北京大学学报(医学版) ›› 2025, Vol. 57 ›› Issue (2): 277-283. doi: 10.19723/j.issn.1671-167X.2025.02.009
徐新杰1, 蔡小娥2, 孟凡超3, 龙波1, 尤欣4, 张嵘5,*(
)
Xinjie XU1, Xiaoe CAI2, Fanchao MENG3, Bo LONG1, Xin YOU4, Rong ZHANG5,*(
)
摘要:
目的: 比较孤独症儿童与健康儿童血浆中缬氨酸水平的差异, 并探究孤独症儿童血浆缬氨酸水平与其发育商评分的相关性。方法: 共招募29例孤独症儿童作为病例组, 同期招募30例同年龄段的正常儿童作为对照组。采用儿童孤独症评定量表(childhood autism rating scale, CARS)对孤独症儿童的核心症状及其严重程度进行评估, 采用Gesell发育量表(Gesell developmental schedules, GDS)评估儿童发育商, 采用高效液相色谱-串联质谱法测定血浆缬氨酸水平, 并比较两组间差异, 分析病例组儿童血浆缬氨酸水平与其发育商评分间的相关性。结果: 与对照组相比, 孤独症组血浆缬氨酸水平显著偏低, 差异有统计学意义(P<0.05)。在GDS量表因子得分方面, 孤独症组儿童在适应性、大运动、精细运动、语言、个人-社交等方面的得分均显著低于对照组儿童, 差异均有统计学意义(P<0.000 1)。孤独症组儿童血浆缬氨酸水平与GDS量表中的精细运动评分(r=0.441, P<0.05)和个人-社交评分(r=0.437, P<0.05)均呈显著正相关, 但与适应性、大运动和语言方面的评分无显著相关(P>0.05)。根据CARS量表评分标准, 将孤独症组儿童根据病情严重程度分为轻中度和重度两个亚组, 在亚组之间进行比较发现, 重度孤独症儿童在GDS量表适应性、精细运动、语言以及个人-社交方面的评分均显著低于轻中度孤独症儿童(P<0.05), 而两个亚组之间在GDS量表大运动评分及血浆缬氨酸水平方面差异均无统计学意义(P>0.05)。结论: 孤独症儿童血浆中缬氨酸水平偏低, 且与其精细运动和个人-社交功能之间存在一定关联。
中图分类号:
| 1 | González MC , Vásquez M , Hernández-Chávez M . Autism spectrum disorder: Clinical diagnosis and ADOS test[J]. Rev Chil Pediatr, 2019, 90 (5): 485- 491. |
| 2 |
Maenner MJ , Shaw KA , Baio J , et al. Prevalence of autism spectrum disorder among children aged 8 years: Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2016[J]. MMWR Surveill Summ, 2020, 69 (4): 1- 12.
doi: 10.15585/mmwr.ss6904a1 |
| 3 |
Zhou H , Xu X , Yan W , et al. Prevalence of autism spectrum disorder in China: A nationwide multi-center population-based study among children aged 6 to 12 years[J]. Neurosci Bull, 2020, 36 (9): 961- 971.
doi: 10.1007/s12264-020-00530-6 |
| 4 |
樊越波, 揭晓锋, 邹小兵. 孤独症患病率回顾[J]. 中国儿童保健杂志, 2008, 16 (4): 439- 440.
doi: 10.3969/j.issn.1008-6579.2008.04.029 |
| 5 |
Croen LA , Zerbo O , Qian Y , et al. The health status of adults on the autism spectrum[J]. Autism, 2015, 19 (7): 814- 823.
doi: 10.1177/1362361315577517 |
| 6 | 赵刚, 韦明, 鄂颖梅, 等. 孤独症谱系障碍儿童饮食行为与家长喂养行为的相关研究[J]. 沈阳医学院学报, 2020, 22 (5): 428- 432. |
| 7 | Ghanizadeh A . Increased glutamate and homocysteine and decreased glutamine levels in autism: A review and strategies for future studies of amino acids in autism[J]. Dis Markers, 2013, 35 (5): 281- 286. |
| 8 | National Center for Biotechnology Information (2024). PubChem compound summary for CID 6287, valine[EB/OL]. [2021-03-08] https://pubchem.ncbi.nlm.nih.gov/compound/Valine. |
| 9 |
Maynard TM , Manzini MC . Balancing act: Maintaining amino acid levels in the autistic brain[J]. Neuron, 2017, 93 (3): 476- 479.
doi: 10.1016/j.neuron.2017.01.015 |
| 10 |
Tǎrlungeanu DC , Deliu E , Dotter CP , et al. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder[J]. Cell, 2016, 167 (6): 1481- 1494.e18.
doi: 10.1016/j.cell.2016.11.013 |
| 11 |
Smith AM , King JJ , West PR , et al. Amino acid dysregulation metabotypes: Potential biomarkers for diagnosis and individualized treatment for subtypes of autism spectrum disorder[J]. Biol Psychiatry, 2019, 85 (4): 345- 354.
doi: 10.1016/j.biopsych.2018.08.016 |
| 12 |
Sperringer JE , Addington A , Hutson SM . Branched-chain amino acids and brain metabolism[J]. Neurochem Res, 2017, 42 (6): 1697- 1709.
doi: 10.1007/s11064-017-2261-5 |
| 13 | 王强. Gesell发育量表对2岁以内孤独症谱系障碍(ASD)患儿的应用效果观察[J]. 世界最新医学信息文摘(连续型电子期刊), 2020, 20 (33): 61- 62. |
| 14 |
Larsson SC , Markus HS . Branched-chain amino acids and Alzheimer's disease: A Mendelian randomization analysis[J]. Sci Rep, 2017, 7 (1): 13604.
