维生素D在孤独症谱系障碍发病机制中的作用研究进展

刘姿镃; 金宇

doi:10.16835/j.cnki.1000-9817.2025054

维生素D在孤独症谱系障碍发病机制中的作用研究进展

doi: 10.16835/j.cnki.1000-9817.2025054

刘姿镃,
金宇^,

中山大学公共卫生学院妇幼卫生学系/儿童青少年心理行为发育研究中心，广东广州 510080

基金项目:

广东省自然科学基金项目 2023A1515012442

详细信息

作者简介:
刘姿镃(1998-)，女，云南省人，在读硕士，主要研究方向为儿童孤独症谱系障碍

通讯作者:
金宇，E-mail: jinyu@mail.sysu.edu.cn

利益冲突声明 所有作者声明无利益冲突。
中图分类号: R591.44 R748 B844.1
计量
- 文章访问数: 83
- HTML全文浏览量: 43
- PDF下载量: 17
- 被引次数: 0
出版历程
- 收稿日期: 2024-10-18
- 修回日期: 2025-01-12
- 网络出版日期: 2025-03-05
- 刊出日期: 2025-02-25

Research progress on the pathogenesis of vitamin D in autism spectrum disorder

LIU Zizi,
JIN Yu^,

Department of Maternal and Child Health/Research Center of Child and Adolescent Psychological and Behavioral Development, School of Public Health, Sun Yat-sen University, Guangzhou (510080), Guangdong Province, China

摘要

摘要: 为从新的视角探讨孤独症谱系障碍(ASD)的发病机制，研究通过文献整理发现维生素D(Vit D)可能通过抑制儿童早期大脑过度生长、调节中枢神经系统代谢，调节免疫、抗炎及影响基因组稳定对ASD的发生发展产生重要作用。对ASD人群进行Vit D补充发现可改善相关症状，然而至今Vit D对ASD的作用机制尚不明确，Vit D治疗对ASD的症状改善结果也因样本量、检测方法、剂量及混杂因素等原因尚存争议。未来可通过进一步多中心、大样本的随机对照试验和Vit D缺乏的ASD动物模型探索Vit D在ASD发病和治疗中的具体作用，为ASD早发现、早干预、早治疗提供可靠的证据。
- 维生素D /
- 孤独性障碍 /
- 研究 /
- 儿童
Abstract: In order to explore the pathogenesis of autism spectrum disorder (ASD) from a new perspective, it is found through literature review that vitamin D(Vit D) may play a significant role in the onset and development of ASD by inhibiting early brain overgrowth, regulating metabolism of central nervous system, modulating immune responses, reducing inflammation and influencing genome stability. Furthermore, Vit D supplementation in individuals with ASD has shown to alleviate symptoms. However, the mechanisms by which Vit D affects ASD remains unclear, and the effectiveness of Vit D treatment in improving ASD symptoms remains controversial due to variations in sample sizes, detection methods, dosage and confounding factors. Future research needs to focus on multi-center, large-scale randomized controlled trials and ASD animal models with Vit D deficiency to further explore the specific role of Vit D in the pathogenesis and treatment of ASD, which could provide reliable evidence for the early detection, intervention and treatment of ASD.
- Vitamin D /
- Autistic disorder /
- Research /
- Child
注释:

1) 利益冲突声明 所有作者声明无利益冲突。

HTML全文

参考文献(48)

