Systemic Inflammation and Cognitive Decrements in Patients With Stage B Heart Failure.

OBJECTIVE: This study aimed to investigate the role of systemic inflammation in reduced cognitive functioning in patients with early-stage heart failure (HF) while determining associations with other cardiovascular risk factors. METHODS: Patients with stage B HF (n = 270; mean [standard deviation] age = 66.1 [10.1] years) were examined cross-sectionally for relationships among cardiovascular disease (CVD) and psychological risk factors, C-reactive protein (CRP), and Montreal Cognitive Assessment (MoCA) scores. A subsample (n = 83) at high risk for stage C HF (B-type natriuretic peptide levels ≥65 pg/ml) were followed up for 12 months for relationships between CRP levels and cognitive function. RESULTS: Baseline smoking (χ2 = 6.33), unmarried (χ2 = 12.0), hypertension (χ2 = 5.72), greater body mass index (d = 0.45), and physical fatigue (d = 0.25) were related to higher CRP levels (p values < .05). Cross-sectionally, CRP levels were negatively related to MoCA scores, beyond CVD (ΔR2 = 0.022, ß = -0.170, p < .010) and psychological risk factors (ΔR2 = 0.016, ß = 0.145, p < .027), and related to mild cognitive impairment criteria (odds ratio = 1.35, 95% confidence interval [CI] = 1.00-1.81, p = .046). Across 12 months, B-type natriuretic peptide high-risk patients with CRP levels ≥3 mg/L had lower MoCA scores (23.6; 95% CI = 22.4-24.8) than did patients with CRP levels <3 mg/L (25.4; 95% CI = 24.4-26.5; p = .024). CONCLUSIONS: Patients with stage B HF and heightened CRP levels had greater cognitive impairment at baseline and follow-up, independent of CVD and potentially psychological risk factors. Low-grade systemic inflammation may be one mechanism involved in cognitive dysfunction at early stages of HF.

Reductions in sleep quality and circadian activity rhythmicity predict longitudinal changes in objective and subjective cognitive functioning in women treated for breast cancer.

PURPOSE: To examine long-term cognitive effects of chemotherapy and identify predictors among women with breast cancer (WBC). PATIENTS AND METHODS: Sixty-nine WBC scheduled to receive chemotherapy, and 64 matched-controls with no cancer, participated. Objective and subjective cognition, total sleep time, nap time, circadian activity rhythms (CAR), sleep quality, fatigue, and depression were measured pre-chemotherapy (Baseline), end of cycle 4 (Cycle-4), and one-year post-chemotherapy (1-Year). RESULTS: WBC showed no change in objective cognitive measures from Baseline to Cycle-4 but significantly improved from both time points to 1-Year. Matched-controls showed an increase in test performance at all time points. WBC had significantly higher self-reported cognitive dysfunction at Cycle-4 and 1-Year compared to baseline and compared to matched-controls. Worse neuropsychological functioning was predicted by less robust CARs (i.e., inconsistent 24 h pattern), worse sleep quality, longer naps, and worse cognitive complaints. Worse subjective cognition was predicted by lower sleep quality and higher fatigue and depressed mood. CONCLUSION: Objective testing showed increases in performance scores from pre- and post-chemotherapy to one year later in WBC, but matched-controls showed an increase in test performance from baseline to Cycle-4 and from Cycle-4 to 1-Year, likely due to a practice effect. The fact that WBC showed no practice effects may reflect a form of learning deficit. Compared with the matched-controls, WBC reported significant worsened cognitive function. In WBC, worse objective and subjective cognitive functioning were predicted by worse sleep and sleep-related behaviors (naps and CAR). Interventions that target sleep, circadian rhythms, and fatigue may benefit cognitive function in WBC.

Religiosity and Spirituality in the Stages of Recovery From Persistent Mental Disorders.

ABSTRACT: The impact of religiosity and spirituality (R/S) on mental health and the importance of incorporating R/S in mental health treatment have been previously explored. However, clarification is needed regarding the effects of R/S in the process of recovery from persistent mental disorders (PMDs). This study identifies how different R/S factors correlate with the stages of recovery, while considering individual psychological well-being and perceived social support. Seventy-five individuals who use Madrid's public services for people with PMD completed questionnaires assessing those factors. We found that during the recovery process, R/S correlated with psychological well-being and perceived social support, and that these variables were associated with the five stages of recovery differently. We further identified the importance of gratitude, compassion, inner peace, and connection with life in the recovery process. Overall, our findings highlight the importance of these R/S variables in particular recovery stages for individuals with PMD.

