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• W1997697132 abstract "Vol. 115, No. 8 PerspectivesOpen AccessLead and Neuroprotection by Iron in ADHD Eric Konofal and Samuele Cortese Eric Konofal Search for more papers by this author and Samuele Cortese Search for more papers by this author Published:1 August 2007https://doi.org/10.1289/ehp.10304Cited by:9AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit We read with special interest the article by Braun et al. (2006). In this large survey, the authors concluded that prenatal exposure to tobacco and environmental lead are risk factors for attention deficit hyperactivity disorder (ADHD).We would like to focus on the potential neuroprotective role of iron against the deleterious effect of lead on the development of ADHD symptoms.Although the mechanisms underlying ADHD remain unclear, both genetic and environmental factors have been implicated. In a recent review on the implication of the dopaminergic system in the etiology of ADHD, Swanson et al. (2007) highlighted the importance of environmental risk factors as possible etiologies of dopamine deficit. Among these environmental factors, Swanson et al. (2007) cited the effects of lead exposure (at levels < 10 μg/dL) on ADHD-related behaviors and ADHD diagnosis.Lead in the central nervous system may contribute to dopaminergic dysfunction inducing alteration of dopamine release and dopamine receptor density (Gedeon et al. 2001; Lidsky et al. 2003). Moreover, lead may disrupt the structure of the blood–brain barrier function essential for brain integrity (Dyatlov et al. 1998). Interestingly, Wang et al. (2007) recently reported that iron supplementation protects the integrity of the blood–brain barrier against lead insults. On the other hand, iron deficiency could increase the toxic effect of lead, suggesting a potent neuroprotective effect of iron supplementation on dopaminergic dysfunction due to lead exposure (Wright 1999; Wright et al. 2003)In a controlled comparison group study, we (Konofal et al. 2004) showed that iron deficiency was correlated to ADHD symptoms severity, hypothesizing that iron supplementation may improve symptoms of ADHD in those subjects with low ferritin levels.Given that lead exposure may contribute to ADHD and iron deficiency may exacerbate deleterious effects caused by lead, we recommend systematically seeking for iron deficiency in children with ADHD. We also think that controlled studies assessing the potential effectiveness of iron supplementation on ADHD symptoms should be encouraged. Such studies could aid the understanding of the complex pathophysiology underlying ADHD and provide effective therapeutic strategies for this disorder.ReferencesBraun JM, Kahn RS, Froehlich T, Auinger P, Lanphear BP. 2006. Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children. Environ Health Perspect 114:1904-190917185283. Link, Google ScholarDyatlov VA, Platoshin AV, Lawrence DA, Carpenter DO. 1998. Lead potentiates cytokine- and glutamate-mediated increases in permeability of the blood-brain barrier. Neurotoxicology 19:283-2919553965. Medline, Google ScholarGedeon Y, Ramesh GT, Wellman PJ, Jadhav AL. 2001. Changes in mesocorticolimbic dopamine and D1/D2 receptor levels after low level lead exposure: a time course study. Toxicol Lett 123(2–3):217-22611641049. Crossref, Medline, Google ScholarKonofal E, Lecendreux M, Arnulf I, Mouren MC. 2004. Iron deficiency in children with attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med 158(12):1113-111515583094. Crossref, Medline, Google ScholarLidsky TI, Schneider JS. 2003. Lead neurotoxicity in children: basic mechanisms and clinical correlates. Brain 126:5-1912477693. Crossref, Medline, Google ScholarSwanson JM, Kinsbourne M, Nigg J, Lanphear B, Stefanatos GA, Volkow Net al.. 2007. Etiologic subtypes of attention-deficit/hyperactivity disorder: brain imaging, molecular genetic and environmental factors and the dopamine hypothesis. Neuropsychol Rev 17(1):39-5917318414. Crossref, Medline, Google ScholarWang Q, Luo W, Zheng W, Liu Y, Xu H, Zheng Get al.. 2007. Iron supplement prevents lead-induced disruption of the blood-brain barrier during rat development. Toxicol Appl Pharmacol 219(1):33-4117234227. Crossref, Medline, Google ScholarWright RO. 1999. The role of iron therapy in childhood plumbism. Curr Opin Pediatr 11(3):255-25810349106. Crossref, Medline, Google ScholarWright RO, Tsaih SW, Schwartz J, Wright RJ, Hu H. 2003. Association between iron deficiency and blood lead level in a longitudinal analysis of children followed in an urban primary care clinic. J Pediatrics 142(1):9-14. Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsCited by Scassellati C, Bonvicini C, Faraone S and Gennarelli M (2012) Biomarkers and Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analyses, Journal of the American Academy of Child & Adolescent Psychiatry, 10.1016/j.jaac.2012.08.015, 51:10, (1003-1019.e20), Online publication date: 1-Oct-2012. Torres-Vega A, Pliego-Rivero B, Otero-Ojeda G, Gómez-Oliván L and Vieyra-Reyes P (2012) Limbic system pathologies associated with deficiencies and excesses of the trace elements iron, zinc, copper, and selenium, Nutrition Reviews, 10.1111/j.1753-4887.2012.00521.x, 70:12, (679-692), Online publication date: 1-Dec-2012. Sinn N and Rucklidge J (2011) The role of nutrition and diet in learning and behaviour of children with symptoms of attention deficit hyperactivity disorder Lifetime Nutritional Influences on Cognition, Behaviour and Psychiatric Illness, 10.1533/9780857092922.3.323, (323-358), . (2010) References The Science of ADHD, 10.1002/9781444328172.refs, (240-326) Sinn N (2008) Nutritional and dietary influences on attention deficit hyperactivity disorder, Nutrition Reviews, 10.1111/j.1753-4887.2008.00107.x, 66:10, (558-568) Meletis C and Zabriskie N (2008) Attention-Deficit Hyperactivity Disorder, Alternative and Complementary Therapies, 10.1089/act.2008.14501, 14:5, (235-242), Online publication date: 1-Oct-2008. Ghanizad A (2008) Regarding the Effects of Iron Supplementation on Attention Deficit Hyperactivity Disorder in Children, Pediatric Neurology, 10.1016/j.pediatrneurol.2008.03.022, 39:1, (73), Online publication date: 1-Jul-2008. Wang H, Chen X, Yang B, Ma F, Wang S, Tang M, Hao M and Ruan D (2008) Case–Control Study of Blood Lead Levels and Attention Deficit Hyperactivity Disorder in Chinese Children, Environmental Health Perspectives, 116:10, (1401-1406), Online publication date: 1-Oct-2008. Yang Y, Wu J and Sun P (2012) Effects of Delta-Aminolevulinic Acid Dehydratase Polymorphisms on Susceptibility to Lead in Han Subjects from Southwestern China, International Journal of Environmental Research and Public Health, 10.3390/ijerph9072326, 9:7, (2326-2338) Vol. 115, No. 8 August 2007Metrics About Article Metrics Publication History Originally published1 August 2007Published in print1 August 2007 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. 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