Yıl: 2021 Cilt: 22 Sayı: 5 Sayfa Aralığı: 250 - 256 Metin Dili: İngilizce DOI: 10.5152/alphapsychiatry.2021.21152 İndeks Tarihi: 28-12-2021

Serum Zonulin Levels Are Higher Among Children withAutism Spectrum Disorders and Correlated withSocial Impairment

Öz:
Objective: Zonulin is a protein that affects the integrity of intercellular connections inthe intestines. It has been emphasized that autoimmune diseases as well as neurode velopmental disorders, for example autism spectrum disorder (ASD), may occur throughalterations in intestinal permeability and blood-brain barrier. We aimed to investigate thegastrointestinal permeability of individuals with ASD by determining serum zonulin levelsand their relationship to symptom severity. Methods: Twenty-five ASD patients and 19 controls were included. Serum zonulin lev els were measured by enzyme-linked immunosorbent assay kits. Clinical severity wasassessed by the Childhood Autism Rating Scale (CARS), and social skills of the controlgroup were evaluated by the Conners’ Parents and Teacher’s Rating Scales-Revised/LongForms (CPRS-CTRS). Results: Mean zonulin levels were significantly higher in the ASD group and positivelycorrelated with CARS scores. After regression analysis, serum zonulin levels predictedCARS total scores. We could not find any significant correlation between zonulin levelsand CPRS-CTRS sociability subscale scores in the control group. Conclusion: The positive correlation between serum zonulin levels and ASD severity mayrequire precaution for impaired intestinal permeability in clinical practice, especially forthe cases in which sociability is severely impaired. However, it is too early to state thatintestinal permeability has a role in the etiology of ASD. Further studies involving specificautism subgroups, and samples with certain dietary differences are needed.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Diğer Erişim Türü: Erişime Açık
  • 1. Kodak T, Bergmann S. Autism spectrum disorder: characteristics, associated behaviors, and early intervention. Pediatr Clin North Am. 2020;67(3):525-535. [CrossRef]
  • 2. American Psychiatric Association. DSM. 5 Diagnostic classification. In: Diagnostic and Statistical Manual of Mental Disorders; 2013.
  • 3. Sandin S, Lichtenstein P, Kuja-Halkola R, et al. The heritability of autism spectrum disorder. JAMA. 2017;318:1182-1184. [CrossRef]
  • 4. Imamura A, Morimoto Y, Ono S, et al. Genetic and environmental factors of schizophrenia and autism spectrum disorder: insights from twin studies. J Neural Transm (Vienna). 2020;127:1501-1515. [CrossRef]
  • 5. Frazier TW, Thompson L, Youngstrom EA, et al. A twin study of heritable and shared environmental contributions to autism. J Autism Dev Disord. 2014;44:2013-2025. [CrossRef]
  • 6. Yenkoyan K, Grigoryan A, Fereshetyan K, Yepremyan D. Advances in understanding the pathophysiology of autism spectrum disorders. Behav Brain Res. 2017;331:92-101. [CrossRef]
  • 7. Madra M, Ringel R, Margolis KG. Gastrointestinal Issues and Autism Spectrum Disorder. Child and Adolescent Psychiatric Clinics of North America; 2020.
  • 8. Rosenfeld CS. Microbiome disturbances and autism spectrum disorders. Drug Metab Dispos. 2015;43:1557-1571. [CrossRef]
  • 9. Eltokhi A, Janmaat IE, Genedi M, Haarman BCM, Sommer IEC. Dysregulation of synaptic pruning as a possible link between intestinal microbiota dysbiosis and neuropsychiatric disorders. J Neurosci Res. 2020;98:1335- 1369. [CrossRef]
  • 10. Fasano A. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol. 2012;42:71-78. [CrossRef]
  • 11. Özyurt G, Öztürk Y, Appak YÇ, et al. Increased zonulin is associated with hyperactivity and social dysfunctions in children with attention deficit hyperactivity disorder. Compr Psychiatry. 2018 1;87:138-142. [CrossRef]
  • 12. Fasano A. Zonulin Regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci. 2012;1258(1):25-33.
