Biological rhythms and melatonin in mood disorders and their treatments.

Affective disorders such as major depression, bipolar disorders and seasonal affective disorders have been described as alterations of various neuronal systems. In addition to the classical monoaminergic hypotheses that have been long proposed to explain the pathophysiology of these disorders, a strong association between circadian rhythms and mood regulation has been suggested in the light of several clinical and preclinical findings. In this review, we summarize the different hypotheses on pathophysiology mechanisms underlying depressive disorders and put a special emphasis on the alterations of melatonin secretion and associated changes in biological rhythms that characterize mood disorders. Causal relationships between alterations in circadian rhythms and mood disorders are strongly supported by the antidepressant efficacy of innovative pharmacological treatments aimed at resynchronizing endogenous rhythms in depressed patients. Genetic, epigenetic and environmental factors generating desynchronization between endogenous biological rhythms and exogenous rhythms driven by environmental and societal constraints are very probably involved in the vulnerability to mood disorders. Further investigations of the molecular/cellular bases of the relationships between stress axis dysfunctions, endogenous biological rhythm dysregulations and associated functional and anatomical brain alterations should allow important progress in the knowledge of pathophysiological mechanisms of affective disorders and the downstream development of innovative, more effective and better tolerated, therapies.