Advances in potential mechanisms of non-invasive electrical vagus nerve  stimulation in the treatment of attention-deficit/hyperactivity disorder

XU He; ZHI Jincao; CHANG Qing; WANG Yan

doi:10.11852/zgetbjzz2024-0605

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Chinese Journal of Child Health Care ›› 2025, Vol. 33 ›› Issue (8) : 883-887. DOI: 10.11852/zgetbjzz2024-0605

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Advances in potential mechanisms of non-invasive electrical vagus nerve stimulation in the treatment of attention-deficit/hyperactivity disorder

XU He¹, ZHI Jincao¹, CHANG Qing¹, WANG Yan^1,2

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Abstract

The vagus nerve (VN) originates from the brainstem, serving as a bidirectional communication bridge between the brain and the body, and is widely distributed throughout the central and peripheral nervous systems. Noninvasive vagus nerve stimulation (nVNS) is a neuromodulation technique with active regulatory functions that has been applied in the treatment of various diseases in recent years, demonstrating significant effects in conditions such as depression and epilepsy. However, there have been relatively few studies on its use in the treatment of attention deficit hyperactivity disorder (ADHD). By summarizing the pathogenesis of ADHD and the mechanism of nVNS, this article identifies associations between the two in terms of neurotransmitters, inflammation, apoptosis, and other aspects, and explore the potential mechanisms that exist between them, so as to provide a theoretical foundation for nVNS treatment of ADHD.

Key words

non-invasive / vagus nerve stimulation / attention-deficit/hyperactivity disorder

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XU He, ZHI Jincao, CHANG Qing, WANG Yan. Advances in potential mechanisms of non-invasive electrical vagus nerve stimulation in the treatment of attention-deficit/hyperactivity disorder[J]. Chinese Journal of Child Health Care. 2025, 33(8): 883-887 https://doi.org/10.11852/zgetbjzz2024-0605

