Inflammatory cytokines and depression in children with cancer: A review of the literature.

Compared to the general pediatric population, pediatric cancer patients are at increased risk of experiencing depressive symptoms during and after their treatment. Clinically, there exist few resources to guide health care professionals in the care of children with cancer who report depressive symptomatology. Pediatric cancer patients experience unique inflammatory changes secondary to their disease and accompanying treatments. It has been reported that inflammatory changes in the context of illness are related to cytokine dysregulation which in turn may influence the expression of depressive symptoms. In this review of current literature, we summarize the existing knowledge, relevant models and studies in progress with respect to this concept.

Mediators of the relationship between race and allostatic load in African and White Americans.

OBJECTIVE: Allostatic load (AL) is a cumulative index of physiological dysregulation, which has been shown to predict cardiovascular events and all-cause mortality. On average, African Americans (AA) have higher AL than their White American (WA) counterparts. This study investigated whether differences in discrimination, negative affect-related variables (e.g., experience and expression of anger, depression), and health practices (e.g., exercise, alcohol use, smoking, subjective sleep quality) mediate racial differences in AL. METHOD: Participants included healthy, AA (n = 76) and WA (n = 100), middle-aged (Mage = 35.2 years) men (n = 98) and women (n = 78). Questionnaires assessed demographics, psychosocial variables, and health practices. Biological data were collected as part of an overnight hospital stay-AL score was composed of 11 biomarkers. The covariates age, gender, and socioeconomic status were held constant in each analysis. RESULTS: Findings showed significant racial differences in AL, such that AA had higher AL than their WA counterparts. Results of serial mediation indicated a pathway whereby racial group was associated with discrimination, which was then associated with increased experience of anger and decreased subjective sleep quality, which were associated with AL (e.g., race → discrimination → experience of anger → subjective sleep quality → AL); in combination, these variables fully mediated the relationship between race and AL (p < .05). CONCLUSION: These results suggest that discrimination plays an important role in explaining racial differences in an important indictor of early disease through its relationship with negative affect-related factors and health practices. (PsycINFO Database Record

Trajectories of Perinatal Depressive and Anxiety Symptoms in a Community Cohort.

OBJECTIVE: The evidence on trajectories of perinatal depression is mostly based on studies composed of women at high risk for poor mental health. Research on maternal anxiety trajectories is also scarce. Using a large community cohort, the All Our Babies study, in Alberta, Canada, we examined trajectories of perinatal depressive and anxiety symptoms and compared characteristics of women across trajectories. METHODS: Anxiety and depressive symptoms were measured at the second and third trimesters and at 4 and 12 months postpartum among 1,445 women recruited between May 2008 and December 2010. The state subscale of the Spielberger State-Trait Anxiety Inventory was used to measure anxiety symptoms, and depressive symptoms were measured with the Edinburgh Postnatal Depression Scale. Semiparametric group-based mixed modeling was performed to identify the optimal trajectory shape, number of groups, and proportion of the sample belonging to each trajectory. Model fit was evaluated using the Bayesian information criterion. Multinomial logistic regression analysis was conducted to compare characteristics across the trajectories. RESULTS: Five distinct trajectory groups with constant and variable patterns were identified for both depressive and anxiety symptoms: minimal, mild, antepartum, postpartum, and chronic. Common risk factors of depression and anxiety across groups with elevated symptoms were history of mental health issues (odds ratios [ORs] varied from 1.83 to 7.64), history of abuse/neglect (ORs varied from 1.67 to 8.97), and low social support (ORs varied from 1.64 to 11.37). The magnitude of the influence of the psychosocial risk factors was greater in the chronic group compared to others, suggesting a dose-related relationship. CONCLUSIONS: Heterogeneity of anxiety and depressive symptoms highlights the importance of multiple mental health assessments during the perinatal period. The patterns and intensity of postpartum depression differed between community and high-risk samples, underlining the significance of defining suitable cutoffs. Research to examine the impact of these trajectories on child outcomes is needed.

Social support moderates the relationship between sleep and inflammation in a population at high risk for developing cardiovascular disease.

