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The Levels of Vitamin D, Vitamin D Receptor, Homocysteine and Complex B Vitamin in Children with Autism Spectrum Disorders

  • Altun, Hatice (Department of Child and Adolescent Psychiatry, Faculty of Medicine, Kahramanmaras Sutcu Imam University) ;
  • Kurutas, Ergul Belge (Department of Biochemistry, Faculty of Medicine, Kahramanmaras Sutcu Imam University) ;
  • Sahin, Nilfer (Department of Child and Adolescent Psychiatry, Faculty of Medicine, Mugla Sitki Kocman University) ;
  • Gungor, Olcay (Department of Pediatric Neurology, Faculty of Medicine, Kahramanmaras Sutcu Imam University) ;
  • Findikli, Ebru (Department of Psychiatry, Faculty of Medicine, Kahramanmaras Sutcu Imam University)
  • 투고 : 2017.05.04
  • 심사 : 2017.08.01
  • 발행 : 2018.11.30

초록

Objective: Autism spectrum disorder (ASD) is a complex neurodevelopmental syndrome with an increasingly prevalent etiology, yet not fully understood. It has been thought that vitamin D, complex B vitamin levels and homocysteine are associated with environmental factors and are important in ASD. The aim of this study was to examine serum vitamin D, vitamin D receptor (VDR), homocysteine, vitamin B6, vitamin B12 and folate levels in ASD. Methods: In this study, serum vitamin D and VDR, homocysteine, vitamins B6, B12 and folate levels were determined in 60 patients with ASD (aged 3 to 12 years) and in 45 age-gender matched healthy controls. In addition, calcium, phosphorus and alkaline phosphatase, which are associated with vitamin D metabolism, were measured from serum in both groups. ASD severity was evaluted by the Childhood Autism Rating Scale (CARS). Results: Serum vitamin D and VDR were substantially reduced in patients with ASD in comparision to control group. However, homocysteine level was significantly higher and vitamin B6, vitamin B12 and folate were also reduced in patients with ASD. Total CARS score showed a positive association with homocysteine and a negative correlation with vitamins D,B6, B12, folate and VDR. Conclusion: This comprehensive study, which examines many parameters has shown that low serum levels of vitamins D, B6, B12, folate and VDR as well as high homocysteine are important in the etiopathogenesis of ASD. However, further studies are required to define the precise mechanism(s) of these parameters and their contributions to the etiology and treatment of ASD.

