Higher zinc concentrations in hair of Parkinson’s disease are associated with psychotic complications and depression

  • Altair Brito Dos Santos
  • Marcos A. Bezerra
  • Marcelo E. Rocha
  • George E. Barreto
  • Kristi A. KohlmeierEmail author
Neurology and Preclinical Neurological Studies - Original Article


Parkinson’s disease (PD) is classically considered a motor disease; however, several non-motor symptoms are also present, including psychiatric complaints. In recent decades, the metals Ca, Fe, and Zn have gained prominence as potential etiologic factors in motoric signs of PD. However, metal alterations could be associated with the non-motor symptoms of PD. We wished to correlate the levels of these metals with the co-occurrence of depression, anxiety, and psychotic symptoms in PD patients. To this end, the Beck Depression Inventory, the Beck Anxiety Inventory, and the Scales for Outcomes in Parkinson’s disease-Psychiatric Complications (SCOPA-PC) were implemented to evaluate mood disorders and psychiatric complications. Flame atomic absorption spectrometry (FAAS) was used to assess concentrations of Ca, Fe, and Zn in hair samples collected from 22 clinically diagnosed PD patients, which represented the entire cohort of accessible patients in a Brazilian health registry, and 33 healthy individuals. While Ca and Fe alterations were not found to be associated with psychiatric complaints in the PD group, significantly higher levels of Zn were correlated in PD patients with depression and some psychotic symptoms. Within individual domains of the SCOPA-PC, significantly higher levels of Zn were correlated with the presence of hallucination, illusion, and paranoid ideation when compared to controls and PD patients who did not present these symptoms. Although our sample size is small and findings need to be replicated in larger and heterogeneous populations, our results provide a new perspective on the use of monitoring of Zn levels as a potential biomarker of psychiatric complaints, and may be useful in the development of more effective therapeutic approaches for the management of PD patients with co-occurrence of psychiatric disorders.


Neurodegeneration Biomarkers Metal imbalance Non-motor symptoms 



Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil for funding support of a Ph.D Grant to Altair Brito dos Santos.


This work was financially supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil. Grant Numbers (99999.012934/2013-05).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict interests.


