Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Role of Vitamin D in Autism Spectrum Disorder

Author(s): Loai Alzghoul*

Volume 25, Issue 41, 2019

Page: [4357 - 4367] Pages: 11

DOI: 10.2174/1381612825666191122092215

Price: $65

Abstract

Autism spectrum disorder (ASD) is a pervasive developmental disorder with heterogeneous etiology. Vitamin D can function as a fat-soluble vitamin as well as a hormone, and can exert its effect through both genomic and non-genomic mechanisms. In the last decades, several studies have examined the relationship between vitamin D levels and ASD. These studies demonstrated that low vitamin D status in early development has been hypothesized as an environmental risk factor for ASD. Both in vivo and in vitro studies have demonstrated that vitamin D deficiency in early life can alter brain development, dysregulates neurotransmitter balance in the brain, decreases body and brain antioxidant ability, and alters the immune system in ways that resemble pathological features commonly seen in ASD. In this review, we focused on the association between vitamin D and ASD. In addition, the above-mentioned mechanisms of action that link vitamin D deficiency with ASD were also discussed. Finally, clinical trials of vitamin D supplementation treatment of ASD have also been discussed.

Keywords: Autism, vitamin D3, vitamin D deficiency, neurotransmitter, antioxidant, supplementation.

« Previous Next »
[1]
Grant WB, Cannell JJ. Autism prevalence in the United States with respect to solar UV-B doses: an ecological study. Dermatoendocrinol 2013; 5(1): 159-64.
[http://dx.doi.org/10.4161/derm.22942] [PMID: 24494049]
[2]
Centers for Disease Control and Prevention. Data & Statistics on Autism Spectrum Disorder 2019.
[3]
Lintas C, Persico AM. Autistic phenotypes and genetic testing: state-of-the-art for the clinical geneticist. J Med Genet 2009; 46(1): 1-8.
[http://dx.doi.org/10.1136/jmg.2008.060871] [PMID: 18728070]
[4]
Abrahams BS, Geschwind DH. Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 2008; 9(5): 341-55.
[http://dx.doi.org/10.1038/nrg2346] [PMID: 18414403]
[5]
Baio J, Wiggins L, Christensen DL, et al. Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2014. MMWR Surveill Summ 2018; 67(6): 1-23.
[http://dx.doi.org/10.15585/mmwr.ss6706a1] [PMID: 29701730]
[6]
Lake JK, Perry A, Lunsky Y. Mental health services for individuals with high functioning autism spectrum disorder. Autism Res Treat 2014; 2014 502420
[http://dx.doi.org/10.1155/2014/502420] [PMID: 25276425]
[7]
Howlin P, Goode S, Hutton J, Rutter M. Adult outcome for children with autism. J Child Psychol Psychiatry 2004; 45(2): 212-29.
[http://dx.doi.org/10.1111/j.1469-7610.2004.00215.x] [PMID: 14982237]
[8]
Billstedt E, Gillberg IC, Gillberg C. Autism after adolescence: population-based 13- to 22-year follow-up study of 120 individuals with autism diagnosed in childhood. J Autism Dev Disord 2005; 35(3): 351-60.
[http://dx.doi.org/10.1007/s10803-005-3302-5] [PMID: 16119476]
[9]
Howlin P, Moss P, Savage S, Rutter M. Social outcomes in mid- to later adulthood among individuals diagnosed with autism and average nonverbal IQ as children. J Am Acad Child Adolesc Psychiatry 2013; 52(6): 572-81.e1.
[http://dx.doi.org/10.1016/j.jaac.2013.02.017] [PMID: 23702446]
[10]
Enstrom AM, Van de Water JA, Ashwood P. Autoimmunity in autism. Curr Opin Investig Drugs 2009; 10(5): 463-73.
[PMID: 19431079]
[11]
Grabrucker AM. Environmental factors in autism. Front Psychiatry 2013; 3: 118.
[http://dx.doi.org/10.3389/fpsyt.2012.00118] [PMID: 23346059]
[12]
Kawicka A, Regulska-Ilow B. How nutritional status, diet and dietary supplements can affect autism. A review. Rocz Panstw Zakl Hig 2013; 64(1): 1-12.
[PMID: 23789306]
[13]
Muhle R, Trentacoste SV, Rapin I. The genetics of autism. Pediatrics 2004; 113(5): e472-86.
[http://dx.doi.org/10.1542/peds.113.5.e472] [PMID: 15121991]
[14]
Persico AM, Napolioni V. Autism genetics. Behav Brain Res 2013; 251: 95-112.
[http://dx.doi.org/10.1016/j.bbr.2013.06.012] [PMID: 23769996]
[15]
Rossi J, Newschaffer C, Yudell M. Autism spectrum disorders, risk communication, and the problem of inadvertent harm. Kennedy Inst Ethics J 2013; 23(2): 105-38.
[http://dx.doi.org/10.1353/ken.2013.0006] [PMID: 23888834]
[16]
Bailey A, Le Couteur A, Gottesman I, et al. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995; 25(1): 63-77.
[http://dx.doi.org/10.1017/S0033291700028099] [PMID: 7792363]
[17]
Folstein S, Rutter M. Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry 1977; 18(4): 297-321.
[http://dx.doi.org/10.1111/j.1469-7610.1977.tb00443.x] [PMID: 562353]
[18]
Hallmayer J, Cleveland S, Torres A, et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry 2011; 68(11): 1095-102.
[http://dx.doi.org/10.1001/archgenpsychiatry.2011.76] [PMID: 21727249]
[19]
Comi AM, Zimmerman AW, Frye VH, Law PA, Peeden JN. Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism. J Child Neurol 1999; 14(6): 388-94.
