Frequent Interpersonal Stress and Inflammatory Reactivity Predict Depressive-Symptom Increases: Two Tests of the Social-Signal-Transduction Theory of Depression.

The social-signal-transduction theory of depression asserts that people who experience ongoing interpersonal stressors and mount a greater inflammatory response to social stress are at higher risk for depression. The current study tested this theory in two adult samples. In Study 1, physically healthy adults (N = 76) who reported more frequent interpersonal tension had heightened depressive symptoms at Visit 2, but only if they had greater inflammatory reactivity to a marital conflict at Visit 1. Similarly, in Study 2, depressive symptoms increased among lonelier and less socially supported breast-cancer survivors (N = 79). This effect was most pronounced among participants with higher inflammatory reactivity to a social-evaluative stressor at Visit 1. In both studies, noninterpersonal stress did not interact with inflammatory reactivity to predict later depressive symptoms.

Inflammation and positive affect: Examining the stress-buffering hypothesis with data from the National Longitudinal Study of Adolescent to Adult Health.

The present study examined the influence of positive affect (PA) on levels of inflammation within the context of Pressman and Cohen's (2005) stress-buffering model, which suggests that PA confers protective health benefits through its ability to mitigate the pathogenic influence of stress. We hypothesized that greater PA would buffer against the influence of perceived psychological stress (PPS) on systemic inflammation, operationalized as C-reactive protein (CRP, mg/L). Specifically, we predicted that PA would moderate the relationship between PPS and CRP. Cross-sectional data were drawn from Wave IV (2008-2009) of the National Longitudinal Study of Adolescent to Adult Health (Add Health). Participants (n=3093) ranged in age from 25 to 34years old (M=29.0±1.79). Using a moderated hierarchical regression analysis, PPS and PA significantly interacted to predict levels of CRP (p<0.05). Examination of the simple slopes revealed a disordinal interaction between PPS and PA, such that higher PA was protective against elevated CRP levels, but only when individuals also reported greater levels of PPS. Thus, the data partially support the stress-buffering model of PA and extend existing evidence regarding the complexity by which PPS and PA influence health. Findings also provide caution of future assumptions that relationships among PA, PPS, and physical health markers, such as CRP, are always positive (e.g., PA) or negative (e.g., PPS) in nature.

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

OBJECTIVES: 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 yoga's impact on cognitive complaints. METHODS: Posttreatment stage 0-IIIA breast cancer survivors (n = 200) were randomized to a 12-week, twice-weekly Hatha yoga intervention or a wait list control group. Participants reported cognitive complaints using the Breast Cancer Prevention Trial Cognitive Problems Scale at baseline, immediately postintervention, and 3-month follow-up. RESULTS: Cognitive complaints did not differ significantly between groups immediately postintervention (p = 0.250). However, at 3-month follow-up, yoga participants' Breast Cancer Prevention Trial Cognitive Problems Scale scores were an average of 23% lower than wait list participants' scores (p = 0.003). These group differences in cognitive complaints remained after controlling for psychological distress, fatigue, and sleep quality. Consistent with the primary results, those who practiced yoga more frequently reported significantly fewer cognitive problems at 3-month follow-up than those who practiced less frequently (p < 0.001). CONCLUSIONS: These findings suggest that yoga can effectively reduce breast cancer survivors' cognitive complaints and prompt further research on mind-body and physical activity interventions for improving cancer-related cognitive problems.

Biopsychosocial contexts influence adult cognitive function concurrently and longitudinally.

