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New research suggests that sleep irregularity may be more clinically relevant than relying on mean values. This study aimed to (1) quantify the relationship between the sleep regularity index (SRI), a novel parameter reflecting the probability that an individual will be in the same state [asleep or awake] 24\u2009h apart, and other actigraphy\u2010derived sleep and rest\u2013activity metrics, (2) evaluate concurrent and prospective associations between the SRI and mental health symptoms (depressive symptoms and substance use), and (3) test sex as a moderator. At baseline, a community\u2010based sample of adolescents (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009295, 56.27% female, 58.98% White, age\u2009=\u200915.44) wore an actiwatch for 1\u2009week to measure rest\u2013activity rhythms and sleep\u2013wake cycles. Actigraphy data were used to derive sleep metrics, SRI, and nonparametric rest\u2013activity indices. Adolescents also completed self\u2010report measures of substance use and depression at baseline and at 6\u2010month follow\u2010up. Partial correlations indicated that individuals with more sleep irregularity had less interdaily stability, less robust relative amplitude, lower sleep efficiency, shorter total sleep time, longer sleep onset latency, more social jetlag, and a later sleep midpoint. Regression analyses revealed that sleep irregularity was associated with a lifetime history of substance use, first\u2010onset substance use, and a prospective increase in depressive symptoms, even after accounting for sleep duration and subjective sleep disturbances. The sleep regularity index may be a potential modifiable risk factor for enhancing adolescent mental health.\n                  <\/jats:p>","DOI":"10.1111\/jsr.14468","type":"journal-article","created":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T18:35:16Z","timestamp":1738521316000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Sleep regularity in adolescents: Associations with sleep, rest\u2013activity indices, and prospective substance use and depression"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0879-0612","authenticated-orcid":false,"given":"Rachel F. 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