Night shift hormone: How does melatonin affect depression?

Melatonin is the main hormone secreted by the pineal gland that modulates the circadian rhythm and mood. Previous studies have shown the therapeutic effects of melatonin, or its important analogue, agomelatine, on depression. In this review study, we aimed to discuss the potential mechanisms of melatonin involved in the treatment of depression. It was noted that disrupted circadian rhythm can lead to depressive state, and melatonin via regulating circadian rhythm shows a therapeutic effect. It was also noted that melatonin induces antidepressant effects via promoting antioxidant system and neurogenesis, and suppressing oxidative stress, neuroinflammation, and apoptosis. The interaction effect between melatonin or agomelatine and serotonergic signaling has a significant effect on depression. It was noted that the psychotropic effects of agomelatine are induced by the synergistic interaction between melatonin and 5-HT2C receptors. Agomelatine also interacts with glutamatergic signaling in brain regions involved in regulating mood and circadian rhythm. Interestingly, it was concluded that melatonin exerts both pro- and anti-inflammatory effects, depending on the grade of inflammation. It was suggested that synergistic interaction between melatonin and 5-HT2C receptors may be able to induce therapeutic effects on other psychiatric disorders. Furthermore, dualistic role of melatonin in regulating inflammation is an important point that can be examined at different levels of inflammation in animal models of depression.