Poor sleep and low social support have each been associated with mortality and morbidity from chronic illness, and a small body of research suggests that the two interact to influence systemic inflammation whereby good social relationships may buffer the relationship between poor sleep and increased inflammation. The current study investigated interactions between sleep and social support in the prediction of inflammation in a clinical population (prehypertensive and hypertensive individuals) at high risk for the development of cardiovascular disease. Using a standardized subjective measure of sleep quality, we found that social support moderated the association between sleep and circulating levels of both IL-6 and CRP, such that poor sleep appeared to confer a risk of increased inflammation only in those participants who also reported low social support. In women, the same relationship was observed for TNF-α. These results extend previous findings into a clinical population and also demonstrate that sleep quality and social support interact in the prediction of two previously uninvestigated clinically relevant inflammatory markers (CRP and TNF-α). High levels of perceived social support may compensate for the negative health impact of poor sleep quality and vice versa.

Trajectories of Sleep Quality and Associations with Mood during the Perinatal Period.

OBJECTIVE: The aim of this study was to investigate trajectories of sleep quality and associations with mood in the perinatal period. Although it is commonly accepted that subjective sleep quality declines during pregnancy and the transition to parenthood, some women may follow qualitatively distinct trajectories. DESIGN, SETTING, AND PARTICIPANTS: Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Data were collected from 293 women at four time points: during early pregnancy, at Time 1 (T1; < 22 w gestational age [GA]; late pregnancy, at Time 2 (T2; 32 w GA); during the postnatal period at Time 3 (T3; 3 mo postpartum); and Time 4 (T4; 6 mo postpartum). A group-based semiparametric mixture model was used to estimate patterns of sleep quality throughout the perinatal period. RESULTS: Four trajectory groups were identified, including patterns defined by high sleep quality throughout (21.5%), mild decrease in sleep quality (59.5%), significant decrease in sleep quality (12.3%) and a group with poor sleep quality throughout (6.7%). Women who had the worst sleep quality at Time 1 and those who experienced significant increases in sleep problems throughout pregnancy were also the groups who reported the highest levels of anxiety and depressive symptoms in early pregnancy and the lowest levels of social support. After controlling for covariates, the groups with worst subjective sleep quality during pregnancy were also the most likely to experience high symptoms of depression in the postpartum period. CONCLUSIONS: Most of the women in our sample reported mild sleep disturbances through the perinatal period. A subgroup of women reported a significant decline in sleep quality from early to late pregnancy and another reported poor subjective sleep quality throughout pregnancy; these groups had the greatest risk of experiencing high symptoms of depression in the postpartum period.

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.

Obstructive sleep apnea and neurocognitive performance: the role of cortisol.

BACKGROUND: Obstructive sleep apnea (OSA) is a prevalent disorder with multiple consequences including negative effects on neurocognitive function. Several domains of cognitive function are impaired in OSA patients, but the mechanisms through which this sleep disorder results in impairment are not clear. Given the well-known effects of cortisol on cognitive function, in particular memory, the dysregulating effects of OSA on cortisol levels are hypothesized as a potential pathway leading to cognitive impairment. METHODS: Fifty-five participants with OSA (mean apnea-hypopnea index [AHI], 30.3) were assessed over 2 days. Over a 24-h period, blood samples were collected every 2h to examine cortisol levels. The following night, sleep was monitored with polysomnography (PSG). Participants were given a battery of neurocognitive tests, which assessed seven cognitive domains. RESULTS: OSA severity assessed by oxygen desaturation index (ODI) was associated with 24-h cortisol levels. AHI, ODI, and nighttime cortisol levels were associated with global deficit scores (GDS) in cognitive functioning, particularly in domains of learning, memory, and working memory (P<.05 for all). Hierarchical linear regression analysis revealed that nighttime cortisol accounted for 9-16% of variance in learning (P=.018), memory (P=.003), and working memory (P=.016) domains, though apnea severity did not significantly predict any additional variance. CONCLUSIONS: In our sample of patients with OSA, nocturnal cortisol levels were associated with neuropsychologic functioning above and beyond the influence of covariates and apnea severity. These findings suggest that OSA-related alterations in cortisol activity may partially explain the pathophysiology of neuropsychologic impairments in sleep apnea.