Religiosity and Suicide: A Large-Scale International and Individual Analysis Considering the Effects of Different Religious Beliefs.

In a cohort of 82,898 participants from 60 countries, this study examined attitudes towards suicide among five religions (Buddhism, Christianity, Hinduism, Islam, and other non-specific religions), while simultaneously considering two different dimensions of religiosity: subjective religiosity and religious practices. At the national level, religiosity was an important negative predictor variable for suicide rates and an important positive predictor variable for negative attitudes towards suicide. At the individual level, however, attitudes towards suicide were found to vary significantly across the different religions. The findings emphasize the importance of considering religion perspectives and religiosity, along with its practices and subjective dimensions, in prevention and attention programmes to suicidal behaviour.

Glyphosate Excretion is Associated With Steatohepatitis and Advanced Liver Fibrosis in Patients With Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease in developed countries.1 Patients with nonalcoholic steatohepatitis (NASH) are considered to be at a higher risk of fibrosis progression and development to cirrhosis and hepatocellular carcinoma.

The Relationship Between Circulating Interleukin-6 Levels and Future Health Service Use in Dementia Caregivers.

OBJECTIVE: Older adults are among the most frequent users of emergency departments (EDs). Nonspecific symptoms, such as fatigue and widespread pain, are among the most common symptoms in patients admitted at the ED. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) are inflammation biomarkers associated with chronic stress (i.e., dementia caregiving) and nonspecific symptoms. This study aimed to determine whether IL-6 and TNF-α were prospectively associated with ED risk in dementia caregivers (CGs). METHODS: Participants were 85 dementia CGs, who reported during three assessments (3, 9, and 15 months after enrollment) if they had visited an ED for any reason. Cox proportional hazards models were used to examine the relations between resting circulating levels of IL-6 and TNF-α obtained at enrollment and subsequent risk for an ED visit, adjusting for age, sex, use of ED 1 month before enrollment, physical and mental health well-being, body mass index, and CG demands. RESULTS: (log) IL-6 significantly predicted ED visits during the 15-month follow-up (B = 1.96, SE = 0.82, p = .017). For every (log) picogram per milliliter increase in IL-6, the risk of visiting an ED was 7.10 times greater. TNF-α was not associated with subsequent ED visits. Exploratory analyses suggested that CGs with levels of IL-6 above the 80th percentile and experiencing high CG demands were at highest risk of an ED visit. CONCLUSIONS: IL-6 levels and CG demands may be useful for predicting vulnerability for future ED visits. Although further studies should be conducted to replicate and extend these findings, interventions that successfully modify inflammation markers, including the underlying pathophysiology related to stress and/or comorbid illnesses, may be useful in preventing costly and detrimental outcomes in this population.

Elevated Resting and Postprandial Digestive Proteolytic Activity in Peripheral Blood of Individuals With Type-2 Diabetes Mellitus, With Uncontrolled Cleavage of Insulin Receptors.

Objective: To examine resting and postprandial peripheral protease activity in healthy controls and individuals with type 2 diabetes mellitus (T2DM) and pre-T2DM. Methods: Individuals with T2DM or pre-T2DM and healthy controls (mean age 55.8 years) were studied before and for a span of 300 minutes following a single high-calorie McDonald's breakfast. Metalloproteases-2/-9 (MMP-2/-9), elastase, and trypsin activities were assessed in whole blood before and following the meal using a novel high-precision electrophoretic platform. Also assessed were circulating levels of inflammatory biomarkers and insulin receptor density on peripheral blood mononuclear cells (PBMCs) in relationship to protease activity. Results: Premeal MMP-2/-9 and elastase activity levels in T2DM and in pre-T2DM participants were significantly elevated as compared to controls. The T2DM group showed a significant increase in elastase activity 15 minutes after the meal; elastase activity continued to increase to the 30-minute time point (p < 0.01). In control participants, MMP-2/-9, elastase, and trypsin were significantly increased at 15 minutes after the meal (p < 0.05) and returned to premeal values within a period of approximately 30 to 60 minutes post meal. PBMCs incubated for 1 hour with plasma from T2DM and pre-T2DM participants had significantly lower levels of insulin receptor density compared to those incubated with plasma from control participants (p < 0.001). Conclusions: The results of this study suggest that individuals with T2DM and pre-T2DM have higher resting systemic protease activity than nonsymptomatic controls. A single high-calorie/high-carbohydrate meal results in further elevations of protease activity in the systemic circulation of T2DM and pre-T2DM, as well as in healthy controls. The protease activity in turn can lead to a downregulation of insulin receptor density, potentially supporting a state of insulin resistance.

