Sleep-light interventions that shift melatonin rhythms earlier improve perimenopausal and postmenopausal depression: preliminary findings

Abstract

Objective: Testing the hypothesis that a sleep-light intervention, which phase-advances melatonin rhythms, will improve perimenopausal-postmenopausal (P-M; by follicle-stimulating hormone) depression.

Methods: In at-home environments, we compared two contrasting interventions: (1) an active phase-advance intervention: one night of advanced/restricted sleep from 9 pm to 1 am , followed by 8 weeks of morning bright white light for 60 min/d within 30 minutes of awakening, and (2) a control phase-delay intervention: one night of delayed/restricted sleep (sleep from 3 to 7 am ) followed by 8 weeks of evening bright white light for 60 min/d within 90 minutes of bedtime. We tested 17 P-M participants, 9 normal controls and 8 depressed participants (DPs) (by Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] criteria). Clinicians assessed mood by structured interviews and subjective mood ratings. Participants wore actigraphs to measure sleep and activity and collected overnight urine samples for the melatonin metabolite, 6-sulfatoxymelatonin (6-SMT), before, during, and after interventions.

Results: Baseline depressed mood correlated with delayed 6-SMT offset time (cessation of melatonin metabolite [6-SMT] secretion) ( r = +0.733, P = 0.038). After phase-advance intervention versus phase-delay intervention, 6-SMT offset (start of melatonin and 6-SMT decrease) was significantly advanced in DPs (mean ± SD, 2 h 15 min ± 12 min; P = 0.042); advance in 6-SMT acrophase (time of maximum melatonin and 6-SMT secretion) correlated positively with mood improvement ( r = +0.978, P = 0.001). Mood improved (+70%, P = 0.007) by both 2 and 8 weeks.

Conclusions: These preliminary findings reveal significantly phase-delayed melatonin rhythms in DP versus normal control P-M women. Phase-advancing melatonin rhythms improves mood in association with melatonin advance. Thus, sleep-light interventions may potentially offer safe, rapid, nonpharmaceutical, well-tolerated, affordable home treatments for P-M depression.

Fig. 1

We obtained measures of objective and subjective mood and sleep quality, 6 SMT onset, acrophase and offset) at baseline, for 8 DP and 9 NC, and during, and after interventions for the women who completed all requirements of the study protocol. Study Flow: Overnight urine samples for 6-sultoxy-melatonin (6-SMT) were collected in week 2 (baseline) and subsequently after 2 weeks of light intervention. Actigraphy began 7 days before the Phase-Advance (PAI) or Phase-Delay Intervention (PDI), during the interventions, and ended 7 days post-intervention.

Fig. 2.

Schematic depicting relative advance from Baseline in 6-SMT Onset, Acrophase and Offset times and ng/hr values in High Symptom Severity (HSS/Depressed) vs Low Symptom Severity (LSS/Normal Control) perimenopausal women.

Fig. 3.

Schematic depicting mean Pre- vs Post-Intervention 6-SMT onset, acrophase and offset times in Menopausal Depressed Participants. A. The active Phase-Advance Intervention (PAI) advanced the mean 6-SMT Acrophase from Pre- to Post-PAI (p = .042) B. The control Phase-Delay Intervention (PDI) did not significantly advance 6-SMT Acrophase (p > .05).

Fig. 4.

Relationship of change in peak urinary melatonin metabolite (6-SMT Acrophase) to post-intervention objective improvement (SIGHADS score). Of N =7 DP, 5 women received PAI and 2 women received PDI. Closed circles denote changes after the active, Phase Advance Intervention (PAI: LWT+AM Bright White Light); open squares denote changes after the control, Phase Delay Intervention (PDI: EWT+PM Bright White Light).

Fig. 5.

Hypothetical conceptual model illustrating relationship of 6-SMT Offset timing to expected (A) baseline symptom severity, and (B) post-intervention symptom improvement after active (PAI; closed circles) and inactive control (PDI; open squares).