Abstract Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, with multiple genetic and environmental risk factors. The interplay between genetic and environmental factors has become the subject of intensified research in the last several years. Vitamin D deficiency has recently been proposed as a possible environmental risk factor for ASD. Vitamin D has a unique role in brain homeostasis, embryogenesis and neurodevelopment, immunological modulation (including the brain's immune system), antioxidation, antiapoptosis, neural differentiation and gene regulation. Children with ASD had significantly lower serum levels of 25-hydroxy vitamin D than healthy children.Therefore vitamin D deficiency during pregnancy and early childhood may be an environmental trigger for ASD.
Molloy CA, Kalkwarf HJ, Manning-Courtney P, Mills JL, Hediger ML. Plasma 25-OH-D concentration in children with autism spectrum disorder[J]. Dev Med Child Neurol, 2010, 52(10): 969-971.
[4]
Kanner L. Autistic disturbances of affective contact[J]. Acta Paedopsychiatr, 1968, 35(4): 100-136.
[5]
Currenti SA. Understanding and determining the etiology of autism[J]. Cell Mol Neurobiol, 2010, 30(2): 161-171.
[6]
Muhle R, Trentacoste SV, Rapin I. The genetics of autism[J]. Pediatrics, 2004, 113(5): e472-e486.
[7]
Grant WB, Soles CM. Epidemiologic evidence supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism[J]. Dermatoendocrinology, 2009, 1(4): 223-228.
[8]
Cannell JJ. Autism and vitamin D[J]. Med Hypotheses, 2008, 70(4): 750-759.
[9]
Holick MF. The vitamin D deficiency pandemic and consequences for nonskeletal health: Mechanisms of action[J]. Mol Aspects Med, 2008, 29(6): 361-368.
[10]
Cantorna MT, Zhu Y, Froicu M, Wittke A. Vitamin D status,1,25-dihydroxyvitamin D3, and the immune system[J]. Am J Clin Nutr, 2004, 80(6): 1717S-1720S.
[11]
Kesby JP, Eyles DW, Burne TH, McGrath JJ. The effects of vitamin D on brain development and adult brain function[J]. Mol Cell Endocrinol, 2011, 347(1-2): 121-127.
[12]
Humble MB, Gustafsson S, Bejerot S. Low serum levels of 25-hydroxyvitamin D (25-OH-D) among psychiatric out-patients in Sweden: Relations with season, age, ethic origin and psychiatric diagnosis[J]. J Steroid Biochem Mol Biol, 2010, 121(1-2): 467-470.
[13]
Meguid NA, Hashish AF, Amwar M, Sidhom G. Reduced serum levels of 25-hydroxy and 1,25-dihydroxy vitamin D in Egyptian children with autism[J]. J Altern Complement Med, 2010, 16(6): 641-645.
[14]
Gallo S, Jean PS, Rodd C, Weiler HA. Vitamin D supplementation of Canadian infants: practices of Montreal mothers[J]. Appl Physiol Nutr Metab, 2010, 35(3): 303-309.
[15]
Herndon AC, DiGuiseppi C, Johnson SL, Leiferman J, Reynolds A.Does nutritional intake differ between children with autism spectrum disorders and children with typical development?[J]. J Autism Dev Disord, 2009, 39(2): 212-222.
[16]
Bakare MO, Munir KM. Autism spectrum disorders (ASD) in Africa:a perspective[J]. Afr J Psychiatry, 2011, 14(3): 208-210.
[17]
Atladottir HO, Parner ET, Schendel D, Dalsgaard S, Thomsen PH, Thorsen P. Time trends in reported diagnoses of childhood neuropsychiatric disorders:a Danish cohort study[J]. Arch Pediatr Adolesc Med, 2007, 161(2): 193-198.
[18]
Lewine JD, Andrews R, Chez M, Patil AA, Devinsky O, Smith M, et al. Magnetoencephalographic patterns of epileptiform activity in children with regressive autism spectrum disorders[J]. Pediatrics, 1999, 104(3): 405-418.
[19]
Kalueff AV, Minasyan A, Keisala T, Kuuslahti M, Miettinen S, Tuohimaa P. The vitamin D neuroendocrine system as a target for novel neurotropic drugs[J]. CNS Neurol Disord Drug Targets, 2006, 5(3): 363-371.
