Biological Trace Element Research

, Volume 169, Issue 1, pp 1–7 | Cite as

Changed Plasma Levels of Zinc and Copper to Zinc Ratio and Their Possible Associations with Parent- and Teacher-Rated Symptoms in Children with Attention-Deficit Hyperactivity Disorder

  • Alena Viktorinova
  • Monika Ursinyova
  • Jana Trebaticka
  • Iveta Uhnakova
  • Zdenka Durackova
  • Vlasta Masanova


Attention-deficit hyperactivity disorder (ADHD) is associated with alterations in the metabolism of some trace elements which may participate in the pathogenesis of this disorder. The aims of the present study were to investigate the trace element status (copper (Cu), zinc (Zn), copper to zinc ratio (Cu/Zn ratio), selenium (Se), and lead (Pb)) of ADHD children and compare them with the control group. Associations between examined elements and ratings of ADHD symptoms were also assessed. Fifty-eight ADHD children and 50 healthy children (aged 6–14 years) were included in the study. The concentrations of Cu, Zn, and Se in the plasma and Pb in the whole blood were measured by atomic absorption spectrometry. We found lower Zn level (p = 0.0005) and higher Cu/Zn ratio (p = 0.015) in ADHD children when compared with the control group. Copper levels in ADHD children were higher than those in the control group, but not significantly (p > 0.05). No significant differences in levels of Se and Pb between both groups were found. Zinc levels correlated with parent-rated score for inattention (r = −0.231, p = 0.029) as well as with teacher-rated score for inattention (r = −0.328, p = 0.014). Cu/Zn ratio correlated with teacher-rated score for inattention (r = 0.298, p = 0.015). Significant associations of Se and Pb with parent- and teacher-rated symptoms were not observed. The results of this study indicate that there are alterations in plasma levels of Cu and Zn as well as significant relationships to symptoms of ADHD.