[http://dx.doi.org/10.1177/088307389901400608] [PMID: 10385847]
[20]
Mandy W, Lai MC. Annual research review: the role of the environment in the developmental psychopathology of autism spectrum condition. J Child Psychol Psychiatry 2016; 57(3): 271-92.
[http://dx.doi.org/10.1111/jcpp.12501] [PMID: 26782158]
[21]
Sealey LA, Hughes BW, Sriskanda AN, et al. Environmental factors in the development of autism spectrum disorders. Environ Int 2016; 88: 288-98.
[http://dx.doi.org/10.1016/j.envint.2015.12.021] [PMID: 26826339]
[22]
Ali A, Vasileva S, Langguth M, et al. Developmental vitamin D deficiency produces behavioral phenotypes of relevance to autism in an animal model. Nutrients 2019; 11(5) E1187
[http://dx.doi.org/10.3390/nu11051187] [PMID: 31137843]
[23]
Jia F, Shan L, Wang B, et al. Bench to bedside review: possible role of vitamin D in autism spectrum disorder. Psychiatry Res 2018; 260: 360-5.
[http://dx.doi.org/10.1016/j.psychres.2017.12.005] [PMID: 29241119]
[24]
Máčová L, Bičíková M, Ostatníková D, Hill M, Stárka L. Vitamin D, neurosteroids and autism. Physiol Res 2017; 66(Suppl. 3): S333-40.
[PMID: 28948817]
[25]
Mazahery H, Camargo CA Jr, Conlon C, Beck KL, Kruger MC, von Hurst PR. Vitamin D and autism spectrum disorder: a literature review. Nutrients 2016; 8(4): 236.
[http://dx.doi.org/10.3390/nu8040236] [PMID: 27110819]
[26]
Wang T, Shan L, Du L, et al. Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis. Eur Child Adolesc Psychiatry 2016; 25(4): 341-50.
[http://dx.doi.org/10.1007/s00787-015-0786-1] [PMID: 26514973]
[27]
Borel P, Caillaud D, Cano NJ. Vitamin D bioavailability: state of the art. Crit Rev Food Sci Nutr 2015; 55(9): 1193-205.
[http://dx.doi.org/10.1080/10408398.2012.688897] [PMID: 24915331]
[28]
Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci USA 2004; 101(20): 7711-5.
[http://dx.doi.org/10.1073/pnas.0402490101] [PMID: 15128933]
[29]
Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J Biol Chem 2003; 278(39): 38084-93.
[http://dx.doi.org/10.1074/jbc.M307028200] [PMID: 12867411]
[30]
Zhu JG, Ochalek JT, Kaufmann M, Jones G, Deluca HF. CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo. Proc Natl Acad Sci USA 2013; 110(39): 15650-5.
[http://dx.doi.org/10.1073/pnas.1315006110] [PMID: 24019477]
[31]
Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 2005; 29(1): 21-30.
[http://dx.doi.org/10.1016/j.jchemneu.2004.08.006] [PMID: 15589699]
[32]
Khanal RC, Peters TM, Smith NM, Nemere I. Membrane receptor-initiated signaling in 1,25(OH)2D3-stimulated calcium uptake in intestinal epithelial cells. J Cell Biochem 2008; 105(4): 1109-16.
[http://dx.doi.org/10.1002/jcb.21913] [PMID: 18773429]
[33]
Monkawa T, Yoshida T, Hayashi M, Saruta T. Identification of 25-hydroxyvitamin D3 1alpha-hydroxylase gene expression in macrophages. Kidney Int 2000; 58(2): 559-68.
[http://dx.doi.org/10.1046/j.1523-1755.2000.00202.x] [PMID: 10916079]
[34]
Neveu I, Naveilhan P, Menaa C, Wion D, Brachet P, Garabédian M. Synthesis of 1,25-dihydroxyvitamin D3 by rat brain macrophages in vitro. J Neurosci Res 1994; 38(2): 214-20.
[http://dx.doi.org/10.1002/jnr.490380212] [PMID: 8078106]
[35]
Wang TT, Tavera-Mendoza LE, Laperriere D, et al. Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol 2005; 19(11): 2685-95.
[http://dx.doi.org/10.1210/me.2005-0106] [PMID: 16002434]
[36]
Pike JW, Meyer MB. The vitamin D receptor: new paradigms for the regulation of gene expression by 1,25-dihydroxyvitamin D(3). Endocrinol Metab Clin North Am 2010; 39(2): 255-69.
[http://dx.doi.org/10.1016/j.ecl.2010.02.007] [PMID: 20511050]
[37]
Marino R, Misra M. Extra-skeletal effects of vitamin D. Nutrients 2019; 11(7) E1460
[http://dx.doi.org/10.3390/nu11071460] [PMID: 31252594]
[38]
Di Somma C, Scarano E, Barrea L, et al. Vitamin D and neurological diseases: an endocrine view. Int J Mol Sci 2017; 18(11) E2482
[http://dx.doi.org/10.3390/ijms18112482] [PMID: 29160835]
[39]
Hii CS, Ferrante A. The non-genomic actions of vitamin D. Nutrients 2016; 8(3): 135.
[http://dx.doi.org/10.3390/nu8030135] [PMID: 26950144]
[40]
Cui X, Gooch H, Groves NJ, et al. Vitamin D and the brain: key questions for future research. J Steroid Biochem Mol Biol 2015; 148: 305-9.
[http://dx.doi.org/10.1016/j.jsbmb.2014.11.004] [PMID: 25448739]
[41]
Zanatta L, Goulart PB, Gonçalves R, et al. 1α,25-dihydroxyvitamin D(3) mechanism of action: modulation of L-type calcium channels leading to calcium uptake and intermediate filament phosphorylation in cerebral cortex of young rats. Biochim Biophys Acta 2012; 1823(10): 1708-19.
