Circadian dimension and severity of depression.

The cyclic nature of depressive illness, disturbance of diurnal mood variations, and disturbed sleep-wake and physiological rhythms all suggest that dysfunction of the circadian time-keeping system may underlie the pathophysiology of depression. Circadian misalignment of the phase-delayed type appears to be the most common shift in unipolar disorder patients and misalignment between the timing of sleep and the pacemaker is correlated with depressive symptom severity. Profiles of diurnal mood variation are associated with risks of depression severity and may predict response to treatments. As circadian disturbances are at the core of depression, normalizing circadian rhythm may be a fruitful avenue for new therapeutic targets in depression. The innovative antidepressant agomelatine possesses resynchronizing properties that may be related to its original profile and offers an opportunity to achieve our goals in treating depressed people.