|
脑铁与注意缺陷多动障碍相关性的研究进展
|
Abstract:
注意缺陷多动障碍(attention deficit hyperactivity disorder, ADHD)患儿生活质量降低,社会功能减弱,同时容易导致抑郁、焦虑和行为障碍等合并症,给家庭和社会造成了巨大的负担。目前仍未有确切的生物标注物与ADHD相关。本篇综述基于近年来国内外相关文献及临床指南,总结脑铁在神经系统发育中的作用、脑铁参与ADHD发生发展的机制以及脑铁协助诊断ADHD的潜在价值,为ADHD患儿诊断和治疗提供参考。
Children with attention deficit hyperactivity disorder (ADHD) exhibit a diminished quality of life and impaired social functioning. Concurrently, they are susceptible to comorbidities such as depression, anxiety, and behavioral disorders, thereby imposing a substantial burden on families and society. At present, no definitive biomarker has been identified to be associated with ADHD. In light of relevant domestic and international literature as well as clinical guidelines in recent years, this review comprehensively summarizes the role of brain iron in the development of the nervous system, the mechanism through which brain iron is involved in the pathogenesis and progression of ADHD, and the potential value of brain iron in facilitating the diagnosis of ADHD, with the aim of providing valuable references for the diagnosis and treatment of children with ADHD.
[1] | Salari, N., Ghasemi, H., Abdoli, N., Rahmani, A., Shiri, M.H., Hashemian, A.H., et al. (2023) The Global Prevalence of ADHD in Children and Adolescents: A Systematic Review and Meta-Analysis. Italian Journal of Pediatrics, 49, Article No. 48. https://doi.org/10.1186/s13052-023-01456-1 |
[2] | Rucklidge, J.J. (2010) Gender Differences in Attention-Deficit/hyperactivity Disorder. Psychiatric Clinics of North America, 33, 357-373. https://doi.org/10.1016/j.psc.2010.01.006 |
[3] | Georgieff, M.K. (2011) Long-term Brain and Behavioral Consequences of Early Iron Deficiency. Nutrition Reviews, 69, S43-S48. https://doi.org/10.1111/j.1753-4887.2011.00432.x |
[4] | Wang, Y., Huang, L., Zhang, L., Qu, Y. and Mu, D. (2017) Iron Status in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis. PLOS ONE, 12, e0169145. https://doi.org/10.1371/journal.pone.0169145 |
[5] | Ward, R.J., Zucca, F.A., Duyn, J.H., Crichton, R.R. and Zecca, L. (2014) The Role of Iron in Brain Ageing and Neurodegenerative Disorders. The Lancet Neurology, 13, 1045-1060. https://doi.org/10.1016/s1474-4422(14)70117-6 |
[6] | Hare, D., Ayton, S., Bush, A. and Lei, P. (2013) A Delicate Balance: Iron Metabolism and Diseases of the Brain. Frontiers in Aging Neuroscience, 5, Article No. 34. https://doi.org/10.3389/fnagi.2013.00034 |
[7] | Porras, C.A. and Rouault, T.A. (2022) Iron Homeostasis in the CNS: An Overview of the Pathological Consequences of Iron Metabolism Disruption. International Journal of Molecular Sciences, 23, Article No. 4490. https://doi.org/10.3390/ijms23094490 |
[8] | Kelly, C., Couch, R.K., Ha, V.T., Bodart, C.M., Wu, J., Huff, S., et al. (2023) Iron Status Influences Mitochondrial Disease Progression in Complex I-Deficient Mice. eLife, 12, e75825. https://doi.org/10.7554/elife.75825 |
[9] | Walter, P.B., Knutson, M.D., Paler-Martinez, A., Lee, S., Xu, Y., Viteri, F.E., et al. (2002) Iron Deficiency and Iron Excess Damage Mitochondria and Mitochondrial DNA in Rats. Proceedings of the National Academy of Sciences, 99, 2264-2269. https://doi.org/10.1073/pnas.261708798 |
[10] | Little, A.G., Lau, G., Mathers, K.E., Leary, S.C. and Moyes, C.D. (2018) Comparative Biochemistry of Cytochrome C Oxidase in Animals. Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 224, 170-184. https://doi.org/10.1016/j.cbpb.2017.11.005 |
[11] | Spence, H., McNeil, C.J. and Waiter, G.D. (2020) The Impact of Brain Iron Accumulation on Cognition: A Systematic Review. PLOS ONE, 15, e0240697. https://doi.org/10.1371/journal.pone.0240697 |