Trace element status Zinc Copper Copper to zinc ratio Oxidative stress 



This study was supported by MVTS TW-010002 grant of Ministry of Education, Slovak Republic. Authors wish to thank all volunteers for their participation in this study and to Mrs. Husekova Z. and Witkova V. for their technical assistance as well as the nurses for taking blood samples from children.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Sagvolden T, Johansen EB, Aase H, Russell VA (2005) A dynamic developmental theory of attention-deficit/hyperactivity disorder (ADHD) predominantly hyperactive/impulsive and combined subtypes. Behav Brain Sci 28:397–468PubMedCrossRefGoogle Scholar
  2. 2.
    Valera EM, Faraone SV, Murray KE, Seidman LJ (2007) Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Biol Psychiatry 61:1361–1369PubMedCrossRefGoogle Scholar
  3. 3.
    Millichap JG (2008) Etiologic classification of attention-deficit/hyperactivity disorder. Pediatrics 121:e358–e365PubMedCrossRefGoogle Scholar
  4. 4.
    Lakshmi Priya MD, Geetha A (2011) Level of trace elements (copper, zinc, magnesium, and selenium) and toxic elements (lead and mercury) in the hair and nail of children with autism. Biol Trace Elem Res 142:148–158PubMedCrossRefGoogle Scholar
  5. 5.
    Llanos RM, Mercer JF (2002) The molecular basis of copper homeostasis copper-related disorders. DNA Cell Biol 21:259–270PubMedCrossRefGoogle Scholar
  6. 6.
    Biederman J (2005) Attention-deficit/hyperactivity disorder: a selective overview. Biol Psychiatry 57:1215–1220PubMedCrossRefGoogle Scholar
  7. 7.
    Toren P, Sofia E, Sela BA et al (1996) Zinc deficiency in ADHD. Biol Psychiatry 40:1308–1310PubMedCrossRefGoogle Scholar
  8. 8.
    Black MM (1998) Zinc deficiency and child development. Am J Clin Nutr 68:464S–469SPubMedPubMedCentralGoogle Scholar
  9. 9.
    Chen J, Berry MJ (2003) Selenium and selenoproteins in the brain and brain diseases. Neurochemistry 86:1–12CrossRefGoogle Scholar
  10. 10.
    Prasad AS, Bao B, Beck FW et al (2004) Antioxidant effect of zinc in humans. Free Radic Biol Med 37:1182–1190PubMedCrossRefGoogle Scholar
  11. 11.
    Oades RD, Sadile AG, Sagvolden T et al (2005) The control of responsiveness in ADHD by catecholamines: evidence for dopaminergic, noradrenergic, and interactive roles. Dev Sci 8:122–131PubMedCrossRefGoogle Scholar
  12. 12.
    Retz W, Freitag CM, Retz-Junginger P et al (2008) A functional serotonin transporter promoter gene polymorphism increases ADHD symptoms in delinquents: interaction with adverse childhood environment. Psychiatry Res 158:123–131PubMedCrossRefGoogle Scholar
  13. 13.
    Yu WR, Jiang H, Wang J, Xie JX (2008) Copper (Cu2+) induces degeneration of dopaminergic neurons in the nigrostriatal system of rats. Neurosci Bull 24:73–78PubMedCrossRefGoogle Scholar
  14. 14.
    Essawy H, El-Ghohary I, El-Missiry KO, Soliman A, El-Rashidi O (2009) Oxidative stress in attention deficit hyperactivity disorder patients. Curr Psychiatr 16:56–69Google Scholar
  15. 15.
    Lepping P, Huber M (2010) Role of zinc in the pathogenesis of attention-deficit hyperactivity disorder: implications for research and treatment. CNS Drugs 24:721–728PubMedGoogle Scholar
  16. 16.
    Grabrucker S, Jannetti L, Eckert M et al (2014) Zinc deficiency dysregulates the synaptic ProSAP/Shank scaffold and might contribute to autism spectrum disorders. Brain 137:137–152PubMedCrossRefGoogle Scholar
  17. 17.
    Cuajungco MP, Lees GJ (1997) Zinc metabolism in the brain: relevance to human neurodegenerative disorders. Neurobiol Dis 4:137–169PubMedCrossRefGoogle Scholar
  18. 18.
    Arnold LE, Bozzolo H, Hollway J et al (2005) Serum zinc correlates with parent- and teacher- rated inattention in children with attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 15:628–636PubMedCrossRefGoogle Scholar
  19. 19.
    Akhondzadeh S, Mohammadi MR, Khademi M (2004) Zinc sulphate as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in children: a double blind and randomized trial [ISRCTN64132371]. BMC Psychiatr 4:9CrossRefGoogle Scholar
  20. 20.
    Bilici M, Yildirim F, Kandil S et al (2004) Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry 28:181–190PubMedCrossRefGoogle Scholar
  21. 21.
    Schweizer U, Brauer AU, Kohrle J et al (2004) Selenium and brain function: a poorly recognized liaison. Brain Res Brain Res Rev 45:164–178PubMedCrossRefGoogle Scholar
