Selenium and manganese in depression – preclinical and clinical studies

Open access


According to the World Health Organization estimates, approximately 10% of the world’s population is affected by depressive disorders. Furthermore, even in high-income countries, many people with depression are not treated, which can lead to serious health consequences and a global economic loss. Unfortunately, the current pharmacotherapy of depressive disorders is characterized by unsatisfactory efficacy and the therapeutic effect is accompanied by many side effects. For this reason, there is still ongoing worldwide research to find new antidepressant therapies. In recent years, many data have been shown that essential elements demonstrate the antidepressant action and increase the effect of antidepressants. In this paper we present the results from the preclinical and clinical studies published over the years which show the involvement of selenium and manganese in depressive disorders. In this article, the relationship between the amount of these microelements in a diet and depression is reviewed and what's more, the association among these elements in different biomaterial and their relations to depressive symptoms is presented. Additionally, we discuss the possible influence of selenium and manganese on modulating neurotransmitter system involved in depression.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Abdalian R Saqui O Fernandes G Allard JP. Effects of manganese from a commercial multi-trace element supplement in a population sample of Canadian patients on long-term parenteral nutrition. J Parenter Enteral Nutr. 2013;37(4):538.

  • 2. Aschner JL Aschner M. Nutritional aspects of manganese homeostasis. Mol Aspects Med. 2005;26(4-5):353.

  • 3. Aschner M. Manganese: brain transport and emerging research needs. Environ Health Perspect. 2000;108(3):429.

  • 4. Becker W Kumpulainen J. Contents of essential and toxic mineral elements in Swedish market-basket diets in 1987. Br J Nutr. 1991;66(2):151.

  • 5. Banikazemi Z Mirzaei H Mokhber N Mobarhan MG. Selenium Intake is Related to Beck’s Depression Score. Iran Red Crescent Med J.2016;18(3):e21993.

  • 6. Benton D Cook R. The impact of selenium supplementation on mood. Biol Psychiatry. 1991;29(11):1092.

  • 7. Bouabid S Delaville C De Deurwaerdere P Lakhdar-Ghazal N Benazzouz A. Manganese-Induced Atypical Parkinsonism Is Associated with Altered Basal Ganglia Activity and Changes in Tissue Levels of Monoamines in the Rat. PLoS One. 2014;9(6): e98952.

  • 8. Bowler RM Roels HA Nakagawa S Drezgic M Diamond E Park R et al. Dose-effect relationships between manganese exposure and neurological neuropsychological and pulmonary function in confined space bridge welders. Occup Environ Med. 2007;64(3):167.

  • 9. Brűning C.A. Souza AC Gai BM Zeni G Nogueira CW. Antidepressant-like effect of m-trifluoromethyl-diphenyl diselenide inthe mouse forced swim-ming test involves opioid and serotonergic systems. Eur J Pharmacol. 2011;658:145.

  • 10. Capita R Alonso-Calleja C. Intake of nutrients associated with an increased risk of cardiovascular disease in a Spanish population. Int J Food Sci Nutr. 2003;54(1):57.

  • 11. Chun OK. Estimation of antioxidant intakes from diet and supplements in U.S. adults. J. Nutr. 2010;140(2):317.

  • 12. Domingo JL Perello G Gine Bordonaba J. Dietary intake of metals by the population of Tarragona County (Catalonia Spain): results from a duplicate diet study. Biol Trace Elem Res. 2012;146(3):420.

  • 13. Donato F de Gomes MG Goes AT Seus N Alves D Jesse CR et al. Involvement of the dopaminergic and serotonergic systems in the antidepressant-like effect caused by 4-phenyl-1- (phenylselanylmethyl)-123-triazole. Life Sci. 2013;93(9-11): 393.

  • 14. Finley JW Penland JG. Adequacy or deprivation of dietary selenium in healthy men: clinical and psychological findings. J Trace Elem Exp Med. 1998;11:11.

  • 15. Fukushima T Tan X Luo Y Wang P Song J Kanda H et al. Correlations among heavy metals in blood and urine and their relations to depressive symptoms in Parkinson’s disease patients. Fukushima J Med Sci. 2014;60(2):108.

  • 16. Fukushima T Tan X Luo Y Wang P Song J Kanda H et al. Heavy metals in blood and urine and its relation to depressive symptoms in Parkinson’s disease patients. Fukushima J Med Sci. 2013;59(2):76.

  • 17. Gao S Jin Y Unverzagt FW Liang C Hall KS Cao J et al. Selenium level and depressive symptoms in a rural elderly Chinese cohort. BMC Psychiatry. 2012;12:72.

  • 18. Gerzson MF Victoria FN Radatz CS de Gomes MG Boeira SP Jacob RG et al. In vitro antioxidant activity and in vivo antidepressantlike effect of α-(phenylselanyl) acetophenone in mice. Pharmacol Biochem Behav. 2012;102(1):21.