  1. Aarsland D, Zaccai J, Brayne C (2005) A systematic review of prevalence studies of dementia in Parkinson’s disease. Mov Disord 20:1255–1263. CrossRefGoogle Scholar
  2. Arnulf I, Leu S, Oudiette D (2008) Abnormal sleep and sleepiness in Parkinson’s disease. Curr Opin Neurol 24:472–477. CrossRefGoogle Scholar
  3. Barone P, Antonini A, Colosimo C et al (2009) The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Disord 24:1641–1649. CrossRefGoogle Scholar
  4. Bengoa-Vergniory N, Roberts RF, Wade-Martins R, Alegre-Abarrategui J (2017) Alpha-synuclein oligomers: a new hope. Acta Neuropathol 134:819–838. CrossRefGoogle Scholar
  5. Bocca B, Alimonti A, Senofonte O et al (2006) Metal changes in CSF and peripheral compartments of parkinsonian patients. J Neurol Sci 248:23–30. CrossRefGoogle Scholar
  6. Braak H, Del Tredici K, Rüb U et al (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211. CrossRefGoogle Scholar
  7. Cunha JA (2001) Manual da versão em português das Escalas Beck. Casa do Psicólogo, São Paulo. On-line version ISSN 2175-3563.
  8. de Bartolomeis A, Latte G, Tomasetti C, Iasevoli F (2014) Glutamatergic postsynaptic density protein dysfunctions in synaptic plasticity and dendritic spines morphology: relevance to schizophrenia and other behavioral disorders pathophysiology, and implications for novel therapeutic approaches. Mol Neurobiol 49:484–511. CrossRefGoogle Scholar
  9. dos Santos AB, Kohlmeier KA, Rocha ME et al (2018) Hair in Parkinson’s disease patients exhibits differences in calcium, iron and zinc concentrations measured by flame atomic absorption spectrometry (FAAS). J Trace Elem Med Biol 47:134–139. CrossRefGoogle Scholar
  10. Fénelon G (2000) Hallucinations in Parkinson’s disease: prevalence, phenomenology and risk factors. Brain 123:733–745. CrossRefGoogle Scholar
  11. Fénelon G (2008) Psychosis in Parkinson’s disease: phenomenology, frequency, risk factors, and current understanding of pathophysiologic mechanisms. CNS Spectr 13:18–25. CrossRefGoogle Scholar
  12. Fénelon G, Alves G (2010) Epidemiology of psychosis in Parkinson’s disease. J Neurol Sci. Google Scholar
  13. Ffytche DH, Creese B, Politis M et al (2017) The psychosis spectrum in Parkinson’s disease. Nat Rev Neurol 13:81–95. CrossRefGoogle Scholar
  14. Fink AL (2006) The aggregation and fibrillation of α-synuclein. Acc Chem Res 39:628–634. CrossRefGoogle Scholar
  15. Forte G, Alimonti A, Violante N et al (2005) Calcium, copper, iron, magnesium, silicon and zinc content of hair in Parkinson’s disease. J Trace Elem Med Biol 19:195–201. CrossRefGoogle Scholar
  16. Fukushima T, Tan X, Luo Y et al (2013) Heavy metals in blood and urine and its relation to depressive symptoms in Parkinson’s disease patients. Fukushima J Med Sci 59:76–80. CrossRefGoogle Scholar
  17. Gammoh NZ, Rink L (2017) Zinc in infection and inflammation. Nutrients 9(6):624. CrossRefGoogle Scholar
  18. Gibson G, Mottram PG, Burn DJ et al (2013) Frequency, prevalence, incidence and risk factors associated with visual hallucinations in a sample of patients with Parkinson’s disease: a longitudinal 4-year study. Int J Geriatr Psychiatry 28(6):626–631. CrossRefGoogle Scholar
  19. Harding AJ, Stimson E, Henderson JM, Halliday GM (2002) Clinical correlates of selective pathology in the amygdala of patients with Parkinson’s disease. Brain 125(Pt 11):2431–2445. CrossRefGoogle Scholar
  20. Iasevoli F, Tomasetti C, Buonaguro EF, de Bartolomeis A (2014) The glutamatergic aspects of schizophrenia molecular pathophysiology: role of the postsynaptic density, and implications for treatment. Curr Neuropharmacol 12:219–238. CrossRefGoogle Scholar
  21. Jaishankar M, Tseten T, Anbalagan N et al (2014) Toxicity, mechanism and health effects of some heavy metals. Interdiscip Toxicol 7:60–72. CrossRefGoogle Scholar
  22. Janzen J, Van’T Ent D, Lemstra AW et al (2012) The pedunculopontine nucleus is related to visual hallucinations in Parkinson’s disease: preliminary results of a voxel-based morphometry study. J Neurol 259(1):147–154. CrossRefGoogle Scholar
  23. Jiao J, Guo H, He Y et al (2016) Meta-analysis of the association between serum iron levels and Parkinson’s disease: evidence from 11 publications. Brain Res 1646:490–493. CrossRefGoogle Scholar
  24. Lai J, Moxey A, Nowak G et al (2012) The efficacy of zinc supplementation in depression: systematic review of randomised controlled trials. J Affect Disord 136(1–2):e31–e39. CrossRefGoogle Scholar
  25. Lauterbach EC (2004) Differential DSM-III psychiatric disorder prevalence profiles in dystonia and Parkinson’s disease. J Neuropsychiatr 16:29–36. CrossRefGoogle Scholar
  26. Leal SS, Botelho HM, Gomes CM (2012) Metal ions as modulators of protein conformation and misfolding in neurodegeneration. Coord Chem Rev 256:2253. CrossRefGoogle Scholar
  27. Marsh L (2013) Depression and Parkinson’s disease: current knowledge. Curr Neurol Neurosci Rep 1:2. Google Scholar
