Psychiatry and Clinical Neurosciences (1999), 53, 195–197

Biological Rhythm

Poor recovery sleep after sleep deprivation in delayed sleep phase syndrome MAKOTO UCHIYAMA, md,1,2 MASAKO OKAWA, md,1 KAYO SHIBUI, md,1 KEIKO KIM, md,1 YOSIHISA KUDO, md,1 TATSURO HAYAKAWA, md,2 YUICHI KAMEI, md2 AND JUJIRO URATA, md2 1

Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Ichikawa, Japan and 2Department of Psychiatry, Kohnodai Hospital, National Center of Neurology and Psychiatry, Ichikawa, Japan

Abstract

To clarify disturbances in sleep regulation in patients with delayed sleep phase syndrome (DSPS), we studied three patients with DSPS and seven healthy controls. Sleep propensity and melatonin rhythms after 24-h sleep deprivation were investigated under dim light condition by using the ultra-short sleep–wake schedule. The sleep propensity curves displayed clear differences between DSPS patients and the controls. During the subjective day when melatonin was not produced, recovery sleep after the sleep deprivation did not occur in DSPS patients, while recovery sleep occurred during the subjective day in controls. This suggests that DSPS may involve problems related to the homeostatic regulation of sleep after sleep deprivation.

Key words

circadian rhythm, delayed sleep phase syndrome, melatonin, sleep disorder, sleep propensity.

INTRODUCTION Delayed sleep phase syndrome (DSPS) is a subtype of the circadian rhythm sleep disorders.1 A main symptom of the syndrome consists of various degrees of chronic sleep phase delay. Current progress in sleep physiology suggests that timing of sleep is regulated both by circadian and homeostatic processes.2 Recent studies on DSPS have aimed to find dysfunction in circadian entraining system,3–5 while no studies concerned aspects of homeostatic sleep regulation. We report here on three patients with DSPS, and document their circadian sleep propensity and melatonin rhythms. Differentiation between circadian and homeostatic sleep regulations in the sleep propensity rhythm is our particular interest.

SUBJECTS AND METHODS Subjects consisted of three patients with DSPS (20year-old male, 27-year-old male and 30-year-old male) and seven healthy controls aged 21 ± 0.5 years (mean

Correspondence address: Makoto Uchiyama, md, phd, Department of Psychophysiology, National Institute of Mental Health, NCNP, 1–7–3 Kohnodai, Ichikawa, 272 Japan.

and SE). Diagnosis of DSPS was made according to the criteria of the International Classification of Sleep Disorders.1 No patients had a history of or suffered from neurological or psychiatric disorders. All subjects gave their informed consent before entering the study. Prior to the investigation in the laboratory, we measured the subjects’ activity amounts continuously for a week in the home environment using an ambulatory device (Actigraph, AMI Inc., New York, USA). Based on the data obtained in this environment, we determined the subjects’ average sleep-onset and rising times. Subjects were asked to get up at their average rising time and to come to the laboratory 12 h after rising. Then, the subjects were kept awake until their average rising time under a dim light condition. Subsequent to this 24-h sleep deprivation, subjects entered nap trials under the ultra-short sleep–wake schedule originally developed by Lavie and Scherson.6 Each cycle consisted of 10min sleep EEG recordings on a bed in a dark (< 1 lux) sound-attenuated room and 20-min enforced wakefulness on an upright chair under a dim light condition (< 5 lux). This ultra-short cycle was repeated 52 times for 26 h. Polysomnographic recordings obtained in the nap trial were scored according to the standard criteria. Sleep propensity for each 30-min

196

cycle was defined as a sum of duration of 2, 3, and 4 sleep stages and REM sleep stage. Blood samplings were performed through indwelling catheter every hour. Serum melatonin level was studied by radioimmunoassay. During the procedure, the room temperature was controlled between 24 and 26°C, and subjects took a light snack (about 150 kcal) and water (about 200 mL) bi-hourly.

RESULTS The results obtained from a patient with DSPS (20year-old male) are shown in Fig. 1, together with those obtained from the control subject. All the data are presented time-locked to each subject’s average rising time. The melatonin rhythm displayed a similar circadian fluctuation pattern, in which the onset and the peak of melatonin production occurred 15–16 h

Figure 1. Sleep propensity (white bar) and melatonin (dotted solid line) rhythms under dim light condition in a patient with (a) delayed sleep phase syndrome and (b) in a control subject. Curves are presented time-locked to each subject’s average rising time.

M. Uchiyama et al.

and 19–20 h after the rising time, respectively. Sleep propensity curves displayed clear differences between DSPS and the control. During the period when melatonin was not produced (left half of the figures), sleep did not occur in the DSPS patient, while sleep occurred during the corresponding period in the control. These findings were also observed in the other two patients. In Fig. 2, mean sleep propensity functions for DSPS patients and for the controls are presented time-locked to melatonin onset. It was noted that recovery sleep after sleep deprivation did not occur in patients with DSPS.

DISCUSSION In the present study, we found that a recovery sleep after 24-h sleep deprivation did not occur in DSPS patients, while it did in controls. This indicates that DSPS may involve problems related to the homeostatic process of sleep regulation; an accumulation of sleep pressure during sleep

•

Figure 2. Mean sleep propensity functions for the ( ) delayed sleep phase syndrome patients (n = 3) and for (s) controls (n = 7) were presented time-locked to melatonin onset. (a) Sleep propensity; (b) melatonin.

Poor recovery sleep after sleep deprivation in delayed sleep phase syndrome

deprivation, and/or a release of sleep pressure after sleep deprivation.2 Thus, it seemed that the only way for a patient to phase-advance the sleep timing may be to phase-advance the circadian pacemaker.3–5 In contrast, controls are expected to have two different means of phase-advancing their sleep onset time; elevating the homeostatic sleep pressure by sleep deprivation, and phase-advancing the circadian pacemaker.2 In this respect, future research should be aimed to clarify the roles of the circadian pacemaker and the homeostatic sleep pressure in the pathophysiology of DSPS.

ACKNOWLEDGMENTS This study was partly supported by a Research Grant for Nervous and Mental Disorders from the Ministry of Health and Welfare (8A-6; 1996–1997), a Research Grant from the Japan Science and Technology Agency (1996–1997), and a Research Grant from the Ministry of Education, Science, and Culture (08671122; 1996–1997).

197

REFERENCES 1. Diagnostic Classification Steering Committee, Thorpy MJ, chairman. International Classification of Sleep Disorders: Diagnostic and coding manual. American Sleep Disorders Association, 1990. 2. Borbely AA, Achermann P, Trachsel L, Tobler I. Sleep initiation and initial sleep intensity: interactions of homeostatic and circadian mechanisms. J. Biol. Rhythms 1990; 4: 149–160. 3. Ozaki S, Uchiyama M, Shirakawa S, Okawa M. Prolonged interval from body temperature nadir to sleep offset in patients with delayed sleep phase syndrome. Sleep 1996; 19: 36–40. 4. Rosenthal NE, Joseph-Vanderpool JR, Levendosky AA et al. Phase-shifting effects of bright morning light as treatment for delayed sleep phase syndrome. Sleep 1990; 13: 354–361. 5. Hoban TM, Sack RL, Lewy AJ, Miller LS, Singer CM. Entrainment of a free-running human with bright light? Chronobiol. Int. 1989; 6: 347–353. 6. Lavie P, Scherson A. Ultrashort sleep-walking schedule. I. Evidence of ultradian rhythmicity in ‘sleepability’. Electroencephalogr. Clin. Neurophysiol. 1981; 52: 163–174.