Rest-Activity Rhythms, Their Modulators, and Brain-Clinical Correlates in Opioid Use Disorder
Authors: Rui Zhang, Peter Manza, Sukru Baris Demiral, Dardo Tomasi, Michele-Vera Yonga, Weizheng Yan, Ehsan Shokri-Kojori, Melanie Schwandt, Leah Vines, Diana Sotelo, Christina Lildharrie, Esther Lin, Natasha T. Giddens, Gene-Jack Wang, Nora D. Volkow
Journal: JAMA Network Open (2025)

Importance Sleep and circadian disruptions are highly prevalent in opioid use disorder (OUD) and are a barrier to successful treatment and recovery; yet few objective data are available, especially for individuals in OUD treatment with opioid agonist therapy. If disruptions remain present despite OUD treatment, this information would yield potential new targets for adjunctive therapy. Objective To systematically investigate different aspects of rest-activity rhythms (RAR), including sleep, physical activity, circadian rhythmicity, and brain functional correlates in individuals with OUD. Design, Setting, and Participants This cross-sectional study conducted from October 12, 2017, through January 11, 2024, recruited participants with OUD from treatment programs or the community in the District of Columbia, Maryland, and Virginia area. Participants included individuals with OUD treated with methadone or buprenorphine, individuals with OUD who remained abstinent without medications, and healthy controls (HCs). Healthy participants were recruited from advertisements. Statistical analyses were conducted between March 1 and May 31, 2024. Main Outcomes and Measures In total, 21 RAR features were derived from 1-week actigraphy data, and principal components were used to extract independent RAR components. Modulators and brain and clinical correlates of RAR were also examined. Results This study included 73 participants (46 [63%] male; mean [SD] age, 43.5 [11.3] years). Among 42 patients with OUD (16 [38%] female; mean [SD] age, 42.7 [11.4] years), 33 receiving medications for opioid use disorder (MOUD) exhibited greater sleep-wake irregularity than 9 patients without MOUD (mean difference, 0.85 [95% CI, 0.00-1.69]) or 31 age- and sex-matched HCs (11 [36%] female; mean [SD] age, 44.5 [11.3] years; mean difference, 0.75 [95% CI, 0.19-1.31). Among participants receiving MOUD, greater sleep irregularity was associated with longer heroin use history ( r 26 = 0.45; P = .02) and lower daytime light exposure ( r 33 = −0.57; P &amp;amp;lt; .001). Compared with HCs, participants with OUD exhibited lower fractional occupancy (percentage of occurrence) in a default mode network–dominated brain state, with individuals experiencing more pronounced sleep-wake irregularities displaying exacerbated impairments ( r 23 = −0.55; P = .007). Conclusions and Relevance Findings of this cross-sectional study showed that sleep irregularity in participants with OUD receiving opioid agonist medications correlated with years of opioid misuse and shorter daylight exposures and was associated with impaired brain state dynamics. These findings suggest that interventions increasing light exposure may improve sleep-wake irregularity and brain functional network dynamics in individuals with OUD receiving opioid agonist medications.