Chronobiology and mood disorders.

The clinical observations of diurnal variation of mood and early morning awakening in depression have been incorporated into established diagnostic systems, as has the seasonal modifier defining winter depression (seasonal affective disorder, SAD). Many circadian rhythms measured in depressive patients are abnormal: earlier in timing, diminished in amplitude, or of greater variability. Whether these disturbances are of etiological significance for the role of circadian rhythms in mood disorders, or a consequence of altered behavior can only be dissected out with stringent protocols (eg, constant routine or forced desynchrony). These protocols quantify contributions of the circadian pacemaker and a homeostatic sleep process impacting on mood, energy, appetite, and sleep. Future studies will elucidate any allelic mutations in "circadian clock" -related or "sleep"-related genes in depression. With respect to treatment, antidepressants and mood stabilizers have no consistent effect on circadian rhythmicity. The most rapid antidepressant modality known so far is nonpharmacological: total or partial sleep deprivation in the second half of the night. The disadvantage of sleep deprivation, that most patients relapse after recovery sleep, can be prevented by coadministration of lithium, pindolol, serotonin (5-HT) reuptake inhibitors, bright light, or a subsequent phase-advance procedure. Phase advance of the sleep-wake cycle alone also has rapid effects on depressed mood, which lasts longer than sleep deprivation. Light is the treatment of choice for SAD and may prove to be useful for nonseasonal depression, alone or as an adjunct to medication. Chronobiological concepts emphasize the important role of zeitgebers to stabilize phase, light being the most important, but dark (and rest) periods, regularity of social schedules and meal times, and use of melatonin or its analogues should also be considered. Advances in chronobiology continue to contribute novel treatments for affective disorders.