Estimation of autistic children by metallomics analysis

Clarification of the pathogenesis and treatment of autism spectrum disorders is one of the challenges today. In this study, we examine scalp hair concentrations of 26 trace elements for 1,967 children with autistic disorders (1,553 males and 414 females). Five-hundred and eighty-four (29.7%), 347 (17.6%) and 114 (5.8%) subjects was found deficient in zinc, magnesium and calcium, respectively, and 2.0% or less in the other essential metals. The incidence rate of mineral deficiency was highly observed in infants aged 0-3 year-old. In contrast, 339 (17.2%), 168 (8.5%) and 94 (4.8%) individuals was found suffering from high burden of aluminium, cadmium and lead, and 2.8% or less from mercury and arsenic burden. These findings suggest that infantile zinc- and magnesium-deficiency and/or toxic metal burdens may epigenetically play principal roles as environmental factors in autistic disorders and that metallomics approach may lead to early screening and prevention of the neurodevelopment disorders.

[1]  Eric Fombonne,et al.  Pervasive developmental disorders in preschool children: confirmation of high prevalence. , 2005, The American journal of psychiatry.

[2]  S. Akbarian,et al.  Epigenetic mechanisms in neurological disease , 2012, Nature Medicine.

[3]  Kazuya Yoshida,et al.  Infantile zinc deficiency: Association with autism spectrum disorders , 2011, Scientific reports.

[4]  Hiroshi Yasuda,et al.  High Toxic Metal Levels in Scalp Hair of Infants and Children , 2005 .

[5]  Chin-thin Wang,et al.  Concentrations of calcium, copper, iron, magnesium, potassium, sodium and zinc in adult female hair with different body mass indexes in Taiwan , 2005, Clinical chemistry and laboratory medicine.

[6]  R. Goyer,et al.  Toxic and essential metal interactions. , 1997, Annual review of nutrition.

[7]  A. Oskarsson,et al.  Exposure of cadmium from infant formulas and weaning foods. , 1999, Food additives and contaminants.

[8]  L. A. Scheplyagina.  Impact of the mother's zinc deficiency on the woman's and newborn's health status. , 2005, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[9]  Kazuya Yoshida,et al.  Two age-related accumulation profiles of toxic metals. , 2012, Current aging science.

[10]  R. Cousins,et al.  Mammalian zinc transporters: nutritional and physiologic regulation. , 2009, Annual review of nutrition.

[11]  L. Rink,et al.  The Essential Toxin: Impact of Zinc on Human Health , 2010, International journal of environmental research and public health.

[12]  A. Prasad.  Impact of the Discovery of Human Zinc Deficiency on Health , 2009, Journal of the American College of Nutrition.

[13]  M. Waalkes,et al.  Effects of cadmium on DNA-(Cytosine-5) methyltransferase activity and DNA methylation status during cadmium-induced cellular transformation. , 2003, Experimental cell research.

[14]  M. Ramírez-Zea,et al.  Role of zinc in maternal and child mental health. , 2009, The American journal of clinical nutrition.

[15]  G. Andrews,et al.  The Adaptive Response to Dietary Zinc in Mice Involves the Differential Cellular Localization and Zinc Regulation of the Zinc Transporters ZIP4 and ZIP5* , 2004, Journal of Biological Chemistry.

[16]  I. B. Razagui,et al.  Maternal and neonatal scalp hair concentrations of zinc, copper, cadmium, and lead , 2005, Biological Trace Element Research.

[17]  L. E. Arnold,et al.  Zinc in attention-deficit/hyperactivity disorder. , 2005, Journal of child and adolescent psychopharmacology.

[18]  C. Akay,et al.  Zinc status in autistic children , 2004 .

[19]  Jan K Buitelaar,et al.  Are autism spectrum disorder and attention-deficit/hyperactivity disorder different manifestations of one overarching disorder? Cognitive and symptom evidence from a clinical and population-based sample. , 2012, Journal of the American Academy of Child and Adolescent Psychiatry.

[20]  T. Kozielec,et al.  The effects of magnesium physiological supplementation on hyperactivity in children with attention deficit hyperactivity disorder (ADHD). Positive response to magnesium oral loading test. , 1997, Magnesium research.

[21]  I. Rodushkin,et al.  Application of double focusing sector field ICP-MS for multielemental characterization of human hair and nails. Part I. Analytical methodology. , 2000, The Science of the total environment.

[22]  D. Pinto,et al.  Structural variation of chromosomes in autism spectrum disorder. , 2008, American journal of human genetics.

[23]  A. Bailey,et al.  Autism as a strongly genetic disorder: evidence from a British twin study , 1995, Psychological Medicine.