Background: Cognitive aging is a complex process that impacts human behavior. Identifying the factors that preserve cognitive functioning is a public health priority, given that 20% of the US population will be at least 65 years old in the next decade. Biopsychosocial determinants of cognitive decline across the lifespan are often examined as ecological factors that independently moderate cognitive aging, despite the known complexity surrounding these relationships. Objective: We aimed to address this gap by exploring the synergistic and simultaneous relationship between risk and protective factors on cognitive functioning. Method: Using the MIDUS study datasets, we examined the relationships among physiological markers, friendship quality, and global cognition functioning, concurrently and longitudinally over ten years. Our participants included 929 healthy (417 men, 512 women) adults (average age at Time 1: 54.6 ± 11.6 years). Exploratory analyses examining the effects of racial minority status were also conducted. Results: Cross-sectionally, age, and friendship quality moderated the relationship between vagally-mediated heart rate variability (vm-HRV) and cognition such that younger adults with greater friendship quality had a negative relationship between vm-HRV and cognitive performance; our unexpected finding suggests the heart-brain relationship is sensitive to the biopsychosocial environment. Longitudinally, higher IL-6 levels at Time 1 predicted poorer cognitive performance a decade later, but only among those with greater levels of friendship quality, especially for white-identifying individuals. Conclusions: The relationships among physiological risk factors, social protective factors and cognitive functioning appear to be temporally different during mid-adulthood. Given many of the whole sample findings were not replicated within the racial minority subgroup, we suggest that these relationships should be examined in a larger and more diverse racial minority sample to determine whether this study lacked the power necessary to detect a relationship or if the relationships are in fact different by racial minority sub-group. In addition, future research should overcome the study's reliance on healthy adults and self-report measures of friendship quality by including adults with pre-existing cognitive impairments, and employing more real-time measures of friendship quality, such as daily diary or ecological momentary assessment.

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-1ß) 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.

Reappraisal and health: How habitual reappraisal and reappraisal ability interact to protect against life stress in young adults.

Inadequate emotion regulation may underlie the development of psychopathology as well as worsened physical health, particularly in the context of life stress. Cognitive reappraisal is typically considered an adaptive strategy to manage negative emotions. However, the extent to which reappraisal is beneficial may hinge upon contextual and individual differences. Specifically, it is unclear whether and how the ability to reappraise effectively (i.e., reappraisal ability) and exposure to stressful life events moderate the association between habitual reappraisal and health. Using a series of questionnaires and an experimental task designed to measure the ability to effectively down-regulate sad emotions using reappraisal, the present study examined the interactive effects of habitual reappraisal, reappraisal ability, and exposure to stressful life events on depressive and anxiety symptoms as well as self-reported physical health in 400 young adults (62.5% women; mean age = 19.8 ± 2.5). Results indicated that habitual reappraisal may protect against elevated depressive symptoms and worsened self-reported physical health for people exposed to more stressful life events. Moreover, reappraising often appeared to be particularly beneficial for those who were less effective in their attempts. Results for anxiety symptoms were not significant, although habitual reappraisal remained significantly associated with anxiety symptoms as a lower-order term. These findings provide novel contributions to the field of emotion regulation and health by clarifying that exposure to stressful life events is a key moderator in the association between reappraisal and some areas of health and by elucidating the important roles of both habitual reappraisal and reappraisal ability. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Depression, Inflammation, and Intestinal Permeability: Associations with Subjective and Objective Cognitive Functioning throughout Breast Cancer Survivorship.

About one-in-three breast cancer survivors have lingering cognitive complaints and objective cognitive impairment. Chronic inflammation and intestinal permeability (i.e., leaky gut), two risk factors for cognitive decline, can also fuel depression-another vulnerability for cognitive decline. The current study tested whether depression accompanied by high levels of inflammation or intestinal permeability predicted lower subjective and objective cognitive function in breast cancer survivors. We combined data from four breast cancer survivor studies (n = 613); some had repeated measurements for a total of 1015 study visits. All participants had a blood draw to obtain baseline measures of lipopolysaccharide binding protein-a measure of intestinal permeability, as well as three inflammatory markers that were incorporated into an inflammatory index: C-reactive protein, interleukin-6, and tumor necrosis factor-α. They reported depressive symptoms on the Center for Epidemiological Studies depression scale (CES-D), and a binary variable indicated clinically significant depressive symptoms (CES-D ≥ 16). The Kohli (749 observations) and the Breast Cancer Prevention Trial (591 observations) scales assessed subjective cognitive function. Objective cognitive function tests included the trail-making test, Hopkins verbal learning test, Conners continuous performance test, n-back test, FAS test, and animal-naming test (239-246 observations). Adjusting for education, age, BMI, cancer treatment type, time since treatment, study visit, and fatigue, women who had clinically elevated depressive symptoms accompanied by heightened inflammation or intestinal permeability reported poorer focus and marginally poorer memory. However, poorer performance across objective cognitive measures was not specific to inflammation-associated depression. Rather, there was some evidence of lower verbal fluency; poorer attention, verbal learning and memory, and working memory; and difficulties with visuospatial search among depressed survivors, regardless of inflammation. By themselves, inflammation and intestinal permeability less consistently predicted subjective or objective cognitive function. Breast cancer survivors with clinically significant depressive symptoms accompanied by either elevated inflammation or intestinal permeability may perceive greater cognitive difficulty, even though depression-related objective cognitive deficits may not be specific to inflammation- or leaky-gut-associated depression.

