Critically-timed sleep+light interventions differentially improve mood in pregnancy vs. postpartum depression by shifting melatonin rhythms.

BACKGROUND: Testing the hypothesis that combined wake + light therapy improves mood in pregnant vs. postpartum depressed participants (DP) by differentially altering melatonin and sleep timing. METHODS: Initially 89 women, 37 pregnant (21 normal controls-NC; 16 DP) and 52 postpartum (27 NCs; 25 DP), were randomized to a parallel trial of a phase-delay intervention (PDI): 1-night of early-night wake therapy (sleep 3-7 am) + 6-weeks of evening bright white light (Litebook Advantage) for 60 min starting 90 min before bedtime, vs. a Phase-advance intervention (PAI): 1-night of late-night wake therapy (sleep 9 pm-1 am) + 6-weeks of morning bright white light for 60 min within 30 min of wake time. Blinded clinicians assessed mood weekly by structured interview, and participants completed subjective ratings, a Morningness-Eveningness questionnaire, actigraphy, and collected 2 overnight urine samples for 6-sulphatoxy melatonin (6-SMT). RESULTS: In pregnant DP, mood improved more after the PDI vs. PAI (p = .016), whereas in postpartum DP, mood improved more after the PAI vs. PDI (p = .019). After wake therapy, 2 weeks of light treatment was as efficacious as 6 weeks (p > .05). In postpartum DP, PAI phase-advanced 6-SMT offset and acrophase (p < .05), which correlated positively with mood improvement magnitude (p = .003). LIMITATIONS: Small N. CONCLUSIONS: Mood improved more after 2 weeks of the PDI in pregnant DP, but more after 2 weeks of PAI in postpartum DP in which improvement magnitude correlated with 6-SMT phase-advance. Thus, critically-timed Sleep + Light Interventions provide safe, efficacious, rapid-acting, well-tolerated, at-home, non-pharmaceutical treatments for peripartum DP.

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.

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.

Late, but not early, wake therapy reduces morning plasma melatonin: relationship to mood in Premenstrual Dysphoric Disorder.

Wake therapy improves mood in Premenstrual Dysphoric Disorder (PMDD), a depressive disorder in DSM-IV. We tested the hypothesis that the therapeutic effect of wake therapy in PMDD is mediated by altering sleep phase with melatonin secretion. We measured plasma melatonin every 30 min (18:00-09:00 h) in 19 PMDD and 18 normal control (NC) women during mid-follicular (MF) and late luteal (LL) menstrual cycle phases, and during LL interventions with early wake therapy (EWT) (sleep 03:00-07:00 h)(control condition) vs. late wake therapy (LWT) (sleep 21:00-01:00 h)(active condition). Melatonin offset was delayed and duration was longer in the symptomatic LL vs. asymptomatic MF phase in both NC and PMDD subjects. LWT, but not EWT, advanced offset and shortened duration vs. the LL baseline, although they improved mood equally. Later baseline LL morning melatonin offset was associated with more depressed mood in PMDD patients, and longer melatonin duration in the MF phase predicted greater mood improvement following LWT. That LWT, but not EWT, advanced melatonin offset and shortened duration while they were equally effective in improving mood suggests that decreasing morning melatonin secretion is not necessary for the therapeutic effects of wake therapy in PMDD.