Refining caregiver vulnerability for clinical practice: determinants of self-rated health in spousal dementia caregivers.

BACKGROUND: Caregivers of a family member with a chronic disability or illness such as dementia are at increased risk for chronic disease. There are many factors that contribute to dementia caregiver vulnerability and these factors can be challenging to assess in clinical settings. Self-rated health (SRH) is an independent measure of survival and physical health in the elderly. As an inclusive measure of health, SRH has been proposed as a reliable way to assess a patient's general health in primary care. Therefore, we sought to identify determinants of poor/fair SRH versus categories of at least good SRH in informal caregivers. METHODS: In a cross-sectional study, we examined 134 elderly (≥55 years) providing in-home care for a spouse with dementia who rated their own health with a single-item question: "In general, would you say your health is excellent, very good, good, fair or poor?". In a multivariable model, we compared caregivers with poor/fair SRH to those with good, very good, or excellent SRH on demographics, health characteristics (health behaviors, physical health indicators, psychosocial factors) and caregiving-specific stress (a composite index/total of four caregiving-specific stressors: years of caregiving, dementia severity, care recipient functional impairment and perceived caregiver burden). RESULTS: Compared with caregivers who rated their own health as either good (31.3%), very good (38.8%) or excellent (14.2%), caregivers with poor/fair SRH (15.7%) were more likely to have lower physical function and total greater caregiving-specific stress. More years of caregiving, severe dementia and care recipient functional impairment, but not perceived caregiver burden, were also more likely among caregivers with poor/fair SRH. Additionally, high negative affect and low positive affect were more likely in caregivers with poor/fair vs. good or excellent and very good or excellent SRH, respectively. CONCLUSIONS: Caregivers with poor/fair SRH were characterized by higher levels of medical comorbidity, low physical function, high negative, but low positive affect and longer duration of caregiving, as well as more severe dementia and greater functional impairment of the care recipient. These findings suggest that caregivers need to be more closely evaluated and targeted for preventive interventions in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT02317523 .

Engagement in Pleasant Leisure Activities and Blood Pressure: A 5-Year Longitudinal Study in Alzheimer Caregivers.

OBJECTIVE: Elevated blood pressure is a significant public health concern, particularly given its association with cardiovascular disease risk, including stroke. Caring for a loved one with Alzheimer disease has been associated with physical health morbidity, including higher blood pressure. Engagement in adaptive coping strategies may help prevent blood pressure elevation in this population. This 5-year longitudinal study examined whether greater participation in pleasant leisure activities was associated with reduced blood pressure in caregivers. METHODS: Participants were 126 in-home spousal Alzheimer's caregivers (M [SD] age = 74.2 [7.9] years) that completed five yearly assessments. Linear mixed-effects models analysis was used to examine the longitudinal relationship between pleasant leisure activities and caregivers' blood pressure, after adjusting for demographic and health characteristics. RESULTS: Greater engagement in pleasant leisure activities was associated with reduced mean arterial blood pressure (B = -0.08, SE = 0.04, p = .040). Follow-up analyses indicated that engagement in activities was significantly associated with reduced diastolic (B = -0.07, SE = 0.03, p = .030) but not systolic blood pressure (B = -0.10, SE = 0.06, p = .114). In addition, mean arterial blood pressure was significantly reduced when caregiving duties ended because of placement of care recipients in nursing homes (B = -3.10, SE = 1.11, p = .005) or death of the care recipient (B = -2.64, SE = 1.14, p = .021). CONCLUSIONS: Greater engagement in pleasant leisure activities was associated with lowered caregivers' blood pressure over time. Participation in pleasant leisure activities may have cardiovascular health benefits for Alzheimer's caregivers.