  • 13. Lammers KM, Lu R, Brownley J, et al. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology. 2008;135:194-204.e3. [CrossRef]
  • 14. Sapone A, De Magistris L, Pietzak M, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006;55:1443-1449. [CrossRef]
  • 15. Fasano A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol. 2012;10:1096- 1100. [CrossRef]
  • 16. Fiorentino M, Sapone A, Senger S, et al. Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Mol Autism. 2016;7:49. [CrossRef]
  • 17. Esnafoglu E, Cırrık S, Ayyıldız SN, et al. Increased serum zonulin levels as an intestinal permeability marker in autistic subjects. J Pediatr. 2017;188:240-244. [CrossRef]
  • 18. Kaufman J, Birmaher B, Brent D, et al. Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997;36:980-988. [CrossRef]
  • 19. Ünal F, Öktem F, Çetin Çuhadaroğlu F, et al. Reliability and validity of the schedule for affective disorders and schizophrenia for school-age children-present and lifetime version, DSM-5 November 2016-Turkish adaptation (K-SADS-PL-DSM-5-T). Turk Psikiyatri Derg. 2019;30:42-50.
  • 20. 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;27:266-274. [CrossRef]
  • 21. Chlebowski C, Green JA, Barton ML, Fein D. Using the childhood autism rating scale to diagnose autism spectrum disorders. J Autism Dev Disord. 2010;40:787-799. [CrossRef]
  • 22. Kaner S, Büyüköztürk Ş, İşeri̇ E, Ak A, Özaydin L. Conners’ Parent Rating Scale Long Form-Revised: factor structure, reliability and validity studies. Çocuk Gençlik Ruh Sağlığı Derg. 2011;18(1):45-58.
  • 23. Kaner S, Büyüköztürk Ş, İşeri E, Ak A, Özaydın L. Conner’s Teachers Rating Scale/Revised Long: assessing the psychometric characteristics of Turkish children. Klinik Psikiyatri. 2011;14:150-163.
  • 24. Wang LW, Tancredi DJ, Thomas DW. The prevalence of gastrointestinal problems in children across the united states with autism spectrum disorders from families with multiple affected members. J Dev Behav Pediatr. 2011;32:351-360. [CrossRef]
  • 25. Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA. Gastrointestinal flora and gastrointestinal status in children with autism—comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 2011;11:22. [CrossRef]
  • 26. Fasano A Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011;91:151-175. [CrossRef]
  • 27. Yarandi SS, Peterson DA, Treisman GJ, Moran TH, Pasricha PJ. Modulatory effects of gut microbiota on the central nervous system: how gut could play a role in neuropsychiatric health and diseases. J Neurogastroenterol Motil. 2016;22:201-212. [CrossRef]
  • 28. Díaz-Coránguez M., Segovia J., López-Ornelas A, et al. Transmigration of neural stem cells across the blood brain barrier induced by glioma cells. PLoS One. 2013;8:e60655. [CrossRef]
  • 29. Garcia RA Translating Knowledge of Autism Spectrum Disorders to Action through Discovery and Exploration. Clemson University; 2014.
  • 30. ZERBO O, Leong A, Barcellos L, et al. Immune mediated conditions in autism spectrum disorders. Brain Behav Immun. 2015;46:232-236. [CrossRef]
  • 31. Alkhayyat M., Qapaja T, Aggarwal M, et al. Epidemiology and risk of psychiatric disorders among celiac disease patients: a population‐based national study. J Gastroenterol Hepatol. 2021. [CrossRef]
  • 32. Vanuytsel T, Vermeire S, Cleynen I. The role of haptoglobin and its related protein, Zonulin, in inflammatory bowel disease. Tissue Barriers. 2013;1:e27321. [CrossRef]
  • 33. Asbjornsdottir B, Snorradottir H, Andresdottir E, et al. Zonulindependent intestinal permeability in children diagnosed with mental disorders: a systematic review and meta-analysis. Nutrients. 2020;12:1982. [CrossRef]
  • 34. Nitschke A, Deonandan R, Konkle AT. The link between autism spectrum disorder and gut microbiota: a scoping review. Autism. 2020;24:1328- 1344. [CrossRef]
