Slow paced breathing via heart rate variability (HRV) biofeedback stimulates vagus-nerve pathways that counter noradrenergic stress and arousal pathways that can influence production and clearance of ...Alzheimer's disease (AD)-related proteins. Thus, we examined whether HRV biofeedback intervention affects plasma Αβ40, Αβ42, total tau (tTau), and phosphorylated tau-181 (pTau-181) levels. We randomized healthy adults (N = 108) to use slow-paced breathing with HRV biofeedback to increase heart rate oscillations (Osc+) or to use personalized strategies with HRV biofeedback to decrease heart rate oscillations (Osc-). They practiced 20-40 min daily. Four weeks of practicing the Osc+ and Osc- conditions produced large effect size differences in change in plasma Aβ40 and Aβ42 levels. The Osc+ condition decreased plasma Αβ while the Osc- condition increased Αβ. Decreases in Αβ were associated with decreases in gene transcription indicators of β-adrenergic signaling, linking effects to the noradrenergic system. There were also opposing effects of the Osc+ and Osc- interventions on tTau for younger adults and pTau-181 for older adults. These results provide novel data supporting a causal role of autonomic activity in modulating plasma AD-related biomarkers.Trial registration: NCT03458910 (ClinicalTrials.gov); first posted on 03/08/2018.
Abstract Background Yoga is a popular mind–body therapy that has demonstrated beneficial effects on psychological, behavioral, and functional outcomes. However, few studies have investigated effects ...on inflammatory processes. This study tested the hypothesis that an Iyengar yoga intervention specifically designed for fatigued breast cancer survivors would lead to decreases in inflammation-related gene expression and circulating markers of proinflammatory cytokine activity. Methods Breast cancer survivors with persistent cancer-related fatigue were randomized to a 12-week Iyengar yoga intervention ( n = 16) or a 12-week health education control condition ( n = 15). Blood samples were collected at baseline, post-intervention, and at a 3-month follow-up for genome-wide transcriptional profiling and bioinformatic analyses. Plasma inflammatory markers and salivary cortisol were also assessed. Results In promoter-based bioinformatics analyses, the yoga group showed reduced activity of the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB), increased activity of the anti-inflammatory glucocorticoid receptor, and reduced activity of cAMP response element-binding protein (CREB) family transcription factors relative to controls (all p s < .05). There was also a significant intervention effect on the soluble tumor necrosis factor receptor type II (sTNF-RII), a marker of TNF activity; plasma levels of sTNF-RII remained stable in the yoga group, whereas levels of this marker increased in the health education group ( p = .028). A similar, non-significant trend was observed for the interleukin 1 receptor antagonist ( p = .16). No significant changes in C reactive protein (CRP), interleukin 6 (IL-6), or diurnal cortisol measures were observed. Conclusions A 12-week restorative Iyengar yoga intervention reduced inflammation-related gene expression in breast cancer survivors with persistent fatigue. These findings suggest that a targeted yoga program may have beneficial effects on inflammatory activity in this patient population, with potential relevance for behavioral and physical health.
Abstract Recent small-scale genomics analyses suggest that physiologic regulation of pro-inflammatory gene expression by endogenous glucocorticoids may be compromised in individuals who experience ...chronic social isolation. The present study assessed the relationship between leukocyte distributional sensitivity to glucocorticoid regulation and subjective social isolation in a large population-based sample of older adults. Initial analyses confirmed that circulating neutrophil percentages were elevated, and circulating lymphocyte and monocyte percentages were suppressed, in direct proportion to circulating cortisol levels. However, leukocyte distributional sensitivity to endogenous glucocorticoids was abrogated in individuals reporting either occasional or frequent experiences of subjective social isolation. This finding held in both non-parametric univariate analyses and in multivariate linear models controlling for a variety of biological, social, behavioral, and psychological confounders. The present results suggest that social factors may alter immune cell sensitivity to physiologic regulation by the hypothalamic–pituitary–adrenal axis in ways that could ultimately contribute to the increased physical health risks associated with social isolation.
Psychosocial stress accelerates myelopoietic production of monocytes and neutrophils that contributes to a variety of health complications ranging from atherosclerosis to anxiety. Here, we show that ...social stress in mice mobilizes hematopoietic stem progenitor cells (HSPCs) from the bone marrow that enter circulation, engraft into the spleen, and establish a persistent extramedullary hematopoietic depot. These splenic progenitors actively proliferate and differentiate into multiple cell types, including monocytes, neutrophils, and erythrocytes. Splenic erythropoiesis partially abrogates stress-induced anemia. Repeated injection with isoprenaline induces progenitor mobilization to the spleen, identifying a key role for β-adrenergic signaling. Moreover, protracted splenic production of CD11b+ cells persists for at least 24 days after the cessation of social stress. Thus, chronic stress establishes a persistent extramedullary hematopoietic depot that can modify a wide range of chronic disease processes and alter homeostasis of the bi-directional regulatory axis between the nervous and immune systems.
