Publications

OBJECTIVES: To examine the associations of actigraphy-assessed sleep timing and regularity with psychological health in early late life women, whose circadian rhythms may be impacted by aging.

DESIGN: Cross-sectional.

PARTICIPANTS: A racially/ethnically diverse sample of 1197 community-dwelling women (mean age 65 years) enrolled in the Study of Women's Health Across the Nation.

MEASURES: Actigraphy-assessed sleep measures included timing (mean midpoint from sleep onset to wake-up) and regularity (standard deviation of midpoint in hours). Psychological health measures included a composite well-being score, the Center for Epidemiological Studies Depression Scale, and the Generalized Anxiety Disorder-7 Scale. Linear and logistic regression models, adjusted for covariates (including sleep duration), tested associations between sleep and psychological health measures.

RESULTS: After covariate adjustment, a sleep midpoint outside of 2:00-4: 00 AM was significantly associated with depressive symptoms (β = 0.88, 95% CI = 0.06, 1.70) and scoring above the cut-point for clinically significant depressive symptoms (OR = 1.72, 95% CI = 1.15, 2.57). Sleep irregularity was significantly associated with lower psychological well-being (β = -0.18, 95% CI = -0.33, -0.03), depressive (β = 1.36, 95% CI = 0.29, 2.44) and anxiety (β = 0.93, 95% CI = 0.40, 1.46) symptoms, and scoring above the cut-point for clinically significant depressive (OR = 1.68, 95% CI = 1.01, 2.79) and anxiety (OR = 1.62, 95% CI = 1.07, 2.43) symptoms.

CONCLUSION: Above and beyond sleep duration, a sleep midpoint outside of 2:00-4:00 AM was associated with depressive symptoms while sleep irregularity was associated with multiple psychological health domains in late life women.

BACKGROUND: Sleep apnea (SA) is a prevalent chronic disease with significant morbidity that negatively impacts a patient's perception of health and quality of life (QoL).

OBJECTIVE: This review synthesized qualitative evidence on the experiences of patients living with SA to understand the disease's impacts on QoL.

METHODS: We performed a systematic review of qualitative studies and searched eight electronic databases from inception dates to 22 September 2020. We analyzed the data using Sandelowski's proposed method of meta-synthesis, and applied Critical Appraisal Skills Program (CASP) and GRADE-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) criteria to appraise the studies' qualities, and synthesized findings, respectively.

RESULTS: Fourteen qualitative studies met the selection criteria. Four themes and 16 subthemes emerged: (1) sleep-related manifestations (n = 14) with four subthemes (sleep disruptors; sleepiness & napping; fatigue & low energy level; decreased cognition), (2) reduced psychological well-being and functioning (n = 14) with seven subthemes (anxiety & feeling vulnerable; hostility; sadness, sense of hopelessness & depression; embarrassment, shame & diminished self-concept; guilt & self-blame; maladaptive coping; self-stigma, (3) impaired physical and role functioning (n = 13) with three subthemes (reduced activities & routine disruption; reduced sexual activities & desire; reduced job performance & participation), (4) impaired social and relational functioning (n = 13) with two subthemes (strained interpersonal relationships; social isolation & loneliness).

CONCLUSIONS: SA patients experienced sleep-disrupting symptoms and daytime sleepiness/fatigue which adversely impacted physical, psycho-cognitive, and social aspects of their lives in complex interactive ways. This understanding can help facilitate patient-centric care and develop comprehensive patient-reported measures to effect good health outcomes.

STUDY OBJECTIVES: To test the feasibility of a novel at-home salivary Dim Light Melatonin Onset (DLMO) assessment protocol to measure the endogenous circadian phase of 10 individuals ( 1 Advanced Sleep-Wake Phase Disorder patient (ASWPD), 4 Delayed Sleep-Wake Phase Disorder patients (DSWPD), and 5 controls).

METHODS: The study involved 10 participants (sex at birth: females = 9; male= 1), who ranged between 27 to 63 years old, with an average age of 38 years old. Our study population consisted of 7 individuals who identified as white and 3 who identified as Asian. Our participants were diverse in gender identity (woman = 7, male = 1, transgender = 1, nonbinary = 1, none = 1).The study tracked the sleep and activity patterns of 10 individuals over a 5-6 week period using self-reported online sleep diaries and objective actigraphy data. Participants completed two self-directed DLMO assessments, approximately one week apart, adhering to objective compliance measures. Participants completed the study entirely remotely: they completed all sleep diaries and other evaluations online and were mailed a kit with all materials needed to perform the actigraphy and at-home sample collections.

