Otizmli Çocuklarda Glutensiz Kazeinsiz Diyet: Oftalmik ve Davranışsal Belirtilerin Klinik Sonuçları

Yıl 2023, Sayı: 21, 828 - 842, 05.01.2024

Öznur Özge Özcan , İbrahim Şahbaz , Emre Taşdöndüren , Mesut Karahan

https://doi.org/10.38079/igusabder.1378810

Öz

Amaç: Otizm spektrum bozukluğunda (ASD) glutensiz kazeinsiz diyetin (GCFD) oftalmik ve davranışsal etkilerini değerlendirmektir.
Yöntem: Çalışma Kasım 2020'den Ocak 2023'e kadar gerçekleştirildi. Kornea refleksi, gözbebeği büyüklüğü, vücut kitle indeksi (BMI), ağırlık, Otistik Bozukluk İndeksi, İletişim, Sosyal Etkileşim ve Stereotip Davranış üzerinde GCFD'nin 8 haftalık bir klinik çalışması yapıldı.
Bulgular: Çalışmaya toplamda 30 çocuk dahil edildi. GCFD, BKİ'yi [%95 CI 4,8895 ile -2,1305 (P < 0,0001)], ağırlığı [%95 CI -8,5153 ila -0,0647 (P = 0,0467)], Otistik Bozukluk İndeksini [%95 CI -28.0359 to -16.2841 (P < 0.0001)], İletişim [%95 CI 3,3325 ila -1,6675 (P < 0,0001)], Sosyal etkileşim [%95 CI -4,3190 ila -2,4010 (P < 0,0001)] ve Stereotip Davranışı [%95 CI -2,3939 ila -0,2461 (P =0,01)] önemli ölçüde azalttı. GCFD ayrıca soldaki [%95 CI -2,2421 ila -1,6779 (P <0,0001)] ve sağ gözbebeği boyutunu [%95 CI -2,2999 ila -1,7201 (P <0,0001)] önemli ölçüde azalttı. Tersine, kornea refleksi önemli ölçüde arttı (%95 CI 0,2159 - 2,1241 (P = 0,01)). IPD için hiçbir fark gözlenmedi.
Sonuç: Bu çalışma, GCFD'nin OSB davranışlarını etkili bir şekilde kontrol edebileceğini ve ayrıca gözbebeği boyutu ve kornea refleksi gibi oftalmik belirteçlerle ilgili otonomik işlevleri düzenleyebileceğini göstermiştir ancak daha fazla araştırmaya ihtiyaç vardır.

Anahtar Kelimeler

Otizm spektrum bozuklukları, bilişsel fonksiyonlar, kornea refleksi, glutensiz kazeinsiz diyet, plusoptix a09, pupil çapı

Etik Beyan

Üsküdar University The Human Ethics Committee approved the protocol (number:61351342/2021-526, date: 26.11.2020). Informed consent was obtained from all participants and their parents. This study was conducted within the framework of the World Medical Association ethical rules.

Destekleyen Kurum

Üsküdar University and Dünya Bursa Göz Hospital

Teşekkür

The authors thankful for the financial support to Üsküdar University and Dünya Bursa Göz Hospital

The Gluten-Casein-Free Diet in Children with Autism: A Clinical Results of the Ophthalmic and Behavioral Manifestations

Öz

Aim: To evaluate the ophthalmic and behavioral effects of a gluten-free casein-free diet (GCFD) in autism spectrum disorder (ASD).
Method: The study was conducted from November 2020 to January 2023. We designed an 8-week clinical trial of GCFD on corneal reflex, pupil size, body mass index (BMI), weight, Autistic Disorder Index, Communication, Social interaction, and Stereotype Behavior.
Results: A total of thirty participants completed the trial. GCFD reduced BMI [%95 CI -4.8895 to -2.1305 (P < 0.0001)], weight [%95 CI -8.5153 to -0.0647 (P = 0.0467)], Autistic Disorder Index [%95 CI -28.0359 to -16.2841 (P < 0.0001)], Communication [%95 CI -3.3325 to -1.6675 (P < 0.0001)], Social Interaction [%95 CI -4.3190 to -2.4010 (P < 0.0001)], and Stereotype Behavior [%95 CI -2.3939 to -0.2461 (P =0.01)] significantly. GCFD also reduced left [%95 CI -2.2421 to -1.6779 (P <0.0001)] and right pupil size [%95 CI -2.2999 to -1.7201 (P <0.0001)] significantly. Conversely, corneal reflex was significantly increased [95% CI 0.2159 to 2.1241 (P = 0.01)]. No differences were observed for IPD.
Conclusion: This study suggested that the GCFD can effectively control ASD behaviors as well as regulate autonomic functions related to ophthalmic markers such as pupil size and corneal reflex, but more research is needed.