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•Social stress mobilizes hematopoietic progenitors from the bone marrow to the spleen•Splenic HSPCs proliferate and differentiate into multiple erythromyeloid cell types•Ectopic splenic erythropoiesis abrogates stress-induced anemia•Extramedullary production of CD11b+ cells persists for at least 24 days
McKim et al. show that social stress enhances innate immune cell production in the bone marrow and mobilizes blood cell progenitors to the spleen, where they establish protracted ectopic production of innate immune cells. This represents a mechanism by which stress causes protracted changes in immunity and inflammation.
•The CTRA involves the up-regulation of transcription of genes linked to inflammation.•The CTRA also involves the down-regulation of transcription of genes linked to anti-viral resistance.•We tested ...a sample of Japanese male workers at an Information Technology firm.•The CTRA is inversely linked to general eudaimonic wellbeing, but not to hedonic wellbeing.•The CTRA is also inversely linked to the perceived significance of one’s work and the interdependence with other workers.
The meaning in life, typically reflected in a sense of purpose, growth, or social embeddedness (called eudaimonic well-being, EWB), has been linked to favorable health outcomes. In particular, this experience is inversely associated with the conserved transcriptional response to adversity (CTRA), which involves up-regulation of genes linked to inflammation and down-regulation of genes linked to viral resistance. So far, however, little is known about how this transcriptome profile might be situated in specific socio-cultural contexts. Here, we tested 106 male workers at a large Japanese IT firm and found that the CTRA is inversely associated not only with general EWB but also with a more contextualized sense of meaning derived from the perceived significance of one’s work and a sense of interdependence with others in the workplace. These results expand previous links between personal well-being and CTRA gene expression to include the socio-cultural determinants of meaning in life.
Although social withdrawal is a prominent symptom of sickness, the mechanisms associated with this behavioral change remain unclear. In animals, the amygdala is a key neural region involved in ...sickness-induced social withdrawal. Consistent with this, in humans, heightened amygdala activity to negative social cues is associated with social avoidance tendencies. Based on these findings, we investigated whether an experimental inflammatory challenge selectively increased amygdala activity to socially threatening images as well as whether this activity related to feelings of social disconnection. Thirty-nine participants were randomly assigned to receive either placebo or low-dose endotoxin, which increases inflammatory activity. Pro-inflammatory cytokines were assessed at 7 hourly time points via blood draws; self-reported feelings of social disconnection and physical sickness symptoms were assessed hourly as well. Two hours post-injection, participants underwent an fMRI procedure to assess amygdala reactivity during the presentation of socially threatening images (fear faces) as well as non-socially threatening images (guns), socially non-threatening images (happy faces), and non-social, non-threatening images (household objects). Endotoxin led to greater amygdala activity in response to socially threatening vs. all other types of images. No such differences were found for placebo participants. Additionally, increased amygdala activity in endotoxin participants during the viewing of socially vs. non-socially threatening images was associated with increased feelings of social disconnection. These findings highlight the amygdala as a neural region that may be important for sickness-induced social withdrawal. The implications of amygdalar involvement in sickness-induced social withdrawal are discussed.
► We investigated neural responses to social stimuli after an inflammatory challenge. ► Inflammation led to greater amygdala to socially threatening vs. other images. ► Amygdala activity was positively correlated with feelings of social disconnection. ► Amygdala activity may be important for sickness-induced social withdrawal.
Background
Preclinical studies have implicated excess release of catecholamines and prostaglandins in the mediation of prometastatic processes during surgical treatment of cancer. In this study, we ...tested the combined perioperative blockade of these pathways in patients with colorectal cancer (CRC).
Methods
In a randomized, double‐blind, placebo‐controlled biomarker trial involving 34 patients, the β‐blocker propranolol and the COX2‐inhibitor etodolac were administered for 20 perioperative days, starting 5 days before surgery. Excised tumors were subjected to whole genome messenger RNA profiling and transcriptional control pathway analyses.
Results
Drugs were well‐tolerated, with minor complications in both the treatment group and the placebo group. Treatment resulted in a significant improvement (P < .05) of tumor molecular markers of malignant and metastatic potential, including 1) reduced epithelial‐to‐mesenchymal transition, 2) reduced tumor infiltrating CD14+ monocytes and CD19+ B cells, and 3) increased tumor infiltrating CD56+ natural killer cells. Transcriptional activity analyses indicated a favorable drug impact on 12 of 19 a priori hypothesized CRC‐related transcription factors, including the GATA, STAT, and EGR families as well as the CREB family that mediates the gene regulatory impact of β‐adrenergic– and prostaglandin‐signaling. Alterations observed in these transcriptional activities were previously associated with improved long‐term clinical outcomes. Three‐year recurrence rates were assessed for long‐term safety analyses. An intent‐to‐treat analysis revealed that recurrence rates were 12.5% (2/16) in the treatment group and 33.3% (6/18) in the placebo group (P = .239), and in protocol‐compliant patients, recurrence rates were 0% (0/11) in the treatment group and 29.4% (5/17) in the placebo group (P = .054).
