Melatonin in Winter Depression

In many animals, the day length response is mediated by circadian rhythm of melatonin (MLT). Although humans are not generally considered to be photoperiodic, the exposure to bright light was shown to be necessary to suppress MLT secretion and to shift the circadian phase. Moreover, seasonal variations in many human functions has been widely acknowledged. Among them seasonal affective disorder (SAD) is probably the most well known. The therapeutic effect of bright light treatment (BLT) on SAD was predicted theoretically and thereafter demonstrated in numerous trials. Association of winter type of SAD with reduced day length and therapeutic response to BLT may suggest that either photoperiodic time measurement or delayed circadian phase or both play a role in etiology of this disease. However, there were many investigations that argued against the involvement of MLT in SAD pathophysiology and antidepressant response to BLT and only few, but more recent investigations have drawn renewed interest to the MLT hypotheses. Some of the results on SAD pathophysiology raise a question about multi-component nature of biological dysfunction in SAD. Such chronobiological mechanisms as phase resetting and daytime measurement could be primarily responsible for those symptoms of SAD that are closely related to circadian and metabolic dysfunctions in winter depressives, while the disturbances in arousal and mood may be closer associated with other (i.e., nonchronobiological) mechanisms. In particular, the findings on BLT effects in SAD suggest that any simple pathophysiological model of SAD is not adequate and that modification of MLT rhythm might not be necessary for favorite therapeutic response to BLT in the majority of winter depressives. In general, despite several demonstrations that the postulated by a theory changes in MLT rhythm are associated with the antidepressant action of BLT and/or change in season, several findings must be considered to lend no support for or even arguing against the involvement of day length and phase responses in SAD pathogenesis and the mechanism by which LT works. Thus, the question of importance of MLT and circadian phase for manifestation of SAD symptoms and effective BLT is still open.