Jeanette M. Bennett

Yoga's Impact on Inflammation, Mood, and Fatigue in Breast Cancer Survivors: A Randomized Controlled Trial

PURPOSE To evaluate yogas impact on inflammation, mood, and fatigue. PATIENTS AND METHODS A randomized controlled 3-month trial was conducted with two post-treatment assessments of 200 breast cancer survivors assigned to either 12 weeks of 90-minute twice per week hatha yoga classes or a wait-list control. The main outcome measures were lipopolysaccharide-stimulated production of proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β), and scores on the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), the vitality scale from the Medical Outcomes Study 36-item Short Form (SF-36), and the Center for Epidemiological Studies-Depression (CES-D) scale. RESULTS Immediately post-treatment, fatigue was not lower (P > .05) but vitality was higher (P = .01) in the yoga group compared with the control group. At 3 months post-treatment, fatigue was lower in the yoga group (P = .002), vitality was higher (P = .01), and IL-6 (P = .027), TNF-α (P = .027), and IL-1β (P = .037) were lower for yoga participants compared with the control group. Groups did not differ on depression at either time (P > .2). Planned secondary analyses showed that the frequency of yoga practice had stronger associations with fatigue at both post-treatment visits (P = .019; P < .001), as well as vitality (P = .016; P = .0045), but not depression (P > .05) than simple group assignment; more frequent practice produced larger changes. At 3 months post-treatment, increasing yoga practice also led to a decrease in IL-6 (P = .01) and IL-1β (P = .03) production but not in TNF-α production (P > .05). CONCLUSION Chronic inflammation may fuel declines in physical function leading to frailty and disability. If yoga dampens or limits both fatigue and inflammation, then regular practice could have substantial health benefits.

Loneliness predicts pain, depression, and fatigue: understanding the role of immune dysregulation.

OBJECTIVE The pain, depression, and fatigue symptom cluster is an important health concern. Loneliness is a common risk factor for these symptoms. Little is known about the physiological mechanisms linking loneliness to the symptom cluster; immune dysregulation is a promising candidate. Latent herpesvirus reactivation, which is reflected by elevated herpesvirus antibody titers, provides a window into immune dysregulation. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are two common herpesviruses. METHODS Participants were 200 breast cancer survivors who were 2 months to 3 years post-treatment at the time of the study. They completed questionnaires and provided a blood sample that was assayed for CMV and EBV antibody titers. RESULTS Lonelier participants experienced more pain, depression, and fatigue than those who felt more socially connected. Lonelier participants also had higher CMV antibody titers which, in turn, were associated with higher levels of the pain, depression, and fatigue symptom cluster. Contrary to expectations, EBV antibody titers were not associated with either loneliness or the symptom cluster. CONCLUSIONS The pain, depression, and fatigue symptom cluster is a notable clinical problem, especially among cancer survivors. Accordingly, understanding the risk factors for these symptoms is important. The current study suggests that loneliness enhances risk for immune dysregulation and the pain, depression, and fatigue symptom cluster. The present data also provide a glimpse into the pathways through which loneliness may impact health.

Loneliness Promotes Inflammation During Acute Stress

Although evidence suggests that loneliness may increase risk for health problems, the mechanisms responsible are not well understood. Immune dysregulation is one potential pathway: Elevated proinflammatory cytokines such as interleukin-6 (IL-6) increase risk for health problems. In our first study (N = 134), lonelier healthy adults exposed to acute stress exhibited greater synthesis of tumor necrosis factor-alpha (TNF-α) and IL-6 by peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharide (LPS) than their less lonely counterparts. Similarly, in the second study (N = 144), lonelier posttreatment breast-cancer survivors exposed to acute stress exhibited greater synthesis of IL-6 and interleukin-1 beta (IL-1β) by LPS-stimulated PBMCs than their counterparts who felt more socially connected. However, loneliness was unrelated to TNF-α in Study 2, although the result was in the expected direction. Thus, two different populations demonstrated that lonelier participants had more stimulated cytokine production in response to stress than less lonely participants, which reflects a proinflammatory phenotype. These data provide a glimpse into the pathways through which loneliness may affect health.

