Unstable sleep and rest-activity rhythms in adolescents at-risk for bipolar disorder: links to mood symptoms and the effect of sleep stabilization.

Background: Adolescents with a parental history of bipolar disorder (BD; High-Risk) are more likely to develop BD than those without such history (Low-Risk). Actigraphy studies in adults indicate that instability in sleep and rest-activity rhythms (RAR) may be associated with progression to BD. However, it remains unclear whether High-and Low-Risk adolescents are differentially affected by sleep/RAR instability and their impact on emerging mood symptoms. Methods: We recruited 50 adolescents unaffected by BD (mean age[SD]=15.97[1.31], 58% female) stratified into High-Risk (N=22) and Low-Risk (N=28) groups. All participants completed two weeks of Baseline actigraphy; a subset of 11 High-Risk participants then completed a two-week sleep Stabilization Manipulation at home. Depression and mania rating scales were collected at Baseline and post-Manipulation. Covariates included age, sex at birth, total tracking days, and ratio of weekday to weekend tracking days; false-discovery rate correction was applied. Results: At Baseline, sleep/RAR instability did not differ between High and Low-Risk groups (P-values>0.05). Among High-Risk participants only, greater sleep duration variability was linked to higher levels of depressive (β[95%CI]=0.012[0.006,0.018]) and mania (β[95%CI]=0.011[0.003,0.019]) symptoms, and lower Circadian Function Index (CFI; composite measure of circadian activity robustness) was linked to greater mania symptoms (β[95%CI]=-8.236[-12.525,-3.940]). The Stabilization protocol reduced variability in sleep duration (P<0.001), midsleep (P=0.005), and CFI (P=0.044) in High-Risk adolescents, and reduced subthreshold mania symptoms, but this did not survive multiple comparison correction. Conclusions: These findings highlight that sleep/RAR instability may have a stronger impact on mood in High-Risk adolescents but simple behavioral interventions stabilizing sleep and rhythms could buffer against BD risk.