Gao L, Tao Y, Zhang L, Jin Q. Vitamin D receptor genetic polymorphisms and tuberculosis: updated systematic review and meta-analysis[J]. Int J Tuberc Lung Dis, 2010, 14(1): 15-23.
[24]
Samuel S, Sitrin MD. Vitamin D's role in cell proliferation and differentiation[J]. Nutr Rev, 2008, 66(10 Suppl 2): S116-S124．
[25]
Bohnsaek BL, Hirschi KK. Nutrient regulation of cell cycle progression[J]．Annu Rev Nutr, 2004, 24(10): 433-453．
[26]
Grant WB, Soles CM. Epidemiologic evidence supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism[J]. Ermatoendocrinol, 2009, 1(4): 223-228.
[27]
Evatt ML, DeLong MR, Grant WB, Cannell JJ, Tangpricha V. Autism spectrum disorders following in utero exposure to antiepileptic drugs[J]. Neurology, 2009, 73(12): 997.
[28]
Chambers ES, Hawrylowicz CM. The impact of vitamin D on regulatory T cells[J]. Curr Allergy Asthma Rep, 2011, 11(1): 29-36.
[29]
Vignali DA, Collison LW, Workman CJ. How regulatory T cells work[J]. Nat Rev Immunol, 2008, 8(7): 523-532.
[30]
Bettelli E, Korn T, Oukka M, Kuchroo VK. Induction and effector functions of T(H)17 cells[J]. Nature, 2008, 453(7198): 1051-1057.
[31]
Mostafa GA, Shehab AA, Fouad NR. Increased frequency of CD4+CD25high regulatory T cells in the peripheral blood of Egyptian children with autism[J]. J Child Neurol, 2010, 25(3): 328-335.
[32]
Jones AP, Tulic MK, Rueter K, Prescott SL. Vitamin D and allergic disease:sunlight at the end of the tunnel?[J]. Nutrients, 2012, 4(1): 13-28.
[33]
Zhang HL, Wu J. Role of vitamin D in immune responses and autoimmune diseases, with emphasis on its role in multiple sclerosis[J]. Neurosci Bull, 2010, 26(6): 445-454.
[34]
Hamza RT, Awwad KS, Ali MK, Hamed AI. Reduced serum concentrations of 25-hydroxy vitamin D in Egyptian patients with systemic lupus erythematosus: relation to disease activity[J]. Med Sci Monit, 2011, 17(12): CR711-CR718.
[35]
Wattjes MP, Doepp F, Bendszus M, Fiehler J. Chronic cerebrospinal venous insufficiency in multiple sclerosis-is multiple sclerosis a disease of the cerebrospinal venous outflow system?[J]. Fortschr Rontgenstr, 2011, 183(6): 523-530.
[36]
Mostafa GA, AL-Ayadhi LY. Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: relation to autoimmunity[J]. J Neuroinflammation, 2012, 9: 201-207.
Humblea MB, Gustafssonb S, Bejerota S. Low serum levels of 25-hydroxyvitamin D (25-OH-D) among psychiatric out-patients in Sweden:Relations with season,age,ethnic origin and psychiatric diagnosis[J]. J Steroid Biochem Mol Biol, 2010, 121(1-2): 467-470.
[39]
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?[J]. Med Hypotheses, 2010, 74(1): 102-106.
[40]
Harms LR, BurneTH, Eyles DW, McGrath JJ. Vitamin D and the brain[J]. Best Pract Res Clin Endocrinol Metab, 2011, 25(4): 657-669.
[41]
Eyles D, Burne T, McGrath J. Vitamin D in fetal brain development[J]. Semin Cell Dev Biol, 2011, 22(6): 629-636.
[42]
Heaney RP, Dowell MS, Hale CA, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D[J]. J Am Coll Nutr, 2003, 22(2): 142-146.
[43]
Bischoff-Ferrari HA, Dietrich T, Orav EJ, Hu FB, Zhang Y, Karlson EW, et al. Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or = 60y[J]. Am J Clin Nutr, 2004, 80(3): 752-758.
[44]
Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes[J]. Am J Clin Nutr, 2006, 84(1): 18-28.
[45]
Cannell JJ, Hollis WB. Use of vitamin D in clinical practice[J].Altern Med Rev, 2008, 13(1): 6-20.
[46]
Cannell JJ.On the aetiology of autism[J]. Acta Paediatr, 2010, 99(8): 1128-1130.
