Abstract Introduction Optimal assessment of circadian rhythm disorders includes measurement of internal phase biomarkers. Salivary melatonin is commonly used in research but remains an un-reimbursed test and thus not integrated into routine clinical practice. Home-based salivary melatonin profiling is feasible yet scarcely used. Methods Patients presenting with severe or complex circadian rhythm disorders at the Beth Israel Deaconess Medical Center between 2018 and 2025 were offered salivary melatonin (and in selected instances cortisol) testing. Testing was done at home; options included a 9 sample dim light onset, a 7 or 9 sample dim light offset, a 9 sample 24-hour phase map, and a combined 9 sample melatonin with simultaneous cortisol. The tests were largely self-pay, directly to the testing service. Detailed instructions were provided, including light/dark control, use of phone applications for lux mapping, and sample timings based on the clinical question. A cold chain was established. Sampling completeness, protocol adherence, internal and behavioral phase-angle metrics, and exploratory phenotype–feature associations were evaluated. Results Among 148 patients evaluated, 118 completed saliva sampling, resulting in 145 valid profiles and 1,327 analyzable samples. Participants (mean age 41.9 ± 16.9 years; 58.6% female) demonstrated high sampling completeness (only 1.7% missing data), indicating robust performance of home-based testing in this cohort. Waveforms were categorized into Delayed (61.4%), Advanced (10.3%), Long Biological Night (1.4%), Sustained Hypermelatoninemia (2.1%), Hypomelatoninemia (9.7%), Dysregulated (10.3%), and Normal (4.8%) based on melatonin onset, peak, offset, amplitude, BN duration, and stability. Dysregulated profiles exhibited misalignment with simultaneously measured cortisol. Long biological night cases showed secretion lasting ~20 hours. Dysregulated and Hypermelatoninemia profiles had the longest BN durations and highest waveform instability. Exploratory analyses suggested female predominance in Dysregulated and older age in Long-BN profiles, though not statistically significant. Conclusion Home-based salivary melatonin profiling is feasible and reliable, and distinct physiologic waveform clusters, particularly Delayed, Dysregulated, and Long-BN patterns, highlight the diagnostic resolution of waveform-based phenotyping. These data complement behavior-based classification and support broader clinical use of domiciliary melatonin profiling for circadian evaluation and phenotype-guided management. Support (if any) Institute for Personalized Sleep Health, Beth Israel Deaconess Medical Center
Liu et al. (2026) studied this question.