doi: 10.1038/s41598-017-12931-1 |
| 15 |
Bjerkenstedt L , Edman G , Hagenfeldt L , et al. Plasma amino acids in relation to cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy controls[J]. Br J Psychiatry, 1985, 147, 276- 282.
doi: 10.1192/bjp.147.3.276 |
| 16 | Tu WJ , Chen H , He J . Application of LC-MS/MS analysis of plasma amino acids profiles in children with autism[J]. J Clin Biochem Nutr, 2012, 51 (3): 248- 249. |
| 17 |
Arnold GL , Hyman SL , Mooney RA , et al. Plasma amino acids profiles in children with autism: Potential risk of nutritional deficiencies[J]. J Autism Dev Disord, 2003, 33 (4): 449- 454.
doi: 10.1023/A:1025071014191 |
| 18 |
Witters P , Debbold E , Crivelly K , et al. Autism in patients with propionic academia[J]. Mol Genet Metab, 2016, 119 (4): 317- 321.
doi: 10.1016/j.ymgme.2016.10.009 |
| 19 | Bala KA , Dǒgan M , Mutluer T , et al. Plasma amino acid profile in autism spectrum disorder (ASD)[J]. Eur Rev Med Pharmacol Sci, 2016, 20 (5): 923- 929. |
| 20 |
Zou M , Li D , Wang L , et al. Identification of amino acid dys-regulation as a potential biomarker for autism spectrum disorder in China[J]. Neurotox Res, 2020, 38 (4): 992- 1000.
doi: 10.1007/s12640-020-00242-9 |
| 21 |
May T , Adesina I , McGillivray J , et al. Sex differences in neurodevelopmental disorders[J]. Curr Opin Neurol, 2019, 32 (4): 622- 626.
doi: 10.1097/WCO.0000000000000714 |
| 22 |
Lavelle A , Sokol H . Gut microbiota-derived metabolites as key actors in inflammatory bowel disease[J]. Nat Rev Gastroenterol Hepatol, 2020, 17 (4): 223- 237.
doi: 10.1038/s41575-019-0258-z |
| 23 |
Lussu M , Noto A , Masili A , et al. The urinary (1) H-NMR metabolomics profile of an Italian autistic children population and their unaffected siblings[J]. Autism Res, 2017, 10 (6): 1058- 1066.
doi: 10.1002/aur.1748 |
| 24 |
Li C , Shen K , Chu L , et al. Decreased levels of urinary free amino acids in children with autism spectrum disorder[J]. J Clin Neurosci, 2018, 54, 45- 49.
doi: 10.1016/j.jocn.2018.05.001 |
| 25 |
Evans C , Dunstan RH , Rothkirch T , et al. Altered amino acid excretion in children with autism[J]. Nutr Neurosci, 2008, 11 (1): 9- 17.
doi: 10.1179/147683008X301360 |
| 26 |
De Angelis M , Piccolo M , Vannini L , et al. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified[J]. PLoS One, 2013, 8 (10): e76993.
doi: 10.1371/journal.pone.0076993 |
| 27 |
Carunchio I , Curcio L , Pieri M , et al. Increased levels of p70S6 phosphorylation in the G93A mouse model of amyotrophic lateral sclerosis and in valine-exposed cortical neurons in culture[J]. Exp Neurol, 2010, 226 (1): 218- 230.
doi: 10.1016/j.expneurol.2010.08.033 |
| 28 |
Nave KA , Werner HB . Myelination of the nervous system: Mechanisms and functions[J]. Annu Rev Cell Dev Biol, 2014, 30, 503- 533.
doi: 10.1146/annurev-cellbio-100913-013101 |
| 29 |
Kakazu E , Kanno N , Ueno Y , et al. Extracellular branched-chain amino acids, especially valine, regulate maturation and function of monocyte-derived dendritic cells[J]. J Immunol, 2007, 179 (10): 7137- 7146.
doi: 10.4049/jimmunol.179.10.7137 |
| 30 | Shen L , Feng C , Zhang K , et al. Proteomics study of peripheral blood mononuclear cells (PBMCs) in autistic children[J]. Front Cell Neurosci, 2019, 13, 105. |
| 31 | Lungba RM , Khan S , Ajibawo-Aganbi U , et al. The role of the gut microbiota and the immune system in the development of autism[J]. Cureus, 2020, 12 (10): e11226. |
| 32 |
Meltzer A , Van de Water J . The role of the immune system in autism spectrum disorder[J]. Neuropsychopharmacology, 2017, 42 (1): 284- 298.
doi: 10.1038/npp.2016.158 |
| [1] | 赵亚楠,范慧芸,王翔宇,罗雅楠,张嵘,郑晓瑛. 孤独症患者过早死亡风险及死亡原因[J]. 北京大学学报(医学版), 2023, 55(2): 375-383. |
| [2] | 陆林,刘晓星,袁凯. 中国脑科学计划进展[J]. 北京大学学报(医学版), 2022, 54(5): 791-795. |
| [3] | 焦翠,王俭妹,况海霞,武志红,柳涛. CACNA1H基因敲除对小鼠孤独症样行为及海马神经元形态学的影响[J]. 北京大学学报(医学版), 2022, 54(2): 209-216. |
| [4] | 石慧峰, 张敬旭, 张嵘, 王晓莉. 中国0~6岁儿童孤独症谱系障碍患病率的meta分析[J]. 北京大学学报(医学版), 2017, 49(5): 798-806. |
| [5] | 秦炯, 韩颖. 儿童神经科临床应关注精神行为问题[J]. 北京大学学报(医学版), 2013, 45(2): 174-. |
|
||