July 11, 2022

Acta Scientific Nutritional Health (ASNH)(ISSN: 2582-1423)

Review Article Volume 6 Issue 8

Zinc Deficiency in Major Depressive Disorder

Dana Shamshtein1 and Timur Liwinski2 *

1School of Psychological Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel
2University Psychiatric Clinics, University of Basel, Basel, Switzerland

*Corresponding Author: Timur Liwinski, University Psychiatric Clinics, University of Basel, Basel, Switzerland.

Received: May 16, 2022; Published: July 11, 2022

Abstract

Major depressive disorder (MDD) is a major public health concern necessitating novel strategies for prevention and treatment. Zinc is an essential trace element involved in a myriad of vital biological processes, including crucial brain processes. Zinc deficiency is a major global health concern. Cross-sectional surveys show that patients with MDD frequently suffer from insufficient zinc supply. Emerging evidence from randomized trials supports the role of zinc in treating MDD. This clinical data is supported by neurobiological evidence generated using animal models linking zinc deficiency with neuronal dysfunction and depressive-like behavior. Importantly, zinc might link inflammation with glutamatergic and serotonergic dysfunction in depression.

This brief review summarizes the most important clinical and basic science evidence for zinc’s role in depression and draws conclusions for the clinical practice.

 

Keywords: Zinc Deficiency; Major Depressive Disorder; Mental Health

References

  1. Greenberg PE., et al. “The Economic Burden of Adults With Major Depressive Disorder in the United States (2005 and 2010)”. The Journal of Clinical Psychiatry 76 (2015): 155-162.
  2. Thornicroft G., et al. “Undertreatment of people with major depressive disorder in 21 countries”. British Journal of Psychiatry 210 (2017): 119-124.
  3. Penninx BW., et al. “Understanding the somatic consequences of depression: biological mechanisms and the role of depression symptom profile”. BMC Medicine 11 (2013): 129.
  4. Lopez AD and Mathers CD. “Measuring the global burden of disease and epidemiological transitions: 2002-2030”. Annals of Tropical Medicine and Parasitology 100 (2006): 481-499.
  5. Otte C., et al. “Major depressive disorder”. Nature Reviews Disease Primers 2 (2016): 16065.
  6. Cipriani A., et al. “Comparative Efficacy and Acceptability of 21 Antidepressant Drugs for the Acute Treatment of Adults With Major Depressive Disorder: A Systematic Review and Network Meta-Analysis”. FOCUS 16 (2018): 420-429.
  7. Cassano P and Fava M. “Tolerability Issues During Long-Term Treatment with Antidepressants”. Annals of Clinical Psychiatry 16 (2004): 15-25.
  8. Berg RC and Høie B. “Effectiveness of psychotherapy for adults with depression: a systematic review of the best available evidence”. Procedia - Social and Behavioral Sciences 5 (2010): 2194-2200.
  9. Szewczyk B., et al. “The role of zinc in neurodegenerative inflammatory pathways in depression”. Progress in Neuro-Psychopharmacology and Biological Psychiatry 35 (2011): 693-701.
  10. Jurowski K., et al. “Biological consequences of zinc deficiency in the pathomechanisms of selected diseases”. JBIC Journal of Biological Inorganic Chemistry 19 (2014): 1069-1079.
  11. National Institutes of Health. Zinc. Fact Sheet for Health Professionals.
  12. Gau J-T., et al. “Serum Zinc Concentrations of Adults in an Outpatient Clinic and Risk Factors Associated With Zinc Deficiency”. Journal of Osteopathic Medicine 120 (2020): 796-805.
  13. Maxfield L., et al. “Zinc Deficiency (2021).
  14. Andreini C., et al. “Counting the Zinc-Proteins Encoded in the Human Genome”. Journal of Proteome Research 5 (2006): 196-201.
  15. Krall RF., et al. “The Function and Regulation of Zinc in the Brain”. Neuroscience 457 (2021): 235-258.
  16. Walker BR and Colledge NR. “Davidson’s principles and practice of medicine e-book”. Elsevier Health Sciences (2013).
  17. Prasad AS. “Zinc deficiency”. BMJ 326 (2003): 409-410.
  18. Dufner-Beattie J., et al. “The mouse acrodermatitis enteropathica gene Slc39a4 ( Zip4 ) is essential for early development and heterozygosity causes hypersensitivity to zinc deficiency”. Human Molecular Genetics 16 (2007): 1391-1399.
  19. Narváez-Caicedo C., et al. “Zinc Deficiency among Lactating Mothers from a Peri-Urban Community of the Ecuadorian Andean Region: An Initial Approach to the Need of Zinc Supplementation”. Nutrients 10 (2018): 869.