[http://dx.doi.org/10.1016/j.bbamcr.2012.06.023] [PMID: 22743040]
[42]
Jones G, Strugnell SA, DeLuca HF. Current understanding of the molecular actions of vitamin D. Physiol Rev 1998; 78(4): 1193-231.
[http://dx.doi.org/10.1152/physrev.1998.78.4.1193] [PMID: 9790574]
[43]
Christakos S, Li S, De La Cruz J, Bikle DD. New developments in our understanding of vitamin metabolism, action and treatment. Metabolism 2019; 98: 112-20.
[http://dx.doi.org/10.1016/j.metabol.2019.06.010] [PMID: 31226354]
[44]
Zerwekh JE. Blood biomarkers of vitamin D status. Am J Clin Nutr 2008; 87(4): 1087S-91S.
[http://dx.doi.org/10.1093/ajcn/87.4.1087S] [PMID: 18400739]
[45]
Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96(7): 1911-30.
[http://dx.doi.org/10.1210/jc.2011-0385] [PMID: 21646368]
[46]
Cannell JJ. Autism and vitamin D. Med Hypotheses 2008; 70(4): 750-9.
[http://dx.doi.org/10.1016/j.mehy.2007.08.016] [PMID: 17920208]
[47]
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(4): 223-8.
[http://dx.doi.org/10.4161/derm.1.4.9500] [PMID: 20592795]
[48]
Dealberto MJ. Prevalence of autism according to maternal immigrant status and ethnic origin. Acta Psychiatr Scand 2011; 123(5): 339-48.
[http://dx.doi.org/10.1111/j.1600-0447.2010.01662.x] [PMID: 21219265]
[49]
Eyles DW. Vitamin D and autism: does skin colour modify risk? Acta Paediatr 2010; 99(5): 645-7.
[http://dx.doi.org/10.1111/j.1651-2227.2010.01797.x] [PMID: 20219042]
[50]
Fernell E, Barnevik-Olsson M, Bågenholm G, Gillberg C, Gustafsson S, Sääf M. Serum levels of 25-hydroxyvitamin D in mothers of Swedish and of Somali origin who have children with and without autism. Acta Paediatr 2010; 99(5): 743-7.
[http://dx.doi.org/10.1111/j.1651-2227.2010.01755.x] [PMID: 20219032]
[51]
Gillberg C, Schaumann H, Gillberg IC. Autism in immigrants: children born in Sweden to mothers born in Uganda. J Intellect Disabil Res 1995; 39(Pt 2): 141-4.
[http://dx.doi.org/10.1111/j.1365-2788.1995.tb00482.x] [PMID: 7787384]
[52]
Vinkhuyzen AAE, Eyles DW, Burne THJ, et al. Gestational vitamin D deficiency and autism spectrum disorder. BJPsych Open 2017; 3(2): 85-90.
[http://dx.doi.org/10.1192/bjpo.bp.116.004077] [PMID: 28446959]
[53]
Gardener H, Spiegelman D, Buka SL. Prenatal risk factors for autism: comprehensive meta-analysis. Br J Psychiatry 2009; 195(1): 7-14.
[http://dx.doi.org/10.1192/bjp.bp.108.051672] [PMID: 19567888]
[54]
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(6): 641-5.
[http://dx.doi.org/10.1089/acm.2009.0349] [PMID: 20569030]
[55]
Tostes MH, Polonini HC, Gattaz WF, Raposo NR, Baptista EB. Low serum levels of 25-hydroxyvitamin D (25-OHD) in children with autism. Trends Psychiatry Psychother 2012; 34(3): 161-3.
[http://dx.doi.org/10.1590/S2237-60892012000300008] [PMID: 25923008]
[56]
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.
[http://dx.doi.org/10.1186/1742-2094-9-201] [PMID: 22898564]
[57]
Gong ZL, Luo CM, Wang L, et al. Serum 25-hydroxyvitamin D levels in Chinese children with autism spectrum disorders. Neuroreport 2014; 25(1): 23-7.
[PMID: 24089013]
[58]
Feng J, Shan L, Du L, et al. Clinical improvement following vitamin D3 supplementation in Autism Spectrum Disorder. Nutr Neurosci 2017; 20(5): 284-90.
[http://dx.doi.org/10.1080/1028415X.2015.1123847] [PMID: 26783092]
[59]
Bener A, Khattab AO, Al-Dabbagh MM. Is high prevalence of Vitamin D deficiency evidence for autism disorder?: In a highly endogamous population. J Pediatr Neurosci 2014; 9(3): 227-33.
[http://dx.doi.org/10.4103/1817-1745.147574] [PMID: 25624924]
[60]
Saad K, Abdel-Rahman AA, Elserogy YM, et al. Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children. Nutr Neurosci 2016; 19(8): 346-51.
[http://dx.doi.org/10.1179/1476830515Y.0000000019] [PMID: 25876214]
[61]
Arastoo AA, Khojastehkia H, Rahimi Z, et al. Evaluation of serum 25-Hydroxy vitamin D levels in children with autism Spectrum disorder. Ital J Pediatr 2018; 44(1): 150.
[http://dx.doi.org/10.1186/s13052-018-0587-5] [PMID: 30558646]
[62]
Fernell E, Bejerot S, Westerlund J, et al. Autism spectrum disorder and low vitamin D at birth: a sibling control study. Mol Autism 2015; 6: 3.
[http://dx.doi.org/10.1186/2040-2392-6-3] [PMID: 25874075]
[63]
Kočovská E, Andorsdóttir G, Weihe P, et al. Vitamin D in the general population of young adults with autism in the faroe islands. J Autism Dev Disord 2014; 44(12): 2996-3005.
[http://dx.doi.org/10.1007/s10803-014-2155-1] [PMID: 24927807]
[64]
Molloy CA, Manning-Courtney P. Prevalence of chronic gastrointestinal symptoms in children with autism and autistic spectrum disorders. Autism 2003; 7(2): 165-71.