  • 19. Gil M Głodek E Rudy M. Ocena spożycia witamin i składnikow minerałow całodziennych racjach pokarmowych studentow Uniwersytetu Rzeszowskiego. Rocz Panstw Zakl Hig. 2012;63(4):441.

  • 20. Gosney MA et al. Effect of micronutrient supplementation on mood in nursing home residents. Gerontology. 2008;54(5):292.

  • 21. Hardy G Hardy I. Selenium: the Se-XY nutraceutical. Nutrition. 2004;20:590.

  • 22. Hong SB Kim JW Choi BS Hong YC Park EJ Shin MS et al. Blood manganese levels in relation to comorbid behavioral and emotional problems in children with attention-deficit/hyperactivity disorder. Psychiatry Res. 2014;220(1-2):418.

  • 23. Ibrahim KS El-Sayed EM. Proposed remedies for some developmental disorders. Toxicol Ind Health. 2013;29(4):367.

  • 24. Institute of Medicine. 2001. Dietary Reference Intakes for Vitamin A Vitamin K Arsenic Boron Chromium Copper Iodine Iron Manganese Molybdenum Nickel Silicon Vanadium and Zinc. Washington DC: The National Academies Press.

  • 25. Jacka F Berk M. Food for thought. Acta Neuropsychiatr. 2007;19:321.

  • 26. Jesse CR Wilhelm EA Bortolatto CF Nogueira CW. Evidence for the involvement of the serotonergic 5-HT2A/C and 5-HT3 receptors in the antidepressant-like effect caused by oral administration of bis selenide in mice. Prog Neuropsychopharmacol. Biol Psychiatry. 2010;34:294.

  • 27. Jędrzejczak R. Żelazo i mangan w żywności. Roczn. PZH. 2004; 55(suppl):13-20.

  • 28. Jiang J Lu S Zhang H Liu G Lin K Huang W et al.: Dietary intake of human essential elements from a Total Diet Study in Shenzhen Guangdong Province China. J Food Comp Anal. 2015;39:1.

  • 29. Kipp AP Strohm D Brigelius-Flohe R Schomburg L Bechthold A Leschik-Bonnet E et al. German Nutrition Society (DGE. Revised reference values for selenium intake. J Trace Elem.Med Biol. 2015;32:195.

  • 30. Krishna S Dodd CA Hekmatyar SK Filipov NM. Brain deposition and neurotoxicity of manganese in adult mice exposed via the drinking water. Arch Toxicol. 2014;88(1):47.

  • 31. Lakhan SE Vieira KF. Nutritional therapies for mental disorders. Nutr J. 2008;7:2.

  • 32. Modrzejewska R Bomba J. Rozpowszechnienie zaburzeń psychicznych i używania substancji psychoaktywnych w populacji 17-letniej młodzieży wielkomiejskiej. Psychiatr Pol. 2010;44(4):79.

  • 33. Mokhber N Namjoo M Tara F Boskabadi H Rayman MP Ghayour-Mobarhan M et al. Effect of supplementation with selenium on postpartum depression: a randomized double-blind placebocontrolled trial. J Matern Fetal Neonatal Med. 2011;24(1):104.

  • 34. Noel L Leblanc JC Guerin T. Determination of several elements in duplicate meals from catering establishments using closed vessel microwave digestion with inductively coupled plasma mass spectrometry detection: estimation of daily dietary intake. Food Addit Contam. 2003;20(1):44.

  • 35. Pasco JA Jacka FN Williams LJ Evans-Cleverdon M Brennan SL Kotowicz MA et al. Dietary selenium and major depression: a nested case-control study. Complement Ther Med. 2012;20(3):119.

  • 36. Peet M. International variations in the outcome of schizophrenia and the prevalence of depression in relation to national dietary practices: an ecological analysis. Br J Psychiatry. 2004;184:404.

  • 37. Penland JG Johnson PE. Dietary calcium and manganese effects on menstrual cycle symptoms. Am J Obstet Gynecol. 1993;168:1417.

  • 38. Pinto Brod LM Fronza MG Vargas JP Ludtke DS Luchese C Wilhelm EA et al. Involvement of monoaminergic system in the antidepressant-like effect of (octylseleno)-xylofuranoside in the mouse tail suspension test. Prog Neuropsychopharmacol Biol Psychiatry. 2016;65:201.

  • 39. Posser T Kaster MP Barauna SC Rocha JB Rodrigues AL Leal RB. Antidepressant-like effect of the organoselenium compound ebselen in mice: evidence for the involvement of the monoaminergic system. Eur J Pharmacol. 2009;602:85.