Anahtar Kelimeler

Autism spectrum disorders, cognitive functions, corneal reflex, gluten-free casein-free diet, plusoptix a09, pupil size

Kaynakça

• 1. Lai MC, Lombardo MV, Baron-Cohen S. Autism. The Lancet. 2014;383:896-910. doi: 10.1016/S0140-6736(13)61539-1.
• 2. Mayer EA, Padua D, Tillisch K. Altered brain-gut axis in autism: Comorbidity or causative mechanisms? Bioessays. 2014;36(10):933–939. doi: 10.1002/bies.201400075.
• 3. Dhaliwal KK, Orsso CE, Richard C, Haqq AM, Zwaigenbaum L. Risk factors for unhealthy weight gain and obesity among children with autism spectrum disorder. Int J Mol Sci. 2019;20(13):3285. doi: 10.3390/ijms20133285.
• 4. Bandini LG, Curtin C, Phillips S, Anderson SE, Maslin M, Must A. Changes in food selectivity in children with autism spectrum disorder. J Autism Dev Disord. 2017;47(2):439–446. doi: 10.1007/s10803-016-2963-6.
• 5. Maneeton N, Maneeton B, Putthisri S, Woottiluk P, Narkpongphun A, Srisurapanont M. Risperidone for children and adolescents with autism spectrum disorder: A systematic review. Neuropsychiatr Dis Treat. 2018;14:1811–1820. doi: 10.2147/NDT.S151802.
• 6. Kang DW, Park JG, Ilhan ZE, et al. Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PloS one. 2013;8(7):e68322. doi: 10.1371/journal.pone.0068322.
• 7. Navarro F, Pearson DA, Fatheree N, Mansour R, Hashmi SS, Rhoads JM. Are 'leaky gut' and behavior associated with gluten and dairy containing diet in children with autism spectrum disorders? Nutr Neurosci. 2015;18(4):177–185. doi: 10.1179/1476830514Y.0000000110.
• 8. Marí-Bauset S, Zazpe I, Mari-Sanchis A, Llopis-González A, Morales-Suárez-Varela M. Evidence of the gluten-free and casein-free diet in autism spectrum disorders: A systematic review. J Child Neurol. 2014;29(12):1718–1727. doi: 10.1177/0883073814531330.
• 9. Priyatna A. Amazing Autisme. Jakarta: Elex Media Kompetindo. 2010. https://opac.perpusnas.go.id/DetailOpac.aspx?id=141789. Accessed September 29, 2023.
• 10. Bandini LG, Anderson SE, Curtin C, et al. Food selectivity in children with autism spectrum disorders and typically developing children. J Pediatr. 2010;157(2):259–264. doi: 10.1016/j.jpeds.2010.02.013.
• 11. Dinan TG, Cryan JF. Regulation of the stress response by the gut microbiota: Implications for psychoneuroendocrinology. Psychoneuroendocrinology. 2012;37(9):1369–1378. doi: 10.1016/j.psyneuen.2012.03.007.
• 12. Ciéslińska A, Kostyra E, Savelkoul HFJ. Treating autism spectrum disorder with gluten-free and casein-free diet: The underlying microbiota-gutbrain axis mechanisms. HSOA J Clin Immunol Immunotherapy. 2017;3(1):9-19.
• 13. Alamri ES. Efficacy of gluten- and casein-free diets on autism spectrum disorders in children. Saudi Med J. 2020;41(10):1041-1046. doi: 10.15537/smj.2020.10.25308.
• 14. Piwowarczyk A, Horvath A, Łukasik J, Pisula E, Szajewska H. Gluten- and casein-free diet and autism spectrum disorders in children: A systematic review. Eur J Nutr. 2018;57(2):433-440. doi: 10.1007/s00394-017-1483-2.
• 15. Alpern M, Mccready DW, Jr Barr. The dependence of the photopupil response on flash duration and intensity. J Gen Physiol. 1963;47(2):265–278. doi: 10.1085/jgp.47.2.265.
• 16. Lowenstein O, Loewenfeld IE. The pupil: Anatomy, Physiology, and Clinical Applications. Detroit: Iowa State University Press, Ames and Wayne State University Press.1993.https://www.scirp.org/(S(351jmbntvnsjt1aadkozje))/reference/referencespapers.aspx?referenceid=2071826. Accessed September 29, 2023.
• 17. Sahraie A, Barbur JL. Pupil response triggered by the onset of coherent motion. Graefes Arch Clin Exp Ophthalmol. 1997;235(8):494–500. doi: 10.1007/BF00947006.