[24]  J. Tainer,et al.  Cancer, cadmium and genome integrity , 2003, Nature Genetics.

[25]  Jack A. Taylor,et al.  Cadmium is a mutagen that acts by inhibiting mismatch repair , 2003, Nature Genetics.

[26]  A. Polge,et al.  Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. II. Pervasive developmental disorder-autism. , 2006, Magnesium research.

[27]  S. Al-Saad,et al.  Toxic trace elements in the hair of children with autism , 2005, Autism : the international journal of research and practice.

[28]  R. Martorell,et al.  Randomized trial of the effect of zinc supplementation on the mental health of school-age children in Guatemala. , 2010, The American journal of clinical nutrition.

[29]  M. Mohammadi,et al.  Zinc sulfate as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in children: A double blind and randomized trial [ISRCTN64132371] , 2004, BMC psychiatry.

[30]  F. George,et al.  Analyses of toxic metals and essential minerals in the hair of arizona children with autism and associated conditions, and their mothers , 2006, Biological Trace Element Research.

[31]  G. Vimpani,et al.  Pregnancy increases mobilization of lead from maternal skeleton. , 1997, The Journal of laboratory and clinical medicine.

[32]  David Wallinga,et al.  A macroepigenetic approach to identify factors responsible for the autism epidemic in the United States , 2012, Clinical Epigenetics.

[33]  L. E. Arnold,et al.  Serum zinc correlates with parent- and teacher- rated inattention in children with attention-deficit/hyperactivity disorder. , 2005, Journal of child and adolescent psychopharmacology.

[34]  A. Geetha,et al.  Level of Trace Elements (Copper, Zinc, Magnesium and Selenium) and Toxic Elements (Lead and Mercury) in the Hair and Nail of Children with Autism , 2011, Biological Trace Element Research.

[35]  M. Inaba,et al.  Elemental Concentrations in Scalp Hair, Nutritional Status and Health‐Related Quality of Life in Hemodialysis Patients , 2012, Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy.

[36]  S. O’Rahilly,et al.  Human genetics illuminates the paths to metabolic disease , 2009, Nature.

[37]  I. Hertz-Picciotto,et al.  Blood lead levels in relation to menopause, smoking, and pregnancy history. , 1995, American journal of epidemiology.

[38]  T. Kozielec,et al.  Assessment of magnesium levels in children with attention deficit hyperactivity disorder (ADHD). , 1997, Magnesium research.

[39]  Max Costa,et al.  Epigenetics in metal carcinogenesis: nickel, arsenic, chromium and cadmium. , 2009, Metallomics : integrated biometal science.

[40]  L. Wolf,et al.  Towards Prenatal Biomonitoring in North Carolina: Assessing Arsenic, Cadmium, Mercury, and Lead Levels in Pregnant Women , 2012, PloS one.

[41]  Kazuya Yoshida,et al.  Relationship between Body Mass Index and Minerals in Male Japanese Adults , 2006 .

[42]  Julie Herbstman,et al.  Prenatal environmental exposures, epigenetics, and disease. , 2011, Reproductive Toxicology.

[43]  Kazuya Yoshida,et al.  Mineral Imbalance in Children with Autistic Disorders , 2005 .

[44]  Laurent Bonneau,et al.  Metal and metalloid multi-elementary ICP-MS validation in whole blood, plasma, urine and hair. Reference values. , 2005, Forensic science international.

[45]  J. Bali,et al.  Magnesium VitB6 Intake Reduces Central Nervous System Hyperexcitability in Children , 2004, Journal of the American College of Nutrition.

[46]  Kazuya Yoshida,et al.  High Accumulation of Aluminum in Hairs of Infants and Children , 2008 .

[47]  Karen Weintraub.  The prevalence puzzle: Autism counts , 2011, Nature.

[48]  K. Haginoya,et al.  A preliminary analysis of trace elements in the scalp hair of patients with severe motor disabilities receiving enteral nutrition , 2006, Brain and Development.

[49]  S. Bek,et al.  Potential effects of zinc on information processing in boys with attention deficit hyperactivity disorder , 2008, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[50]  W. Lukiw,et al.  Mercury exposure, nutritional deficiencies and metabolic disruptions may affect learning in children , 2009, Behavioral and Brain Functions.

[51]  Yuichi Yasuda,et al.  Metallomics study using hair mineral analysis and multiple logistic regression analysis: relationship between cancer and minerals , 2009, Environmental health and preventive medicine.

[52]  V. Hughes.  Epidemiology: Complex disorder , 2012, Nature.

[53]  Gary D Bader,et al.  Functional impact of global rare copy number variation in autism spectrum disorders , 2010, Nature.