Ionic Glutamate Modulators in Depression (Zinc, Magnesium)

Abstract Considerable evidence has accumulated over the past 10 years demonstrating an important role of zinc and magnesium, potent modulators of glutamate receptors, in depression and antidepressant treatment. Clinical reports revealed reduced serum zinc and magnesium in depression, which can be normalized by successful antidepressant treatment. A preliminary clinical study demonstrated the benefit of zinc supplementation in antidepressant therapy in both treatment nonresistant and resistant patients. The clinical efficacy of magnesium treatment was observed in major depression and depressed elderly diabetics with hypomagnesemia. Preclinical studies demonstrated antidepressant activity of zinc and magnesium in a variety of rodent tests and models of depression and suggest a causative role for zinc and magnesium deficiency in the induction of depressive-like symptoms in rodents. This chapter provides an overview of the clinical and experimental evidence that implicates zinc and magnesium in the pathophysiology and therapy of depression in the context of the glutamate hypothesis of this disease. Zinc Physiological Functions of Zinc Zinc is one of the most abundant trace elements in the human body. It is a key structural component of a great number of proteins and a cofactor of enzymes regulating a variety of cellular processes and cellular signaling pathway