Background Depressive symptoms, such as depressed mood, are common in older adults and associated with an increased risk for morbidity and mortality. Given the evidence that sleep disturbance and alterations in interferon (IFN)-γ biology are associated with depression risk, this study examines the separate and joint contributions of poor sleep maintenance and IFN-γ to depressed mood in older adults. Methods Community-dwelling, non-depressed older adults (n = 36, 72.1 ± 6.8 years) underwent a night of polysomnography to assess sleep maintenance [i.e. wake time after sleep onset (WASO)]. The morning after polysomnography, plasma levels of IFN-γ were evaluated along with self-reported depressed mood throughout the day. Multivariate linear regression tested associations of WASO and IFN-γ with the severity of depressed mood. In addition, moderation and mediation models examined the role of IFN-γ for the relationship between WASO and depressed mood. Results A greater amount of WASO (p < 0.05) and higher levels of IFN-γ (p < 0.01) were both associated with the severity of depressed mood. Moreover, IFN-γ moderated the relationship between WASO and depressed mood (p < 0.01), such that WASO was more strongly related to the depressed mood among those with higher IFN-γ, than among those with lower IFN-γ. However, IFN-γ did not mediate the relationship between WASO and depressed mood. Conclusion In this study of older adults, poor sleep maintenance and higher levels of IFN-γ were both related to depressed mood. Moreover, IFN-γ moderated the relationship between poor sleep maintenance and depressed mood. Together, these findings suggest that older adults with higher IFN-γ are at heightened risk for depressive symptoms following sleep disturbance.

Dysregulation of sleep heightens pain sensitivity and may contribute to pain chronification. Interventions which consolidate and lengthen sleep have the potential to improve pain control. The main objective of this systematic review was to examine the effects of sleep-promoting pharmacotherapy on pain intensity in patients with chronic pain. Multiple electronic databases were searched from inception to January 2022 to identify relevant randomized controlled trials (RCTs). Two independent reviewers screened titles, abstracts, and full-text articles; extracted data; and assessed risk of bias for each included study. The GRADE approach was used to determine the strength of evidence. The search identified 624 articles. After full-text screening, 10 RCTs (n 5 574 randomized participants) involving 3 pharmacologic interventions (melatonin, zopiclone, and eszopiclone) and 7 different chronic pain populations were included. Minimum clinically significant pain reduction $30% was reported in 4 studies. There is low-quality evidence (downgraded due to inconsistency and imprecision) that 2 to 8 weeks treatment with a sleep-promoting medication alone or in combination with an analgesic (6 trials, n 5 397) decreases pain intensity compared with placebo or the same analgesic treatment alone (SMD 20.58 [95% confidence interval 21.00, 20.17], P 5 0.006). Analyses of associations between changes in sleep and pain outcomes were only provided in 2 articles, with inconsistent findings. Notably, pain-relieving effects were most consistent in melatonin trials. Only 3 studies implemented polysomnography to obtain objective sleep measures. Low-quality evidence indicates that pharmacologic sleep promotion may decrease pain intensity in chronic pain populations. More research is needed to fully understand the influence of sleep-targeting interventions on pain control.

Study Objectives Disturbances of sleep maintenance and sleep duration are common in older adults and associated with an increased risk for age-related mortality and morbidity. Converging evidence implicates inflammation as an underlying mechanism, especially in females. However, it is unknown what specific aspects of sleep disturbance impact inflammatory mechanisms in older adults. Methods Using data from community-dwelling older adults who participated in the Sleep Health and Aging Research (SHARE) field study (n=262, mean age 71.9±8.0y), we conducted a secondary analysis to examine whether disturbance of sleep maintenance (i.e., greater amount of wake time after sleep onset [WASO]) and sleep duration (i.e., shorter total sleep time [TST]) assessed by sleep diary and actigraphy are associated with greater activation of nuclear factor (NF)-κB and signal transducer and activator of transcription (STAT) family proteins STAT1, STAT3, and STAT5 in peripheral blood monocytic cells. In addition, moderation effects of sex were explored. Results Data were available for sleep diary (n=82), actigraphy (n=74), and inflammatory signaling and transcriptional measures (n=132). As assessed by sleep diary, greater amount of WASO (β=0.39, p&lt;0.01), but not TST, was associated with higher levels of NF-κB. Whereas diary-assessed sleep measures were not associated with STAT family proteins, a moderation analysis revealed that greater diary-assessed WASO was associated with higher levels of STAT1 (p&lt;0.05), STAT3 (p&lt;0.05), and STAT5 (p&lt;0.01) in females, but not in males. Actigraphy-assessed sleep measures were not associated either with NF-κB or STAT activation. Conclusions In older adults, self-reported disturbance of sleep maintenance assessed by sleep diary was uniquely associated with higher levels of NF-κB, along with higher levels of STAT family proteins in females, but not in males. Our data suggest that improving subjective sleep maintenance might mitigate age-related increases in inflammatory signaling and transcriptional pathways, possibly more strongly in females, with the potential to reduce mortality risk in older adults.