Self-esteem variability predicts arterial stiffness trajectories in healthy adolescent females.

OBJECTIVE: There is mounting evidence that high levels of self-esteem are associated with better health outcomes, particularly in older adults dealing with serious medical illnesses. Much less is known about how this linkage unfolds developmentally, particularly during times like adolescence, when youngsters' self-views are typically in flux. Here we explore the self-esteem of adolescent females over a 2.5-year period, and how it covaries with trajectories of vascular function assessed over the same timeframe. METHOD: One-hundred and thirty adolescent females completed the Rosenberg Self-Esteem scale every 6 months for 2.5 years. Vascular function was measured three times over the same period, using peripheral artery tonometry. Indices of endothelial function and arterial stiffness were derived from these measurements. RESULTS: Hierarchical Linear Modeling revealed an association between self-esteem variability and arterial stiffness trajectories, ß = 9.0 × 10-3, SE = 4.4 × 10-3, p = .04. To the extent that their self-esteem fluctuated over the 2.5-year study, participants showed increasing trajectories of arterial stiffness, independent of various demographic and biobehavioral confounders. This association was also independent of participants' trait-like self-esteem over the same period of time. Neither trait self-esteem nor self-esteem variability was related to endothelial function. CONCLUSION: These findings suggest that fluctuating self-esteem may accelerate the early stages of vascular stiffening in young women, regardless of whether self-views are generally positive or negative.

Psychometric characteristics of the Pittsburgh Sleep Quality Index in English speaking non-Hispanic whites and English and Spanish speaking Hispanics of Mexican descent.

STUDY OBJECTIVES: The current study investigated the factor structure of the Pittsburgh Sleep Quality Index (PSQI) among English speaking non-Hispanic whites (NHW) and English and Spanish speaking Hispanics of Mexican descent (HMD). DESIGN: The PSQI was administered during a telephone interview. In order to test the factor structure of the PSQI structure across ethnic/language groups, multiple group confirmatory analysis with covariates (MIMIC) was employed. The 1- and 3-factor versions of the PSQI previously reported in the literature were examined. SETTING: San Diego County. PARTICIPANTS: Community-dwelling English speaking, NHW (n = 1,698) and English (n = 654) and Spanish (n = 792) speaking HMD. MEASUREMENT AND RESULTS: A single-factor scoring model fit across language/ethnic groups; however, a 3-factor model provided a better than the 1-factor model in all language/ethnic groups. The subscale sleep medications loaded poorly and was removed from all models. CONCLUSION: Across groups, a 3-factor model of the PSQI more reliably assessed sleep quality than a single-factor global score. Results indicate that the 3-factor structure of the PSQI was uniform across English speaking NHW and English and Spanish speaking HMD.

Effects of Aerobic Fitness and Adiposity on Coagulation Biomarkers in Men vs. Women with Elevated Blood Pressure.

A hypercoagulable state is a potential mechanism linking elevated blood pressure (BP), adiposity and a sedentary lifestyle to development of coronary heart disease (CHD). We examined relationships among aerobic fitness and adiposity in 76 sedentary subjects with elevated BP. Blood levels of plasminogen activator inhibitor-1 (PAI-1), D-dimer, von Willebrand factor (vWF) and thrombomodulin were assessed as biomarkers of coagulation. In individuals with elevated BP, percent body fat and fitness were associated with biomarkers indicative of a hypercoagulable state, even after demographic and metabolic factors were considered. D-dimer was positively associated with percent body fat (beta=0.37, p=0.003). PAI-1 was higher in men than in women (beta=-0.31, p=0.015) and associated with lower VO2peak (beta=-0.35, p=0.024). Thrombomodulin was positively associated with VO2peak (beta=0.56, p< 0.01). vWF was not significantly associated with fitness or adiposity. Our results emphasise that both percent body fat and physical fitness are important in the maintenance of haemostatic balance.

Acute exercise enhancement of pneumococcal vaccination response: a randomised controlled trial of weaker and stronger immune response.