Inflammation and reactivation of latent herpesviruses in older adults

Inflammation increases with age and is associated with many chronic diseases that are prevalent among older adults. Persistent pathogens such as latent herpesviruses and chronic bacterial infections can act as a source of inflammation. Herpesviruses, including Epstein-Barr virus (EBV) and cytomegalovirus (CMV), establish latent infections following primary infection and reactivate when the cellular immune system is compromised. EBV and CMV replication can induce proinflammatory cytokine production and thus could influence systemic inflammation. The present study addressed relationships among EBV and CMV antibody titers, and levels of C-reactive protein (CRP) and interleukin-6 (IL-6) in a sample of 222 community dwelling older adults (mean(age)=64.1±14.1 years). Participants were divided into two groups based on whether they were EBV seropositive and CMV seronegative (EBV+CMV-), or EBV and CMV seropositive (EBV+CMV+). Among individuals who were EBV+CMV-, EBV antibody titers were not associated with either CRP or IL-6 levels. However, among those who were EBV+CMV+, higher EBV antibody titers were related to elevated levels of CRP and IL-6 in those individuals with higher CMV antibody titers; there was no relationship between EBV antibody titers and CRP or IL-6 levels in those participants with lower CMV antibody titers. These data suggest that the combination of latent EBV and CMV reactivation (indexed by antibody titers) may boost CRP and IL-6 production. Thus, reactivation of multiple herpesviruses may drive inflammation and could contribute to poorer health among older adults.

Yoga and self-reported cognitive problems in breast cancer survivors: a randomized controlled trial

Cancer survivors often report cognitive problems. Furthermore, decreases in physical activity typically occur over the course of cancer treatment. Although physical activity benefits cognitive function in noncancer populations, evidence linking physical activity to cognitive function in cancer survivors is limited. In our recent randomized controlled trial, breast cancer survivors who received a yoga intervention had lower fatigue and inflammation following the trial compared with a wait list control group. This secondary analysis of the parent trial addressed yogas impact on cognitive complaints.

Fatigue and herpesvirus latency in women newly diagnosed with breast cancer.

Fatigue is a notable clinical problem in cancer survivors, and understanding its pathophysiology is important. The current study sought to determine biomarkers of fatigue that exist before cancer treatment. Relationships between the expression of latent Epstein-Barr virus (EBV) and cytomegalovirus (CMV) and fatigue were examined in 158 women newly diagnosed with breast cancer or awaiting a positive diagnostic result. Higher CMV antibody titers, but not EBV antibody titers, were associated with a greater likelihood of being fatigued. Associations between fatigue and higher CMV antibody titers remained after controlling for alcohol use, smoking, comorbidities, depressive symptoms, age, BMI, cancer stage, and sleep problems. More sleep problems and higher levels of depressive symptoms were also associated with a greater likelihood of being fatigued. CMV antibody titers, but not EBV antibody titers, were associated with higher levels of C-reactive protein (CRP), but CRP was not associated with fatigue. When the cellular immune system is compromised, reactivation of latent herpesviruses may fuel chronic inflammatory responses. Prior work has suggested that fatigue may be related to inflammation and its associated sickness behaviors; accordingly, our findings may be tapping into this same physiological substrate.

Caffeine and stress alter salivary α‐amylase activity in young men

We examined the effects of caffeine and a psychological stressor on salivary α‐amylase (sAA) in healthy young males (age 18–30 years) who consumed caffeine on a daily basis.

Social support and socioeconomic status interact to predict Epstein-Barr virus latency in women awaiting diagnosis or newly diagnosed with breast cancer.