• 18. Ellis CJ. The pupillary light reflex in normal subjects. Br J Ophthalmol. 1981;65(11):754–759. doi: 10.1136/bjo.65.11.754.
• 19. Lobato-Rincón LL, Cabanillas-Campos Mdel C, Bonnin-Arias C, Chamorro-Gutiérrez E, Murciano-Cespedosa A, Sánchez-Ramos Roda C. Pupillary behavior in relation to wavelength and age. Front Hum Neurosci. 2014;8:221. doi: 10.3389/fnhum.2014.00221.
• 20. Ly V, Bottelier M, Hoekstra PJ, Arias Vasquez A, Buitelaar JK, Rommelse NN. Elimination diets' efficacy and mechanisms in attention deficit hyperactivity disorder and autism spectrum disorder. Eur Child Adolesc Psychiatry. 2017;26(9):1067–1079. doi: 10.1007/s00787-017-0959-1.
• 21. Laeng B, Ørbo M, Holmlund T, Miozzo M. Pupillary stroop effects. Cogn Process. 2011;12(1):13–21. doi: 10.1007/s10339-010-0370-z.
• 22. Nassar MR, Rumsey KM, Wilson RC, Parikh K, Heasly B, Gold JI. Rational regulation of learning dynamics by pupil-linked arousal systems. Nat. Neurosci. 2012;15(7):1040–1046. doi: 10.1038/nn.3130.
• 23. DiCriscio AS, Troiani V. Pupil adaptation corresponds to quantitative measures of autism traits in children. Sci Rep. 2017;7:6476 doi: 10.1038/s41598-017-06829-1.
• 24. Daluwatte C, Miles JH, Sun J, Yao G. Association between pupillary light reflex and sensory behaviors in children with autism spectrum disorders. Res Dev Disabil. 2015;37:209–215. doi: 10.1016/j.ridd.2014.11.019.
• 25. Lynch G. Using pupillometry to assess the atypical pupillary light reflex and LC-NE system in ASD. Behav Sci. 2018;2(11):108. doi: 10.3390/bs8110108.
• 26. Nyström P, Gliga T, Nilsson Jobs E, et al. Enhanced pupillary light reflex in infancy is associated with autism diagnosis in toddlerhood. Nat Commun. 2018;9:1678. doi: 10.1038/s41467-018-03985-4.
• 27. Şahbaz İ, Taşdöndüren E, Özcan ÖÖ, et al. Comparison of interpupillary distance, pupillary diameter and corneal reflex measured with Plusoptix A09 in normally developing children and autism. İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi. 2022;18:668-677. doi: 10.38079/igusabder.1088174.
• 28. Nuske HJ, Vivanti G, Dissanayake C. Brief report: evidence for normative resting-state physiology in autism. J Autism Dev Disord. 2014;44(8):2057-63. doi: 10.1007/s10803-014-2068-z.
• 29. Keller A, Rimestad ML, Friis Rohde J, et. al. The effect of a combined gluten- and casein-free diet on children and adolescents with autism spectrum disorders: A systematic review and meta-analysis. Nutrients. 2021;13(2):470. doi: 10.3390/nu13020470.
• 30. APA. Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM 5). (2013). Washington, DC: American Psychiatric Association. https://psycnet.apa.org/record/2013-14907-000. Accessed September 29, 2023.
• 31. Declaration of Helsinki. The World Medical Association (WMA). (1998). The WMA declaration of Helsinki 1960 with recommendations on biomedical research on human subjects (modified in 1975, 1980 and 1989). Chirurgia (Bucur), 93(2), 138–140. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.wma.net/wp-content/uploads/2016/11/DoH-Oct2008.pdf. Accessed September 29, 2023.
• 32. 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. doi: 10.1186/1471-230X-11-22.
• 33. Feingold BF. Hyperkinesis and learning disabilities linked to artificial food flavors and colors. Am J Nurs. 2011;75(5):797–803.
• 34. Mazurek MO, Vasa RA, Kalb LG, et. al. Anxiety, sensory over-responsivity, and gastrointestinal problems in children with autism spectrum disorders. J Abnorm Child Psychol. 2013;41(1):165-176. doi: 10.1007/s10802-012-9668-x.