RESULTS: Salivary DLMO times were calculated for 8/10 participants using the Hockeystick method. DLMO times were on average 3 hours and 18 minutes earlier than self-reported sleep onset times (DSPD: 12:04 AM, controls: 9:55 PM.) Among the 6 participants for whom we calculated two separate DLMO times, DLMOs 1 and 2 were 96% correlated (p<0.0005.).

CONCLUSIONS: Our results indicate that self-directed, at-home DLMO assessments are feasible and accurate. The current protocol may serve as a framework to reliably assess circadian phase in both clinical and general populations.

The Circadia Study (Circadia) is a novel "direct-to-participant" research study investigating the genetics of circadian rhythm disorders of advanced and delayed sleep phase and non-24 hour rhythms. The goals of the Circadia Study are twofold: (i) to create an easy-to-use toolkit for at-home circadian phase assessment for patients with circadian rhythm disorders through the use of novel in-home based surveys, tests, and collection kits; and (ii) create a richly phenotyped patient resource for genetic studies that will lead to new genetic loci associated with circadian rhythm disorders revealing possible loci of interest to target in the development of therapeutics for circadian rhythm disorders. Through these goals, we aim to broaden our understanding and elucidate the genetics of circadian rhythm disorders across a diverse patient population while increasing accessibility to circadian rhythm disorder diagnostics reducing health disparities through self-directed at-home dim light melatonin onset (DLMO) collections.

Aging alters the amplitude and phase of centrally regulated circadian rhythms. Here we evaluate whether peripheral circadian rhythmicity in the plasma lipidome is altered by aging through retrospective lipidomics analysis on plasma samples collected in 24 healthy individuals (9 females; mean ± SD age: 40.9 ± 18.2 years) including 12 younger (4 females, 23.5 ± 3.9 years) and 12 middle-aged older, (5 females, 58.3 ± 4.2 years) individuals every 3 h throughout a 27-h constant routine (CR) protocol, which allows separating evoked changes from endogenously generated oscillations in physiology. Cosinor regression shows circadian rhythmicity in 25% of lipids in both groups. On average, the older group has a  14% lower amplitude and a  2.1 h earlier acrophase of the lipid circadian rhythms (both, p ≤ 0.001). Additionally, more rhythmic circadian lipids have a significant linear component in addition to the sinusoidal across the 27-h CR in the older group (44/56) compared to the younger group (18/58, p < 0.0001). Results from individual-level data are consistent with group-average results. Results indicate that prevalence of endogenous circadian rhythms of the human plasma lipidome is preserved with healthy aging into middle-age, but significant changes in rhythmicity include a reduction in amplitude, earlier acrophase, and an altered temporal relationship between central and lipid rhythms.

STUDY OBJECTIVES: We examined the impact of adding a single-high-melanopic-illuminance task lamp in an otherwise low-melanopic-illuminance environment on alertness, neurobehavioral performance, learning, and mood during an 8-h simulated workday.

METHODS: Sixteen healthy young adults [mean(±SD) age = 24.2 ± 2.9, 8F] participated in a 3-day inpatient study with two 8-h simulated workdays and were randomized to either ambient fluorescent room light ( 30 melanopic EDI lux, 50 lux), or room light supplemented with a light emitting diode task lamp ( 250 melanopic EDI lux, 210 lux) in a cross-over design. Alertness, mood, and cognitive performance were assessed throughout the light exposure and compared between conditions using linear mixed models.

RESULTS: The primary outcome measure of percentage correct responses on the addition task was significantly improved relative to baseline in the supplemented condition (3.15% ± 1.18%), compared to the ambient conditions (0.93% ± 1.1%; FDR-adj q = 0.005). Additionally, reaction time and attentional failures on the psychomotor vigilance tasks were significantly improved with exposure to supplemented compared to ambient lighting (all, FDR-adj q ≤ 0.030). Furthermore, subjective measures of sleepiness, alertness, happiness, health, mood, and motivation were also significantly better in the supplemented, compared to ambient conditions (all, FDR-adj q ≤ 0.036). There was no difference in mood disturbance, affect, declarative memory, or motor learning between the conditions (all, FDR-adj q ≥ 0.308).

CONCLUSIONS: Our results show that supplementing ambient lighting with a high-melanopic-illuminance task lamp can improve daytime alertness and cognition. Therefore, high-melanopic-illuminance task lighting may be effective when incorporated into existing suboptimal lighting environments.

CLINICAL TRIALS: NCT04745312. Effect of Lighting Supplementation on Daytime Cognition. https://clinicaltrials.gov/ct2/show/NCT04745312.

CONTEXT: Perturbations to the hypothalamic-pituitary-adrenal (HPA) axis have been hypothesized to increase postmenopausal cardiometabolic risk. Although sleep disturbance, a known risk factor for cardiometabolic disease, is prevalent during the menopause transition, it is unknown whether menopause-related sleep disturbance and estradiol decline disturb the HPA axis.

