Chronotypes & Melatonin Dynamics — References

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Parent Topic: Chronotypes & Melatonin Dynamics | References Hub: 01 - Foundations References MOC

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Primary Literature & Landmark Studies

Burgess et al. (2010)

• Citation: Burgess, H. J., Revell, V. L., Molina, T. A., & Eastman, C. I. (2010). Human phase response curves to three days of daily melatonin: 0.5 mg versus 3.0 mg. The Journal of Clinical Endocrinology & Metabolism, 95(7), 3325–3331.
• Identifiers: DOI: 10.1210/jc.2009-2590 (DOI · SciDB · Scholar) | PMID: 20410229 (PubMed · Europe PMC)
• Study Design: Controlled laboratory circadian trial in healthy adults ($N=36$) constructing complete Phase Response Curves (PRCs) to 3 consecutive days of 0.5 mg vs. 3.0 mg oral melatonin under ultradian light-dark cycles.
• Key Quantitative Outcomes:
  • Both 0.5 mg and 3.0 mg produced robust maximum phase advances of ~1.5 to 1.8 hours.
  • Optimal phase-advance timing for 0.5 mg was ~3.2 hours before DLMO (approx. 5 hours before habitual sleep onset), achieving full chronobiotic efficacy without elevating daytime plasma melatonin levels.

Patke et al. (2017)

• Citation: Patke, A., Murphy, P. J., Onat, O. E., Krieger, A. C., Özçelik, T., Campbell, S. S., & Young, M. W. (2017). Mutation of the human circadian clock gene CRY1 in familial delayed sleep phase disorder. Cell, 169(2), 203–215.e13.
• Identifiers: DOI: 10.1016/j.cell.2017.03.027 (DOI · SciDB · Scholar) | PMID: 28388406 (PubMed · Europe PMC)
• Study Design: Human genetic linkage analysis across 6 kindreds ($N=70$ family members) combined with mechanistic biochemical and cellular circadian period assays.
• Key Quantitative Outcomes:
  • Identified a dominant splice-site variant (CRY1 c.1657+3A>C) causing skipping of exon 11 ($\text{CRY1 }\Delta 11$), which strengthens binding to CLOCK:BMAL1, lengthens the endogenous circadian period ($\tau$) by ~30 minutes, and delays DLMO and sleep onset by 2–4 hours.

Drake et al. (2013)

• Citation: Drake, C., Roehrs, T., Shambroom, J., & Roth, T. (2013). Caffeine effects on sleep taken 0, 3, or 6 hours before going to bed. Journal of Clinical Sleep Medicine, 9(11), 1195–1200.
• Identifiers: DOI: 10.5664/jcsm.3170 (DOI · SciDB · Scholar) | PMID: 24235903 (PubMed · Europe PMC)
• Study Design: Randomized, double-blind, placebo-controlled crossover trial in healthy normal sleepers ($N=12$).
• Key Quantitative Outcomes:
  • 400 mg of caffeine administered 6 hours before bedtime reduced objective total sleep time (measured via home sleep monitor) by 41 to 63 minutes ($p<0.05$), doubled sleep onset latency, and significantly reduced slow-wave sleep—even when participants perceived no subjective sleep disruption at the 6-hour mark.

Facer-Childs et al. (2019)

• Citation: Facer-Childs, E. R., Middleton, B., Skene, D. J., & Bagshaw, A. P. (2019). Resetting the late timing of ‘night owls’ has a positive impact on mental health and performance. Sleep Medicine, 60, 236–247.
• Identifiers: DOI: 10.1016/j.sleep.2019.05.001 (DOI · SciDB · Scholar) | PMID: 31202686 (PubMed · Europe PMC)
• Study Design: 3-week randomized controlled trial in extreme late chronotypes ($N=22$, average ${\text{MSF}}_{sc}=05:18$).
• Key Quantitative Outcomes:
  • Targeted zeitgeber intervention (waking 2–3 h earlier with outdoor light, fixed breakfast upon waking, no caffeine after 15:00, no dinner after 19:00) advanced salivary DLMO by 1.97 hours ($p=0.002$) and cortisol peak timing by 2.15 hours, while significantly lowering DASS-21 depression ($p=0.008$) and stress scores ($p=0.017$) and improving morning grip strength and cognitive reaction time.