• 35. Diken İH, Ardıç A, Diken Ö, Gilliam JE. Exploring the validity and reliability of Turkish version of gilliam autism rating scale-2: turkish standardization study. Eğitim ve Bilim. 2012;37(166):318-327.
• 36. Akçamuş MÇ, Bakkaloğlu H, Demir Ş, Bahap-Kudret Z. The validity and reliability study of the Repetitive Behavior Scale-Revised- Turkish Version in autism spectrum disorder. Alpha Psychiatry. 2019;1(20):65-72. doi: 10.5455/apd.42649.
• 37. WHO. (2006). WHO Child Growth Standards: Length/Height-for-Age, Weight-for-Age, Weight-for-Length, Weight-for-Height and Body Mass Index-for-Age: Methods and Development. Switzerland: World Health Organization. https://www.who.int/publications/i/item/924154693X. Accessed September 29, 2023.
• 38. Payerols A, Eliaou C, Trezeguet V, Villain M, Daien V. Accuracy of PlusOptix A09 distance refraction in pediatric myopia and hyperopia. BMC Ophthalmol. 2016;16:72. doi: 10.1186/s12886-016-0247-8.
• 39. Yan XR, Jiao WZ, Li ZW, Xu WW, Li FJ, Wang LH. Performance of the Plusoptix A09 photoscreener in detecting amblyopia risk factors in Chinese children attending an eye clinic. PloS one. 2015;10(6):e0126052. doi: 10.1371/journal.pone.0126052.
• 40. Chiarotti F, Venerosi A. Epidemiology of autism spectrum disorders: A review of worldwide prevalence estimates since 2014. Brain Sci. 2020;10(5):274. doi: 10.3390/brainsci10050274.
• 41. Coury DL, Anagnostou E, Manning-Courtney P, et al. Use of psychotropic medication in children and adolescents with autism spectrum disorders. Pediatrics. 2012;130(Suppl 2):S69–S76. doi: 10.1542/peds.2012-0900D.
• 42. Frazier TW, Shattuck PT, Narendorf SC, Cooper BP, Wagner M, Spitznagel EL. Prevalence and correlates of psychotropic medication use in adolescents with an autism spectrum disorder with and without caregiver-reported attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2011;21(6):571–579. doi: 10.1089/cap.2011.0057.
• 43. Jobski K, Höfer J, Hoffmann F, Bachmann C. Use of psychotropic drugs in patients with autism spectrum disorders: A systematic review. Acta Psychiatr Scand. 2017;135(1):8–28. doi: 10.1111/acps.12644.
• 44. Houghton R, Ong RC, Bolognani F. Psychiatric comorbidities and use of psychotropic medications in people with autism spectrum disorder in the United States. Autism Res. 2017;10(12):2037–2047. doi: 10.1002/aur.1848.
• 45. Cohen N, Moyal N, Henik A. Executive control suppresses pupillary responses to aversive stimuli. Biol Psychol. 2015;112:1–11. doi: 10.1016/j.biopsycho.2015.09.006.
• 46. Nuske HJ, Vivanti G, Dissanayake C. No evidence of emotional dysregulation or aversion to mutual gaze in preschoolers with autism spectrum disorder: An eye-tracking pupillometry study. J Autism Dev Disord. 2015;45(11):3433-45. doi: 10.1007/s10803-015-2479-5.
• 47. Anderson CJ, Colombo J. Larger tonic pupil size in young children with autism spectrum disorder. Dev Psychobiol. 2009;51(2):207–211. doi: 10.1002/dev.20352.
• 48. Anderson CJ, Colombo J, Jill Shaddy D. Visual scanning and pupillary responses in young children with Autism Spectrum Disorder. J Clin Exp Neuropsychol. 2006;28(7):1238–1256. doi: 10.1080/13803390500376790.
• 49. Knivsberg AM, Reichelt KL, Nødland M. Reports on dietary intervention in autistic disorders. Nutr Neurosci. 2001;4(1):25–37. doi: 10.1080/1028415x.2001.11747348.
• 50. Pellissier LP, Gandía J, Laboute T, Becker JAJ, Le Merrer J. μ opioid receptor, social behaviour and autism spectrum disorder: Reward matters. Br J Pharmacol. 2018;75(14):2750-2769. doi: 10.1111/bph.13808.