[1]	LORD C, ELSABBAGH M, BAIRD G, et al. Autism spectrum disorder[J]. Lancet, 2018, 392(10146): 508-520. doi: 10.1016/S0140-6736(18)31129-2
[2]	Global Burden of Disease Study 2021 Autism Spectrum Collaborators. The global epidemiology and health burden of the autism spectrum: findings from the Global Burden of Disease Study 2021[J]. Lancet Psychiatry, 2025, 12(2): 111-121. doi: 10.1016/S2215-0366(24)00363-8
[3]	JIANG X, CHEN X, SU J, et al. Prevalence of autism spectrum disorder in mainland China over the past 6 years: a systematic review and Meta-analysis[J]. BMC Psychiatry, 2024, 24(1): 404. doi: 10.1186/s12888-024-05729-9
[4]	HARRIS J. Leo kanner and autism: a 75-year perspective[J]. Int Rev Psychiatry, 2018, 30(1): 3-17. doi: 10.1080/09540261.2018.1455646
[5]	MASINI E, LOI E, VEGA-BENEDETTI A F, et al. An overview of the main genetic, epigenetic and environmental factors involved in autism spectrum disorder focusing on synaptic activity[J]. Int J Mol Sci, 2020, 21(21): 8290. doi: 10.3390/ijms21218290
[6]	ABDELKADER A, ALRADINI F, ALOSAIMI A, et al. Unveiling the influences of prenatal and maternal factors on the journey of an autistic child[J]. Front Psychiatry, 2024, 15: 1467821. doi: 10.3389/fpsyt.2024.1467821
[7]	PERETTI S, MARIANO M, MAZZOCCHETTI C, et al. Diet: the keystone of autism spectrum disorder?[J]. Nutr Neurosci, 2019, 22(12): 825-839. doi: 10.1080/1028415X.2018.1464819
[8]	ALTUN H, KURUTAŞ E B, ŞAHIN N, et al. The levels of vitamin D, vitamin D receptor, homocysteine and complex B vitamin in children with autism spectrum disorders[J]. Clin Psychopharmacol Neurosci, 2018, 16(4): 383-390. doi: 10.9758/cpn.2018.16.4.383
[9]	GARCÍA-SERNA A M, MORALES E. Neurodevelopmental effects of prenatal vitamin D in humans: systematic review and Meta-analysis[J]. Mol Psychiatry, 2020, 25(10): 2468-2481. doi: 10.1038/s41380-019-0357-9
[10]	BROUWER-BROLSMA E M, VRIJKOTTE T G M, FESKENS E J M. Maternal vitamin D concentrations are associated with faster childhood reaction time and response speed, but not with motor fluency and flexibility, at the age of 5-6 years: the Amsterdam born children and their development (ABCD) study[J]. Br J Nutr, 2018, 120(3): 345-352. doi: 10.1017/S0007114518001319
[11]	CHIEN M C, HUANG C Y, WANG J H, et al. Effects of vitamin D in pregnancy on maternal and offspring health-related outcomes: an umbrella review of systematic review and Meta-analyses[J]. Nutr Diabetes, 2024, 14(1): 35. doi: 10.1038/s41387-024-00296-0
[12]	SASS L, VINDING R K, STOKHOLM J, et al. High-dose vitamin D supplementation in pregnancy and neurodevelopment in childhood: a prespecified secondary analysis of a randomized clinical trial[J]. JAMA Netw Open, 2020, 3(12): e2026018. doi: 10.1001/jamanetworkopen.2020.26018
[13]	ARASTOO A A, KHOJASTEHKIA H, RAHIMI Z, et al. Evaluation of serum 25-hydroxy vitamin D levels in children with autism spectrum disorder[J]. Ital J Pediatr, 2018, 44(1): 150. doi: 10.1186/s13052-018-0587-5
[14]	ZHANG M, WU Y, LU Z, et al. Effects of vitamin D supplementation on children with autism spectrum disorder: a systematic review and Meta-analysis[J]. Clin Psychopharmacol Neurosci, 2023, 21(2): 240-251. doi: 10.9758/cpn.2023.21.2.240
[15]	CUI J, ZHAI Z, WANG S, et al. The role and impact of abnormal vitamin levels in autism spectrum disorders[J]. Food Funct, 2024, 15(3): 1099-1115. doi: 10.1039/D3FO03735E