Acute exercise at the time of vaccination can enhance subsequent immune responses. However, the potential benefit of this effect will be its efficacy in boosting poor responses, and thus protection in at-risk populations. The current study tested the effect of exercise on the response to either a full- or half-dose Pneumococcal (Pn) vaccination to elicit stronger and weaker responses. Subjects were 133 young healthy adults, randomised to one of four groups: exercise or control task, receiving a full- or half-dose Pn vaccination. Prior to vaccination, exercise groups completed a 15 min arm and shoulder exercise task, control groups rested quietly. Antibody levels to 11 Pn strains were evaluated at baseline and 1-month. Across all participants, exercise groups showed significantly greater increase in antibody levels than control groups. When doses were compared, it emerged that those who exercised had significantly larger responses than those who rested in the half-dose group, but in the full-dose groups responses were similar. This data indicates the effectiveness of exercise as a vaccine adjuvant, particularly in weaker responses. Thus, given the potential public health benefits of no-cost behavioural intervention to enhance response to vaccination, testing in at-risk populations should be pursued.

Higher physical fatigue predicts adherence to a 12-week exercise intervention in women with elevated blood pressure.

OBJECTIVE: To investigate predictors of exercise adherence to a 12-week exercise intervention for sedentary women and men with elevated blood pressure (BP). METHODS: Fifty-one otherwise healthy and unmedicated adults (27 women and 24 men) with elevated BP (≥120/80 mmHg but <179/109 mmHg) participated in a 12-week exercise intervention involving cardiovascular and strength training. Participants kept weekly exercise logs detailing minutes spent exercising each week. The following were assessed before and after the intervention: cardiorespiratory fitness (in mL/kg/min), body mass index (BMI), level of habitual physical activity, physical fatigue, self-efficacy for exercise habits, and social support. RESULTS: Regression analysis revealed that mean exercise minutes/week were predicted by higher age (p < .05), higher cardiorespiratory fitness (p < .05), and a gender by physical fatigue interaction (p < .01; R2 = 0.34, F = 3.248, p < .01). Women who reported higher physical fatigue prior to the intervention spent more time exercising during the 12-week intervention than those with lower levels of physical fatigue. This relationship persisted after controlling for age, BMI, cardiorespiratory fitness, level of habitual physical activity prior to the intervention, self-efficacy for exercise habits, and social support (p < .01). The gender by physical fatigue interaction explained 13.9% of the variance in mean minutes exercised/week above and beyond the effects of covariates. CONCLUSION: Both gender and fatigue should be considered when developing exercise interventions, such that more initial physical fatigue in women is associated with a tendency to devote greater amounts of time to exercising.

Racial differences in sleep architecture: the role of ethnic discrimination.

African Americans have been consistently shown to have less deep (slow wave sleep; SWS) and more light (Stages 1 and 2) sleep than Caucasian Americans. This paper explored whether discrimination, a stressor that uniquely impacts certain ethnic groups, contributes to differences in sleep architecture. The sleep of 164 African and Caucasian Americans was examined with laboratory based polysomnography (PSG). Experiences of perceived discrimination (The Scale of Ethnic Experience) and sociodemographic factors were also assessed. After adjusting for age, body mass index (BMI), socioeconomic status (SES) and smoking status, African Americans slept approximately 4.5% more total sleep time (TST) in Stage 2 sleep and 4.7% less TST in SWS than Caucasian Americans (ps<.05). Perceived discrimination was a partial mediator of ethnic differences in sleep architecture. Individuals who reported experiencing more discrimination slept more time in Stage 2 and less time in SWS (ps<.05). Results suggest that the impact of stress related to ethnic group membership plays a part in explaining differences in sleep architecture.

Is obstructive sleep apnea associated with cortisol levels? A systematic review of the research evidence.