References

[1] Rajaprakash M, Leppert ML. Attention-deficit/hyperactivity disorder[J]. Pediatr Rev, 2022,43(3):135-147.
[2] Thomas R, Sanders S, Doust J, et al. Prevalence of attention-deficit/hyperactivity disorder: A systematic review and meta-analysis[J]. Pediatrics, 2015,135(4):e994-e1001.
[3] Drechsler R, Brem S, Brandeis D, et al. ADHD: Current concepts and treatments in children and adolescents[J]. Neuropediatrics, 2020,51(5):315-335.
[4] 欧阳胤飞, 彭琲, 黄金丽, 等. 非侵入性神经调控治疗帕金森病神经调节机制的MRI研究进展[J]. 磁共振成像, 2023,14(10):125-131.
Ouyang YF, Peng F, Huang J, et al. MRI research progress on the neuromodulation mechanism of non-invasive neuromodulation forparkinson's disease[J]. Clin J Magn Reson Imag, 2023,14(10):125-131.(in Chinese)
[5] 刘畅, 张玉梅. 非侵入性迷走神经刺激与认知功能研究进展[J]. 中国医刊, 2021,56(4):366-369.
Liu C, Zhang YM. Advances in noninvasive vagus nerve stimulation and cognitive function[J]. Chinese Journal of Medicine, 2021,56(4):366-369.(in Chinese)
[6] Colzato L, Beste C. A literature review on the neurophysiological underpinnings and cognitive effects of transcutaneous vagus nerve stimulation: Challenges and future directions[J]. J Neurophysiology, 2020,123(5):1739-1755.
[7] Wang B, Dudko OK. A theory of synaptic transmission[J]. Elife, 2021,10:e73585.
[8] 李雪军, 王淑敏, 姜之炎, 等. 注意缺陷多动障碍模型及其病理机制研究进展[J]. 中国比较医学杂志, 2023,33(5):145-152.
Li XJ, Wang SM, Jiang ZY, et al. Research progress on models and pathological mechanisms of attention deficit hyperactivity disorder[J]. Chin J Comp Med, 2023,33(5):145-152.(in Chinese)
[9] Levy F. The dopamine theory of attention deficit hyperactivity disorder (ADHD)[J]. Aust N Z J Psychiatry, 1991,25(2):277-283.
[10] Bouchatta O, Manouze H, Bouali-Benazzouz R, et al. Neonatal 6-OHDA lesion model in mouse induces attention-deficit/hyperactivity disorder (ADHD)-like behaviour[J]. Sci Rep, 2018,8(1):15349.
[11] Lee YA, Kim YJ, Lee JS, et al. Imbalance between dopamine and serotonin caused by neonatal habenula lesion[J]. Behav Brain Res, 2021,409:113316.
[12] Madhyastha S, Rao MS, Renno WM. Serotonergic and adrenergic neuroreceptor manipulation ameliorates core symptoms of ADHD through modulating dopaminergic receptors in spontaneously hypertensive rats[J]. Int J Mol Sci, 2024,25(4):2300.
[13] Corona JC. Role of oxidative stress and neuroinflammation in attention-deficit/hyperactivity disorder[J]. Antioxidants (Basel), 2020,9(11):1039.
[14] Dunn GA, Nigg JT, Sullivan EL. Neuroinflammation as a risk factor for attention deficit hyperactivity disorder[J]. Pharmacol Biochem Behav, 2019,182:22-34.
[15] Avcil S. Evaluation of the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and mean platelet volume as inflammatory markers in children with attention-deficit hyperactivity disorder[J]. Psychiatry Clin Neurosci, 2018,72(7):522-530.
[16] Önder A, Gizli ÇÖ, Sürer AA. Elevated neutrophil-to-lymphocyte ratio in children and adolescents with attention-deficit/hyperactivity disorder[J]. Int J Psychiatry Clin Pract, 2021,25(1):43-48.
[17] Darwish AH, Elgohary TM, Nosair NA. Serum interleukin-6 level in children with attention-deficit hyperactivity disorder (ADHD)[J]. J Child Neurol, 2019,34(2):61-67.
[18] Oades RD, Myint AM, Dauvermann MR, et al. Attention-deficit hyperactivity disorder (ADHD) and glial integrity: An exploration of associations of cytokines and kynurenine metabolites with symptoms and attention[J]. Behav Brain Funct, 2010,6:32.
[19] Azzi A. Oxidative stress: What is it? can it be measured? where is it located? can it be good or bad? can it be prevented? can it be cured?[J]. Antioxidants (Basel), 2022,11(8):1431.
[20] Kul M, Unal F, Kandemir H, et al. Evaluation of oxidative metabolism in child and adolescent patients with attention deficit hyperactivity disorder[J]. Psychiatry Investig, 2015,12(3):361-366.
[21] Salem HA, Elsherbiny N, Alzahrani S, et al. Neuroprotective effect of morin hydrate against attention-deficit/hyperactivity disorder (ADHD) induced by MSG and/or protein malnutrition in rat pups: Effect on oxidative/monoamines/inflammatory balance and apoptosis[J]. Pharmaceuticals (Basel), 2022,15(8):1012.
[22] Amini-Khoei H, Haghani-Samani E, Beigi M, et al. On the role of corticosterone in behavioral disorders, microbiota composition alteration and neuroimmune response in adult male mice subjected to maternal separation stress[J]. Int Immunopharmacol, 2019,66:242-250.
[23] Tengeler AC, Dam SA, Wiesmann M, et al. Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice[J]. Microbiome, 2020,8(1):44.
[24] Boonchooduang N, Louthrenoo O, Chattipakorn N, et al. Possible links between gut-microbiota and attention-deficit/hyperactivity disorders in children and adolescents[J]. Eur J Nutr, 2020,59(8):3391-3403.
[25] Prehn-Kristensen A, Zimmermann A, Tittmann L, et al. Reduced microbiome alpha diversity in young patients with ADHD[J]. Plos One, 2018,13(7):e200728.
