Sleep Composition of Patients With Colorectal Cancer and Their Sleep-Partner Caregivers: Physical Health Correlates of Sleep Diary and Actigraphy Measurements.

BACKGROUND: Disturbed sleep is frequently identified in adult patients with cancer and their caregivers, with detrimental impact on physical health. Less known is the extent to which self-reported and actigraph-measured sleep patterns are similar between patients and their sleep-partner caregivers, and how these different modes of sleep measurements are related to physical health. METHODS: Patients diagnosed with colorectal cancer and their sleep-partner caregivers (81 dyads) completed a questionnaire for physical functioning and collected saliva samples for seven consecutive days, from which cortisol slope was quantified. Additionally, participants completed a daily sleep diary and wore actigraph for 14 consecutive days, from which sleep duration, sleep onset latency (SOL), and duration of wake after sleep onset (WASO) were calculated. RESULTS: Participants reported sleep patterns that fell within or close to the optimal range, which were similar between patients and their caregivers. Self-reported and actigraph-measured sleep duration had moderate levels of agreement (ICC = 0.604), whereas SOL and WASO had poor agreement (ICC = 0.269). Among patients, longer self-reported WASO was associated with poorer physical health and flatter cortisol slope (p ≤ 0.013). Among caregivers, longer self-reported SOL was associated with poorer physical functioning, actigraph-measured WASO was associated with steeper cortisol slope, and longer self-reported sleep markers studied than actigraph-measured were associated with poorer physical functioning (p ≤ 0.042). CONCLUSION: Findings suggest that employing multiple assessment modes for sleep and physical health is vital for comprehensive understanding of sleep health. Furthermore, when addressing patients' sleep health, it may be beneficial to include their sleep-partner caregivers who may experience similar disturbed sleep.

Correspondence of plasma and salivary cortisol patterns in women with breast cancer.

INTRODUCTION: The 'diurnal slope' of salivary cortisol has been used as a measure of stress and circadian function in a variety of reports with several detailing its association with cancer progression. The relationship of this slope, typically a negative value from high morning concentrations to low evening concentrations, to the underlying daily variation in total plasma cortisol throughout the 24-hour cycle, however, has never been reported. METHODS: To examine the relationship between the diurnal salivary cortisol slope and the underlying pattern of plasma cortisol in individuals with cancer, we examined a cohort of women with advanced breast cancer (n = 97) who had saliva and plasma collected during a modified 24-hour, constant posture protocol. RESULTS: We found that the steepness of the diurnal slope of salivary cortisol was correlated with the amplitude of plasma cortisol rhythm when the slope was calculated from samples taken at wake + 30 min and 9 PM (r = -0.29, p > 0.05). Other variants of salivary slope calculations were not significantly correlated with the amplitude of the plasma cortisol rhythm. Diurnal salivary cortisol slope steepness was not correlated with the time between habitual waking and the computed circadian peak of cortisol, but there was a correlation between diurnal slope steepness and the time between habitual waking and the time of the awakening spike of morning cortisol (r values <-0.23, p values <0.05). CONCLUSION: It therefore appears that in women with advanced breast cancer, diurnal salivary cortisol slope primarily represents aspects of the cortisol awakening response in relation to evening levels more than the circadian rhythm of total plasma cortisol.

Evening salivary cortisol as a single stress marker in women with metastatic breast cancer.

BACKGROUND: Flattened diurnal salivary cortisol patterns predict shorter subsequent survival with breast, lung, and renal cell carcinomas. The underlying cause of this flattened slope is undetermined, though it has been hypothesized to be secondary to a deficit in the amplitude of the circadian clock. To gain greater insight into the portions of the diurnal salivary curve that are associated with cancer survival, we examined (1) which points in the diurnal curve are predictive of the slope of the curve and (2) whether elevated evening cortisol levels alone are associated with reduced HPA-axis feedback inhibition (i.e., decreased sensitivity to the dexamethasone suppression test). METHOD: We examined study hypotheses on adult women with advanced breast cancer (age = 54.3 ± 9.58 years; n = 99) using non-parametric Wilcoxon's rank-sum tests, Spearman correlation coefficients and an accuracy formula based on a confusion matrix. Cortisol was sampled five times per day for three consecutive days, with dexamethasone administered late on the second day. RESULTS: Salivary cortisol concentrations did not vary between those with flat and steep slopes during the morning (p's > .05), but did vary in the evening (p's < 0.05). Furthermore, the concentration of the 2100h alone was 86% accurate in discriminating between individuals classified as having "flat" or "steep" slopes. Dexamethasone suppression was only associated with diurnal salivary cortisol slope (p = .0042). CONCLUSIONS: Evening cortisol levels are a sensitive indicator flattened diurnal cortisol slope, suggesting evening cortisol may also be a useful predictor of breast cancer survival. Future research should focus on determining the causes of abnormally increased evening cortisol.

Modeling caffeine concentrations with the Stanford Caffeine Questionnaire: preliminary evidence for an interaction of chronotype with the effects of caffeine on sleep.

OBJECTIVE: To examine the validity of a novel caffeine intake questionnaire and to examine the effects of caffeine on sleep in college students. METHODS: One-week, ad libitum behavior of 50 university students (28 female, 22 male; aged 20.9 ± 1.78 years) was examined with sleep logs, wrist actigraphy, and a novel daily questionnaire assessing caffeine intake at different times of day. Saliva samples were collected for caffeine assessment (questionnaire validation) and DNA extraction, and for analysis of a single nucleotide polymorphism in the adenosine receptor 2A (ADORA2A) gene. RESULTS: The caffeine questionnaire was able to accurately predict salivary concentrations of caffeine (R(2) = 0.41, P<0.001). Estimations of integrated salivary caffeine concentration during sleep were correlated with wake after sleep onset (WASO) most strongly in morning-type individuals (R(2) = 0.49; P<0.001, ANOVA), less so in intermediate chronotypes (R(2) = 0.16; P<0.001, ANOVA), and not significantly in evening-types (R(2) = 0.00098; P = 0.13, ANOVA). Using multivariate modeling methods we found that the ADORA2A genotype did not moderate the effects of caffeine on WASO, but did independently alter WASO such that those with the CC genotype had nearly three-times as much WASO as those with CT or TT. CONCLUSIONS: Our questionnaire was able to accurately predict salivary caffeine concentrations and helped to describe a novel relationship between the effects of caffeine on sleep and genotype and chronotype.

A physiologically based mathematical model of melatonin including ocular light suppression and interactions with the circadian pacemaker.

The rhythm of plasma melatonin concentration is currently the most accurate marker of the endogenous human circadian pacemaker. A number of methods exist to estimate circadian phase and amplitude from the observed melatonin rhythm. However, almost all these methods are limited because they depend on the shape and amplitude of the melatonin pulse, which vary among individuals and can be affected by environmental influences, especially light. Furthermore, these methods are not based on the underlying known physiology of melatonin secretion and clearance, and therefore cannot accurately quantify changes in secretion and clearance observed under different experimental conditions. A published physiologically-based mathematical model of plasma melatonin can estimate synthesis onset and offset of melatonin under dim light conditions. We amended this model to include the known effect of melatonin suppression by ocular light exposure and to include a new compartment to model salivary melatonin concentration, which is widely used in clinical settings to determine circadian phase. This updated model has been incorporated into an existing mathematical model of the human circadian pacemaker and can be used to simulate experimental protocols under a number of conditions.