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과제정보

연구 과제 주관 기관 : Kahramanmaras Sutcu Imam University

참고문헌

  1. Cannell JJ. On the aetiology of autism. Acta Paediatr 2010;99:1128-1130. https://doi.org/10.1111/j.1651-2227.2010.01883.x
  2. Kinney DK, Barch DH, Chayka B, Napoleon S, Munir KM. Environmental risk factors for autism: do they help cause de novo genetic mutations that contribute to the disorder? Med Hypotheses 2010;74:102-106. https://doi.org/10.1016/j.mehy.2009.07.052
  3. Ucuz II, Dursun OB, Aydin N. The effects of vitamin D3 on brain development and autism. Klinik Psikofarmakol Bulteni 2015;25:302-311. https://doi.org/10.5455/bcp.20141024012912
  4. Goksugur SB, Tufan AE, Semiz M, Gunes C, Bekdas M, Tosun M, et al. Vitamin D status in children with attention-deficit-hyperactivity disorder. Pediatr Int 2014;56:515-519. https://doi.org/10.1111/ped.12286
  5. Itzhaky D, Amital D, Gorden K, Bogomolni A, Arnson Y, Amital H. Low serum vitamin D concentrations in patients with schizophrenia. Isr Med Assoc J 2012;14:88-92.
  6. Gong ZL, Luo CM, Wang L, Shen L, Wei F, Tong RJ, et al. Serum 25-hydroxyvitamin D levels in Chinese children with autism spectrum disorders. Neuroreport 2014;25:23-27.
  7. Humble MB, Gustafsson S, Bejerot S. Low serum levels of 25-hydroxyvitamin D (25-OHD) among psychiatric out-patients in Sweden: relations with season, age, ethnic origin and psychiatric diagnosis. J Steroid Biochem Mol Biol 2010;121:467-470. https://doi.org/10.1016/j.jsbmb.2010.03.013
  8. Eyles D, Burne T, McGrath J. Vitamin D in fetal brain development. Semin Cell Dev Biol 2011;22:629-636. https://doi.org/10.1016/j.semcdb.2011.05.004
  9. Harms LR, Burne TH, Eyles DW, McGrath JJ. Vitamin D and the brain. Best Pract Res Clin Endocrinol Metab 2011;25:657-669. https://doi.org/10.1016/j.beem.2011.05.009
  10. Grant WB, Soles CM. Epidemiologic evidence supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism. Dermatoendocrinol 2009;1:223-228. https://doi.org/10.4161/derm.1.4.9500
  11. Cannell JJ, Hollis BW. Use of vitamin D in clinical practice. Altern Med Rev 2008;13:6-20.
  12. Meguid NA, Hashish AF, Anwar M, Sidhom G. Reduced serum levels of 25-hydroxy and 1,25-dihydroxy vitamin D in Egyptian children with autism. J Altern Complement Med 2010;16:641-645. https://doi.org/10.1089/acm.2009.0349
  13. Mostafa GA, Al-Ayadhi LY. Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: relation to autoimmunity. J Neuroinflammation 2012;9:201.
  14. Ugur C, Gurkan CK. Serum vitamin D and folate levels in children with autism spectrum disorders. Res Autism Spectr Disord 2014;8:1641-1647. https://doi.org/10.1016/j.rasd.2014.09.002
  15. Adams JB, Audhya T, McDonough-Means S, Rubin RA, Quig D, Geis E, et al. Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity. Nutr Metab (Lond) 2011;8:34. https://doi.org/10.1186/1743-7075-8-34
  16. Goltzman D, Hendy GN, White JH. Vitamin D and its receptor during late development. Biochim Biophys Acta 2015;1849:171-180. https://doi.org/10.1016/j.bbagrm.2014.05.026
  17. Perla-Kajan J, Twardowski T, Jakubowski H. Mechanisms of homocysteine toxicity in humans. Amino Acids 2007;32:561-572. https://doi.org/10.1007/s00726-006-0432-9
  18. Malinowska J, Kolodziejczyk J, Olas B. The disturbance of hemostasis induced by hyperhomocysteinemia; the role of antioxidants. Acta Biochim Pol 2012;59:185-194.
  19. Kaluzna-Czaplinska J, Zurawicz E, Michalska M, Rynkowski J. A focus on homocysteine in autism. Acta Biochim Pol 2013;60:137-142.
  20. Herrmann W, Herrmann M, Obeid R. Hyperhomocysteinaemia: a critical review of old and new aspects. Curr Drug Metab 2007;8:17-31. https://doi.org/10.2174/138920007779315008