[http://dx.doi.org/10.1177/1362361303007002004] [PMID: 12846385]
[65]
Adams JB, Audhya T, McDonough-Means S, et al. Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity. Nutr Metab (Lond) 2011; 8(1): 34.
[http://dx.doi.org/10.1186/1743-7075-8-34] [PMID: 21651783]
[66]
Uğur Ç, Gürkan CK. Serum vitamin D and folate levels in children with autism spectrum disorders. Res Autism Spectr Disord 2014; 8(12): 1641-7.
[http://dx.doi.org/10.1016/j.rasd.2014.09.002]
[67]
Alzghoul L, Al-Eitan LN, Aladawi M, Odeh M, Abu Hantash O. The association between serum vitamin D3 levels and autism among Jordanian boys. J Autism Dev Disord 2019.
[http://dx.doi.org/10.1007/s10803-019-04017-w] [PMID: 30993503]
[68]
Erben RG, Soegiarto DW, Weber K, et al. Deletion of deoxyribonucleic acid binding domain of the vitamin D receptor abrogates genomic and nongenomic functions of vitamin D. Mol Endocrinol 2002; 16(7): 1524-37.
[http://dx.doi.org/10.1210/mend.16.7.0866] [PMID: 12089348]
[69]
Veenstra TD, Prüfer K, Koenigsberger C, Brimijoin SW, Grande JP, Kumar R. 1,25-Dihydroxyvitamin D3 receptors in the central nervous system of the rat embryo. Brain Res 1998; 804(2): 193-205.
[http://dx.doi.org/10.1016/S0006-8993(98)00565-4] [PMID: 9757035]
[70]
Shirazi HA, Rasouli J, Ciric B, Rostami A, Zhang GX. 1,25-Dihydroxyvitamin D3 enhances neural stem cell proliferation and oligodendrocyte differentiation. Exp Mol Pathol 2015; 98(2): 240-5.
[http://dx.doi.org/10.1016/j.yexmp.2015.02.004] [PMID: 25681066]
[71]
Chabas JF, Stephan D, Marqueste T, et al. Cholecalciferol (vitamin D3) improves myelination and recovery after nerve injury. PLoS One 2013; 8(5) e65034
[http://dx.doi.org/10.1371/journal.pone.0065034] [PMID: 23741446]
[72]
Neveu I, Naveilhan P, Baudet C, Brachet P, Metsis M. 1,25-dihydroxyvitamin D3 regulates NT-3, NT-4 but not BDNF mRNA in astrocytes. Neuroreport 1994; 6(1): 124-6.
[http://dx.doi.org/10.1097/00001756-199412300-00032] [PMID: 7703399]
[73]
Almeras L, Eyles D, Benech P, et al. Developmental vitamin D deficiency alters brain protein expression in the adult rat: implications for neuropsychiatric disorders. Proteomics 2007; 7(5): 769-80.
[http://dx.doi.org/10.1002/pmic.200600392] [PMID: 17295352]
[74]
Eyles DW, Burne TH, McGrath JJ. Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol 2013; 34(1): 47-64.
[http://dx.doi.org/10.1016/j.yfrne.2012.07.001] [PMID: 22796576]
[75]
Ali A, Cui X, Eyles D. Developmental vitamin D deficiency and autism: putative pathogenic mechanisms. J Steroid Biochem Mol Biol 2018; 175: 108-18.
[http://dx.doi.org/10.1016/j.jsbmb.2016.12.018] [PMID: 28027915]
[76]
Eyles D, Brown J, Mackay-Sim A, McGrath J, Feron F. Vitamin D3 and brain development. Neuroscience 2003; 118(3): 641-53.
[http://dx.doi.org/10.1016/S0306-4522(03)00040-X] [PMID: 12710973]
[77]
Pan P, Jin DH, Chatterjee-Chakraborty M, et al. The effects of vitamin D3 during pregnancy and lactation on offspring physiology and behavior in sprague-dawley rats. Dev Psychobiol 2014; 56(1): 12-22.
[http://dx.doi.org/10.1002/dev.21086] [PMID: 23129442]
[78]
Eyles DW, Rogers F, Buller K, et al. Developmental vitamin D (DVD) deficiency in the rat alters adult behaviour independently of HPA function. Psychoneuroendocrinology 2006; 31(8): 958-64.
[http://dx.doi.org/10.1016/j.psyneuen.2006.05.006] [PMID: 16890375]
[79]
Burne TH, O’Loan J, McGrath JJ, Eyles DW. Hyperlocomotion associated with transient prenatal vitamin D deficiency is ameliorated by acute restraint. Behav Brain Res 2006; 174(1): 119-24.
[http://dx.doi.org/10.1016/j.bbr.2006.07.015] [PMID: 16930734]
[80]
Burne TH, McGrath JJ, Eyles DW, Mackay-Sim A. Behavioural characterization of vitamin D receptor knockout mice. Behav Brain Res 2005; 157(2): 299-308.
[http://dx.doi.org/10.1016/j.bbr.2004.07.008] [PMID: 15639181]
[81]
Kalueff AV, Lou YR, Laaksi I, Tuohimaa P. Increased anxiety in mice lacking vitamin D receptor gene. Neuroreport 2004; 15(8): 1271-4.
[http://dx.doi.org/10.1097/01.wnr.0000129370.04248.92] [PMID: 15167547]
[82]
Minasyan A, Keisala T, Lou YR, Kalueff AV, Tuohimaa P. Neophobia, sensory and cognitive functions, and hedonic responses in vitamin D receptor mutant mice. J Steroid Biochem Mol Biol 2007; 104(3-5): 274-80.
