• Depression and serum levels of heavy metals in human studies: a systematic review
  • Mohammad Mahdi Fadavi,1,* Ghasem Fadavi,2 Fatemeh Mohammadi-Nasrabadi,3
    1. Medical student at the School of Medicine, Tehran University of Medical Sciences (TUMS)
    2. Assistant professor, Food, Halal and Agricultural Products Research Group, Research Center of Food Technology and Agricultural Products, Standard Research Institute
    3. Associate Professor (Research), Food and Nutrition Policy and Planning Research Department, National Nutrition and Food Technology Research Institute (NNFTRI), Faculty of Nutrition Sciences and Food technology, Shahid Beheshti University of Medical Sciences


  • Introduction: Environmental pollutants, including heavy metals, can affect neurobiological processes. Depression is one of the most common neurologic disorders and some evidence has emerged showing that heavy metal pollutants are associated with depressive symptoms and their severity. Therefore, the current review was aimed at providing evidence of the relationship between serum levels of heavy metals and depression.
  • Methods: A literature search on PubMed, MEDLINE, SCOPUS, Web of Science, and google scholar has been conducted, and 21 articles published on the association of serum levels of Lead (Pb), Cadmium (Cd), Mercury (Hg), Arsenic (As) and depression in humans have been included, cited, reviewed, and summarized. The review included all field and community trials and observational studies in all population groups. Searching electronic databases, study selection, and data extraction have been conducted by two researchers independently. Pb and Cd levels were determined by atomic absorption spectrometry. Total serum Hg levels were determined using a direct mercury analyzer. The outcome variable depression was defined based on a diagnosis through records of hospitalization, physician’s diagnosis, the treatment for depression, or otherwise stated International Classification of Diseases (ICD- 10). A narrative synthesis was implemented to summarize findings if meta-analyses were not appropriate.
  • Results: Depression was found to be significantly higher in males with higher serum Pb levels. An increased serum Cd level was associated with an increase in depression; however, inconsistent results were found in associations between blood cadmium levels and depressive symptoms in the elderly population. Higher levels of Hg were negatively associated with depression and with increased fish consumption. Reviewed studies were mostly measuring As in urine instead of serum; therefore, not included. Most of the studies especially in the last decade tested the association by adjusting socio-demographics, family histories, lifestyles, smoking, and food intake variables. It is revealed that the observed symptoms in most cases are linked to the alteration of the functionality within monoamines pathways. These pathways generate from the dorsal raphe nucleus (5-HT pathways) to the amygdala and from the median raphe nucleus (mainly dopamine pathways) to the hippocampus. The two systems regulate successively evoked depression.
  • Conclusion: The review did not confirm a relationship between the levels of selected heavy metals and depression except for Cd. Further studies are needed to reduce the risks posed by heavy metals and to more comprehensively determine the effects of various environmental pollutants and their interactions.
  • Keywords: Heavy metal, Depression, Lead (Pb), Cadmium (Cd), Mercury (Hg)