  21. Pasca SP, Nemes B, Vlase L, Gagyi CE, Dronca E, Miu AC, et al. High levels of homocysteine and low serum paraoxonase 1 arylesterase activity in children with autism. Life Sci 2006;78:2244-2248. https://doi.org/10.1016/j.lfs.2005.09.040
  22. Kaluzna-Czaplinska J, Michalska M, Rynkowski J. Homocysteine level in urine of autistic and healthy children. Acta Biochim Pol 2011;58:31-34.
  23. Stanger O, Fowler B, Piertzik K, Huemer M, Haschke-Becher E, Semmler A, et al. Homocysteine, folate and vitamin B12 in neuropsychiatric diseases: review and treatment recommendations. Expert Rev Neurother 2009;9:1393-1412. https://doi.org/10.1586/ern.09.75
  24. McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med 2006;354:2764-2772. https://doi.org/10.1056/NEJMoa054025
  25. Ali A, Waly MI, Al-Farsi YM, Essa MM, Al-Sharbati MM, Deth RC. Hyperhomocysteinemia among Omani autistic children: a case-control study. Acta Biochim Pol 2011;58:547-551.
  26. Al-Farsi YM, Waly MI, Deth RC, Al-Sharbati MM, Al-Shafaee M, Al-Farsi O, et al. Low folate and vitamin B12 nourishment is common in Omani children with newly diagnosed autism. Nutrition 2013;29:537-541. https://doi.org/10.1016/j.nut.2012.09.014
  27. Sucuoglu B, Oktem F, Akkok F, Gokler B. [A study of the scales for the assessment of the children with autism]. J Psychiatry Psychol Psychopharmacol 1996;4:116-121. Turkish.
  28. Fernell E, Bejerot S, Westerlund J, Miniscalco C, Simila H, Eyles D, et al. Autism spectrum disorder and low vitamin D at birth: a sibling control study. Mol Autism 2015;6:3. https://doi.org/10.1186/2040-2392-6-3
  29. Kocovska E, Andorsdottir G, Weihe P, Halling J, Fernell E, Stora T, et al. Vitamin d in the general population of young adults with autism in the Faroe Islands. J Autism Dev Disord 2014;44:2996-3005. https://doi.org/10.1007/s10803-014-2155-1
  30. Saad K, Abdel-Rahman AA, Elserogy YM, Al-Atram AA, Cannell JJ, Bjorklund G, et al. Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children. Nutr Neurosci 2016;19:346-351. https://doi.org/10.1179/1476830515Y.0000000019
  31. Feng J, Shan L, Du L, Wang B, Li H, Wang W, et al. Clinical improvement following vitamin D3 supplementation in autism spectrum disorder. Nutr Neurosci 2017;20:284-290. https://doi.org/10.1080/1028415X.2015.1123847
  32. Must A, Phillips SM, Curtin C, Anderson SE, Maslin M, Lividini K, et al. Comparison of sedentary behaviors between children with autism spectrum disorders and typically developing children. Autism 2014;18:376-384. https://doi.org/10.1177/1362361313479039
  33. Mari-Bauset S, Llopis-Gonzalez A, Zazpe-Garcia I, Mari-Sanchis A, Morales-Suarez-Varela M. Nutritional status of children with autism spectrum disorders (ASDs): a case-control study. J Autism Dev Disord 2015;45:203-212. https://doi.org/10.1007/s10803-014-2205-8
  34. Emond A, Emmett P, Steer C, Golding J. Feeding symptoms, dietary patterns, and growth in young children with autism spectrum disorders. Pediatrics 2010;126:e337-e342. https://doi.org/10.1542/peds.2009-2391
  35. Rossignol DA, Frye RE. Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism. Front Physiol 2014;5:150.
  36. Groves NJ, McGrath JJ, Burne TH. Vitamin D as a neurosteroid affecting the developing and adult brain. Annu Rev Nutr 2014;34:117-141. https://doi.org/10.1146/annurev-nutr-071813-105557
  37. Coskun S, Simsek S, Camkurt MA, Cim A, Celik SB. Association of polymorphisms in the vitamin D receptor gene and serum 25-hydroxyvitamin D levels in children with autism spectrum disorder. Gene 2016;588:109-114. https://doi.org/10.1016/j.gene.2016.05.004
  38. Yan J, Feng J, Craddock N, Jones IR, Cook EH Jr, Goldman D, et al. Vitamin D receptor variants in 192 patients with schizophrenia and other psychiatric diseases. Neurosci Lett 2005;380:37-41. https://doi.org/10.1016/j.neulet.2005.01.018