[16]	YE X, ZHOU Q, REN P, et al. The synaptic and circuit functions of vitamin D in neurodevelopment disorders[J]. Neuropsychiatr Dis Treat, 2023, 19: 1515-1530. doi: 10.2147/NDT.S407731
[17]	SAILIKE B, ONZHANOVA Z, AKBAY B, et al. Vitamin D in central nervous system: implications for neurological disorders[J]. Int J Mol Sci, 2024, 25(14): 7809. doi: 10.3390/ijms25147809
[18]	LO C S, KIANG K M, LEUNG G K. Anti-tumor effects of vitamin D in glioblastoma: mechanism and therapeutic implications[J]. Lab Invest, 2022, 102(2): 118-125. doi: 10.1038/s41374-021-00673-8
[19]	RAHDAR M, DAVOUDI S, DEHGHAN S, et al. Reversal of electrophysiological and behavioral deficits mediated by 5-HT7 receptor upregulation following LP-211 treatment in an autistic-like rat model induced by prenatal valproic acid exposure[J]. Neuropharmacology, 2024, 257: 110057. doi: 10.1016/j.neuropharm.2024.110057
[20]	DEMAYO M M, HARRIS A D, SONG Y J C, et al. Age-related parietal GABA alterations in children with autism spectrum disorder[J]. Autism Res, 2021, 14(5): 859-872. doi: 10.1002/aur.2487
[21]	MAROTTA R, RISOLEO M C, MESSINA G, et al. The neurochemistry of autism[J]. Brain Sci, 2020, 10(3): 163. doi: 10.3390/brainsci10030163
[22]	KASATKINA L A, TARASENKO A S, KRUPKO O O, et al. Vitamin D deficiency induces the excitation/inhibition brain imbalance and the proinflammatory shift[J]. Int J Biochem Cell Biol, 2020, 119: 105665. doi: 10.1016/j.biocel.2019.105665
[23]	PIZZELLA A, PENNA E, LIU Y, et al. Alterations of synaptic plasticity in Angelman syndrome model mice are rescued by 5-HT7R stimulation[J]. Prog Neurobiol, 2024, 242: 102684. doi: 10.1016/j.pneurobio.2024.102684
[24]	PATRICK R P, AMES B N. Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism[J]. Faseb J, 2014, 28(6): 2398-2413. doi: 10.1096/fj.13-246546
[25]	DE MARZIO M, LASKY-SU J, CHU S H, et al. The metabolic role of vitamin D in children's neurodevelopment: a network study[J]. Sci Rep, 2024, 14(1): 16929. doi: 10.1038/s41598-024-67835-8
[26]	APARECIDA NEDEL PERTILE R, KILTSCHEWSKIJ D, GEAGH-AN M, et al. Developmental vitamin D-deficiency increases the expression of microRNAs involved in dopamine neuron development[J]. Brain Res, 2022, 1789: 147953. doi: 10.1016/j.brainres.2022.147953
[27]	DICARLO G E, WALLACE M T. Modeling dopamine dysfunction in autism spectrum disorder: from invertebrates to vertebrates[J]. Neurosci Biobehav Rev, 2022, 133: 104494. doi: 10.1016/j.neubiorev.2021.12.017
[28]	TORDJMAN S, CHARRIER A, KAZATCHKINE M, et al. Natural IgG anti-f (ab')(2) autoantibody activity in children with autism[J]. Biomedicines, 2023, 11(3): 715. doi: 10.3390/biomedicines11030715
[29]	LONG J, DANG H, SU W, et al. Interactions between circulating inflammatory factors and autism spectrum disorder: a bidirectional Mendelian randomization study in European population[J]. Front Immunol, 2024, 15: 1370276. doi: 10.3389/fimmu.2024.1370276
[30]	EL-SHARKAWY A, MALKI A. Vitamin D signaling in inflammation and cancer: molecular mechanisms and therapeutic implications[J]. Molecules, 2020, 25(14): 3219. doi: 10.3390/molecules25143219
[31]	SASSI F, TAMONE C, D'AMELIO P. Vitamin D: nutrient, hormone, and immunomodulator[J]. Nutrients, 2018, 10(11): 1656. doi: 10.3390/nu10111656
[32]	VUILLERMOT S, LUAN W, MEYER U, et al. Vitamin D treatment during pregnancy prevents autism-related phenotypes in a mouse model of maternal immune activation[J]. Mol Autism, 2017, 8: 9. doi: 10.1186/s13229-017-0125-0
