Mitochondrial health, physical functioning, and daily affect: Bioenergetic mechanisms of dementia caregiver well-being.

OBJECTIVE: Chronic stress adversely affects mental and physical well-being. However, health outcomes vary among people experiencing the same stressor. Individual differences in physical and emotional well-being may depend on mitochondrial biology, as energy production is crucial for stress regulation. This study investigated whether mitochondrial respiratory capacity corresponds to individual differences in dementia spousal caregivers' mental and physical health. METHODS: Spousal caregivers of individuals with Alzheimer's disease and related dementias (N = 102, mean age = 71, 78% female, 83% White) provided peripheral blood samples and completed self-report questionnaires on quality of life, caregiver burden, and a 7-day affect scale. Multiple and mixed linear regression were used to test the relationship between mitochondrial biology and well-being. RESULTS: Spare respiratory capacity (b = 12.76, CI[5.23, 20.28 ], p = .001), maximum respiratory capacity (b = 8.45, CI [4.54, 12.35], p < .0001), and ATP-linked respiration (b = 10.11, CI [5.05, 15.18], p = .0001) were positively associated with physical functioning. At average (b = -2.23, CI [-3.64, -.82], p = .002) and below average (b = -4.96, CI [-7.22, 2.70], p < .0001) levels of spare respiratory capacity, caregiver burden was negatively associated with daily positive affect. At above average levels of spare respiratory capacity, caregiver burden was not associated with positive affect (p = .65). CONCLUSIONS: Findings suggest that better mitochondrial health is associated with better psychological and physical health - a pattern consistent with related research. These findings provide some of the earliest evidence that cellular bioenergetics are related to well-being.

High Heart Rate Variability Buffers the Effect of Attachment Insecurity on Sleep Quality.

OBJECTIVE: Sleep quality is an important health-protective factor. Psychosocial factors, including attachment orientation, may be valuable for understanding who is at risk of poor sleep quality and associated adverse health outcomes. High attachment anxiety is reliably associated with adverse health outcomes, whereas high attachment avoidance is associated with adverse health outcomes when co-occurring with poor self-regulatory capacity, indexed by heart rate variability (HRV). We examined the associations between attachment anxiety, attachment avoidance, HRV, and sleep quality. METHODS: Using longitudinal data from a sample of 171 older adults measured four times over 1 year ( M = 66.18 years old; 67.83% women), we separated the between-person variance (which we call "trait") and within-person variance (which we call "state") for attachment anxiety, attachment avoidance, and HRV (via the root mean square of successive differences). Sleep quality was measured with the Pittsburgh Sleep Quality Index. RESULTS: Higher trait attachment anxiety was associated with poorer global sleep quality ( B = 0.22, p = .005). Higher state attachment avoidance was associated with poorer sleep quality ( B = -0.13, p = .01), except for those with higher trait HRV. Higher state attachment anxiety was associated with poorer sleep quality ( B = -0.15, p = .002), except for those with higher or mean trait HRV. Higher trait attachment anxiety was associated with poorer sleep quality ( B = -0.31, p = .02), except for those with higher trait HRV. CONCLUSIONS: High trait HRV mitigated the adverse effects of attachment insecurity on sleep quality. Our results suggest that people with high trait HRV had greater self-regulation capacity, which may enable them to enact emotion regulation strategies effectively.

Grief Symptoms Promote Inflammation During Acute Stress Among Bereaved Spouses.

The death of a spouse is associated with maladaptive immune alterations; grief severity may exacerbate this link. We investigated whether high grief symptoms were associated with an amplified inflammatory response to subsequent stress among 111 recently bereaved older adults. Participants completed a standardized psychological stressor and underwent a blood draw before, 45 min after, and 2 hr after the stressor. Those experiencing high grief symptoms (i.e., scoring > 25 on the Inventory of Complicated Grief) experienced a 45% increase in interleukin-6 (IL-6; a proinflammatory cytokine) per hour, whereas those experiencing low grief symptoms demonstrated a 26% increase. In other words, high grief was related to a 19% increase in IL-6 per hour relative to low grief. The grief levels of recently bereaved people were associated with the rate of change in IL-6 following a subsequent stressor, above and beyond depressive symptoms. This is the first study to demonstrate that high grief symptoms promote inflammation following acute stress.

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.

Timing, duration, and differential susceptibility to early life adversities and cardiovascular disease risk across the lifespan: Implications for future research.

Early life adversities (ELA), include experiences such as child maltreatment, household dysfunction, bullying, exposure to crime, discrimination, bias, and victimization, and are recognized as social determinants of cardiovascular disease (CVD). Strong evidence shows exposure to ELA directly impacts cardiometabolic risk in adulthood and emerging evidence suggests there may be continuity in ELA's prediction of cardiometabolic risk over the life course. Extant research has primarily relied on a cumulative risk framework to evaluate the relationship between ELA and CVD. In this framework, risk is considered a function of the number of risk factors or adversities that an individual was exposed to across developmental periods. The cumulative risk exposure approach treats developmental periods and types of risk as equivalent and interchangeable. Moreover, cumulative risk models do not lend themselves to investigating the chronicity of adverse exposures or consider individual variation in susceptibility, differential contexts, or adaptive resilience processes, which may modify the impact of ELA on CVD risk. To date, however, alternative models have received comparatively little consideration. Overall, this paper will highlight existing gaps and offer recommendations to address these gaps that would extend our knowledge of the relationship between ELA and CVD development. We focus specifically on the roles of: 1) susceptibility and resilience, 2) timing and developmental context; and 3) variation in risk exposure. We propose to expand current conceptual models to incorporate these factors to better guide research that examines ELA and CVD risk across the life course.