Multiplexing and Beyond in Biobehavioral Research.

In contrast to traditional singleplex assays that provide values for only a single analyte in a single biological sample, multiplex assays are a time- and resource-efficient high-throughput approach that provides the opportunity to determine numerous analytes within a single- and small-sample volume. In this editorial on an article by Dorn et al. in this issue of Psychosomatic Medicine, we provide a brief description of the advantages and challenges related to multiplex assays. Although the use of multiplexing as a tool has been relatively limited in biobehavioral research, more recent studies are taking advantage of this technology to obtain deeper insight into regulatory patterns in health and disease states. Multiplex approaches range from several targets to global target profiling that importantly enable unbiased biomarker and pathway discovery.

Pilot Randomized Study of a Gratitude Journaling Intervention on Heart Rate Variability and Inflammatory Biomarkers in Patients With Stage B Heart Failure.

OBJECTIVE: Stage B, asymptomatic heart failure (HF) presents a therapeutic window for attenuating disease progression and development of HF symptoms, and improving quality of life. Gratitude, the practice of appreciating positive life features, is highly related to quality of life, leading to development of promising clinical interventions. However, few gratitude studies have investigated objective measures of physical health; most relied on self-report measures. We conducted a pilot study in Stage B HF patients to examine whether gratitude journaling improved biomarkers related to HF prognosis. METHODS: Patients (n = 70; mean [standard deviation] age = 66.2 [7.6] years) were randomized to an 8-week gratitude journaling intervention or treatment as usual. Baseline (T1) assessments included the six-item Gratitude Questionnaire, resting heart rate variability (HRV), and an inflammatory biomarker index. At T2 (midintervention), the six-item Gratitude Questionnaire was measured. At T3 (postintervention), T1 measures were repeated but also included a gratitude journaling task. RESULTS: The gratitude intervention was associated with improved trait gratitude scores (F = 6.0, p = .017, η = 0.10), reduced inflammatory biomarker index score over time (F = 9.7, p = .004, η = 0.21), and increased parasympathetic HRV responses during the gratitude journaling task (F = 4.2, p = .036, η = 0.15), compared with treatment as usual. However, there were no resting preintervention to postintervention group differences in HRV (p values > .10). CONCLUSIONS: Gratitude journaling may improve biomarkers related to HF morbidity, such as reduced inflammation; large-scale studies with active control conditions are needed to confirm these findings. TRIAL REGISTRATION: Clinicaltrials.govidentifier:NCT01615094.

Beta-adrenergic receptor mediated inflammation control by monocytes is associated with blood pressure and risk factors for cardiovascular disease.

Overwhelming data indicate that individuals with even mildly elevated blood pressure (BP) are at great risk for developing clinical hypertension and future cardiovascular disease (CVD). There remains a lack of consensus regarding treatment strategies for mildly elevated BP, termed prehypertension, and the knowledge of pathophysiology and mechanisms of its clinical outcomes remains limited. Our primary aim was to investigate ßAR-mediated inflammation control (BARIC) responses of blood monocytes to isoproterenol (Iso) in relation to BP and CVD risk factors, including obesity, depressive mood, fasting glucose, triglycerides, and cholesterol levels in the 64 prehypertensive compared to 84 individuals with normal BP. BARIC was determined by measuring the degree of inhibition in lipopolysaccharides-stimulated monocytic intracellular TNF production by ex vivo Iso treatment (10(-8)M). Depressive mood was assessed by Beck Depression Inventory (BDI). Fasting metabolic and lipid panels were assessed, and plasma levels of inflammatory cytokines TNF, IL-1ß, IL-6 were measured in a subset to confirm proinflammatory state of prehypertensive participants. Prehypertensive participants were older, heavier, included more men, and presented higher levels of fasting glucose, triglycerides, cholesterol, and plasma TNF compared to normotensive participants (p's<.05). BARIC was significantly attenuated in the prehypertensive compared to normotensive group (p<.05). BARIC was negatively associated with systolic BP, diastolic BP, age, BMI, fasting glucose, triglycerides, total and low density cholesterol levels, and somatic depressive symptoms in all participants (p's<.0001 to .05). However, among the prehypertensive individuals BARIC was positively associated with SBP even after controlling for the covariates (age, gender, race, BMI, glucose and lipid panel, somatic BDI scores) (p<.05). This differing nature of the BARIC-SBP relationship between the two BP groups may be attributed to moderating factors such as cardiorespiratory fitness or depressive symptoms that could not be clearly deciphered in this current study. Nonetheless, our findings indicate the associations between inflammation dysregulation mediated by sympathoadrenal activation and BP that is observable even among individuals with normal to mildly elevated BP. BARIC may be a useful and sensitive indicator of elevated risk for vascular inflammatory disease that can be detected even at lower BP levels, especially given its associations with traditional CVD risk factors and the critical role of monocytes in atherogenic processes.