The pathophysiology of obstructive sleep apnea (OSA) has been associated with dysregulation of the hypothalamic pituitary adrenal (HPA) axis; however a relationship between OSA and altered cortisol levels has not been conclusively established. We conducted a systematic review using the PRISMA Guidelines based on comprehensive database searches for 1) studies of OSA patients compared to controls in whom cortisol was measured and 2) studies of OSA patients treated with continuous positive airway pressure (CPAP) in whom cortisol was measured pre and post treatment. Five electronic databases were searched along with the reference lists of retrieved studies. The primary outcomes were 1) differences in cortisol between OSA and control subjects and 2) differences in cortisol pre-post CPAP treatment. Sampling methodology, sample timing and exclusion criteria were evaluated. Fifteen studies met the inclusion criteria. Heterogeneity of studies precluded statistical pooling. One study identified differences in cortisol between OSA patients and controls. Two studies showed statistically significant differences in cortisol levels pre-post CPAP. The majority of studies were limited by assessment of cortisol at a single time point. The available studies do not provide clear evidence that OSA is associated with alterations in cortisol levels or that treatment with CPAP changes cortisol levels. Methodological concerns such as infrequent sampling, failure to match comparison groups on demographic factors known to impact cortisol levels (age, body mass index; BMI), and inconsistent control of variables known to influence HPA function may have limited the results.

A Model for Studying Neuropsychological Effects of Sleep Intervention: The Effect of 3-week Continuous Positive Airway Pressure Treatment.

PURPOSE: Patients with obstructive sleep apnea (OSA) commonly have cognitive complaints. There are few randomized studies that have examined neuropsychological effects of continuous positive airway pressure (CPAP) treatment in patients with OSA. In this double-blind trial, we examined if a 3-week CPAP treatment compared with placebo CPAP treatment has specific therapeutic effects on cognitive impairments in patients with OSA and if there are specific domains of cognitive impairments sensitive to 3-week CPAP treatment. SUBJECTS AND METHODS: Thirty-eight newly diagnosed patients with untreated OSA underwent neuropsychological testing before and after 3-weeks CPAP or Placebo CPAP treatment. The two treatment groups (therapeutic CPAP, and placebo-CPAP) were compared using repeated measures analysis of variance (ANOVA). RESULTS AND CONCLUSION: Impairments in neuropsychological functioning ranged from 2.6% to 47.1% before treatment. In response to 3 weeks of treatment, there was no significant time by treatment interaction for a global deficit score of neuropsychological functioning. Only the Stroop Color (number correct) test showed significant improvement specific to CPAP treatment. The study demonstrates the importance of further randomized placebo controlled studies in this area.

Multiwave associations between depressive symptoms and endothelial function in adolescent and young adult females.

OBJECTIVE: Depression has been linked to endothelial dysfunction, and some research suggests that past depressive episodes are associated with a lasting, negative impact on the endothelium. However, investigations in this area have been predominantly cross-sectional, raising questions about the direction of these associations. Using a multiwave design, we sought to extend previous research in this area by examining whether depressive symptoms have a lasting negative influence on endothelial function. METHODS: A total of 135 adolescent and young adult females with no known or suspected major health problems were followed for 2½ years. Endothelial function was assessed at three time points throughout the study. The Beck Depression Inventory was administered, and information about health practices was collected every 6 months. RESULTS: Self-reported depressive symptoms covaried with endothelial functioning on a within-person basis (ß = -0.23, p < .05). As a participant's depression symptoms rose beyond her typical level, her endothelial function declined commensurately. This association persisted after controlling for health practices and adiposity. There was no evidence that depressive symptoms predicted endothelial function at later time points or interacted with time to predict the trajectories of endothelial function over the follow-up period. CONCLUSIONS: Depressive symptoms were concurrently associated with endothelial function in this cohort of healthy adolescent girls and young women. On visits when participants endorsed depressive symptoms that were higher than their mean level of depression, they tended to have worse endothelial function. We did not observe a lasting negative effect of depression on endothelial function.

Depressed mood and flow-mediated dilation: a systematic review and meta-analysis.