  20. Caulfield LE and Black RE. Zinc deficiency. “Comparative quantification of health risks: global and regional burden of disease attributable to selected major risk factors” 1 (2004).
  21. Khalid N., et al. “A Question Mark on Zinc Deficiency in 185 Million People in Pakistan-Possible Way Out”. Critical Reviews in Food Science and Nutrition 54 (2014): 1222-1240.
  22. Fischer Walker CL., et al. “Global and regional child mortality and burden of disease attributable to zinc deficiency”. European Journal of Clinical Nutrition 63 (2009): 591-597.
  23. Maverakis E., et al. “Acrodermatitis enteropathica and an overview of zinc metabolism”. Journal of the American Academy of Dermatology 56 (2007): 116-124.
  24. Swardfager W., et al. “Zinc in Depression: A Meta-Analysis”. Biological Psychiatry 74 (2013): 872-878.
  25. Maserejian NN., et al. “Low dietary or supplemental zinc is associated with depression symptoms among women, but not men, in a population-based epidemiological survey”. Journal of Affective Disorders 136 (2012): 781-788.
  26. Lehto SM., et al. “Dietary zinc intake and the risk of depression in middle-aged men: A 20-year prospective follow-up study”. Journal of Affective Disorders 150 (2013): 682-685.
  27. Stanisławska M., et al. “The Severity of Depressive Symptoms vs. Serum Mg and Zn Levels in Postmenopausal Women”. Biological Trace Element Research 157 (2014): 30-35.
  28. Kim T-H., et al. “Associations between Dietary Pattern and Depression in Korean Adolescent Girls”. Journal of Pediatric and Adolescent Gynecology 28 (2015): 533-537.
  29. Amani R., et al. “Correlation Between Dietary Zinc Intakes and Its Serum Levels with Depression Scales in Young Female Students”. Biological Trace Element Research 137 (2010): 150-158.
  30. Anbari-Nogyni Z., et al. “Relationship of zinc status with depression and anxiety among elderly population”. Clinical Nutrition ESPEN 37 (2020): 233-239.
  31. Gonoodi K., et al. “Relationship of Dietary and Serum Zinc with Depression Score in Iranian Adolescent Girls”. Biological Trace Element Research 186 (2018): 91-97.
  32. Li Z., et al. “Association of total zinc, iron, copper and selenium intakes with depression in the US adults”. Journal of Affective Disorders 228 (2018): 68-74.
  33. Twayej AJ., et al. “Lowered zinc and copper levels in drug-naïve patients with major depression: Effects of antidepressants, ketoprofen and immune activation”. The World Journal of Biological Psychiatry 21 (2020): 127-138.
  34. Yosaee S., et al. “Zinc in depression: From development to treatment: A comparative/ dose response meta-analysis of observational studies and randomized controlled trials”. General Hospital Psychiatry 74 (2022): 110-117.
  35. da Silva LEM., et al. “Zinc supplementation combined with antidepressant drugs for treatment of patients with depression: a systematic review and meta-analysis”. Nutrition Reviews 79 (2021): 1-12.
  36. Huang EP. “Metal ions and synaptic transmission: Think zinc”. Proceedings of the National Academy of Sciences 94 (1997): 13386-13387.
  37. Wang J., et al. “Zinc, Magnesium, Selenium and Depression: A Review of the Evidence, Potential Mechanisms and Implications”. Nutrients 10 (2018): 584.
  38. Gao H-L., et al. “Zinc Deficiency Reduces Neurogenesis Accompanied by Neuronal Apoptosis Through Caspase-Dependent and -Independent Signaling Pathways”. Neurotoxicity Research 16 (2009): 416-425.
  39. Pfaender S., et al. “Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem Cells”. Neural Plasticity 2016 (2016): 1-15.
  40. Eisch AJ and Petrik D. “Depression and Hippocampal Neurogenesis: A Road to Remission?” Science 338 (2012): 72-75.
  41. Tena-Campos M., et al. “The zinc binding receptor GPR39 interacts with 5-HT1A and GalR1 to form dynamic heteroreceptor complexes with signaling diversity”. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1852 (2015): 2585-2592.
  42. Młyniec K., et al. “Investigation of the GPR39 zinc receptor following inhibition of monoaminergic neurotransmission and potentialization of glutamatergic neurotransmission”. Brain Research Bulletin 115 (2015): 23-29.
  43. Młyniec K., et al. “Study of antidepressant drugs in GPR39 (zinc receptor-/-) knockout mice, showing no effect of conventional antidepressants, but effectiveness of NMDA antagonists”. Behavioural Brain Research 287 (2015): 135-138.
  44. Petrilli MA., et al. “The Emerging Role for Zinc in Depression and Psychosis”. Frontiers in Pharmacology 8 (2017).