  39. Newton LA, Sandhu K, Livingstone C, Leslie R, Davis J. Clinical diagnostics for homocysteine: a rogue amino acid? Expert Rev Mol Diagn 2010;10:489-500. https://doi.org/10.1586/erm.10.19
  40. Mattson MP, Shea TB. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci 2003;26:137-146. https://doi.org/10.1016/S0166-2236(03)00032-8
  41. Ho PI, Ortiz D, Rogers E, Shea TB. Multiple aspects of homocysteine neurotoxicity: glutamate excitotoxicity, kinase hyperactivation and DNA damage. J Neurosci Res 2002;70:694-702. https://doi.org/10.1002/jnr.10416
  42. Lipton SA, Kim WK, Choi YB, Kumar S, D'Emilia DM, Rayudu PV, et al. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proc Natl Acad Sci U S A 1997;94:5923-5928. https://doi.org/10.1073/pnas.94.11.5923
  43. Kruman II, Culmsee C, Chan SL, Kruman Y, Guo Z, Penix L, et al. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci 2000;20:6920-6926. https://doi.org/10.1523/JNEUROSCI.20-18-06920.2000
  44. Nye C, Brice A. Combined vitamin B6-magnesium treatment in autism spectrum disorder. Cochrane Database Syst Rev 2005;(4):CD003497.
  45. Desai A, Sequeira JM, Quadros EV. The metabolic basis for developmental disorders due to defective folate transport. Biochimie 2016;126:31-42. https://doi.org/10.1016/j.biochi.2016.02.012
  46. Kennedy DO. B Vitamins and the brain: mechanisms, dose and efficacy--a review. Nutrients 2016;8:68. https://doi.org/10.3390/nu8020068
  47. Fujiwara T, Morisaki N, Honda Y, Sampei M, Tani Y. Chemicals, nutrition, and autism spectrum disorder: a minireview. Front Neurosci 2016;10:174.
  48. Schmidt RJ, Tancredi DJ, Ozonoff S, Hansen RL, Hartiala J, Allayee H, et al. Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. Am J Clin Nutr 2012;96:80-89. https://doi.org/10.3945/ajcn.110.004416
  49. Moretti R, Torre P, Antonello RM, Cattaruzza T, Cazzato G, Bava A. Vitamin B12 and folate depletion in cognition: a review. Neurol India 2004;52:310-318.
  50. Fulceri F, Morelli M, Santocchi E, Cena H, Del Bianco T, Narzisi A, et al. Gastrointestinal symptoms and behavioral problems in preschoolers with autism spectrum disorder. Dig Liver Dis 2016;48:248-254. https://doi.org/10.1016/j.dld.2015.11.026
  51. Williams KE, Gibbons BG, Schreck KA. Comparing selective eaters with and without developmental disabilities. J Dev Phys Disabil 2005;17:299-309. https://doi.org/10.1007/s10882-005-4387-7
  52. Xia W, Zhou Y, Sun C, Wang J, Wu L. A preliminary study on nutritional status and intake in Chinese children with autism. Eur J Pediatr 2010;169:1201-1206. https://doi.org/10.1007/s00431-010-1203-x
  53. Kaluzna-Czaplinska J, Michalska M, Rynkowski J. Vitamin supplementation reduces the level of homocysteine in the urine of autistic children. Nutr Res 2011;31:318-321. https://doi.org/10.1016/j.nutres.2011.03.009
  54. Hjiej H, Doyen C, Couprie C, Kaye K, Contejean Y. [Substitutive and dietetic approaches in childhood autistic disorder: interests and limits]. Encephale 2008;34:496-503. French. https://doi.org/10.1016/j.encep.2007.10.011
  55. Adams JB, Audhya T, McDonough-Means S, Rubin RA, Quig D, Geis E, et al. Effect of a vitamin/mineral supplement on children and adults with autism. BMC Pediatr 2011;11:111. https://doi.org/10.1186/1471-2431-11-111
  56. Ramaekers VT, Blau N, Sequeira JM, Nassogne MC, Quadros EV. Folate receptor autoimmunity and cerebral folate deficiency in low-functioning autism with neurological deficits. Neuropediatrics 2007;38:276-281. https://doi.org/10.1055/s-2008-1065354
  57. Castro K, Klein Lda S, Baronio D, Gottfried C, Riesgo R, Perry IS. Folic acid and autism: what do we know? Nutr Neurosci 2016;19:310-317. https://doi.org/10.1179/1476830514Y.0000000142

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