62,63 Since then, not much has changed in the recommended light treatment regimen, except that light intensity can be as great as 10 000 lux,64 and perhaps 1 h per day is sufficient, as long as it is scheduled immediately upon awakening. Once treatment is satisfactory, the duration of light exposure can almost always be reduced.65 Several other studies have supported these findings, but some have not66,67: these studies were usually parallel-designed, so that patients themselves did not have the opportunity to compare light exposure at different times (which would have minimized the placebo component). In 1998, three independent research groups Inhibitors,research,lifescience,medical published large-N studies in which morning light was shown to

be more antidepressant than evening light thereby moving the field towards consensus about the superiority of morning light.45,68,69 However, superior efficacy of morning light does not necessarily prove the PSH, because it could be more Inhibitors,research,lifescience,medical antidepressant at this time for some reason other than causing

a phase advance. However, it has been shown that the antidepressant response to morning light does, in some circumstances, correlate with the amount of phase advance in the DLMO. This was first reported with respect to treatment group means,61 followed by an analysis70 of individual DLMOs and depression scores collected independently.36,63 More recently, this latter finding was essentially replicated Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical using another data set.71 Further support of the PSH along these lines will be discussed below. It should also be noted that a very small subgroup of SAD patients appear to be cueing to dusk and should be treated with evening bright light; clinically, these patients

can be identified by a history of early morning awakening year round, going to bed much earlier in the winter.65 In any event, the earliest and most common use of the DLMO has been to assess the phase-shifting effects of light. Bright light has also been used to treat a number of other circadian phase disorders, such as advanced sleep phase syndrome (ASPS), delayed sleep phase syndrome (DSPS), jet Inhibitors,research,lifescience,medical lag, and shift work maladaptation (see below). The melatonin PRC The phase-shifting effects of melatonin are also Dacomitinib described by a PRC. The melatonin PRC is about 12 h out of phase with the light. PRC.13,44 Both PRCs are phase-locked to each other, as well as to the melatonin profile (Figure 2). As mentioned above, waketime is usually designated ZT 0. Sleep time is therefore usually ZT 16. In the melatonin PRC studies of sighted people, the baseline plasma DLMO10 was designated CT 14. It is also designated CT 14 in free-running blind people. We call this phase marker the MO in blind people. inhibitor Lapatinib Saliva can also be used (at this time of the night, salivary melatonin levels are about one -third those of plasma).72 Measuring the MO in blind people provides a reference point to determine the phase of the endogenous circadian pacemaker and the melatonin PRC.