OBJECTIVE: This systematic and quantitative review evaluates the literature on associations between depressed mood and flow-mediated dilation (FMD), a measure of endothelial function, in adults. METHODS: Published English-language articles (through December 2010) were identified from literature searches, assessed for data extraction, and evaluated for quality. RESULTS: The literature includes cross-sectional (n = 9) and retrospective examinations (n = 3) of how FMD correlates with clinical or subclinical depression in healthy adults and cardiovascular patients (total N across 12 studies = 1491). FMD was assessed using a variety of methodologies. Samples were predominately older white and Asian subjects with higher socioeconomic status. In eight of the 12 articles selected for this review, at least one significant inverse association was noted between depressed mood and FMD, with primarily moderate effect sizes. The overall meta-analysis (random-effects model) revealed a combined effect size of correlation coefficient r = 0.19 (95% confidence interval = 0.08-0.29, p = .001). Significant combined effects were found for subgroups of studies that a) received better quality ratings (r = 0.29), b) examined patients with cardiovascular disease or with cardiovascular disease risk factors/comorbidity (r = 0.29), c) used maximum vasodilation to quantify FMD (r = 0.27), and d) assessed samples that had a mean age of 55 years and older (r = 0.15). CONCLUSIONS: Diverse studies support the inverse correlation between depressed mood and endothelial function, as measured by FMD. This literature would be strengthened by prospective studies, increased methodological consistency in FMD testing, and broader sampling (e.g., African Americans, younger age, lower socioeconomic status).

Macrophage migratory inhibitory factor (MIF) may be a key factor in inflammation in obstructive sleep apnea.

STUDY OBJECTIVES: This study investigated the 24-hour variation of macrophage migratory inhibitory factor (MIF), a cytokine which induces insensitivity to the anti-inflammatory effects of glucocorticoids, in patients with untreated obstructive sleep apnea (OSA) as compared to healthy adults with no OSA. PARTICIPANTS: Fifty-three men and women with OSA (mean apnea/hypopnea index [AHI] = 39.5) and 24 healthy adults (Non-OSA, AHI = 5.1). MEASUREMENTS: Over a 24-h period, blood was collected every 2 h for MIF and cortisol determination. The following night, sleep was monitored with polysomnography. RESULTS: MIF showed a strong 24-h variation, with a peak at 04:00 and a nadir at 22:00. Patients with OSA showed 25% higher MIF levels (area under the curve) over 24 h than healthy controls. Furthermore, MIF levels were significantly associated with AHI and total arousal index (ArI), even after adjusting for BMI. Cortisol showed the expected 24-h variation (peaking at 06:00), but no cortisol differences were observed between OSA and Non-OSA groups. CONCLUSION: MIF is elevated in patients with OSA and is related to OSA severity, while there was no difference in cortisol levels. MIF is a pro-inflammatory cytokine which additionally inhibits the anti-inflammatory effects of glucocorticoids. Thus, elevated MIF levels in OSA may contribute to elevated inflammation.

Effects of continuous positive airway pressure on fatigue and sleepiness in patients with obstructive sleep apnea: data from a randomized controlled trial.

OBJECTIVES: Complaints of fatigue are frequent in patients with obstructive sleep apnea (OSA); however, the impact of continuous positive airway pressure (CPAP) on fatigue remains unclear. METHODS: Fifty-nine men and women with OSA were randomly assigned to therapeutic or placebo CPAP in a double-blind fashion for a 3-week intervention period. Four outcome measures were assessed: (1) fatigue/vigor measured with the Multidimensional Fatigue Symptom Inventory--Short Form (MFSI-sf), the (2) fatigue and (3) vigor subscales of the Profile of Mood States--Short Form (POMS), and (4) the Epworth Sleepiness Scale (ESS). Data were analyzed using repeated-measures analysis of variance. RESULTS: Compared with patients receiving placebo CPAP, those patients treated with therapeutic CPAP showed significant reductions in the apnea-hypopnea index, as well as decreases in both measures of fatigue and increases in vigor (P values < 0.05). The beneficial effect of therapeutic treatment was most pronounced in patients with high levels of fatigue at study onset. Significant treatment effects in sleepiness scores were not observed in the entire sample (P > 0.05); however, in a subset of patients with excessive sleepiness at the onset of treatment, ESS scores were significantly reduced with use of therapeutic CPAP (P < 0.05). CONCLUSIONS: Results suggest that 3 weeks of therapeutic CPAP significantly reduced fatigue and increased energy in patients with OSA. Therapeutic CPAP significantly reduced daytime sleepiness in patients who reported excessive sleepiness at the onset of treatment.