[26] Lee MJ, Lai HC, Kuo YL, et al. Association between gut microbiota and emotional-behavioral symptoms in children with attention-deficit/hyperactivity disorder[J]. J Pers Med, 2022,12(10):1634.
[27] Goggins E, Mitani S, Tanaka S. Clinical perspectives on vagus nerve stimulation: present and future[J]. Clin Sci (Lond), 2022,136(9):695-709.
[28] Bonaz B, Sinniger V, Pellissier S. Therapeutic potential of vagus nerve stimulation for inflammatory bowel diseases[J]. Front Neurosci, 2021,15:650971.
[29] Janitzky K. Impaired phasic discharge of locus coeruleus neurons based on persistent high tonic discharge-a new hypothesis with potential implications for neurodegenerative diseases[J]. Front Neurol, 2020,11:371.
[30] Bonaz B, Bazin T, Pellissier S. The vagus nerve at the interface of the microbiota-gut-brain axis[J]. Front Neurosci, 2018,12:49.
[31] Sarkar A, Lehto SM, Harty S, et al. Psychobiotics and the manipulation of bacteria-gut-brain signals[J]. Trends Neurosci, 2016,39(11):763-781.
[32] Andalib S, Divani AA, Ayata C, et al. Vagus nerve stimulation in ischemic stroke[J]. Curr Neurol Neurosci Rep, 2023,23(12):947-962.
[33] Isabella AJ, Moens CB. Development and regeneration of the vagus nerve[J]. Semin Cell Dev Biol, 2024,156:219-227.
[34] Xia XM, Duan Y, Wang YP, et al. Vagus nerve stimulation as a promising neuroprotection for ischemic stroke via alpha7nAchR-dependent inactivation of microglial NLRP3 inflammasome[J]. Acta Pharmacol Sin, 2024,45(7):1349-1365.
[35] 康君伟, 董晓阳, 汤运梁, 等. 迷走神经电刺激治疗慢性意识障碍的临床疗效及潜在机制研究进展[J]. 中国康复医学杂志, 2022,37(8):1137-1141.
Kang JW, Dong XY, Tang YL, et al. Advances in clinical efficacy and potential mechanismsof vagus nerve electrical stimulation in the treatment of chronic disorders of consciousness[J]. Chin J Rehabil Med, 2022,37(8):1137-1141.(in Chinese)
[36] Kilgard MP, Rennaker RL, Alexander J, et al. Vagus nerve stimulation paired with tactile training improved sensory function in a chronic stroke patient[J]. NeuroRehabilitation, 2018,42(2):159-165.
[37] 刘林, 江钟立. 迷走神经电刺激在记忆障碍疾病中的研究进展[J]. 中国康复医学杂志, 2021,36(11):1460-1464.
Liu L, Jiang ZL. Research progress of vagus nerve electrical stimulation in memory disorders[J]. Chin J Rehabil Med, 2021,36(11):1460-1464.(in Chinese)
[38] 雷欢, 安军明, 曹坤, 等. 经皮耳穴迷走神经电刺激治疗失眠障碍的研究现状[J]. 针灸临床杂志, 2024,40(2):89-93.
Lei H, An JM, Cao K, et al. Research status of transcutaneous auricular vagus nerve stimulation in treatment of insomnia[J]. Journal of Clinical Acupuncture Moxibustion, 2024,40(2):89-93.(in Chinese)
[39] Bonaz B, Sinniger V, Pellissier S. Anti-inflammatory properties of the vagus nerve: Potential therapeutic implications of vagus nerve stimulation[J]. J Physiol, 2016,594(20):5781-5790.
[40] Pereira MR, Leite PE. The involvement of parasympathetic and sympathetic nerve in the inflammatory reflex[J]. J Cell Physiol, 2016,231(9):1862-1869.
[41] 宋宇尘. 安神定志灵调控注意缺陷多动障碍神经炎症的机制研究[D]. 南京:南京中医药大学, 2021.
Song YC. Study on mechanism of anshen dingzhiling regulating neuroinflammation in attention deficit hyperactivity disorder[D]. Nanjing:Nanjing University of Chinese Medicine, 2021.(in Chinese)
[42] 王勇, 王臻颉. 阿立哌唑治疗儿童注意缺陷多动障碍合并破坏性行为障碍的效果及对炎症因子水平的影响[J]. 中国医药杂志, 2021,16(3):440-443.
Wang Y,Wang ZJ. Effect of aripiprazole on attention deficit hyperactivity disorder combined with disruptive behavior disorder in children and its effect on levels of inflammatory cytokines[J]. China Medicine, 2021,16(3):440-443.(in Chinese)
[43] Chen X, He X, Luo S, et al. Vagus nerve stimulation attenuates cerebral microinfarct and colitis-induced cerebral microinfarct aggravation in mice[J]. Front Neurol, 2018,9:798.
[44] Zhao XP, Zhao Y, Qin XY, et al. Non-invasive vagus nerve stimulation protects against cerebral ischemia/reperfusion injury and promotes microglial m2 polarization via interleukin-17a inhibition[J]. J Mol Neurosci, 2019,67(2):217-226.
[45] Lai Y, Deng J, Wang M, et al. Vagus nerve stimulation protects against acute liver injury induced by renal ischemia reperfusion via antioxidant stress and anti-inflammation[J]. Biomed Pharmacother, 2019,117:109062.
[46] 吴晨蕾, 王孟飞, 周荣易. 氧化应激在注意缺陷多动障碍发病机制中的研究进展[J]. 中国当代儿科杂志, 2024,26(2):201-206.
Wu CL, Wang MF, Zhou RY. Recent research on the role of oxidative stress in the pathogenesis of attention deficit hyperactivity disorder[J]. Chin J Contempo Pediatr, 2024,26(2):201-206.(in Chinese)
[47] 杨佃旭. 经皮迷走神经耳支刺激对药物难治性癫痫大鼠的治疗效果及其机制探讨[D]. 上海:上海交通大学, 2016.
Yang DX. Effect and mechanism of transcutaneous vagus nerve auricular branch stimulation on drug-refractory epilepsy rats[D]. Shanghai:Shanghai Jiao Tong University, 2016.(in Chinese)
[48] Réus GZ, Scaini G, Jeremias GC, et al. Brain apoptosis signaling pathways are regulated by methylphenidate treatment in young and adult rats[J]. Brain Res, 2014,1583:269-276.
[49] 阎樱, 王亚萍. 哌醋甲酯对ADHD动物模型SHR大鼠前额叶皮质层细胞凋亡的影响[J]. 中国妇幼健康研究, 2016,27(12):1450-1452.
Yan Y, Wang YP. Effect of methylphenidate on prefrontal cortex cells apoptosis in SHR of ADHD model[J].Chinese Journal of Woman and Child Health Research, 2016,27(12):1450-1452.(in Chinese)