[http://dx.doi.org/10.1016/j.jsbmb.2007.03.032] [PMID: 17482806]
[83]
Lam KS, Aman MG, Arnold LE. Neurochemical correlates of autistic disorder: a review of the literature. Res Dev Disabil 2006; 27(3): 254-89.
[http://dx.doi.org/10.1016/j.ridd.2005.03.003] [PMID: 16002261]
[84]
Polšek D, Jagatic T, Cepanec M, Hof PR, Simić G. Recent developments in neuropathology of autism spectrum disorders. Transl Neurosci 2011; 2(3): 256-64.
[http://dx.doi.org/10.2478/s13380-011-0024-3] [PMID: 22180840]
[85]
Obata K. Synaptic inhibition and γ-aminobutyric acid in the mammalian central nervous system. Proc Jpn Acad, Ser B, Phys Biol Sci 2013; 89(4): 139-56.
[http://dx.doi.org/10.2183/pjab.89.139] [PMID: 23574805]
[86]
Chez MG, Chang M, Krasne V, Coughlan C, Kominsky M, Schwartz A. Frequency of epileptiform EEG abnormalities in a sequential screening of autistic patients with no known clinical epilepsy from 1996 to 2005. Epilepsy Behav 2006; 8(1): 267-71.
[http://dx.doi.org/10.1016/j.yebeh.2005.11.001] [PMID: 16403678]
[87]
Spence SJ, Schneider MT. The role of epilepsy and epileptiform EEGs in autism spectrum disorders. Pediatr Res 2009; 65(6): 599-606.
[http://dx.doi.org/10.1203/PDR.0b013e31819e7168] [PMID: 19454962]
[88]
Lee E, Lee J, Kim E. Excitation/inhibition imbalance in animal models of autism spectrum disorders. Biol Psychiatry 2017; 81(10): 838-47.
[http://dx.doi.org/10.1016/j.biopsych.2016.05.011] [PMID: 27450033]
[89]
Uzunova G, Pallanti S, Hollander E. Excitatory/inhibitory imbalance in autism spectrum disorders: implications for interventions and therapeutics. World J Biol Psychiatry 2016; 17(3): 174-86.
[http://dx.doi.org/10.3109/15622975.2015.1085597] [PMID: 26469219]
[90]
Aldred S, Moore KM, Fitzgerald M, Waring RH. Plasma amino acid levels in children with autism and their families. J Autism Dev Disord 2003; 33(1): 93-7.
[http://dx.doi.org/10.1023/A:1022238706604] [PMID: 12708584]
[91]
Fatemi SH, Halt AR, Stary JM, Kanodia R, Schulz SC, Realmuto GR. Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices. Biol Psychiatry 2002; 52(8): 805-10.
[http://dx.doi.org/10.1016/S0006-3223(02)01430-0] [PMID: 12372652]
[92]
Groves NJ, Kesby JP, Eyles DW, McGrath JJ, Mackay-Sim A, Burne TH. Adult vitamin D deficiency leads to behavioural and brain neurochemical alterations in C57BL/6J and BALB/c mice. Behav Brain Res 2013; 241: 120-31.
[http://dx.doi.org/10.1016/j.bbr.2012.12.001] [PMID: 23238039]
[93]
Jiang P, Zhang LH, Cai HL, et al. Neurochemical effects of chronic administration of calcitriol in rats. Nutrients 2014; 6(12): 6048-59.
[http://dx.doi.org/10.3390/nu6126048] [PMID: 25533012]
[94]
Sikoglu EM, Navarro AA, Starr D, et al. Vitamin D3 supplemental treatment for mania in youth with bipolar spectrum disorders. J Child Adolesc Psychopharmacol 2015; 25(5): 415-24.
[http://dx.doi.org/10.1089/cap.2014.0110] [PMID: 26091195]
[95]
Barberis C, Tribollet E. Vasopressin and oxytocin receptors in the central nervous system. Crit Rev Neurobiol 1996; 10(1): 119-54.
[http://dx.doi.org/10.1615/CritRevNeurobiol.v10.i1.60] [PMID: 8853957]
[96]
Sofroniew MV, Weindl A, Schrell U, Wetzstein R. Immunohistochemistry of vasopressin, oxytocin and neurophysin in the hypothalamus and extrahypothalamic regions of the human and primate brain. Acta Histochem Suppl 1981; 24: 79-95.
[PMID: 6785843]
[97]
Stoop R. Neuromodulation by oxytocin and vasopressin in the central nervous system as a basis for their rapid behavioral effects. Curr Opin Neurobiol 2014; 29: 187-93.
[http://dx.doi.org/10.1016/j.conb.2014.09.012] [PMID: 25463629]
[98]
Yamasue H, Domes G. Oxytocin and autism spectrum disorders. Curr Top Behav Neurosci 2018; 35: 449-65.
[http://dx.doi.org/10.1007/7854_2017_24] [PMID: 28766270]
[99]
Modahl C, Green L, Fein D, et al. Plasma oxytocin levels in autistic children. Biol Psychiatry 1998; 43(4): 270-7.
[http://dx.doi.org/10.1016/S0006-3223(97)00439-3] [PMID: 9513736]
[100]
Andari E, Duhamel JR, Zalla T, Herbrecht E, Leboyer M, Sirigu A. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci USA 2010; 107(9): 4389-94.
[http://dx.doi.org/10.1073/pnas.0910249107] [PMID: 20160081]
[101]
Domes G, Kumbier E, Heinrichs M, Herpertz SC. Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome. Neuropsychopharmacology 2014; 39(3): 698-706.
[http://dx.doi.org/10.1038/npp.2013.254] [PMID: 24067301]
[102]
Hollander E, Novotny S, Hanratty M, et al. Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger’s disorders. Neuropsychopharmacology 2003; 28(1): 193-8.
