252.
  • Ikeda Y, Umemura K. [Analysis of reference values of serum S100B concentrations of Japanese adults]. Rinsho Byori. 2005 May;53(5):395-9. Japanese.
  • Raabe A, Grolms C, Keller M, Döhnert J, Sorge O, Seifert V. Correlation of computed tomography findings and serum brain damage markers following severe head injury. Acta Neurochir (Wien). 1998;140(8):787-91; discussion 791-2.
  • Henriksson AE. S100B and the influence of seasonal variation. Scand J Clin Lab Invest. 2016;76(4):338-40.
  • Morera-Fumero AL, Díaz-Mesa E, Abreu-Gonzalez P, Fernandez-Lopez L, Cejas-Mendez MDR. Day/night changes in serum S100B protein concentrations in acute paranoid schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2017;75:207-12.
  • Fernández-López L, Molina-Carballo A, Cubero-Millán I, Checa-Ros A, Machado-Casas I, Blanca-Jover E, et al. Indole tryptophan metabolism and cytokine S100B in children with attention-deficit/hyperactivity disorder: daily fluctuations, responses to methylphenidate, and interrelationship with depressive symptomatology. J Child Adolesc Psychopharmacol. 2020;30(3):177-88.
  • Shaker NM, Taha GRA, 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(5):191.
  • Barger BD, Campbell JM, McDonough JD. Prevalence and onset of regression within autism spectrum disorders: a meta-analytic review. J Autism Dev Disord. 2013;43(4):817-28.
There are 30 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Article
Authors

Ayşe Nihal Eraslan 0000-0002-7655-7927

İbrahim Durukan 0000-0002-1844-6911

Şahin Bodur 0000-0002-4942-7932

Özge Demircan This is me 0000-0002-7174-2154

Publication Date December 30, 2021
Submission Date August 2, 2021
Published in Issue Year 2021 Volume: 23 Issue: 3

Cite

APA Eraslan, A. N., Durukan, İ., Bodur, Ş., Demircan, Ö. (2021). Evaluation of Serum S100B Levels in Male Children Younger than 6 Years Old with Autism Spectrum Disorder: A Psychiatric and Biochemical Perspective. Duzce Medical Journal, 23(3), 263-269. https://doi.org/10.18678/dtfd.976021
AMA Eraslan AN, Durukan İ, Bodur Ş, Demircan Ö. Evaluation of Serum S100B Levels in Male Children Younger than 6 Years Old with Autism Spectrum Disorder: A Psychiatric and Biochemical Perspective. Duzce Med J. December 2021;23(3):263-269. doi:10.18678/dtfd.976021
Chicago Eraslan, Ayşe Nihal, İbrahim Durukan, Şahin Bodur, and Özge Demircan. “Evaluation of Serum S100B Levels in Male Children Younger Than 6 Years Old With Autism Spectrum Disorder: A Psychiatric and Biochemical Perspective”. Duzce Medical Journal 23, no. 3 (December 2021): 263-69. https://doi.org/10.18678/dtfd.976021.
EndNote Eraslan AN, Durukan İ, Bodur Ş, Demircan Ö (December 1, 2021) Evaluation of Serum S100B Levels in Male Children Younger than 6 Years Old with Autism Spectrum Disorder: A Psychiatric and Biochemical Perspective. Duzce Medical Journal 23 3 263–269.
IEEE A. N. Eraslan, İ. Durukan, Ş. Bodur, and Ö. Demircan, “Evaluation of Serum S100B Levels in Male Children Younger than 6 Years Old with Autism Spectrum Disorder: A Psychiatric and Biochemical Perspective”, Duzce Med J, vol. 23, no. 3, pp. 263–269, 2021, doi: 10.18678/dtfd.976021.
ISNAD Eraslan, Ayşe Nihal et al. “Evaluation of Serum S100B Levels in Male Children Younger Than 6 Years Old With Autism Spectrum Disorder: A Psychiatric and Biochemical Perspective”. Duzce Medical Journal 23/3 (December 2021), 263-269. https://doi.org/10.18678/dtfd.976021.
JAMA Eraslan AN, Durukan İ, Bodur Ş, Demircan Ö. Evaluation of Serum S100B Levels in Male Children Younger than 6 Years Old with Autism Spectrum Disorder: A Psychiatric and Biochemical Perspective. Duzce Med J. 2021;23:263–269.
MLA Eraslan, Ayşe Nihal et al. “Evaluation of Serum S100B Levels in Male Children Younger Than 6 Years Old With Autism Spectrum Disorder: A Psychiatric and Biochemical Perspective”. Duzce Medical Journal, vol. 23, no. 3, 2021, pp. 263-9, doi:10.18678/dtfd.976021.
Vancouver Eraslan AN, Durukan İ, Bodur Ş, Demircan Ö. Evaluation of Serum S100B Levels in Male Children Younger than 6 Years Old with Autism Spectrum Disorder: A Psychiatric and Biochemical Perspective. Duzce Med J. 2021;23(3):263-9.