Nitric oxide: Antidepressant mechanisms and inflammation.

Millions of individuals worldwide suffers from mood disorders, especially major depressive disorder (MDD), which has a high rate of disease burden in society. Although targeting the biogenic amines including serotonin, and norepinephrine have provided invaluable links with the pharmacological treatment of MDD over the last four decades, a growing body of evidence suggest that other biologic systems could contribute to the pathophysiology and treatment of MDD. In this chapter, we highlight the potential role of nitric oxide (NO) signaling in the pathophysiology and thereby treatment of MDD. This has been investigated over the last four decades by showing that (i) levels of NO are altered in patients with major depression; (ii) modulators of NO signaling exert antidepressant effects in patients with MDD or in the animal studies; (iii) NO signaling could be targeted by a variety of antidepressants in animal models of depression; and (iv) NO signaling can potentially modulate the inflammatory pathways that underlie the pathophysiology of MDD. These findings, which hypothesize an NO involvement in MDD, can provide a new insight into novel therapeutic approaches for patients with MDD in the future.