Entrainment of sleep and dim-light salivary melatonin onset (DLSMO) in young adolescents using a fixed schedule

CARSKADON MA, ACEBO CC, RICHARDSON G, TATE B, SEIFER R: Sleep Research 1996; 25: 544.
E.P. Bradley Hospital and Miriam Hospital, Brown University School of Medicine, Providence, RI 02906 and Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115.

Abstract:

One of the most consistent behavioral changes of adolescence is a delay of the timing of sleep; that is, adolescents tend to go to sleep later at night and (if undisturbed) to sleep later in the morning than preadolescents. Whether biological processes involving circadian timing mechanisms may also influence this delay shift of adolescents is unknown. We have begun to examine this issue in a series of studies. We have previously found test-retest reliability of Dim-Light Salivary Melatonin Onset (DLSMO) in adolescents over a 4-month interval (r = .75, p<.001, N=13). For the present study we examine the validity of DLSMO as a phase marker in this age group by comparing DLSMO phase under conditions of self-selected ("wild-type") sleep-wake schedule versus DLSMO phase following entrainment to a fixed light:dark (L:D) schedule. Our hypothesis is that adherence to a fixed L:D will alter circadian phase as indexed by DLSMO.
Procedures. Subjects were recruited through a laboratory open house for parents and children at which procedures were explained and demonstrated. 19 subjects (10 boys, 9 girls aged 11.2 to 14.4 (mean =12.9±0.8) years) passed health screening and were scheduled as participants (n=16) or alternates for 4 runs of a 3-week study during the summer of 1995. The 19 children underwent all the procedures described below, and 14 completed the entire study as described in a companion abstract¹. Subjects wore wrist actigraphs throughout the study and completed the Social Rhythm Metric² and sleep logs and called the laboratory daily to report bed and rise times. During days 1 through 7, subjects lived on their self-selected ("wild-type") sleep-wake schedules and reported to the lab on the evening of the 8th day for DLSMO determination. They were given opaque eye shades that night and instructed to sleep at home wearing the eye shades nightly from 10:00 pm to 8:00 am excluding as much light as possible from their eyes for the next 9 nights (Entrainment). At the end of Entrainment, subjects returned to the lab for a second evening of saliva collection. Schedule compliance was checked by examination of the actigraph record, and data were dropped for one 12-year-old boy who failed to comply to Entrainment. Saliva samples (2 ml) were collected at 30-min. intervals in 40-50 lux. For "wild-type" DLSMO, sample times were determined by reported bedtimes (last sample = mean bedtime for 6 nights). For Entrainment DLSMO, samples from all subjects were collected between 1730 and 2200. Frozen saliva samples were shipped to Elias, Inc. for radioimmunoassay of melatonin. In saliva, a value above 4 pg/ml is comparable to the plasma threshold of 10 pg/ml and was therefore selected as the threshold for melatonin onset.
Results. DLSMO values were available at "wild-type" and entrained assessment points in 12 children (7 boys, 5 girls). The other subjects failed to achieve the onset threshold value before saliva collection was halted on one or both evenings. DLSMO values during "wild-type" and entrained conditions are shown in Figure 1. Differences between the mean values were not statistically significant ("wild-type" mean = 21:29±59 minutes; entrained mean = 21:12±29 minutes), but dispersion of the values was markedly and significantly reduced (T = 2.55, df = 11, p = .03) in the entrained versus the "wild-type" condition. Thus as shown in Figure 1, all six subjects with "wild-type" DLSMO later than 21:30 (closed circles) phase advanced as a result of entrainment, four of five with "wild-type" DLSMO earlier than 21:30 (open circles) phase delayed during entrainment, and in one subject (triangle) DLSMO phase remained at 21:30 for both assessments. When actigraphically-estimated sleep onset and sleep offset times averaged over the 4 nights before DLSMO determinations were examined, they showed a similar entrainment pattern (see Figure 2 for Sleep Onset). "Wild-type" DLSMO phase was significantly correlated with the mean actigraphically-estimated "wild-type" sleep onset and sleep offset times ("wild-type" DLSMO vs. "wild-type" sleep onset r = .85, p=.001; "wild-type" DLSMO vs. "wild-type" sleep offset r = .76, p=.004).
Discussion. The responsiveness of DLSMO to change in phase associated with implementation of a fixed L:D schedule highlights the usefulness of DLSMO as a circadian phase marker in adolescents. As expected, the young adolescents' "wild-type" DLSMO phase was correlated with sleep schedule, consistent with the primary role of sleep/wake schedule in modulating light:dark exposure and oscillator entrainment.

¹Carskadon MA, Richardson GS, Tate BA, Acebo C, Seifer R. Circadian parameters in adolescence: preliminary results using the "Long Nights Protocol." Sleep Research 25 (in press).
²Monk TM, Flaherty JF, Frank E, Hoskinson K, Kupfer DJ. The social rhythm metric. An instrument to quantify the daily rhythm of life. J Nerv Ment Dis, 1990, 178: 120-126.
Research supported by MH52415.