  • 40. Rayman M Thompson A Warren-Perry M Galassini R Catterick J Hall E et al.: Impact of selenium on mood and quality of life: a randomized controlled trial. Biol Psychiatry. 2006;59:147.

  • 41. Robberecht HJ Hendrix P Van Cauwenbergh R Deelstra HA. Actual daily dietary intake of selenium in Belgium using duplicate portion sampling. Z Lebensm Unters Forsch. 1994;199(4):251.

  • 42. Robberecht HJ Hendrix P Van Cauwenbergh R Deelstra HA. Daily dietary manganese intake in Belgium using duplicate portion sampling. Z Lebensm Unters Forsch. 1994;199(6):446.

  • 43. Roca M Kohls E Gili M Watkins E Owens M Hegerl U et al. Prevention of depression through nutritional strategies in high-risk persons: rationale and design of the MooDFOOD prevention trial. BMC Psychiatry. 2016;16:192.

  • 44. Rose M Baxter M Brereton N Baskaran C. Dietary exposure to metals and other elements in the 2006 UK Total Diet Study and some trends over the last 30 years. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2010;27(10):1380.

  • 45. Rubio-Lopez N Morales-Suarez-Varela M Pico Y Livianos-Aldana L Llopis-Gonzalez A. Nutrient Intake and Depression Symptoms in Spanish Children: The ANIVA Study. Int J Environ Res Public Health. 2016;13(3):352.

  • 46. Rybakowski J. Możliwości leczenia zaburzeń depresyjnych i lękowych przez lekarzy podstawowej opieki zdrowotnej. Psychiatr w Prakt Ogolnolek. 2001;1(1):11.

  • 47. Sartori Oliveira CE Gai BM Godoi B Zeni G Nogueira CW. The antidepressant-like action of a simple selenium-containing molecule methyl phenyl selenide in mice. Eur J Pharmacol. 2012;690:119.

  • 48. Savegnago L Jesse CR Pinto LG Rocha JB Nogueira CW Zeni G. Monoaminergic agents modulate antidepressant-like effect caused by diphenyl diselenide in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(6):1261.

  • 49. Sher L. Role of selenium depletion in the etiopathogenesis of depression in patient with alcoholism. Med Hypotheses. 2002;59(3): 330.

  • 50. Sher L. Depression and suicidal behavior in alcohol abusing adolescents: possible role of selenium deficiency. Minerva Pediatr. 2008;60(2):201.

  • 51. Shiue I.: Urinary heavy metals phthalates and polyaromatic hydrocarbons independent of health events are associated with adult depression: USA NHANES 2011-2012. Environ Sci Pollut Res Int. 2015;22(21):17095.

  • 52. Shor-Posner G Lecusay R Miguez MJ Moreno-Black G Zhang G Rodriguez N et al. Psychological burden in the era of HAART: impact of selenium therapy. Int J Psychiatry Med. 2003;33:55.

  • 53. Talarowska M Orzechowska A Szemraj J Su KP Maes M Gałecki P. Manganese superoxide dismutase gene expression and cognitive functions in recurrent depressive disorder. Neuropsychobiology. 2014;70(1):23.

  • 54. Talarowska M Szemraj J Berk M Maes M Gałecki P. Oxidant/ antioxidant imbalance is an inherent feature of depression. BMC Psychiatry. 2015;15:71.

  • 55. Ulewicz-Magulska B. (2008). Selen w roślinnych surowcach leczniczych zawartość rozi wzajemne relacje z innymi pierwiastkami. PhD. Thesis. Medical Academy of Gdansk Gdańsk.

  • 56. Victoria FN Anversa R Penteado F Castro M Lenardao EJ Savegnago L. Antioxidant and antidepressant-like activities of semisynthetic α-phenylseleno citronellal. Eur J Pharmacol. 2014;742:131.

  • 57. Wąsowicz W Gromadzinska J Rydzynski K Tomczak J. Selenium status of low-selenium area residents: Polish experience. Toxicol Lett. 2003;137(1-2):95.

  • 58. World Health Organization 2016 Depression. A Global Public Health Concern. [Accesed on 27.04.2017].

  • 59. Yamagata AT Guimaraes NC Santana DF Goncalves MR Souza VC Barbosa Junior F et al. Gender influence on manganese induced depression-like behavior and Mn and Fe deposition in different regions of CNS and excretory organs in intraperitoneally exposed rats. Toxicology. 2017;376:137.

  • 60. Ziemlański S. Normy żywienia człowieka. Fizjologiczne podstawy. Warszawa: Wydawnictwo Lekarskie PZWL; 2001.

Journal information
Impact Factor

CiteScore 2018: 0.32

SCImago Journal Rank (SJR) 2018: 0.154
Source Normalized Impact per Paper (SNIP) 2018: 0.285

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 519 294 14
PDF Downloads 274 177 12