Progenitor cells are mobilized by acute psychological stress but not beta-adrenergic receptor agonist infusion.

OBJECTIVES: Stimuli that activate the sympathetic nervous system, such as acute psychological stress, rapidly invoke a robust mobilization of lymphocytes into the circulation. Experimental animal studies suggest that bone marrow-derived progenitor cells (PCs) also mobilize in response to sympathetic stimulation. Here we tested the effects of acute psychological stress and brief pharmacological ß-adrenergic (ßAR) stimulation on peripheral PC numbers in humans. METHODS: In two studies, we investigated PC mobilization in response to an acute speech task (n=26) and ßAR-agonist (isoproterenol) infusion (n=20). A subset of 8 participants also underwent the infusion protocol with concomitant administration of the ßAR-antagonist propranolol. Flow cytometry was used to enumerate lymphocyte subsets, total progenitor cells, total haematopoietic stem cells (HSC), early HSC (multi-lineage potential), late HSC (lineage committed), and endothelial PCs (EPCs). RESULTS: Both psychological stress and ßAR-agonist infusion caused the expected mobilization of total monocytes and lymphocytes and CD8(+) T lymphocytes. Psychological stress also induced a modest, but significant, increase in total PCs, HSCs, and EPC numbers in peripheral blood. However, infusion of a ßAR-agonist did not result in a significant change in circulating PCs. CONCLUSION: PCs are rapidly mobilized by psychological stress via mechanisms independent of ßAR-stimulation, although the findings do not exclude ßAR-stimulation as a possible cofactor. Considering the clinical and physiological relevance, further research into the mechanisms involved in stress-induced PC mobilization seems warranted.

Trait mindfulness is associated with blood pressure and interleukin-6: exploring interactions among subscales of the Five Facet Mindfulness Questionnaire to better understand relationships between mindfulness and health.

Mindfulness based interventions have been associated with improvements in physical health; however, the mechanisms underlying these changes are unclear. The current study explored relationships between trait mindfulness, blood pressure (BP) and interleukin-6 (IL-6). Relationships between physical health variables and (1) a composite score of mindfulness, (2) individual facets of mindfulness and (3) interactions between theoretically relevant pairs of mindfulness subscales were investigated. One hundred and thirty healthy, young adults [M (SD) age = 21.7(2.7) years] reported trait levels of mindfulness (Five Facet Mindfulness Questionnaire, subscales include: observing, describing, acting with awareness (AWA), nonjudging and nonreactivity), had their resting BP measured and underwent a blood draw to assesses circulating IL-6 levels. Age, gender, body mass index, race/ethnicity, depression and perceived stress were obtained and used as covariates. A composite score of trait mindfulness was associated with lower BP and a trend suggested that it was also associated with lower IL-6. Investigation of individual facets of mindfulness revealed interactions between the subscales AWA and nonjudging, such that higher endorsement of AWA was associated with lower BP only when nonjudging was also high. A second interaction was observed between the subscales observing and nonreactivity, such that higher endorsement of observing was associated with lower IL-6 only when levels of nonreactivity were also high. Trait mindfulness was associated with both BP and IL-6. Examining interactions between facets of mindfulness variables may be important in understanding how mindfulness based interventions influence physiology.

Depressive symptoms and spiritual wellbeing in asymptomatic heart failure patients.

