Adrenomedullin (ADM) and nitric oxide (NO) have been implicated in the pathogenesis of certain psychiatric disorders such as schizophrenia and bipolar disorder. ADM induces vasorelaxation by activating adenylate cyclase and stimulating the release of NO. These two molecules are known to influence cerebral activity. In this study, we aimed to examine the serum levels of ADM and NO in patients with major depression (MD). We enrolled 50 patients with MD and 50 healthy control subjects. The diagnosis of MD was established on the basis of a structured clinical interview using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The severity of depressive symptoms was evaluated using Hamilton's 17-item Depression Rating Scale. The mean serum levels of ADM and NO in patients with MD were significantly higher than those in healthy subjects (p = 0.001, for both). The severity of psychomotor retardation in patients with MD was significantly correlatedwith the ADM (r = 0.37, p = 0.007) and NO levels (r = 0.29, p = 0.038). The patients with obvious psychomotor retardation had significantly higher levels of ADM and NO than did the patients with no psychomotor retardation (p = 0.025, p = 0.030). A significantly positive correlation was found between ADM and NO levels in patients with MD (r = 0.79, p = 0.001). Serum levels of ADM and NO levels were not correlated with the severity or duration of depression or depressive symptoms (except psychomotor retardation). In conclusion, our study indicates that serum levels of ADM and NO are elevated in patients with MD and that increased serum levels of ADM and NO may be associated with psychomotor retardation. The ADM-NO system may serve as a new target in the treatment of patients with MD and psychomotor retardation. (C) 2013 Elsevier Inc. All rights reserved.