  22. 22.
    Buchman AL, Neely M, Grossie VR, Truong L (2001) Organ heavy-metal accumulation during parenteral nutrition is associated with pathologic abnormalities in rats. Nutrition 17:600–606PubMedCrossRefGoogle Scholar
  23. 23.
    Foltinova J, Foltin V, Neu E (2007) Occurrence of lead in placenta-important information for prenatal and postnatal development of child. Neuro Endocrinol Lett 28:335–340PubMedGoogle Scholar
  24. 24.
    Jeff DA, Beckles RA, Navoa RV, McLemore GL (2002) Increased high-affinity nicotin receptor-binding in rats exposed to lead during development. Neurotoxicol Teratol 24:805–811CrossRefGoogle Scholar
  25. 25.
    Costa LG, Aschner M, Vitalone A et al (2004) Developmental neuropathology of environmental agents. Ann Rev Pharmacol Toxicol 44:87–110CrossRefGoogle Scholar
  26. 26.
    Nigg GM, Knottnerus MM, Martel M et al (2008) Low blood lead levels associated with clinically diagnosed attention-deficit/hyperactivity disorder and mediated by weak cognitive control. Biol Psychiatry 63:325–331PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Trebaticka J, Kopasova S, Hradecna Z et al (2006) Treatment of ADHD with French maritime pine bark extract, Pycnogenol. Eur Child Adolesc Psychiatry 15:329–335PubMedCrossRefGoogle Scholar
  28. 28.
    Qi JX (1990) Determination of Cu, Zn, Fe, Ca, Mg, Na and K in serum flame by atomic absorption spectroscopy. In: AA Instruments At Work, AA-93. Varian 1–2Google Scholar
  29. 29.
    Ursinyova M, Hladikova V (1998) Determination of selenium in serum using atomic absorption spectrometry. Chem List 92:495–498Google Scholar
  30. 30.
    Ursinyova M, Hladikova V, Sovcikova E (1995) Determination of lead in whole blood using atomic absorption spectrometry. Chem List 89:388–392Google Scholar
  31. 31.
    Kozielec T, Starobrat-Hermelin B, Kotkowiak L (1994) Deficiency of certain trace elements in children with hyperactivity. Psychiatr Pol 28:345–353PubMedGoogle Scholar
  32. 32.
    Starobrat-Hermelin B (1998) The effect of deficiency of selected bioelements on hyperactivity in children with certain specified mental disorders. Ann Acad Med Stetin 44:297–314PubMedGoogle Scholar
  33. 33.
    Gromova OA, Avdenko TV, Burtsev EM (1998) Effects of cerebrolysin on the oxidant homeostasis, the content of microelements and electrolytes in children with minimal brain dysfunction. Zh Nevrol Psikhiatr Im Korsakova 98:27–30Google Scholar
  34. 34.
    Shah F, Kazi TG, Afridi HI et al (2011) Evaluation of status of trace and toxic metals in biological samples (scalp hair, blood, and urine) of normal and anemic children of two age groups. Biol Trace Elem Res 141:131–149PubMedCrossRefGoogle Scholar
  35. 35.
    Mezzetti A, Pierdomenico SD, Costantini F et al (1998) Cooper/zinc ratio and systemic oxidant load: effect of aging and aging related degenerative diseases. Free Radic Biol Med 25:676–681PubMedCrossRefGoogle Scholar
  36. 36.
    Walsh WJ, Isaacson HR, Rehman F, Hall A (1997) Elevated blood copper/zinc ratios in assaultive young males. Physiol Behav 62:327–329PubMedCrossRefGoogle Scholar
  37. 37.
    DiGirolamo AM, Ramirez ZM (2009) Role of zinc in maternal and child mental health. Am J Clin Nutr 89:940–945CrossRefGoogle Scholar
  38. 38.
    Ghanizadeh A, Berk M (2013) Zinc for treating of children and adolescents with attention-deficit hyperactivity disorder: a systematic review of randomized controlled clinical trials. Eur J Clin Nutr 67:122–124PubMedCrossRefGoogle Scholar
  39. 39.
    Mahmoud MM, El-Mazary AA, Maher RM et al (2011) Zinc, ferritin, magnesium and copper in a group of Egyptian children with attention deficit hyperactivity disorder. Ital J Pediatr 29:37–60Google Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Alena Viktorinova
    • 1
  • Monika Ursinyova
    • 2
  • Jana Trebaticka
    • 3
  • Iveta Uhnakova
    • 2
  • Zdenka Durackova
    • 1
  • Vlasta Masanova
    • 2
  1. 1.Institute of Medical Chemistry, Biochemistry, and Clinical Biochemistry, Faculty of MedicineComenius UniversityBratislavaSlovak Republic
  2. 2.Laboratory of Toxic and Essential Elements, Department of Environmental MedicineSlovak Medical UniversityBratislavaSlovak Republic
  3. 3.Department of Pediatric Psychiatry, Faculty of MedicineComenius UniversityBratislavaSlovak Republic

Personalised recommendations