OBJECTIVE Both higher socioeconomic status (SES) and supportive personal relationships confer health benefits, including better immune function. This study assessed the joint impact of SES and social support on the expression of a latent herpesvirus, Epstein-Barr virus (EBV), in a group of highly stressed women. METHODS Two-hundred and twenty four women either awaiting further evaluation following an abnormal mammogram or newly diagnosed with breast cancer completed questionnaires and provided blood samples to assess EBV viral capsid antigen (VCA) IgG antibody titers. RESULTS More highly educated women with more support from friends had lower EBV VCA antibody titers, reflecting a stronger cellular immune response to the latent virus; however, among less educated women, friend support was not associated with EBV antibody titers. As revealed in an ancillary analysis, more highly educated women with more friend support had lower systolic blood pressure (SBP); however, friend support was not associated with SBP among less educated women. Neither depression nor perceived stress mediated these associations. Neither cancer status nor cancer stage among those diagnosed with cancer was significantly related to these outcomes. CONCLUSION Lower SES women may not reap the same immunological benefits from friend support when experiencing a stressful life event as their higher SES counterparts.

The trajectory of life. Decreasing physiological network complexity through changing fractal patterns

In this position paper, we submit a synthesis of theoretical models based on physiology, non-equilibrium thermodynamics, and non-linear time-series analysis. Based on an understanding of the human organism as a system of interconnected complex adaptive systems, we seek to examine the relationship between health, complexity, variability, and entropy production, as it might be useful to help understand aging, and improve care for patients. We observe the trajectory of life is characterized by the growth, plateauing and subsequent loss of adaptive function of organ systems, associated with loss of functioning and coordination of systems. Understanding development and aging requires the examination of interdependence among these organ systems. Increasing evidence suggests network interconnectedness and complexity can be captured/measured/associated with the degree and complexity of healthy biologic rhythm variability (e.g., heart and respiratory rate variability). We review physiological mechanisms linking the omics, arousal/stress systems, immune function, and mitochondrial bioenergetics; highlighting their interdependence in normal physiological function and aging. We argue that aging, known to be characterized by a loss of variability, is manifested at multiple scales, within functional units at the small scale, and reflected by diagnostic features at the larger scale. While still controversial and under investigation, it appears conceivable that the integrity of whole body complexity may be, at least partially, reflected in the degree and variability of intrinsic biologic rhythms, which we believe are related to overall system complexity that may be a defining feature of health and its loss through aging. Harnessing this information for the development of therapeutic and preventative strategies may hold an opportunity to significantly improve the health of our patients across the trajectory of life.

Female temperament, tumor development and life span : Relation to glucocorticoid and tumor necrosis factor α levels in rats

Behavioral characteristics closely associated with specific physiological profiles present an important area of research in understanding health disparities. In particular, glucocorticoid overproduction may be an important factor moderating disease progression; natural variance in production of this steroid has been proposed as one mechanism underlying individual differences in health and disease. In the current paper, we examined immune parameters in female rats of two different behavioral types previously shown to have differential glucocorticoid production and life spans. We categorized young female rats according to their behavioral response to novelty (high- or low-locomotion), and compared their glucocorticoid production, adrenal size, thymus size, tumor necrosis factor-alpha (TNF-alpha) production, tumor development and life span. As expected, high-locomotion females produced more glucocorticoids and had larger adrenal glands during young adulthood than did low-locomotion females. High-locomotion females had significantly smaller thymuses and reduced TNF-alpha levels compared to low-locomotion, suggesting altered immune function in young adulthood. Finally, high-locomotion females had shorter life spans than did low-locomotion females, and this was particularly true in females that developed pituitary tumors, but not in those that developed mammary tumors. These results, along with other published findings, suggest that high-locomotion rodent females experience life-long elevations in glucocorticoid responses to novelty, and that these elevated levels may be comparable to chronic stress. This naturally occurring endocrine profile may influence immune responses which in turn could affect disease susceptibility. Variance in immune function across personality types may be partially moderated by natural variance in glucocorticoid production.