Phase-shifts in melatonin, 6-sulphatoxymelatonin and alertness rhythms after treatment with moderately bright light at night

Abstract

Objectives: Shift work and rapid travel across several time zones leads to desynchronization of internal circadian rhythms from the external environment and from each other with consequent problems of behaviour, physiology and performance. Field studies of travellers and shift workers are expensive and difficult to control. This investigation concerns the simulation of such rhythm disturbance in a laboratory environment. The main objectives are to assess the ability of controlled exposure to moderately bright light and darkness/sleep to delay circadian rhythms in volunteers without environmental isolation and, secondly, to evaluate the use of different indices of melatonin (MT) secretion together with self-rated alertness as marker rhythms.

Patients: Six normal volunteers aged 22-26 years (mean +/- SD 24.3 +/- 1.4).

Design: Subjects were exposed to the following periods of moderately bright light (1200 lux) on three consecutive days in early December 1991: Day (D)1: 2000-0200 h, D2: 2200-0400 h and D3: 2400-0600 h. Each period was followed by 8 hours of darkness (< 1 lux). Hourly blood, sequential 4-hourly urine (8-hourly when asleep) and hourly saliva (except when asleep) samples were taken throughout a 24-hour period on D0 (baseline), D4 (1 day post-light treatment) and D7 (4 days post-light treatment). During waking hours, subjective alertness was rated every 2 hours on a visual analogue scale.

Measurements: MT was measured in plasma and saliva, and its metabolite, 6-sulphatoxymelatonin (aMT6s), was measured in urine. MT, aMT6s and alertness scores were analysed by ANOVA and a cosinor analysis program.

Results: A delay shift was present in the aMT6s, plasma MT and salivary MT rhythms (degree of shift: 2.67 +/- 0.3 h (P < 0.001, n = 5); 2.35 +/- 0.29 h (P < 0.001, n = 6); and 1.97 +/- 0.32 h (P < 0.01, n = 6), mean +/- SEM, respectively) 1 day post-light treatment compared to baseline. Adaptation to the initial phase position was apparent by the 4th post-treatment day. Significant correlations were obtained between plasma MT onset (degree of shift: 3.12 +/- 0.74 h (P < 0.001, n = 6, mean +/- SEM)) and the acrophases (calculated peak times) of plasma MT (P < 0.001), salivary MT (P < 0.05) and urinary aMT6s (P < 0.01). A significant phase delay in the alertness rhythm was also evident 1 day post-treatment (3.08 +/- 0.67 h (P < 0.01, n = 6, mean +/- SEM)) with adaptation by the 2nd post-treatment day.

Conclusions: This study suggests that these methods of determining MT secretion are comparable and give reliable assessments of the MT circadian phase position even after a phase-shift. Significant phase-shifts of similar magnitude can be induced in both MT and alertness rhythms using moderate intensity bright light at night.