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.

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.

Childhood ADHD, Going Beyond the Brain: A Meta-Analysis on Peripheral Physiological Markers of the Heart and the Gut.

Attention-Deficit/Hyperactivity Disorder (ADHD) is the most common neurodevelopmental disorder diagnosed in children. Questions regarding its increased diagnostic rates and pharmacological treatments in developing children have led to a more holistic review of the multi-system pathophysiology observed in ADHD. The dopaminergic neurotransmitter system, known for its influence on reward-motivated behaviors and motor control, and the frontostriatal systems, that mediate motor, cognition, and behavior, are associated with ADHD's development. However, studies have shown that these neural systems do not wholly account for ADHD's multilayered and heterogeneous symptom presentation. For instance, the literature suggests that emotional dysregulation, the inability to regulate one's emotional responses to provoking stimuli, is associated with increased risk for social impairment in ADHD. A broader examination of physiological systems in children with ADHD has found potential markers in the heart-brain and gut-brain axes that correspond with certain behaviors associated with emotional dysregulation in recent studies. Hence, the purpose of this meta-analysis is to aggregate ten applicable published case studies and analyze task-related heart rate reactivity (HRR; n = 5 studies) and gut microbiota (n = 5 studies) data in children with and without ADHD. Data from a total of 531 youth with ADHD and 603 youth without ADHD revealed significant small and medium effect sizes for higher Chao1 levels and Actinobacteria levels in the ADHD group, respectively, but no evidence of altered task-related HRR. Thus, further research into multi-system psychophysiological measures of emotional dysregulation and ADHD is warranted. The clinical, empirical, and educational implications of these findings are discussed. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42021236819).

Distress disorder histories predict HRV trajectories during and after stress.

BACKGROUND: Breast cancer survivors face a number of physical health threats including cardiovascular disease, the leading cause of death among breast cancer survivors. Low heart rate variability (HRV) represents one well-established risk factor for poor cardiovascular health. Among physically healthy adults and breast cancer survivors, distress disorders may contribute to lower HRV, enhancing morbidity and mortality. This study examined how a distress disorder history altered survivors' HRV trajectories during and after an experimental stressor. METHODS: Breast cancer survivors (n = 178; mean age = 51.22) who finished treatment for stages 0-IIIa cancer within the past two years completed a diagnostic interview assessing lifetime presence of psychological disorders. They also participated in a Trier Social Stress Test (TSST). HRV data provided information on survivors' cardiovascular responses at baseline, during the TSST, and during recovery. HRV recovery data at 45 min and 120 min post-TSST was also collected. Survivors also completed questionnaires before and after the TSST assessing task performance, stress levels, ability to cope, and hopelessness. Covariates included body mass index, age, cancer stage, cardiovascular medications, exercise, menopause status, fatigue, current depressive and anxiety symptoms, and physical comorbidities. RESULTS: Women with a distress disorder history had significantly lower HRV before, during, and after the TSST compared to women without such a history. Survivors with distress disorders found the TSST to be more threatening, and reported feeling less control over their performance than those without distress disorders. CONCLUSIONS: Breast cancer survivors with a distress disorder history may have lower autonomic flexibility before, during, and after stress exposure. Distress disorder histories also heighten several stress-related risk perceptions leading up to and following the TSST. These findings highlight distress disorder histories as a unique correlate of poorer cardiovascular function among survivors.

Low-Dose Metformin Treatment Reduces In Vitro Growth of the LL/2 Non-small Cell Lung Cancer Cell Line.