Depression adversely predicts prognosis in individuals with symptomatic heart failure. In some clinical populations, spiritual wellness is considered to be a protective factor against depressive symptoms. This study examined associations among depressive symptoms, spiritual wellbeing, sleep, fatigue, functional capacity, and inflammatory biomarkers in 132 men and women with asymptomatic stage B heart failure (age 66.5 years ± 10.5). Approximately 32 % of the patients scored ≥10 on the Beck Depression Inventory, indicating potentially clinically relevant depressive symptoms. Multiple regression analysis predicting fewer depressive symptoms included the following significant variables: a lower inflammatory score comprised of disease-relevant biomarkers (p < 0.02), less fatigue (p < 0.001), better sleep (p < 0.04), and more spiritual wellbeing (p < 0.01) (overall model F = 26.6, p < 0.001, adjusted R square = 0.629). Further analyses indicated that the meaning (p < 0.01) and peace (p < 0.01) subscales, but not the faith (p = 0.332) subscale, of spiritual wellbeing were independently associated with fewer depressive symptoms. Interventions aimed at increasing spiritual wellbeing in patients lives, and specifically meaning and peace, may be a potential treatment target for depressive symptoms asymptomatic heart failure.

Leukocyte ß-adrenergic receptor sensitivity and depression severity in patients with heart failure.

OBJECTIVES: Clinical outcomes are worse for patients with heart failure (HF) and elevated depression symptoms. Depression-related sympathoimmune dysregulation may be one mechanism leading to poorer HF prognosis. Sympathetically mediated adrenergic activity is known to regulate immune activity via ß-adrenergic receptors (ß-ARs). However, studies show conflicting relationships between leukocyte ß-AR sensitivity and depression symptoms. The aim of this study was to determine in patients with HF the relationship of leukocyte ß-AR sensitivity with two diverse measures of depression, self-report questionnaire versus clinical diagnostic interview. METHODS: Patients with HF (N = 73, mean [standard deviation] age = 56.3 [13.0]) completed the Beck Depression Inventory-1A and a modified Structured Clinical Interview for the DSM-IV. Leukocyte ß-AR sensitivity was determined from isoproterenol-stimulated cyclic adenosine monophosphate levels; plasma norepinephrine and epinephrine were also assessed. RESULTS: Patients with major depression determined by Structured Clinical Interview for the DSM-IV had significantly higher ß-AR sensitivity than did nondepressed patients (F(6,72) = 9.27, p = .003, η = 0.12). The Beck Depression Inventory-1A revealed a more complex relationship. Minimal, mild, and moderate-to-severe depression symptom groups had significant differences in ß-AR sensitivity (F(7,72) = 7.03, p = .002, η = 0.18); mild symptoms were associated with reduced ß-AR sensitivity and moderate-to-severe symptoms with higher ß-AR sensitivity compared with patients with minimal depressive symptoms. CONCLUSIONS: Clinical depression was associated with elevated ß-AR sensitivity in patients with HF. By deconstructing depression measurements, a greater depth of information may be garnered to potentially reveal subtypes of depression symptoms and their relation to ß-AR sensitivity.

Endothelial function and sleep: associations of flow-mediated dilation with perceived sleep quality and rapid eye movement (REM) sleep.

Endothelial function typically precedes clinical manifestations of cardiovascular disease and provides a potential mechanism for the associations observed between cardiovascular disease and sleep quality. This study examined how subjective and objective indicators of sleep quality relate to endothelial function, as measured by brachial artery flow-mediated dilation (FMD). In a clinical research centre, 100 non-shift working adults (mean age: 36 years) completed FMD testing and the Pittsburgh Sleep Quality Index, along with a polysomnography assessment to obtain the following measures: slow wave sleep, percentage rapid eye movement (REM) sleep, REM sleep latency, total arousal index, total sleep time, wake after sleep onset, sleep efficiency and apnea-hypopnea index. Bivariate correlations and follow-up multiple regressions examined how FMD related to subjective (i.e., Pittsburgh Sleep Quality Index scores) and objective (i.e., polysomnography-derived) indicators of sleep quality. After FMD showed bivariate correlations with Pittsburgh Sleep Quality Index scores, percentage REM sleep and REM latency, further examination with separate regression models indicated that these associations remained significant after adjustments for sex, age, race, hypertension, body mass index, apnea-hypopnea index, smoking and income (Ps < 0.05). Specifically, as FMD decreased, scores on the Pittsburgh Sleep Quality Index increased (indicating decreased subjective sleep quality) and percentage REM sleep decreased, while REM sleep latency increased (Ps < 0.05). Poorer subjective sleep quality and adverse changes in REM sleep were associated with diminished vasodilation, which could link sleep disturbances to cardiovascular disease.