[http://dx.doi.org/10.1038/sj.npp.1300021] [PMID: 12496956]
[103]
Prüfer K, Jirikowski GF. 1.25-Dihydroxyvitamin D3 receptor is partly colocalized with oxytocin immunoreactivity in neurons of the male rat hypothalamus. Cell Mol Biol 1997; 43(4): 543-8.
[PMID: 9220147]
[104]
Toell A, Polly P, Carlberg C. All natural DR3-type vitamin D response elements show a similar functionality in vitro. Biochem J 2000; 352(Pt 2): 301-9.
[http://dx.doi.org/10.1042/bj3520301] [PMID: 11085922]
[105]
Whitfield GK, Jurutka P, Haussler CA, et al. Nuclear Vitamin D Receptor: Structure-Function, Molecular Control of Gene Transcription, and Novel Bioactions In: Feldman D, Ed Vitamin D New York: Elsevier Inc 2005.
[106]
Muller CL, Anacker AMJ, Veenstra-VanderWeele J. The serotonin system in autism spectrum disorder: from biomarker to animal models. Neuroscience 2016; 321: 24-41.
[http://dx.doi.org/10.1016/j.neuroscience.2015.11.010] [PMID: 26577932]
[107]
Leboyer M, Philippe A, Bouvard M, et al. Whole blood serotonin and plasma beta-endorphin in autistic probands and their first-degree relatives. Biol Psychiatry 1999; 45(2): 158-63.
[http://dx.doi.org/10.1016/S0006-3223(97)00532-5] [PMID: 9951562]
[108]
Chugani DC, Muzik O, Behen M, et al. Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children. Ann Neurol 1999; 45(3): 287-95.
[http://dx.doi.org/10.1002/1531-8249(199903)45:3<287:AID-ANA3>3.0.CO;2-9] [PMID: 10072042]
[109]
Devlin B, Cook EH Jr, Coon H, et al. CPEA genetics network. Autism and the serotonin transporter: the long and short of it. Mol Psychiatry 2005; 10(12): 1110-6.
[http://dx.doi.org/10.1038/sj.mp.4001724] [PMID: 16103890]
[110]
McDougle CJ, Naylor ST, Cohen DJ, Volkmar FR, Heninger GR, Price LH. A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder. Arch Gen Psychiatry 1996; 53(11): 1001-8.
[http://dx.doi.org/10.1001/archpsyc.1996.01830110037005] [PMID: 8911223]
[111]
Maciag D, Simpson KL, Coppinger D, et al. Neonatal antidepressant exposure has lasting effects on behavior and serotonin circuitry. Neuropsychopharmacology 2006; 31(1): 47-57.
[http://dx.doi.org/10.1038/sj.npp.1300823] [PMID: 16012532]
[112]
Whitaker-Azmitia PM. Behavioral and cellular consequences of increasing serotonergic activity during brain development: a role in autism? Int J Dev Neurosci 2005; 23(1): 75-83.
[http://dx.doi.org/10.1016/j.ijdevneu.2004.07.022] [PMID: 15730889]
[113]
Patrick RP, Ames BN. Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism. FASEB J 2014; 28(6): 2398-413.
[http://dx.doi.org/10.1096/fj.13-246546] [PMID: 24558199]
[114]
Pizzorno JGlutathione. Integr Med (Encinitas) 2014; 13(1): 8-12.
[PMID: 26770075]
[115]
Jones DP. Extracellular redox state: refining the definition of oxidative stress in aging. Rejuvenation Res 2006; 9(2): 169-81.
[http://dx.doi.org/10.1089/rej.2006.9.169] [PMID: 16706639]
[116]
James SJ, Melnyk S, Fuchs G, et al. Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am J Clin Nutr 2009; 89(1): 425-30.
[http://dx.doi.org/10.3945/ajcn.2008.26615] [PMID: 19056591]
[117]
James SJ, Melnyk S, Jernigan S, et al. Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet 2006; 141B(8): 947-56.
[http://dx.doi.org/10.1002/ajmg.b.30366] [PMID: 16917939]
[118]
Essa MM, Guillemin GJ, Waly MI, et al. Increased markers of oxidative stress in autistic children of the Sultanate of Oman. Biol Trace Elem Res 2012; 147(1-3): 25-7.
[http://dx.doi.org/10.1007/s12011-011-9280-x] [PMID: 22127832]
[119]
James SJ, Cutler P, Melnyk S, et al. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr 2004; 80(6): 1611-7.
[http://dx.doi.org/10.1093/ajcn/80.6.1611] [PMID: 15585776]
[120]
Rose S, Melnyk S, Pavliv O, et al. Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Transl Psychiatry 2012; 2(7): e134-4.
[http://dx.doi.org/10.1038/tp.2012.61] [PMID: 22781167]
[121]
Chen KB, Lin AM, Chiu TH. Systemic vitamin D3 attenuated oxidative injuries in the locus coeruleus of rat brain. Ann N Y Acad Sci 2003; 993: 313-24.
[http://dx.doi.org/10.1111/j.1749-6632.2003.tb07539.x] [PMID: 12853323]
[122]
Lin AM, Fan SF, Yang DM, Hsu LL, Yang CH. Zinc-induced apoptosis in substantia nigra of rat brain: neuroprotection by vitamin D3. Free Radic Biol Med 2003; 34(11): 1416-25.
[http://dx.doi.org/10.1016/S0891-5849(03)00105-9] [PMID: 12757852]
[123]
Garcion E, Thanh XD, Bled F, et al. 1,25-Dihydroxyvitamin D3 regulates gamma 1 transpeptidase activity in rat brain. Neurosci Lett 1996; 216(3): 183-6.