[33]	BJØRKLUND G, MEGUID N A, EL-BANA M A, et al. Oxidative stress in autism spectrum disorder[J]. Mol Neurobiol, 2020, 57(5): 2314-2332. doi: 10.1007/s12035-019-01742-2
[34]	ERDOGAN M A, NESIL P, ALTUNTAS I, et al. Amelioration of propionic acid-induced autism spectrum disorder in rats through dapagliflozin: the role of IGF-1/IGFBP-3 and the Nrf2 antioxidant pathway[J]. Neuroscience, 2024, 554: 16-25. doi: 10.1016/j.neuroscience.2024.07.013
[35]	ABDOU H M, SAAD A M, ABD ELKADER H A E, et al. Role of vitamin D(3) in mitigating sodium arsenite-induced neurotoxicity in male rats[J]. Toxicol Res (Camb), 2024, 13(6): tfae203. doi: 10.1093/toxres/tfae203
[36]	DELUCA H F. Vitamin D: historical overview[J]. Vitam Horm, 2016, 100: 1-20.
[37]	SAECHUA C, SARACHANA T, CHONCHAIYA W, et al. Impact of gene polymorphisms involved in the vitamin D metabolic pathway on the susceptibility to and severity of autism spectrum disorder[J]. Sci Rep, 2024, 14(1): 28333. doi: 10.1038/s41598-024-79994-9
[38]	ZHANG Z, LIU J, JIANG G, et al. Vitamin D receptor gene variants and serum vitamin D in childhood autism spectrum disorder[J]. Mol Biol Rep, 2022, 49(10): 9481-9488. doi: 10.1007/s11033-022-07829-9
[39]	JEON S M, SHIN E A. Exploring vitamin D metabolism and function in cancer[J]. Exp Mol Med, 2018, 50(4): 1-14.
[40]	ONG L T C, BOOTH D R, PARNELL G P. Vitamin D and its effects on DNA methylation in development, aging, and disease[J]. Mol Nutr Food Res, 2020, 64(23): e2000437. doi: 10.1002/mnfr.202000437
[41]	SAAD K, ABDEL-RAHMAN A A, ELSEROGY Y M, et al. Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children[J]. Nutr Neurosci, 2016, 19(8): 346-351. doi: 10.1179/1476830515Y.0000000019
[42]	MORADI H, SOHRABI M, TAHERI H, et al. Comparison of the effects of perceptual-motor exercises, vitamin D supplementation and the combination of these interventions on decreasing stereotypical behavior in children with autism disorder[J]. Int J Dev Disabil, 2018, 66(2): 122-132.
[43]	PRINCIPI N, ESPOSITO S. Vitamin D deficiency during pregnancy and autism spectrum disorders development[J]. Front Psychiatry, 2019, 10: 987. doi: 10.3389/fphys.2019.00987
[44]	MAZAHERY H, CONLON C A, BECK K L, et al. Inflammation (IL-1β) modifies the effect of vitamin D and Omega-3 long chain polyunsaturated fatty acids on core symptoms of autism spectrum disorder: an exploratory pilot study[J]. Nutrients, 2020, 12(3): 661. doi: 10.3390/nu12030661
[45]	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[J]. Nutr Neurosci, 2019, 22(12): 863-866. doi: 10.1080/1028415X.2018.1458421
[46]	FENG J, SHAN L, DU L, et al. Clinical improvement following vitamin D3 supplementation in autism spectrum disorder[J]. Nutr Neurosci, 2017, 20(5): 284-290. doi: 10.1080/1028415X.2015.1123847
[47]	LI B, XU Y, ZHANG X, et al. The effect of vitamin D supplementation in treatment of children with autism spectrum disorder: a systematic review and Meta-analysis of randomized controlled trials[J]. Nutr Neurosci, 2022, 25(4): 835-845. doi: 10.1080/1028415X.2020.1815332
[48]	程爽, 熊振芳, 蔡艺, 等. 维生素D治疗孤独症谱系障碍患儿疗效及安全性的Meta分析[J]. 药物流行病学杂志, 2021, 30(12): 801-805, 826. CHENG S, XIONG Z F, CAI Y, et al. Meta-analysis on the efficacy and safety of vitamin D therapy on children with autism spectrum disorder[J]. Chin J Pharmac Epidemiol, 2021, 30(12): 801-805, 826. (in Chinese)