Sleep, fatigue, depression, and circadian activity rhythms in women with breast cancer before and after treatment: a 1-year longitudinal study.

PURPOSE: Sleep disturbance, fatigue and depression are common complaints in patients with cancer, and often contribute to worse quality of life (QoL). Circadian activity rhythms (CARs) are often disrupted in cancer patients. These symptoms worsen during treatment, but less is known about their long-term trajectory. METHODS: Sixty-eight women with stage I-III breast cancer (BC) scheduled to receive ≥4 cycles of chemotherapy, and age-, ethnicity-, and education-matched normal, cancer-free controls (NC) participated. Sleep was measured with actigraphy (nocturnal total sleep time [nocturnal TST] and daytime total nap time [NAPTIME]) and with the Pittsburgh Sleep Quality Index (PSQI); fatigue with the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF); depression with the Center of Epidemiological Studies-Depression (CES-D). CARs were derived from actigraphy. Several measures of QoL were administered. Data were collected at three time points: before (baseline), end of cycle 4 (cycle 4), and 1 year post-chemotherapy (1 year). RESULTS: Compared to NC, BC had longer NAPTIME, worse sleep quality, more fatigue, more depressive symptoms, more disrupted CARs, and worse QoL at baseline (all p values <0.05). At cycle 4, BC showed worse sleep, increased fatigue, more depressive symptoms, and more disrupted CARs compared to their own baseline levels and to NC (all p values <0.05). By 1 year, BC's fatigue, depressive symptoms, and QoL returned to baseline levels but were still worse than those of NC, while NAPTIME and CARs did not differ from NC's. CONCLUSION: Additional research is needed to determine if beginning treatment of these symptoms before the start of chemotherapy will minimize symptom severity over time.

In vivo ß-adrenergic receptor responsiveness: ethnic differences in the relationship with symptoms of depression and fatigue.

BACKGROUND: Depressive symptoms and fatigue frequently overlap in clinical samples and the general population. The link of depressive symptoms and fatigue with increased risk of cardiovascular disease has been partly explained by shared biological mechanisms including sympathetic overactivity. Prolonged sympathetic overactivity downregulates the responsiveness of the ß-adrenergic receptor (ß-AR), a receptor that mediates several end-organ sympathetic responses. PURPOSE: The authors studied whether depression and fatigue are related to reduced ß-AR responsiveness within the human body (in vivo) in an ethnically diverse sample of African and Caucasian Americans. METHODS: The chronotropic25 dose (CD25) was used to determine in vivo ß-AR responsiveness in 93 healthy participants. Psychometric measures included the Center of Epidemiological Studies-Depression Scale and the Multidimensional Fatigue Symptom Inventory. RESULTS: Hierarchical regression analyses (adjusted for age, gender, body mass index, blood pressure, smoking, and ethnicity) revealed that mental fatigue was significantly related to reduced ß-AR responsiveness (i.e., higher CD25 values) in the whole sample. Moderation analyses indicated significant ethnicity × depression/fatigue interactions. Depressive symptoms, total fatigue, emotional fatigue, mental fatigue, and physical fatigue were related to reduced ß-AR responsiveness in Caucasian American but not in African Americans. CONCLUSIONS: Our findings suggest that symptoms of depression and fatigue are related to decreased in vivo ß-AR responsiveness in Caucasian Americans. The lack of this association in African Americans highlights the importance for considering ethnicity as a potential moderator in research focusing on associations between psychological variables and cardiovascular function.

Positive affect and sleep in spousal Alzheimer caregivers: a longitudinal study.

This article examines the longitudinal relation between positive affect (PA) and sleep in 126 spousal Alzheimer's disease caregivers. Caregivers underwent 4 yearly assessments for the Positive and Negative Affect Schedule, the self-rated Pittsburgh Sleep Quality Index, and actigraphy to objectify nighttime total sleep time, wake after sleep onset, and percentage of sleep. Increased levels of PA and a greater positivity (i.e., positive-to-negative affect) ratio were significantly associated with better subjective sleep over the entire study period. Yearly increases in PA-even when controlling for negative affect (NA)-and in the positivity ratio were also associated with better subjective sleep. PA and actigraphy measures showed no significant relations. Increased PA is longitudinally associated with better sleep in dementia caregivers largely independent of NA.