[http://dx.doi.org/10.1016/0304-3940(96)87802-5] [PMID: 8897488]
[124]
Halicka HD, Zhao H, Li J, Traganos F, Studzinski GP, Darzynkiewicz Z. Attenuation of constitutive DNA damage signaling by 1,25-dihydroxyvitamin D3. Aging (Albany NY) 2012; 4(4): 270-8.
[http://dx.doi.org/10.18632/aging.100450] [PMID: 22498490]
[125]
Garcion E, Sindji L, Leblondel G, Brachet P, Darcy F. 1,25-dihydroxyvitamin D3 regulates the synthesis of gamma-glutamyl transpeptidase and glutathione levels in rat primary astrocytes. J Neurochem 1999; 73(2): 859-66.
[http://dx.doi.org/10.1046/j.1471-4159.1999.0730859.x] [PMID: 10428085]
[126]
Garcion E, Sindji L, Montero-Menei C, Andre C, Brachet P, Darcy F. Expression of inducible nitric oxide synthase during rat brain inflammation: regulation by 1,25-dihydroxyvitamin D3. Glia 1998; 22(3): 282-94.
[http://dx.doi.org/10.1002/(SICI)1098-1136(199803)22:3<282:AID-GLIA7>3.0.CO;2-7] [PMID: 9482214]
[127]
Ibi M, Sawada H, Nakanishi M, et al. Protective effects of 1 alpha,25-(OH)(2)D(3) against the neurotoxicity of glutamate and reactive oxygen species in mesencephalic culture. Neuropharmacology 2001; 40(6): 761-71.
[http://dx.doi.org/10.1016/S0028-3908(01)00009-0] [PMID: 11369030]
[128]
Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D. New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab 2002; 13(3): 100-5.
[http://dx.doi.org/10.1016/S1043-2760(01)00547-1] [PMID: 11893522]
[129]
Gottfried C, Bambini-Junior V, Francis F, Riesgo R, Savino W. The impact of neuroimmune alterations in autism spectrum disorder. Front Psychiatry 2015; 6: 121.
[http://dx.doi.org/10.3389/fpsyt.2015.00121] [PMID: 26441683]
[130]
Atladóttir HO, Pedersen MG, Thorsen P, et al. Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics 2009; 124(2): 687-94.
[http://dx.doi.org/10.1542/peds.2008-2445] [PMID: 19581261]
[131]
Ashwood P, Van de Water J. Is autism an autoimmune disease? Autoimmun Rev 2004; 3(7-8): 557-62.
[http://dx.doi.org/10.1016/j.autrev.2004.07.036] [PMID: 15546805]
[132]
Mostafa GA, Al-Ayadhi LY. The possible relationship between allergic manifestations and elevated serum levels of brain specific auto-antibodies in autistic children. J Neuroimmunol 2013; 261(1-2): 77-81.
[http://dx.doi.org/10.1016/j.jneuroim.2013.04.003] [PMID: 23726766]
[133]
Mostafa GA, Al-Ayadhi LY. Increased serum levels of anti-ganglioside M1 auto-antibodies in autistic children: relation to the disease severity. J Neuroinflammation 2011; 8: 39.
[http://dx.doi.org/10.1186/1742-2094-8-39] [PMID: 21513576]
[134]
Enstrom AM, Onore CE, Van de Water JA, Ashwood P. Differential monocyte responses to TLR ligands in children with autism spectrum disorders. Brain Behav Immun 2010; 24(1): 64-71.
[http://dx.doi.org/10.1016/j.bbi.2009.08.001] [PMID: 19666104]
[135]
Sweeten TL, Posey DJ, McDougle CJ. High blood monocyte counts and neopterin levels in children with autistic disorder. Am J Psychiatry 2003; 160(9): 1691-3.
[http://dx.doi.org/10.1176/appi.ajp.160.9.1691] [PMID: 12944347]
[136]
Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Van de Water J. Altered T cell responses in children with autism. Brain Behav Immun 2011; 25(5): 840-9.
[http://dx.doi.org/10.1016/j.bbi.2010.09.002] [PMID: 20833247]
[137]
Gupta S, Aggarwal S, Rashanravan B, Lee T. Th1- and Th2-like cytokines in CD4+ and CD8+ T cells in autism. J Neuroimmunol 1998; 85(1): 106-9.
[http://dx.doi.org/10.1016/S0165-5728(98)00021-6] [PMID: 9627004]
[138]
Ahmad SF, Zoheir KMA, Ansari MA, et al. Dysregulation of Th1, Th2, Th17, and T regulatory cell-related transcription factor signaling in children with autism. Mol Neurobiol 2017; 54(6): 4390-400.
[http://dx.doi.org/10.1007/s12035-016-9977-0] [PMID: 27344332]
[139]
Alzghoul L, Abdelhamid SS, Yanis AH, Qwaider YZ, Aldahabi M, Albdour SA. The association between levels of inflammatory markers in autistic children compared to their unaffected siblings and unrelated healthy controls. Turk J Med Sci 2019; 49(4): 1047-53.
[http://dx.doi.org/10.3906/sag-1812-167] [PMID: 31269787]
[140]
Meltzer A, Van de Water J. The role of the immune system in autism spectrum disorder. Neuropsychopharmacology 2017; 42(1): 284-98.
[http://dx.doi.org/10.1038/npp.2016.158] [PMID: 27534269]
[141]
Delvin E, Souberbielle JC, Viard JP, Salle B. Role of vitamin D in acquired immune and autoimmune diseases. Crit Rev Clin Lab Sci 2014; 51(4): 232-47.
[http://dx.doi.org/10.3109/10408363.2014.901291] [PMID: 24813330]
[142]
Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients 2013; 5(7): 2502-21.
[http://dx.doi.org/10.3390/nu5072502] [PMID: 23857223]
[143]
Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D: modulator of the immune system. Curr Opin Pharmacol 2010; 10(4): 482-96.