  • 35. Fasano A, Hill I, Zonulin S Serum Zonulin, Gut permeability, and the pathogenesis of autism spectrum disorders: cause, effect, or an epiphenomenon? J Pediatr. 2017;188:15-17. [CrossRef]
  • 36. Cupaioli FA, Mosca E, Magri C, et al. Assessment of haptoglobin alleles in autism spectrum disorders. Sci Rep. 2020;10:7758. [CrossRef]
  • 37. Rose DR, Yang H, Serena G, et al. Differential immune responses and microbiota profiles in children with autism spectrum disorders and comorbid gastrointestinal symptoms. Brain Behav Immun. 2018;70:354- 368. [CrossRef]
APA Kara H, Açıkel B, Cetinkaya M, Tuncer S (2021). Serum Zonulin Levels Are Higher Among Children withAutism Spectrum Disorders and Correlated withSocial Impairment. , 250 - 256. 10.5152/alphapsychiatry.2021.21152
Chicago Kara Halil,Açıkel Burak,Cetinkaya Miray,Tuncer Sibel cigdem Serum Zonulin Levels Are Higher Among Children withAutism Spectrum Disorders and Correlated withSocial Impairment. (2021): 250 - 256. 10.5152/alphapsychiatry.2021.21152
MLA Kara Halil,Açıkel Burak,Cetinkaya Miray,Tuncer Sibel cigdem Serum Zonulin Levels Are Higher Among Children withAutism Spectrum Disorders and Correlated withSocial Impairment. , 2021, ss.250 - 256. 10.5152/alphapsychiatry.2021.21152
AMA Kara H,Açıkel B,Cetinkaya M,Tuncer S Serum Zonulin Levels Are Higher Among Children withAutism Spectrum Disorders and Correlated withSocial Impairment. . 2021; 250 - 256. 10.5152/alphapsychiatry.2021.21152
Vancouver Kara H,Açıkel B,Cetinkaya M,Tuncer S Serum Zonulin Levels Are Higher Among Children withAutism Spectrum Disorders and Correlated withSocial Impairment. . 2021; 250 - 256. 10.5152/alphapsychiatry.2021.21152
IEEE Kara H,Açıkel B,Cetinkaya M,Tuncer S "Serum Zonulin Levels Are Higher Among Children withAutism Spectrum Disorders and Correlated withSocial Impairment." , ss.250 - 256, 2021. 10.5152/alphapsychiatry.2021.21152
ISNAD Kara, Halil vd. "Serum Zonulin Levels Are Higher Among Children withAutism Spectrum Disorders and Correlated withSocial Impairment". (2021), 250-256. https://doi.org/10.5152/alphapsychiatry.2021.21152
APA Kara H, Açıkel B, Cetinkaya M, Tuncer S (2021). Serum Zonulin Levels Are Higher Among Children withAutism Spectrum Disorders and Correlated withSocial Impairment. Alpha psychiatry (Online), 22(5), 250 - 256. 10.5152/alphapsychiatry.2021.21152
Chicago Kara Halil,Açıkel Burak,Cetinkaya Miray,Tuncer Sibel cigdem Serum Zonulin Levels Are Higher Among Children withAutism Spectrum Disorders and Correlated withSocial Impairment. Alpha psychiatry (Online) 22, no.5 (2021): 250 - 256. 10.5152/alphapsychiatry.2021.21152
MLA Kara Halil,Açıkel Burak,Cetinkaya Miray,Tuncer Sibel cigdem Serum Zonulin Levels Are Higher Among Children withAutism Spectrum Disorders and Correlated withSocial Impairment. Alpha psychiatry (Online), vol.22, no.5, 2021, ss.250 - 256. 10.5152/alphapsychiatry.2021.21152
AMA Kara H,Açıkel B,Cetinkaya M,Tuncer S Serum Zonulin Levels Are Higher Among Children withAutism Spectrum Disorders and Correlated withSocial Impairment. Alpha psychiatry (Online). 2021; 22(5): 250 - 256. 10.5152/alphapsychiatry.2021.21152
Vancouver Kara H,Açıkel B,Cetinkaya M,Tuncer S Serum Zonulin Levels Are Higher Among Children withAutism Spectrum Disorders and Correlated withSocial Impairment. Alpha psychiatry (Online). 2021; 22(5): 250 - 256. 10.5152/alphapsychiatry.2021.21152
IEEE Kara H,Açıkel B,Cetinkaya M,Tuncer S "Serum Zonulin Levels Are Higher Among Children withAutism Spectrum Disorders and Correlated withSocial Impairment." Alpha psychiatry (Online), 22, ss.250 - 256, 2021. 10.5152/alphapsychiatry.2021.21152
ISNAD Kara, Halil vd. "Serum Zonulin Levels Are Higher Among Children withAutism Spectrum Disorders and Correlated withSocial Impairment". Alpha psychiatry (Online) 22/5 (2021), 250-256. https://doi.org/10.5152/alphapsychiatry.2021.21152