[12] | Tang, S., Liu, X., Nie, L., Chen, Z., Ran, Q. and He, L. (2022) Diagnosis of Children with Attention-Deficit/Hyperactivity Disorder (ADHD) Comorbid Autistic Traits (ATs) by Applying Quantitative Magnetic Resonance Imaging Techniques. Frontiers in Psychiatry, 13, Article ID: 1038471. https://doi.org/10.3389/fpsyt.2022.1038471 |
[13] | Adisetiyo, V., Jensen, J.H., Tabesh, A., Deardorff, R.L., Fieremans, E., Di Martino, A., et al. (2014) Multimodal MR Imaging of Brain Iron in Attention Deficit Hyperactivity Disorder: A Noninvasive Biomarker That Responds to Psychostimulant Treatment? Radiology, 272, 524-532. https://doi.org/10.1148/radiol.14140047 |
[14] | Cortese, S., Brown, T.E., Corkum, P., Gruber, R., O’Brien, L.M., Stein, M., et al. (2013) Assessment and Management of Sleep Problems in Youths with Attention-Deficit/Hyperactivity Disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 52, 784-796. https://doi.org/10.1016/j.jaac.2013.06.001 |
[15] | Cusick, S.E. and Georgieff, M.K. (2016) The Role of Nutrition in Brain Development: The Golden Opportunity of the “First 1000 Days”. The Journal of Pediatrics, 175, 16-21. https://doi.org/10.1016/j.jpeds.2016.05.013 |
[16] | Tseng, P., Cheng, Y., Yen, C., Chen, Y., Stubbs, B., Whiteley, P., et al. (2018) Peripheral Iron Levels in Children with Attention-Deficit Hyperactivity Disorder: A Systematic Review and Meta-Analysis. Scientific Reports, 8, Article No. 788. https://doi.org/10.1038/s41598-017-19096-x |
[17] | Sever, Y., Ashkenazi, A., Tyano, S. and Weizman, A. (1997) Iron Treatment in Children with Attention Deficit Hyperactivity Disorder: A Preliminary Report. Neuropsychobiology, 35, 178-180. https://doi.org/10.1159/000119341 |
[18] | Konofal, E., Lecendreux, M., Deron, J., Marchand, M., Cortese, S., Zaïm, M., et al. (2008) Effects of Iron Supplementation on Attention Deficit Hyperactivity Disorder in Children. Pediatric Neurology, 38, 20-26. https://doi.org/10.1016/j.pediatrneurol.2007.08.014 |
[19] | Degremont, A., Jain, R., Philippou, E. and Latunde-Dada, G.O. (2020) Brain Iron Concentrations in the Pathophysiology of Children with Attention Deficit/Hyperactivity Disorder: A Systematic Review. Nutrition Reviews, 79, 615-626. https://doi.org/10.1093/nutrit/nuaa065 |
[20] | McCann, J.C. and Ames, B.N. (2007) An Overview of Evidence for a Causal Relation between Iron Deficiency during Development and Deficits in Cognitive or Behavioral Function. The American Journal of Clinical Nutrition, 85, 931-945. https://doi.org/10.1093/ajcn/85.4.931 |
[21] | Donfrancesco, R., Parisi, P., Vanacore, N., Martines, F., Sargentini, V. and Cortese, S. (2012) Iron and ADHD: Time to Move beyond Serum Ferritin Levels. Journal of Attention Disorders, 17, 347-357. https://doi.org/10.1177/1087054711430712 |
[22] | Garcia-Malo, C., Novo-Ponte, S., Castro-Villacañas Farzamnia, A., Boi, S., Miranda Castillo, C., Romero Peralta, S., et al. (2021) Correlation between Systemic Iron Parameters and Substantia Nigra Iron Stores in Restless Legs Syndrome. Sleep Medicine, 85, 191-195. https://doi.org/10.1016/j.sleep.2021.07.027 |
[23] | Shvarzman, R., Crocetti, D., Rosch, K.S., Li, X. and Mostofsky, S.H. (2022) Reduced Basal Ganglia Tissue-Iron Concentration in School-Age Children with Attention-Deficit/Hyperactivity Disorder Is Localized to Limbic Circuitry. Experimental Brain Research, 240, 3271-3288. https://doi.org/10.1007/s00221-022-06484-7 |
[24] | Adisetiyo, V., Gray, K.M., Jensen, J.H. and Helpern, J.A. (2019) Brain Iron Levels in Attention-Deficit/Hyperactivity Disorder Normalize as a Function of Psychostimulant Treatment Duration. NeuroImage: Clinical, 24, Article ID: 101993. https://doi.org/10.1016/j.nicl.2019.101993 |
[25] | Rubia, K. (2018) Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation. Frontiers in Human Neuroscience, 12, Article No. 100. https://doi.org/10.3389/fnhum.2018.00100 |