[http://dx.doi.org/10.1016/j.coph.2010.04.001] [PMID: 20427238]
[144]
Zeitelhofer M, Adzemovic MZ, Gomez-Cabrero D, et al. Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 2017; 114(9): E1678-87.
[http://dx.doi.org/10.1073/pnas.1615783114] [PMID: 28196884]
[145]
Maddur MS, Miossec P, Kaveri SV, Bayry J. Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies. Am J Pathol 2012; 181(1): 8-18.
[http://dx.doi.org/10.1016/j.ajpath.2012.03.044] [PMID: 22640807]
[146]
Dankers W, Colin EM, van Hamburg JP, Lubberts E. Vitamin D in autoimmunity: molecular mechanisms and therapeutic potential. Front Immunol 2017; 7: 697-7.
[http://dx.doi.org/10.3389/fimmu.2016.00697] [PMID: 28163705]
[147]
Lee GR. The Balance of Th17 versus Treg Cells in Autoimmunity. Int J Mol Sci 2018; 19(3): 730.
[http://dx.doi.org/10.3390/ijms19030730] [PMID: 29510522]
[148]
Hirahara K, Nakayama T. CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm. Int Immunol 2016; 28(4): 163-71.
[http://dx.doi.org/10.1093/intimm/dxw006] [PMID: 26874355]
[149]
Edmiston E, Ashwood P, Van de Water J. Autoimmunity, autoantibodies, and autism spectrum disorder. Biol Psychiatry 2017; 81(5): 383-90.
[http://dx.doi.org/10.1016/j.biopsych.2016.08.031] [PMID: 28340985]
[150]
Hughes HK, Mills Ko E, Rose D, Ashwood P. Immune dysfunction and autoimmunity as pathological mechanisms in autism spectrum disorders. Front Cell Neurosci 2018; 12(405): 405.
[http://dx.doi.org/10.3389/fncel.2018.00405] [PMID: 30483058]
[151]
Al-Ayadhi LY, Mostafa GA. Elevated serum levels of interleukin-17A in children with autism. J Neuroinflammation 2012; 9: 158-8.
[http://dx.doi.org/10.1186/1742-2094-9-158] [PMID: 22748016]
[152]
Enstrom A, Onore C, Hertz-Picciotto I, et al. Detection of IL-17 and IL-23 in plasma samples of children with autism. Am J Biochem Biotechnol 2008; 4(2): 114-20.
[http://dx.doi.org/10.3844/ajbbsp.2008.114.120] [PMID: 27688738]
[153]
Joshi S, Pantalena LC, Liu XK, et al. 1,25-dihydroxyvitamin D(3) ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Mol Cell Biol 2011; 31(17): 3653-69.
[http://dx.doi.org/10.1128/MCB.05020-11] [PMID: 21746882]
[154]
Edfeldt K, Liu PT, Chun R, et al. T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism. Proc Natl Acad Sci USA 2010; 107(52): 22593-8.
[http://dx.doi.org/10.1073/pnas.1011624108] [PMID: 21149724]
[155]
Loser K, Beissert S. Regulation of cutaneous immunity by the environment: an important role for UV irradiation and vitamin D. Int Immunopharmacol 2009; 9(5): 587-9.
[http://dx.doi.org/10.1016/j.intimp.2009.01.024] [PMID: 19539561]
[156]
Jia F, Wang B, Shan L, Xu Z, Staal WG, Du L. Core symptoms of autism improved after vitamin D supplementation. Pediatrics 2015; 135(1): e196-8.
[http://dx.doi.org/10.1542/peds.2014-2121] [PMID: 25511123]
[157]
Jia F, Shan L, Wang B, et al. Fluctuations in clinical symptoms with changes in serum 25(OH) vitamin D levels in autistic children: Three cases report. Nutr Neurosci 2018; 1-4.
[PMID: 29629638]
[158]
Bent S, Ailarov A, Dang KT, Widjaja F, Lawton BL, Hendren RL. Open-label trial of vitamin D3 supplementation in children with autism spectrum disorder. J Altern Complement Med 2017; 23(5): 394-5.
[http://dx.doi.org/10.1089/acm.2016.0297] [PMID: 28437142]
[159]
Ucuz İİ, Dursun OB, Esin IS, et al. The relationship between Vitamin D, autistic spectrum disorders, and cognitive development: do glial cell line-derived neurotrophic factor and nerve growth factor play a role in this relationship? Int J Dev Disabil 2015; 61(4): 222-30.
[http://dx.doi.org/10.1179/2047387714Y.0000000054]
[160]
Azzam HME, Sayyah H, Youssef S, et al. Autism and vitamin D: an intervention study. MECPsych 2015; 22(1): 9-14.
[http://dx.doi.org/10.1097/01.XME.0000457269.05570.78]
[161]
Kerley CP, Power C, Gallagher L, Coghlan D. Lack of effect of vitamin D3 supplementation in autism: a 20-week, placebo-controlled RCT. Arch Dis Child 2017; 102(11): 1030-6.
[http://dx.doi.org/10.1136/archdischild-2017-312783] [PMID: 28626020]
[162]
Vuillermot S, Luan W, Meyer U, Eyles D. Vitamin D treatment during pregnancy prevents autism-related phenotypes in a mouse model of maternal immune activation. Mol Autism 2017; 8: 9.
[http://dx.doi.org/10.1186/s13229-017-0125-0] [PMID: 28316773]
[163]
Stubbs G, Henley K, Green J. Autism: will vitamin D supplementation during pregnancy and early childhood reduce the recurrence rate of autism in newborn siblings? Med Hypotheses 2016; 88: 74-8.
[http://dx.doi.org/10.1016/j.mehy.2016.01.015] [PMID: 26880644]

Rights & Permissions Print Cite
Article Metrics
37
3
© 2024 Bentham Science Publishers | Privacy Policy