The emerging role of copper in depression

Copper (Cu) is an essential trace element in the brain and serves as an important cofactor for numerous enzymes involved in a wide range of biochemical processes including neurobehavioral, mitochondrial respiration, and antioxidant effects. Recent studies have demonstrated that copper dyshomeostasis is tightly associated with the development of depression by inducing oxidative stress and inflammatory responses. However, these findings have remained controversial so far. Cumulative studies have shown a positive association, while some other studies showed no association and even a negative association between serum/plasma copper level and depression. Based on these conflicted results, the association was speculated to be due to the clinical features of the population, stages of the disease, severity of copper excess, and types of specimens detected in these studies. In addition, there was an inverse association between dietary copper intake and depression. Furthermore, increasing copper intake could influence dietary zinc and iron intake to prevent and treat depression. Thus, copper supplementation may be a good measure to manage depression. This review provided a deeper understanding of the potential applicability of copper in the prevention and treatment of depression.