Lung cancer maintains a relatively small survival rate (~19%) over a 5-year period and up to 80-85% of all lung cancer diagnoses are Non-Small Cell Lung Cancer (NSCLC). To determine whether metformin reduces non-small cell lung cancer (NSCLC) LL/2 cell growth, cells were grown in vitro and treated with metformin for 48 h. qPCR was used to assess genes related to cell cycle regulation and pro-apoptotic markers, namely Cyclin D, CDK4, p27, p21, and HES1. Treatment with 10 mM metformin significantly reduced HES1 expression (p = 0.011). Furthermore, 10 mM metformin treatment significantly decreased REDD1 (p = 0.0082) and increased p-mTOR Ser2448 (p = 0.003) protein expression. Control cells showed significant reductions in phosphorylated p53 protein expression (p = 0.0367), whereas metformin treated cells exhibited reduced total p53 protein expression (p = 0.0078). There were no significant reductions in AMPK, PKB/AKT, or STAT3. In addition, NSCLC cells were treated for 48 h. with 10 mM metformin, 4 µM gamma-secretase inhibitor (GSI), or the combination of metformin (10 mM) and GSI (4 µM) to determine the contribution of respective signaling pathways. Metformin treatment significantly reduced total nucleus expression of the proliferation maker Ki-67 with an above 65% reduction in Ki-67 expression between control and metformin-treated cells (p = 0.0021). GSI (4 µM) treatment significantly reduced Ki-67 expression by ~20% over 48 h (p = 0.0028). Combination treatment (10 mM metformin and 4 µM GSI) significantly reduced Ki-67 expression by more than 50% over 48 h (p = 0.0245). As such, direct administration of metformin (10 mM for 48 h) proved to be an effective pharmaceutical agent in reducing the proliferation of cultured non-small cell cancer cells. These intriguing in vitro results, therefore, support the further study of metformin in appropriate in vivo models as an anti-oncogenic agent and/or an adjunctive therapy.

Low-Dose Metformin as a Monotherapy Does Not Reduce Non-Small-Cell Lung Cancer Tumor Burden in Mice.

Non-small-cell lung cancer (NSCLC) makes up 80-85% of lung cancer diagnoses. Lung cancer patients undergo surgical procedures, chemotherapy, and/or radiation. Chemotherapy and radiation can induce deleterious systemic side effects, particularly within skeletal muscle. To determine whether metformin reduces NSCLC tumor burden while maintaining skeletal muscle health, C57BL/6J mice were injected with Lewis lung cancer (LL/2), containing a bioluminescent reporter for in vivo tracking, into the left lung. Control and metformin (250 mg/kg) groups received treatments twice weekly. Skeletal muscle was analyzed for changes in genes and proteins related to inflammation, muscle mass, and metabolism. The LL/2 model effectively mimics lung cancer growth and tumor burden. The in vivo data indicate that metformin as administered was not associated with significant improvement in tumor burden in this immunocompetent NSCLC model. Additionally, metformin was not associated with significant changes in key tumor cell division and inflammation markers, or improved skeletal muscle health. Metformin treatment, while exhibiting anti-neoplastic characteristics in many cancers, appears not to be an appropriate monotherapy for NSCLC tumor growth in vivo. Future studies should pursue co-treatment modalities, with metformin as a potentially supportive drug rather than a monotherapy to mitigate cancer progression.

Caffeine and stress alter salivary alpha-amylase activity in young men.

OBJECTIVE: We examined the effects of caffeine and a psychological stressor on salivary alpha-amylase (sAA) in healthy young males (age 18-30 years) who consumed caffeine on a daily basis. METHODS: Using a between-subjects, double-blind, placebo-controlled design, 45 participants received either 200 or 400 mg of caffeine (Vivarin) or placebo, rested for 20 min, and then performed 20 min of mental arithmetic. Saliva samples (assayed for sAA and caffeine), blood pressure, and heart rate were taken before (baseline) and 15 min after the math stressor (stress). RESULTS: Baseline sAA activity did not differ among the treatment groups; however, there was a statistically significant time by caffeine group interaction. Changes in sAA activity across the session were dependent on the amount of caffeine consumed. Following the challenge period, sAA activity among the placebo group was the lowest and sAA activity among the 400 mg treatment group was the highest. Separate repeated-measures ANOVAs conducted for each drug treatment group revealed that sAA activity increased in response to stress and caffeine (i.e., 200 and 400 mg groups) but not to stress alone (i.e., placebo group). CONCLUSIONS: Findings provide evidence for acute sAA changes in response to caffeine and stress in habitual caffeine users.