Conclusions
The favorable biomarker impacts and clinical outcomes provide a rationale for future randomized placebo‐controlled trials in larger samples to assess the effects of perioperative propranolol/etodolac treatment on oncological clinical outcomes.
Simultaneous 20‐day perioperative inhibition of β‐adrenergic and COX2 signaling in patients with colorectal cancer has a favorable impact on tumor biomarkers associated with metastatic progression. Our results suggest scientific, medical, and safety justifications to conduct large‐scale clinical trials, assessing long‐term cancer outcomes.
The experiences of mothers and fathers are different in ways that could affect their well-being. Yet few studies have comprehensively examined gender differences in parents’ well-being. In the ...current research, we investigated such gender differences in a large representative sample (Study 1a; N = 13,007), in a community sample using validated well-being measures (Study 1b; N = 472), and in a large experience sampling study measuring happiness during caregiving activities and during interactions with children (Study 2; N = 4,930). Fathers reported greater happiness, subjective well-being, psychological need satisfaction, and daily uplifts than did men without children (Studies 1a and 1b). During caregiving experiences, fathers reported greater happiness, whereas mothers reported lower happiness, compared with their other activities. Fathers also reported relatively higher happiness when interacting with their children than did mothers (Study 2). Across all three studies and more than 18,000 participants, parenthood was associated with more positive well-being outcomes for fathers than for mothers.
Suboptimal adherence to self-administered medications is a common problem. The purpose of this study was to determine the effectiveness of a video-game intervention for improving adherence and other ...behavioral outcomes for adolescents and young adults with malignancies including acute leukemia, lymphoma, and soft-tissue sarcoma.
A randomized trial with baseline and 1- and 3-month assessments was conducted from 2004 to 2005 at 34 medical centers in the United States, Canada, and Australia. A total of 375 male and female patients who were 13 to 29 years old, had an initial or relapse diagnosis of a malignancy, and currently undergoing treatment and expected to continue treatment for at least 4 months from baseline assessment were randomly assigned to the intervention or control group. The intervention was a video game that addressed issues of cancer treatment and care for teenagers and young adults. Outcome measures included adherence, self-efficacy, knowledge, control, stress, and quality of life. For patients who were prescribed prophylactic antibiotics, adherence to trimethoprim-sulfamethoxazole was tracked by electronic pill-monitoring devices (n = 200). Adherence to 6-mercaptopurine was assessed through serum metabolite assays (n = 54).
Adherence to trimethoprim-sulfamethoxazole and 6-mercaptopurine was greater in the intervention group. Self-efficacy and knowledge also increased in the intervention group compared with the control group. The intervention did not affect self-report measures of adherence, stress, control, or quality of life.
The video-game intervention significantly improved treatment adherence and indicators of cancer-related self-efficacy and knowledge in adolescents and young adults who were undergoing cancer therapy. The findings support current efforts to develop effective video-game interventions for education and training in health care.
Objective: Fatigue is a common side effect of cancer treatment, but there is considerable variability in fatigue severity and persistence among survivors. This study aimed to characterize ...longitudinal trajectories of fatigue after breast cancer treatment and to identify predictors of varying fatigue trajectories. Methods: Women (N = 191) from the Mind-Body Study completed assessments after primary treatment for early stage breast cancer and at regular follow-ups that occurred up to 6 years after treatment (M = 4.3 years). Growth mixture models were used to characterize fatigue trajectories, and demographic, medical, and biobehavioral risk factors were examined as predictors of trajectory group. Results: Five trajectories were identified, characterized as High, Recovery, Late, Low, and Very Low fatigue. The High and Recovery groups (40% of sample) evidenced elevated fatigue at posttreatment that declined in Recovery but persisted in the High group. In bivariate analyses, trajectory groups differed significantly on depressive symptoms, sleep disturbance, childhood adversity, body mass index, and the inflammatory marker soluble TNF receptor type II, which were higher in the High and/or Recovery groups. In multivariate models, depressive symptoms and childhood adversity distinguished High and Recovery from other groups. Rates of chemotherapy were higher in the Recovery than in the High or Late group, whereas rates of endocrine therapy were higher in the High than in the Recovery group. Conclusions: There are distinct longitudinal trajectories of fatigue after breast cancer treatment. Psychological factors are strongly associated with adverse fatigue trajectories, and together with treatment exposures may increase risk for cancer-related fatigue.
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