Reduced phase-advance of plasma melatonin after bright morning light in the luteal, but not follicular, menstrual cycle phase in premenstrual dysphoric disorder: an extended study

Abstract

The authors previously observed blunted phase-shift responses to morning bright light in women with premenstrual dysphoric disorder (PMDD). The aim of this study was to determine if these findings could be replicated using a higher-intensity, shorter-duration light pulse and to compare these results with the effects of an evening bright-light pulse. In 17 PMDD patients and 14 normal control (NC) subjects, the authors measured plasma melatonin at 30-min intervals from 18:00 to 10:00 h in dim (<30 lux) or dark conditions the night before (Night 1) and after (Night 3) a bright-light pulse (administered on Night 2) in both follicular and luteal menstrual cycle phases. The bright light (either 3000 lux for 6 h or 6000 lux for 3 h) was given either in the morning (AM light), 7 h after the dim light melatonin onset (DLMO) measured the previous month, or in the evening (PM light), 3 h after the DLMO. In the luteal, but not in the follicular, phase, AM light advanced melatonin offset between Night 1 and Night 3 significantly less in PMDD than in NC subjects. The effects of PM light were not significant, nor were there significant effects of the light pulse on melatonin measures of onset, duration, peak, or area under the curve. These findings replicated the authors' previous finding of a blunted phase-shift response to morning bright light in the luteal, but not the follicular, menstrual cycle phase in PMDD compared with NC women, using a brighter (6000 vs. 3000 lux) light pulse for a shorter duration (3 vs. 6 h). As the effect of PM bright light on melatonin phase-shift responses did not differ between groups or significantly alter other melatonin measures, these results suggest that in PMDD there is a luteal-phase subsensitivity or an increased resistance to morning bright-light cues that are critical in synchronizing human biological rhythms. The resulting circadian rhythm malsynchonization may contribute to the occurrence of luteal phase depressive symptoms in women with PMDD.

Figure 1

Effects of single day/night exposure of AM and PM light on melatonin profiles from 18:00 to 10:00 h, in follicular and luteal phases, in normal controls and PMDD patients.

Figure 2

Effects of AM and PM light on melatonin offset times in follicular and luteal phases. Data points represent change (delta) scores of individual subjects; horizontal lines denote means of the respective NC and PMDD groups.

Figure 3

Phase-shift responses to AM and PM light, during follicular and luteal menstrual phases, in normal control women and PMDD patients. Arrows in parentheses depict an advance with PM Light in Follicular Phase Synthesis Offset in NC, and delays with AM Light in Luteal Phase Synthesis Offset and Offset in PMDD.

Figure 4

Schematic representation of differences between midsleep time ((sleep offset time sleep onset time –)/2) and melatonin onset time (PAD Onset), and melatonin offset time (PAD Offset).

Figure 5

Magnitude of change in late luteal melatonin (LL MLT) offset (A) and duration(B) after morning lightinrelation to follicular illumination amplitude (measured by Actillume) at baseline.