  28. Miyake Y, Tanaka K, Fukushima W et al (2011) Dietary intake of metals and risk of Parkinson’s disease: a case-control study in Japan. J Neurol Sci 306:98–102. CrossRefGoogle Scholar
  29. Miyasaki JM, Al Hassan K, Lang AE, Voon V (2007) Punding prevalence in Parkinson’s disease. Mov Disord 22(8):1179–1181. CrossRefGoogle Scholar
  30. Mlyniec K (2015) Zinc in the glutamatergic theory of depression. Curr Neuropharmacol 13(4):505–513. CrossRefGoogle Scholar
  31. Młyniec K, Davies CL, de Agüero Sánchez IG et al (2014) Essential elements in depression and anxiety. Part I. Pharmacol Rep 66:534–544. CrossRefGoogle Scholar
  32. Mostile G, Cicero CE, Giuliano L et al (2017) Iron and Parkinson’s disease: a systematic review and meta-analysis. Mol Med Rep 15(5):3383–3389. CrossRefGoogle Scholar
  33. Petrilli MA, Kranz TM, Kleinhaus K et al (2017) The emerging role for zinc in depression and psychosis. Front Pharmacol 8:414. CrossRefGoogle Scholar
  34. Ranjbar E, Shams J, Sabetkasaei M et al (2014) Effects of zinc supplementation on efficacy of antidepressant therapy, inflammatory cytokines, and brain-derived neurotrophic factor in patients with major depression. Nutr Neurosci 17:65–71. CrossRefGoogle Scholar
  35. Reijnders JS, Ehrt U, Weber WE et al (2008) A systematic review of prevalence studies of depression in Parkinson’s disease. Mov Disord 23:183–189. CrossRefGoogle Scholar
  36. Romana Pezzella F, Colosimo C, Vanacore N et al (2005) Prevalence and clinical features of hedonistic homeostatic dysregulation in Parkinson’s disease. Mov Disord 20:77–81. CrossRefGoogle Scholar
  37. Schwartz TL, Sachdeva S, Stahl SM (2012) Glutamate neurocircuitry: theoretical underpinnings in schizophrenia. Front Pharmacol 3:195. CrossRefGoogle Scholar
  38. Solati Z, Jazayeri S, Tehrani-Doost M et al (2015) Zinc monotherapy increases serum brain-derived neurotrophic factor (BDNF) levels and decreases depressive symptoms in overweight or obese subjects: a double-blind, randomized, placebo-controlled trial. Nutr Neurosci 18:162–168. CrossRefGoogle Scholar
  39. Stelmashook EV, Isaev NK, Genrikhs EE et al (2014) Role of zinc and copper ions in the pathogenetic mechanisms of Alzheimer’s and Parkinson’s diseases. Biochemistry 79:391–396. Google Scholar
  40. Surmeier DJ, Schumacker PT, Guzman JD et al (2017) Calcium and Parkinson’s disease. Biochem Biophys Res Commun 483(4):1013–1019. CrossRefGoogle Scholar
  41. Swardfager W, Herrmann N, Mazereeuw G et al (2013) Zinc in depression: a meta-analysis. Biol Psychiatry 74:872–878. CrossRefGoogle Scholar
  42. Swardfager W, Herrmann N, Mazereeuw G, Lanctôt KL (2015) Reply to: serum zinc and the risk of depression in men: observations from a 20-year follow-up study. Biol Psychiatry 77:e13–e14. CrossRefGoogle Scholar
  43. Szewczyk B, Poleszak E, Sowa-Kućma M et al (2010) The involvement of NMDA and AMPA receptors in the mechanism of antidepressant-like action of zinc in the forced swim test. Amino Acids 39:205–217. CrossRefGoogle Scholar
  44. Tsai G, Lin P-Y (2010) Strategies to enhance N-methyl-D-aspartate receptor-mediated neurotransmission in schizophrenia, a critical review and meta-analysis. Curr Pharm Des 16:522–537. CrossRefGoogle Scholar
  45. Uversky VN, Li J, Fink AL (2001) Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular link between Parkinson’s disease and heavy metal exposure. J Biol Chem 276:44284–44296. CrossRefGoogle Scholar
  46. Vashum KP, McEvoy M, Milton AH et al (2014) Dietary zinc is associated with a lower incidence of depression: findings from two Australian cohorts. J Affect Disord 166:249–257. CrossRefGoogle Scholar
  47. Visser M, Verbaan D, van Rooden SM et al (2007) Assessment of psychiatric complications in Parkinson’s disease: the SCOPA-PC. Mov Disord 22:2221–2228. CrossRefGoogle Scholar
  48. Wang Y, Shi M, Chung KA et al (2012) Phosphorylated α-synuclein in Parkinson’s disease. Sci Trans Med 4:121ra20. Google Scholar
  49. Willams DR, Warren JD, Lees AJ (2008) Using the presence of visual hallucinations to differentiate Parkinson’s disease from atypical parkinsonism. J Neurol Neurosurg Psychiatry 1:2. Google Scholar
  50. Yu X, Du T, Song N et al (2013) Decreased iron levels in the temporal cortex in postmortem human brains with Parkinson’s disease. Neurology 80:492–495. CrossRefGoogle Scholar
  51. Zhang G, Zhang G et al (2014) Impulisve and compulsive behaviors in Parkinson’s disease. Front Aging Neurosci 6:318. Google Scholar
  52. Zhao H-W, Lin J, Wang X-B et al (2013) Assessing plasma levels of selenium, copper, iron and zinc in patients of Parkinson’s disease. PLoS One 8:e83060. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Drug Design and PharmacologyUniversity of CopenhagenCopenhagenDenmark
  2. 2.Departamento de Ciências e TecnologiasUniversidade Estadual do Sudoeste da BahiaJequiéBrazil
  3. 3.Department of Biological SciencesUniversity of LimerickLimerickIreland

Personalised recommendations