Phenotypic divergence in sleep and circadian cycles linked by affective state and environmental risk related to psychosis

Study Objectives: Environmental cues influence circadian rhythm timing and neurochemicals involved in the regulation of affective behavior. How this interplay makes them a probable nonspecific risk factor for psychosis is unclear. We aimed to identify the relationship between environmental risk for psychosis and circadian timing phenotypes sampled from the general population. Methods: Using an online survey, we devised a cumulative risk exposure score for each of the 1898 survey respondents based on 23 empirically verified transdiagnostic risks for psychosis, three dimensions of affect severity, psychotic-like experiences, and help-seeking behavior. Quantitative phenotyping of sleep and circadian rhythms was undertaken using at-home polysomnography, melatonin and cortisol profiles, and 3-week rest-activity behavior in individuals with a high-risk exposure load (top 15% of survey respondents, n = 22) and low-risk exposure load (bottom 15% of respondents, n = 22). Results: Psychiatric symptoms were present in 100% of the high-load participants and 14% of the low-load participants. Compared to those with a low-load, high-load participants showed a later melatonin phase which was reflected by a greater degree of dispersion in circadian timing. Phase relationships between later circadian melatonin phase and later actigraphic sleep onsets were maintained and these were strongly correlated with self-reported sleep mid-points. No differences were identified from polysomnography during sleep between groups. Conclusion: Distinguishing circadian timing from other sleep phenotypes will allow adaptation for dosage of time-directed intervention, useful in stabilizing circadian timekeeping physiology and potentially reducing the multisystemic disruption in mental health disorders