Circadian rhythm disturbances in manic-depressive illness.

Clinical features of manic-depressive illness, such as diurnal variation in mood, early morning awakening, and cyclicity and seasonality of recurrences, have led to speculation that the circadian system may be involved in its pathophysiology. At least three types of circadian rhythm abnormalities have been described in such patients: blunting of circadian rhythms' amplitudes, advanced position (or even nonentrainment) of circadian rhythms' phases, and doubling of the length of the sleep-wake cycle from 24 to 48 h. Several types of experiments indicate that alterations in the timing of sleep and wakefulness relative to other circadian rhythms (i.e., changes in internal phase relationships) may trigger the onset or offset of episodes of depression and mania. Whether drugs used to treat manic-depressive illness act through their effects on the circadian system is currently being investigated. Direct manipulations of the circadian system are also being investigated as new approaches to treatment.