OBJECTIVE: We examined the effect of experimental fragmentation of sleep and suppression of estradiol as a model of menopause on cortisol levels in healthy young women.

METHODS: Twenty-two women completed a 5-night inpatient study during the mid-to-late follicular phase (estrogenized). A subset (n = 14) repeated the protocol after gonadotropin-releasing hormone agonist-induced estradiol suppression. Each inpatient study included 2 unfragmented sleep nights followed by 3 experimental sleep fragmentation nights. This study took place with premenopausal women at an academic medical center. Interventions included sleep fragmentation and pharmacological hypoestrogenism, and main outcome measures were serum bedtime cortisol levels and cortisol awakening response (CAR).

RESULTS: Bedtime cortisol increased 27% (P = .03) and CAR decreased 57% (P = .01) following sleep fragmentation compared to unfragmented sleep. Polysomnographic-derived wake after sleep-onset (WASO) was positively associated with bedtime cortisol levels (P = .047) and negatively associated with CAR (P < .01). Bedtime cortisol levels were 22% lower in the hypoestrogenized state compared to the estrogenized state (P = .02), while CAR was similar in both estradiol conditions (P = .38).

CONCLUSION: Estradiol suppression and modifiable menopause-related sleep fragmentation both independently perturb HPA axis activity. Sleep fragmentation, commonly seen in menopausal women, may disrupt the HPA axis, which in turn may lead to adverse health effects as women age.

Parenting children with conduct problems (CP) is challenging, yet very little research has examined parenting using both quantitative and qualitative methods, from the perspective of the child and their parent/caregiver, and separately for those with high vs. low levels of callous-unemotional traits (HCU vs. LCU). One hundred and forty-six boys aged 11-16 [Typically developing (TD) n = 31; CP/HCU n = 35; CP/LCU n = 35] and their parents/caregivers completed the Alabama Parenting Questionnaire and provided a written qualitative statement describing their respective experiences of parenting/being parented. Parents/caregivers of CP/HCU boys reported more difficulty with child monitoring and supervision than parents of TD boys. This was echoed in qualitative reports of parents of CP/HCU boys reporting concerns regarding their child's safety. Parents/caregivers of both groups of CP boys reported more inconsistent discipline than parents of TD boys. Parental qualitative descriptions of challenging behavior in CP/HCU boys, and difficulties with setting boundaries and motivating CP/LCU boys, provided further insight to the potential triggers for inconsistent discipline. Qualitative reports from boys with CP indicated that they understood the parenting challenges their parents/caregivers faced. These findings replicate and extend previous work on the associations between parenting and CP. Children with CP/HCU and CP/LCU show some commonalities and differences in their parenting experiences and CP children and their parents/caregivers do not necessarily share all the same perceptions or concerns. CP interventions often involve parent/family engagement and this research highlights the continued importance of examining both parent and child perspectives.

OBJECTIVES: Many women experience sleep problems during midlife. Associations of adverse lifetime experiences-more common among women-with sleep outcomes are understudied.

METHODS: We studied 476 women enrolled in Project Viva 1999-2002. At enrollment, participants reported any lifetime history of abuse and/or financial hardship. At midlife follow-up ∼20 years later, they reported a history of up to 10 adverse childhood experiences (ACEs); 7-day sleep quality (patient-reported outcomes measurement information system sleep disturbance and sleep-related impairment T-scores); and past month average sleep duration. We examined associations of adverse experiences with sleep outcomes, adjusted for childhood sociodemographic variables. We also explored mediation by current depression and anxiety symptoms, hot flash severity, general health, and body mass index.

RESULTS: ACEs were common: 301 women (63%) reported one or more. Each additional ACE was associated with higher midlife sleep disturbance (adjusted β = 0.65 points, 95% confidence interval [CI]: 0.27, 1.02) and sleep-related impairment (0.98, 95% CI: 0.54, 1.41) T-scores, and with sleep duration <6 hour/night (odds ratio 1.19, 95% CI: 1.00, 1.42), but not with continuous sleep duration (-2 minutes, 95% CI: -5, 1). Adverse experiences in adulthood were less consistently associated with sleep quality but were associated with sleep duration, for example, financial hardship during the index pregnancy was associated with 75 minutes (95% CI: -120, -29) shorter sleep duration 2 decades later. Associations of ACEs with sleep disturbance and sleep-related impairment were mediated by midlife depression anxiety and physical health but not by hot flash severity or body mass index.

CONCLUSIONS: Adverse lifetime experiences have deleterious associations with sleep duration and quality in midlife women.