Dim Light Melatonin Onset Profile Phenotypes in a Real-World Clinical Population with Home-Based, Self-Collected Salivary Assessments: Identification, Prevalence, and Potential Clinical Relevance

Recent methodological advances have enabled minimally invasive, convenient self-assessment of central circadian phase in home-based settings [1]. In this report, we describe salivary melatonin onset secretion profiles in 261 participants (36% male; age range, 9-83 years) who were recruited from 18 clinics in North America or by self-referral. All participants received a standardized, at-home central circadian phase assessment kit by mail or directly through their provider, along with written and video sample collection instructions. The standard protocol consisted of 7 or 9 saliva samples collected at 1-hour intervals in dim light on a single occasion, starting up to 7 hours prior to an individuals habitual bedtime and proceeding until 1-5 hours past bedtime. The number of samples and the start and end times were highly dependent on the nature and timing of the individuals primary concern and were dictated by the referring sleep-health provider. Samples were frozen immediately after collection and then returned to a central laboratory via 2-day shipping after an additional 48 hours of home freezing. Samples were subsequently kept frozen until the day of melatonin assay. Of the 261 participants, 91 (34.9%) exhibited DLMOs within the Predicted Onset Window (POW). The remaining 170 participants (65.2%) showed profiles that did not meet criteria for a predicted, aligned phase onset, including 162 (62.1% of the total sample) that could be classified into atypical phenotypes, distributed as follows: 28 showed a Delayed Melatonin Onset (10.7%), 28 showed an Advanced Melatonin Onset (10.7%), 27 exhibited Hypermelatoninemia (10.3%), 36 exhibited Hypomelatoninemia (13.8%), and 43 presented with Irregular/Multipeak profiles (16.5%). The remaining 8 participants (3.1%) exhibited profiles that could not be reliably classified. These results highlight the unexpectedly high proportion of non-predicted melatonin patterns and demonstrate that over 80% of profiles can be reliably assigned to clinically meaningful circadian phenotypes. The Discussion explores how real-world melatonin profiling can identify relevant circadian contributors to sleep disruption that symptom reports alone may fail to detect. We also describe and discuss these phenotypes in detail, considering their biological contexts and potential clinical relevance.