[26] | Cortese, S., Lecendreux, M., Bernardina, B.D., Mouren, M.C., Sbarbati, A. and Konofal, E. (2008) Attention-Deficit/Hyperactivity Disorder, Tourette’s Syndrome, and Restless Legs Syndrome: The Iron Hypothesis. Medical Hypotheses, 70, 1128-1132. https://doi.org/10.1016/j.mehy.2007.10.013 |
[27] | Brass, S.D., Chen, N., Mulkern, R.V. and Bakshi, R. (2006) Magnetic Resonance Imaging of Iron Deposition in Neurological Disorders. Topics in Magnetic Resonance Imaging, 17, 31-40. https://doi.org/10.1097/01.rmr.0000245459.82782.e4 |
[28] | Haber, S.N. and Knutson, B. (2009) The Reward Circuit: Linking Primate Anatomy and Human Imaging. Neuropsychopharmacology, 35, 4-26. https://doi.org/10.1038/npp.2009.129 |
[29] | Jellen, L.C., Lu, L., Wang, X., Unger, E.L., Earley, C.J., Allen, R.P., et al. (2013) Iron Deficiency Alters Expression of Dopamine-Related Genes in the Ventral Midbrain in Mice. Neuroscience, 252, 13-23. https://doi.org/10.1016/j.neuroscience.2013.07.058 |
[30] | Tewari, A., Jog, R. and Jog, M.S. (2016) The Striatum and Subthalamic Nucleus as Independent and Collaborative Structures in Motor Control. Frontiers in Systems Neuroscience, 10, Article No. 17. https://doi.org/10.3389/fnsys.2016.00017 |
[31] | Rosch, K.S., Crocetti, D., Hirabayashi, K., Denckla, M.B., Mostofsky, S.H. and Mahone, E.M. (2018) Reduced Subcortical Volumes among Preschool-Age Girls and Boys with ADHD. Psychiatry Research: Neuroimaging, 271, 67-74. https://doi.org/10.1016/j.pscychresns.2017.10.013 |
[32] | Seymour, K.E., Tang, X., Crocetti, D., Mostofsky, S.H., Miller, M.I. and Rosch, K.S. (2017) Anomalous Subcortical Morphology in Boys, but Not Girls, with ADHD Compared to Typically Developing Controls and Correlates with Emotion Dysregulation. Psychiatry Research: Neuroimaging, 261, 20-28. https://doi.org/10.1016/j.pscychresns.2017.01.002 |
[33] | Ramsey, A.J., Hillas, P.J. and Fitzpatrick, P.F. (1996) Characterization of the Active Site Iron in Tyrosine Hydroxylase. Redox States of the Iron. Journal of Biological Chemistry, 271, 24395-24400. https://doi.org/10.1074/jbc.271.40.24395 |
[34] | Luo, Y., Weibman, D., Halperin, J.M. and Li, X. (2019) A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD). Frontiers in Human Neuroscience, 13, Article No. 42. https://doi.org/10.3389/fnhum.2019.00042 |
[35] | Möller, H.E., Bossoni, L., Connor, J.R., Crichton, R.R., Does, M.D., Ward, R.J., et al. (2019) Iron, Myelin, and the Brain: Neuroimaging Meets Neurobiology. Trends in Neurosciences, 42, 384-401. https://doi.org/10.1016/j.tins.2019.03.009 |
[36] | Cortese, S., Konofal, E., Lecendreux, M., Arnulf, I., Mouren, M., Darra, F., et al. (2005) Restless Legs Syndrome and Attention-Deficit/Hyperactivity Disorder: A Review of the Literature. Sleep, 28, 1007-1013. https://doi.org/10.1093/sleep/28.8.1007 |
[37] | Kraegeloh‐Mann, I. (2021) Interference with Prenatal, Perinatal, and Neonatal Brain Development Is Associated with a High Risk for Autism and Attention‐Deficit/Hyperactivity Disorder. Developmental Medicine & Child Neurology, 64, 10. https://doi.org/10.1111/dmcn.15056 |
[38] | Rigler, T., Manor, I., Kalansky, A., Shorer, Z., Noyman, I. and Sadaka, Y. (2016) New DSM-5 Criteria for ADHD—Does It Matter? Comprehensive Psychiatry, 68, 56-59. https://doi.org/10.1016/j.comppsych.2016.03.008 |
[39] | Dusek, P., Dezortova, M. and Wuerfel, J. (2013) Imaging of Iron. In: International Review of Neurobiology, Elsevier, 195-239. https://doi.org/10.1016/b978-0-12-410502-7.00010-7 |
[40] | Ide, S., Kakeda, S., Ueda, I., Watanabe, K., Murakami, Y., Moriya, J., et al. (2014) Internal Structures of the Globus Pallidus in Patients with Parkinson’s Disease: Evaluation with Quantitative Susceptibility Mapping (QSM). European Radiology, 25, 710-718. https://doi.org/10.1007/s00330-014-3472-7 |