2026 ECNP Congress

PS01-1237

Chronotherapy in a sighted woman with non-24-hour sleep-wake rhythm disorder: a case study

Corrado Garbazza — L. Wüst, N. Waldthaler, H.C. Slawik, C. Cajochen · University Psychiatric Clinics UPK Basel, Centre for Chronobiology, Basel, Switzerland

2026 ECNP Congress

Introduction

Non-24-hour sleep–wake disorder (N24SWD) is a circadian rhythm disorder characterized by the inability of the endogenous circadian system to entrain to the 24-hour light–dark cycle, resulting in a progressively shifting sleep schedule. Although commonly observed in blind individuals, it is rare in sighted patients and associated with substantial impairment in social, educational, and occupational functioning. The underlying mechanisms remain incompletely understood, particularly regarding the role of intrinsic circadian period and sensitivity to light. Chronotherapeutic interventions combining melatonin and timed light exposure are recommended, but clinical evidence in sighted individuals remains limited [1,2].

Aims

This study aimed to (i) characterize the circadian phenotype of a sighted patient with N24SWD using actigraphy and melatonin profiling, (ii) assess circadian responsiveness to light using a melatonin suppression test, and (iii) evaluate the effectiveness of a combined chronotherapeutic intervention.

Methods

A 24-year-old sighted woman underwent 25 days of actigraphy, polysomnography, and two dim light melatonin onset (DLMO) assessments conducted six days apart. Circadian phase was estimated using the hockey-stick method. The endogenous circadian period (τ) was derived from actigraphy and DLMO shifts. Following diagnosis, treatment consisted of 3 mg melatonin at 20:00 and 30 minutes of bright light therapy at 09:00 daily. Follow-up actigraphy and DLMO assessments were conducted after 9 months. A laboratory-based melatonin suppression test with nocturnal bright light exposure (~3000 lx) was performed approximately one year after diagnosis. Descriptive analyses were used to quantify circadian phase shifts, phase angle differences, and percentage melatonin suppression.

Results

Baseline assessments demonstrated a free-running circadian rhythm with τ = 25.6 h. DLMO shifted by 8 h 32 min over six days (from 17:55 to 03:27), confirming non-entrainment. The phase angle between DLMO and sleep onset was approximately 5 hours. After chronotherapy, stable entrainment to a 24-hour rhythm was achieved. Follow-up DLMO occurred at 22:53 and 00:34, indicating consolidation in the late evening. The phase angle decreased to approximately 2.5 hours. Actigraphy confirmed alignment of sleep–wake timing with the 24-hour day. Temporary interruption of treatment resulted in an immediate delay of sleep onset by approximately 3 hours, despite maintenance of a fixed wake time, leading to reduced sleep duration and daytime sleepiness. During the melatonin suppression test in the lab, melatonin levels peaked at 18.1 pg/mL at 03:30 and decreased to 7.1 pg/mL 45 minutes after bright light exposure, corresponding to a reduction of approximately 61%, consistent with preserved circadian light responsiveness [3,4].

Conclusions

This case study shows that combined chronotherapy with timed melatonin and morning bright light can successfully entrain a free-running circadian rhythm in a sighted patient with N24SWD. The preserved melatonin suppression response suggests intact photic input pathways, supporting the hypothesis that intrinsic circadian dysregulation rather than impaired light sensitivity underlies the disorder. Rapid relapse upon treatment interruption highlights the need for sustained intervention. These findings support the clinical utility of combined chronotherapy and emphasize the importance of individualized treatment timing. Further research is needed to identify predictors of treatment response and long-term outcomes in sighted N24SWD [5].

References

  1. Okawa, M., Uchiyama, M., 2007. Circadian rhythm sleep disorders: Characteristics and entrainment pathology in delayed sleep phase and non-24 sleep–wake syndrome. Sleep Med. Rev. 11 (6), 485–496.
  2. Malkani, R.G., Abbott, S.M., Reid, K.J., Zee, P.C., 2018. Diagnostic and treatment challenges of sighted non-24-hour sleep–wake disorder. J. Clin. Sleep Med. 14 (4), 603–613.
  3. Khalsa, S.B.S., Jewett, M.E., Cajochen, C., Czeisler, C.A., 2003. A phase response curve to single bright light pulses in human subjects. J. Physiol. 549 (3), 945–952.
  4. Garbazza, C., Bromundt, V., Eckert, A., Brunner, D.P., Meier, F., Hackethal, S., Cajochen, C., 2016. Non-24-hour sleep–wake disorder revisited: A case study. Front. Neurol. 7, 17.
  5. Hayakawa, T., Uchiyama, M., Kamei, Y., Shibui, K., Tagaya, H., Asada, T., Okawa, M., Takahashi, K., 2005. Clinical analyses of sighted patients with non-24-hour sleep–wake syndrome. Sleep 28 (8), 945–952.