Molecular circadian rhythm shift due to bright light exposure before bedtime is related to subthreshold bipolarity

Abstract

This study examined the link between circadian rhythm changes due to bright light exposure and subthreshold bipolarity. Molecular circadian rhythms, polysomnography, and actigraphy data were studied in 25 young, healthy male subjects, divided into high and low mood disorder questionnaire (MDQ) score groups. During the first 2 days of the study, the subjects were exposed to daily-living light (150 lux) for 4 hours before bedtime. Saliva and buccal cells were collected 5 times a day for 2 consecutive days. During the subsequent 5 days, the subjects were exposed to bright light (1,000 lux), and saliva and buccal cell samples were collected in the same way. Molecular circadian rhythms were analyzed using sine regression. Circadian rhythms of cortisol (F = 16.956, p < 0.001) and relative PER1/ARNTL gene expression (F = 122.1, p < 0.001) showed a delayed acrophase in both groups after bright light exposure. The high MDQ score group showed a significant delay in acrophase compared to the low MDQ score group only in salivary cortisol (F = 8.528, p = 0.008). The high MDQ score group showed hypersensitivity in cortisol rhythm shift after bright light exposure, suggesting characteristic molecular circadian rhythm changes in the high MDQ score group may be related to biological processes downstream from core circadian clock gene expression.

Figure 1. Altered molecular circadian rhythms of salivary cortisol and relative PER1/ARNTL expression levels following bright light exposure before bedtime.

Twenty-five young, healthy male subjects were exposed to 150 lux artificial light at night (ALAN) before bedtime for 2 consecutive days. The circadian rhythms of salivary cortisol concentration (A) and relative PER1/ARNTL expression levels (B) are indicated as black circles connected with a continuous black line. After the 150 lux ALAN exposure, the same 25 subjects were exposed to 1,000 lux ALAN for 5 consecutive nights. The circadian rhythms of salivary cortisol concentration (A) and relative PER1/ARNTL expression levels (B) are indicated by white closed circles connected with a dashed black line. Data are expressed as mean ± standard error of the mean (SEM).

Figure 2. Altered molecular circadian rhythms of salivary cortisol concentration and relative PER1/ARNTL expression levels following bright light exposure before bedtime in high and low mood disorder questionnaire (MDQ) score groups.

Fourteen young, healthy male subjects with subthreshold bipolarity (high MDQ score group) were exposed to 150 lux artificial light at night (ALAN) for 2 consecutive days. The circadian rhythms of salivary cortisol concentration (A) and relative PER1/ARNTL expression levels (C) are indicated by black circles connected with a continuous black line. After exposure to 150 lux ALAN, the same 14 subjects in the high MDQ score group were exposed to 1,000 lux ALAN for 5 consecutive days. The circadian rhythms of salivary cortisol concentration (A) and relative PER1/ARNTL expression levels (C) are indicated by white closed circles connected with a dashed black line. Eleven young, healthy male subjects with low risk of bipolar disorder (low MDQ score group) were exposed to 150 lux ALAN for 2 consecutive days. The circadian rhythms of salivary cortisol concentration (B) and relative PER1/ARNTL expression levels (D) are indicated by black circles connected with a continuous black line. After exposure to 150 lux ALAN, the same 11 subjects in the low MDQ score group were exposed to 1,000 lux ALAN for 5 consecutive days. The circadian rhythms of salivary cortisol concentration (B) and relative PER1/ARNTL expression levels (D) are indicated by white closed circles connected with a dashed black line. Data are expressed as mean ± standard error of the mean (SEM).

Figure 3. Protocol design.

Sleep was scheduled from 00:00 to 07:00 during the 8 days of the experiment. On study days 1 and 2, the participants were exposed to 150 lux daily-living artificial light at night (ALAN) before bedtime. On study days 3, 4, 5, 6, and 7, the participants were exposed to 1,000 lux bright ALAN before bedtime. All daily-living and bright ALAN exposures were scheduled from 20:00 to 24:00. Samplings of salivary and buccal epithelial cells were scheduled with 4-hour intervals starting at 20:00 on study day 1 to 16:00 on study day 3 and from 20:00 on study day 6 to 16:00 on study day 8. No samples were collected during sleep times. Nocturnal polysomnography (NPSG) was conducted at three time points (Night 0, Night 1, and Night 2). Night 0 was in fact 3 nights before the main experimental study, during the regular sleep-wake cycle and daily-living ALAN exposure before sleep in order to reduce interference from the first-night effect. Nights 1 and 2 were the last nights of the 150 lux and the 1,000 lux ALAN exposure, respectively.