Mental health is the health of the whole body: How psychoneuroimmunology & health psychology can inform & improve treatment.

BACKGROUND: Converging and accumulating evidence for the cross-communication among the nervous, immune, and endocrine systems, a field of study known as psychoneuroimmunology, implicates immunological dysfunction as a shared and common mechanism of both mental and physical illness. For example, psychiatric disorders like schizophrenia, bipolar disorder, major depression, and anxiety disorders have higher prevalence rates across a spectrum of autoimmune conditions compared to the general population. Additionally, subclinical immunological abnormalities are observed in a variety of psychiatric conditions, with chronic inflammation most extensively studied in the pathophysiology of depression. These observations blur the historical distinctions between mental and physical illness, yet clinical practice remains fragmented and primarily focused on differentially treating individual symptoms. PROPOSED THESIS: Therapeutically targeting inflammation offers translational opportunities for integrating mental and physical healthcare, a key niche of the interdisciplinary field of health psychology. CONCLUSION: Utilizing a psychoneuroimmunological lens, health psychologists and clinicians can reconceptualize healthcare through integrative treatment approaches and advocacy for comprehensive policy-level reform at both the individual-level of care as well as community-wide prevention approaches.

Higher trait reappraisal predicts stronger HPA axis habituation to repeated stress.

Undergoing stress can be advantageous when it leads to adaptation and growth; however, failure of the hypothalamic-pituitary-adrenal (HPA) axis to habituate (i.e., nonhabituation) involves continuing to become highly activated in response to repeated exposure of the same stimulus and is considered maladaptive. Although 50-75% of individuals assessed in a laboratory exhibit adaptive habituation to repeated stress, variability in habituation suggests psychological processes used in response to stress may play a role, such as emotion regulation (ER). Nonetheless, no research to date has investigated whether ER strategies affect HPA axis habituation. We investigated whether tendency to use two ER strategies, reappraisal and suppression, influenced HPA axis habituation among 84 healthy young adults (60.7% female; Mage = 24.8 years, SD = 6.0) exposed to a standardized experimental stress paradigm on two consecutive days. HPA axis stress responses were assessed using salivary cortisol concentrations. We also examined whether non-manipulated state ER strategies (i.e., those used by the participant during and following the stressor on the first day) modulated HPA axis habituation over and above trait-use in a subsample (N = 60). Trait, but not state, reappraisal was associated with stronger HPA axis habituation. Neither trait nor state suppression were significantly associated with HPA axis habituation. These findings expand our current understanding of how ER can affect stress-related health outcomes and suggest habitual reappraisal plays an important role in adaption of the HPA axis to stress.

Post-traumatic stress and psychological health following infidelity in unmarried young adults.

Infidelity is often conceptualized as a traumatic event; however, little research has explored this topic empirically, particularly in unmarried adults. We determined the prevalence of infidelity-related post-traumatic stress disorder (PTSD) symptoms among unmarried adults who experienced a partner's infidelity and whether probable infidelity-related PTSD was associated with additional psychological health outcomes (i.e., depressive symptoms, perceived stress, and anxiety symptoms). We also investigated whether negative post-traumatic cognitions mediated the associations between infidelity-related PTSD symptoms and psychological health. This study included 73 adults (M age = 19.42, SE = 0.19 years) who experienced infidelity within a committed nonmarital relationship within the last 5 years. Controlling for gender, race, and exposure to Diagnostic and Statistical Manual of Psychiatric Disorders Criterion A traumas, 45.2% of our sample reported symptoms suggesting probable infidelity-related PTSD. Whether used as continuous or categorical predictor, infidelity-related PTSD symptoms were significantly associated with depressive symptoms, although results for perceived stress and anxiety symptoms were mixed. Post-traumatic cognitions acted as a partial mediator for depressive symptoms and full mediator for perceived stress and anxiety symptoms. This empirical evidence suggests that infidelity may produce PTSD symptoms at a relatively high rate, even in unmarried young adults, and may put individuals at risk for poorer psychological health, partially through post-traumatic cognitions.