  45. Pittenger C., et al. “The NMDA Receptor as a Therapeutic Target in Major Depressive Disorder”. CNS and Neurological Disorders - Drug Targets 6 (2007): 101-115.
  46. Doboszewska U., et al. “Zinc in the Monoaminergic Theory of Depression: Its Relationship to Neural Plasticity”. Neural Plasticity 2017 (2017): 1-18.
  47. Rosa AO., et al. “Involvement of NMDA receptors and l-arginine-nitric oxide pathway in the antidepressant-like effects of zinc in mice”. Behavioural Brain Research 144 (2013): 87-93.
  48. Brites D and Fernandes A. “Neuroinflammation and Depression: Microglia Activation, Extracellular Microvesicles and microRNA Dysregulation”. Frontiers in Cellular Neuroscience (2015): 9.
  49. Remus JL and Dantzer R. “Inflammation Models of Depression in Rodents: Relevance to Psychotropic Drug Discovery”. International Journal of Neuropsychopharmacology 19 (2016): pyw028.
  50. Hongxia L., et al. “Zinc inhibited LPS-induced inflammatory responses by upregulating A20 expression in microglia BV2 cells”. Journal of Affective Disorders 249 (2019): 136-142.
  51. Kirsten TB., et al. “Zinc, but not paracetamol, prevents depressive-like behavior and sickness behavior, and inhibits interferon-gamma and astrogliosis in rats”. Brain, Behavior, and Immunity 87 (2020): 489-497.
  52. Alizadeh F., et al. “Prenatal zinc supplementation attenuates lipopolysaccharide-induced behavioral impairments in maternal immune activation model”. Behavioural Brain Research 377 (2020): 112247.
  53. Prakash A., et al. “Zinc: indications in brain disorders”. Fundamental and Clinical Pharmacology 29 (2015): 131-149.
  54. Nowak G. “Does interaction between zinc and glutamate system play a significant role in the mechanism of antidepressant action?” Acta Poloniae Pharmaceutica 58 (2001): 73-75.
  55. Liuzzi JP., et al. “Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response”. Proceedings of the National Academy of Sciences 102 (2005): 6843-6848.
  56. Petrilli MA., et al. “The Emerging Role for Zinc in Depression and Psychosis”. Frontiers in Pharmacology (2017): 8.
  57. Parrott J., et al. “American Society for Metabolic and Bariatric Surgery Integrated Health Nutritional Guidelines for the Surgical Weight Loss Patient 2016 Update: Micronutrients”. Surgery for Obesity and Related Diseases 13 (2017): 727-741.
  58. Freitas B., et al. “Micronutrient supplementation adherence and influence on the prevalences of anemia and iron, zinc and vitamin A deficiencies in preemies with a corrected age of six months”. Clinics 71 (2016): 440-448.
  59. Hess SY., et al. “Use of Serum Zinc Concentration as an Indicator of Population Zinc Status”. Food and Nutrition Bulletin 28 (2007): S403-429.
  60. Hambidge KM and Krebs NF. “Zinc Deficiency: A Special Challenge”. The Journal of Nutrition 137 (2007): 1101-1105.
  61. Maret W and Sandstead HH. “Zinc requirements and the risks and benefits of zinc supplementation”. Journal of Trace Elements in Medicine and Biology 20 (2006): 3-18.
  62. Simmons WK., et al. “Depression-Related Increases and Decreases in Appetite: Dissociable Patterns of Aberrant Activity in Reward and Interoceptive Neurocircuitry”. American Journal of Psychiatry 173 (2016): 418-428.
  63. Khosravi M., et al. “The relationship between dietary patterns and depression mediated by serum levels of Folate and vitamin B12”. BMC Psychiatry 20 (2020): 63.

Citation

Citation: Dana Shamshtein and Timur Liwinski. “Zinc Deficiency in Major Depressive Disorder". Acta Scientific Nutritional Health 6.8 (2022): 47-53.

Copyright

Copyright: © 2022 Dana Shamshtein and Timur Liwinski. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.




Metrics

Acceptance rate30%
Acceptance to publication20-30 days
Impact Factor1.316

Indexed In





News and Events


  • Certification for Review
    Acta Scientific certifies the Editors/reviewers for their review done towards the assigned articles of the respective journals.
  • Submission Timeline for Upcoming Issue
    The last date for submission of articles for regular Issues is October 10, 2022.
  • Publication Certificate
    Authors will be issued a "Publication Certificate" as a mark of appreciation for publishing their work.
  • Best Article of the Issue
    The Editors will elect one Best Article after each issue release. The authors of this article will be provided with a certificate of “Best Article of the Issue”.
  • Welcoming Article Submission
    Acta Scientific delightfully welcomes active researchers for submission of articles towards the upcoming issue of respective journals.
  • Contact US