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Abstract:

One of the most consistent behavioral changes of adolescence is a delay of the timing of sleep; that is, adolescents tend to go to sleep later at night and (if undisturbed) to sleep later in the morning than preadolescents. Whether biological processes involving circadian timing mechanisms may also influence this delay shift of adolescents is unknown. We have begun to examine this issue in a series of studies. We have previously found test-retest reliability of Dim-Light Salivary Melatonin Onset (DLSMO) in adolescents over a 4-month interval (r = .75, p<.001, N=13). For the present study we examine the validity of DLSMO as a phase marker in this age group by comparing DLSMO phase under conditions of self-selected ("wild-type") sleep-wake schedule versus DLSMO phase following entrainment to a fixed light:dark (L:D) schedule. Our hypothesis is that adherence to a fixed L:D will alter circadian phase as indexed by DLSMO. Procedures. Subjects were recruited through a laboratory open house for parents and children at which procedures were explained and demonstrated. 19 subjects (10 boys, 9 girls aged 11.2 to 14.4 (mean =12.9±0.8) years) passed health screening and were scheduled as participants (n=16) or alternates for 4 runs of a 3-week study during the summer of 1995. The 19 children underwent all the procedures described below, and 14 completed the entire study as described in a companion abstract¹. Subjects wore wrist actigraphs throughout the study and completed the Social Rhythm Metric² and sleep logs and called the laboratory daily to report bed and rise times. During days 1 through 7, subjects lived on their self-selected ("wild-type") sleep-wake schedules and reported to the lab on the evening of the 8th day for DLSMO determination. They were given opaque eye shades that night and instructed to sleep at home wearing the eye shades nightly from 10:00 pm to 8:00 am excluding as much light as possible from their eyes for the next 9 nights (Entrainment). At the end of Entrainment, subjects returned to the lab for a second evening of saliva collection. Schedule compliance was checked by examination of the actigraph record, and data were dropped for one 12-year-old boy who failed to comply to Entrainment. Saliva samples (2 ml) were collected at 30-min. intervals in 40-50 lux. For "wild-type" DLSMO, sample times were determined by reported bedtimes (last sample = mean bedtime for 6 nights). For Entrainment DLSMO, samples from all subjects were collected between 1730 and 2200. Frozen saliva samples were shipped to Elias, Inc. for radioimmunoassay of melatonin. In saliva, a value above 4 pg/ml is comparable to the plasma threshold of 10 pg/ml and was therefore selected as the threshold for melatonin onset. Results. DLSMO values were available at "wild-type" and entrained assessment points in 12 children (7 boys, 5 girls). The other subjects failed to achieve the onset threshold value before saliva collection was halted on one or both evenings. DLSMO values during "wild-type" and entrained conditions are shown in Figure 1. Differences between the mean values were not statistically significant ("wild-type" mean = 21:29±59 minutes; entrained mean = 21:12±29 minutes), but dispersion of the values was markedly and significantly reduced (T = 2.55, df = 11, p = .03) in the entrained versus the "wild-type" condition. Thus as shown in Figure 1, all six subjects with "wild-type" DLSMO later than 21:30 (closed circles) phase advanced as a result of entrainment, four of five with "wild-type" DLSMO earlier than 21:30 (open circles) phase delayed during entrainment, and in one subject (triangle) DLSMO phase remained at 21:30 for both assessments. When actigraphically-estimated sleep onset and sleep offset times averaged over the 4 nights before DLSMO determinations were examined, they showed a similar entrainment pattern (see Figure 2 for Sleep Onset). "Wild-type" DLSMO phase was significantly correlated with the mean actigraphically-estimated "wild-type" sleep onset and sleep offset times ("wild-type" DLSMO vs. "wild-type" sleep onset r = .85, p=.001; "wild-type" DLSMO vs. "wild-type" sleep offset r = .76, p=.004). Discussion. The responsiveness of DLSMO to change in phase associated with implementation of a fixed L:D schedule highlights the usefulness of DLSMO as a circadian phase marker in adolescents. As expected, the young adolescents' "wild-type" DLSMO phase was correlated with sleep schedule, consistent with the primary role of sleep/wake schedule in modulating light:dark exposure and oscillator entrainment. ¹Carskadon MA, Richardson GS, Tate BA, Acebo C, Seifer R. Circadian parameters in adolescence: preliminary results using the "Long Nights Protocol." Sleep Research 25 (in press). ²Monk TM, Flaherty JF, Frank E, Hoskinson K, Kupfer DJ. The social rhythm metric. An instrument to quantify the daily rhythm of life. J Nerv Ment Dis, 1990, 178: 120-126. Research supported by MH52415.