"Get a Grip on Hypertension": EXPLORING THE USE OF ISOMETRIC HANDGRIP TRAINING IN CARDIOPULMONARY REHABILITATION PATIENTS.

PURPOSE: Isometric handgrip (IHG) training lowers systolic and diastolic blood pressure (SBP and DBP, respectively), but the efficacy of IHG training in cardiopulmonary rehabilitation patients is unknown. The purpose of this study was to determine if IHG decreases blood pressure in cardiopulmonary rehabilitation patients. METHODS: Cardiopulmonary rehabilitation program participants (n = 11; 50-80 yr old) were randomized to IHG (n = 6) or control (CON; no treatment; n = 5) groups. IHG participants completed an IHG training program at 30% maximal voluntary contraction, 3 d/wk for 6 wk. Resting SBP, DBP, and heart rate were assessed weekly. RESULTS: Mean regression for SBP following IHG was negative (-1.04 ± 0.80). Mean regression in the CON group was positive (0.50 ± 0.88), but there was no significant difference between groups. Separate analysis of weeks 1 to 7 yielded a negative mean regression (-1.12 ± 0.54) in the IHG group, but positive (1.2 ± 0.60) in the CON group. A Wilcoxon test of these differences yielded significance for SBP (P = .009). In 3 of 6 IHG participants, SBP was lower (mean ± SD: -16 ± 11 mm Hg; P = .12), and in 2 IHG participants, DBP was lower (-9 ± 1 mm Hg; P = .06) compared with baseline. In 2 of 5 CON participants, SBP was not significantly lower (-11 ± 7 mm Hg) and, in 3 of 5 CON participants, DBP was lower (-7 ± 4 mm Hg; P = .04). CONCLUSIONS: Our data suggest that standard IHG training may be inadequate for blood pressure management immediately following a major cardiac or pulmonary event. Future work with a larger cohort and more developed training protocol to determine the efficacy of IHG training in patients with cardiopulmonary disease is warranted.

Health and Disease-Emergent States Resulting From Adaptive Social and Biological Network Interactions.

Health is an adaptive state unique to each person. This subjective state must be distinguished from the objective state of disease. The experience of health and illness (or poor health) can occur both in the absence and presence of objective disease. Given that the subjective experience of health, as well as the finding of objective disease in the community, follow a Pareto distribution, the following questions arise: What are the processes that allow the emergence of four observable states-(1) subjective health in the absence of objective disease, (2) subjective health in the presence of objective disease, (3) illness in the absence of objective disease, and (4) illness in the presence of objective disease? If we consider each individual as a unique biological system, these four health states must emerge from physiological network structures and personal behaviors. The underlying physiological mechanisms primarily arise from the dynamics of external environmental and internal patho/physiological stimuli, which activate regulatory systems including the hypothalamic-pituitary-adrenal axis and autonomic nervous system. Together with other systems, they enable feedback interactions between all of the person's system domains and impact on his system's entropy. These interactions affect individual behaviors, emotional, and cognitive responses, as well as molecular, cellular, and organ system level functions. This paper explores the hypothesis that health is an emergent state that arises from hierarchical network interactions between a person's external environment and internal physiology. As a result, the concept of health synthesizes available qualitative and quantitative evidence of interdependencies and constraints that indicate its top-down and bottom-up causative mechanisms. Thus, to provide effective care, we must use strategies that combine person-centeredness with the scientific approaches that address the molecular network physiology, which together underpin health and disease. Moreover, we propose that good health can also be promoted by strengthening resilience and self-efficacy at the personal and social level, and via cohesion at the population level. Understanding health as a state that is both individualized and that emerges from multi-scale interdependencies between microlevel physiological mechanisms of health and disease and macrolevel societal domains may provide the basis for a new public discourse for health service and health system redesign.

Female temperament, tumor development and life span: relation to glucocorticoid and tumor necrosis factor alpha 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.