• 51. Sheth F, Shah J, Patel K. et al. A novel case of two siblings harbouring homozygous variant in the NEUROG1 gene with autism as an additional phenotype: A case report. BMC Neurol. 2023;23:20. doi: 10.1186/s12883-023-03065-1.
• 52. Kinlin LM, Vresk L, Friedman JN. Vision loss in a child with autism spectrum disorder. Paediatr Child Health. 2019;24(3):148-150. doi: 10.1093/pch/pxy058.
• 53. Gutiérrez C, Santoni JLM, Merino P, de Liaño PG. Ophthalmologic manifestations in autism spectrum disorder. Turk J Ophthalmol. 2022;52(4):246-251. doi: 10.4274/tjo.galenos.2021.46588.
• 54. Singman E, Matta N, Fairward A, Silbert D. Evaluation of plusoptiX photoscreening during examinations of children with autism. Strabismus. 2013;21(2):103-5. doi: 10.3109/09273972.2013.786736.
• 55. Hafid A, Ahami AOT. The efficacy of the gluten-free casein-fren diet for Morroccan autistic children. Curr Res Nutr Food Sci Jour. 2018;6(3):734-741. doi: 10.12944/CRNFSJ.6.3.15.
• 56. Harris C, Card B. A pilot study to evaluate nutritional influences on gastrointestinal symptoms and behavior patterns in children with Autism Spectrum Disorder. Complement Ther Med. 2012;20:437-440. doi: 10.1016/j.ctim.2012.08.004.
• 57. Pennesi CM, Klein LC. Effectiveness of the gluten-free, casein-free diet for children diagnosed with autism spectrum disorder: Based on parental report. Nutritional Neuroscience. 2012;15(2):85–91. doi: 10.1179/1476830512Y.0000000003.
• 58. Mulloy A, Lang R, O'Reilly M, Sigafoos J, Lancioni G, Rispoli M. Gluten-free and casein-free diets in the treatment of autism spectrum disorders: A systematic review. Res Autism Spect Dis. 2009;217:2-12. doi: 10.1016/j.rasd.2009.10.008.
• 59. Ghalichi F, Ghaemmaghami J, Malek A, Ostadrahimi A. Effect of gluten free diet on gastrointestinal and behavioral indices for children with autism spectrum disorders: A randomized clinical trial. World J Pediatr. 2016;12(4):436–442. doi: 10.1007/s12519-016-0040-z.
• 60. Seung H, Rogalski Y, Shankar M, Elder J. The Gluten-and Casein-free diet and Autism: Communication outcomes from a preliminary double-blind clinical trial. J Med Speech Lang Pathol. 2007;15:337-345.
• 61. Piwowarczyk A, Horvath A, Pisula E, Kawa R, Szajewska H. Gluten-free diet in children with autism spectrum disorders: A randomized, controlled, single-blinded trial. J Autism Dev Disord. 2020;50(2):482-490. doi: 10.1007/s10803-019-04266-9.
• 62. González-Domenech PJ, Díaz Atienza F, García Pablos C, Fernández Soto ML, Martínez-Ortega JM, Gutiérrez-Rojas L. Influence of a combined gluten-free and casein-free diet on behavior disorders in children and adolescents diagnosed with autism spectrum disorder: a 12-month follow-up clinical trial. J Autism Dev Disord. 2020;50(3):935-948. doi: 10.1007/s10803-019-04333-1.
• 63. Elder JH, Shankar M, Shuster J, Theriaque D, Burns S, Sherrill L. The gluten-free, casein-free diet in autism: Results of a preliminary double blind clinical trial. J Autism Dev Disord. 2006;36(3):413-20. doi: 10.1007/s10803-006-0079-0.
• 64. Santos JX, Rasga C, Marques AR, et. al. A role for gene-environment interactions in autism spectrum disorder is supported by variants in genes regulating the effects of exposure to xenobiotics. Front Neurosci. 2022;19(16):862315. doi: 10.3389/fnins.2022.862315.
• 65. Tordjman S, Somogyi E, Coulon N. et al. Gene × Environment interactions in autism spectrum disorders: Role of epigenetic mechanisms. Front Psychiatry. 2014;4(5):53. doi: 10.3389/fpsyt.2014.00053.
• 66. Fan X, Miles JH, Takahashi N, Yao G. Abnormal transient pupillary light reflex in individuals with autism spectrum disorders. J Autism Dev Disord, 2009;39(11):1499–1508. doi: 10.1007/s10803-009-0767-7.