Bereavement among widowed Latinos in the United States: A systematic review of methodology and findings.

This study systematically reviewed the methodology and findings of 19 peer-reviewed studies on the experience of bereavement among widowed Latinos, including risk and protective factors to the health of this vulnerable population. Of these studies, 10 included quantitative data, 3 were qualitative studies, and 6 were narrative reviews. Results emphasized the relevance of cultural beliefs about death, rituals, religion, and Latino values (i.e., familismo, respeto, simpatía, personalismo) as common themes in the included studies, along with expressions of grief (e.g., Ataque de nervios, somatization) that vary by gender and acculturation. Risk factors associated with diminished well-being in this population included being a male, financial strain, cultural stressors, having an undocumented legal status, experiencing widowhood at a younger age, and having poor physical health. Effective coping strategies identified included having adequate social support primarily from family, religion and religious practices, the use of folk medicine, volunteering, and the use of emotional release strategies. Moreover, the results highlight that researches informing the health needs of widowed Latinos in the US is limited, and studies with enhanced methodological rigor are needed to better understand the complex needs of this vulnerable population.

Can stress promote the pathophysiology of brain metastases? A critical review of biobehavioral mechanisms.

Chronic stress can promote tumor growth and progression through immunosuppressive effects and bi-directional interactions between tumor cells and their microenvironment. ß-Adrenergic receptor signaling plays a critical role in mediating stress-related effects on tumor progression. Stress-related mechanisms that modulate the dissemination of tumor cells to the brain have received scant attention. Brain metastases are highly resistant to chemotherapy and contribute considerably to morbidity and mortality in various cancers, occurring in up to 20% of patients in some cancer types. Understanding the mechanisms promoting brain metastasis could help to identify interventions that improve disease outcomes. In this review, we discuss biobehavioral, sympathetic, neuroendocrine, and immunological mechanisms by which chronic stress can impact tumor progression and metastatic dissemination to the brain. The critical role of the inflammatory tumor microenvironment in tumor progression and metastatic dissemination to the brain, and its association with stress pathways are delineated. We also discuss translational implications for biobehavioral and pharmacological interventions.

Miles over mind: Transnational death and its association with psychological distress among undocumented Mexican immigrants.

Objective: This study examined the association between transnational death and psychological distress among undocumented Mexican immigrants. The Minority Stress Model and a disenfranchised grief perspective were used as frameworks for this study.Method: Respondent driven sampling (RDS) was used to collect data from clinical interviews with 248 undocumented Mexican immigrants residing near the US-Mexico border.Results: After controlling for relevant covariates, experiencing transnational death was a significant predictor of clinically significant distress in this at-risk population.Conclusions: Our findings underscore the need to contextualize transnational death among undocumented immigrants from a perspective of disenfranchised grief that requires the development of contextually and culturally sensitive interventions aimed at addressing the high prevalence of transnational death and its associated distress in this marginalized population.

Implications for Reward Processing in Differential Responses to Loss: Impacts on Attachment Hierarchy Reorganization.

When an attachment relationship is severed, so is homeostatic maintenance, leading to dysregulation of multiple physiological systems. Expanding upon Sbarra and Hazan's original model, we suggest that the degree to which an individual's physiological systems remain dysregulated depends on the state of one's attachment hierarchy-namely, whether an individual continues to seek a lost partner for support as their primary attachment figure. To recover from the loss of a romantic partner, an individual's attachment hierarchy must be reorganized. Our model proposes that an individual will go through a series of physiological changes before their attachment hierarchy is reorganized, which can either help or hinder their recovery. We consider the role of reward processing, including endogenous opioids, in this recovery process. Along the way, we identify mechanisms for continued dysregulation of biological systems among those who take longer to recover from a loss.

An Evaluation of Perceived Health Risk and Depressive Symptoms Before a Disaster in Predicting Postdisaster Inflammation.

OBJECTIVE: Exposure to major life stressors is associated with subsequent enhanced inflammation-related disease processes. Depressive symptoms exacerbate stress-induced inflammatory responses. Moreover, those who report a high degree of perceived health risk before being exposed to a major life stressor such as a disaster are at risk for poor health outcomes. The present study examined whether perceived health risk and depressive symptoms before a disaster were associated with postdisaster inflammation markers. METHODS: The sample included 124 participants (mean [standard deviation] age = 55 [16] years; 69% women). At a baseline visit, participants completed self-report measures of perceived health risk and depressive symptoms (Center for Epidemiologic Studies Depression Scale) in addition to a blood draw for the assessment of inflammation markers (C-reactive protein, tumor necrosis factor receptor 1, and interleukin 6). All participants lived near a large petrochemical complex where an unexpected explosion occurred. A second blood sample was obtained 2 to 6 months after the explosion. RESULTS: No significant differences in inflammation markers were found between predisaster and postdisaster assessment (p > .21). An interaction between predisaster perceived health risk and depressive symptoms in predicting postdisaster circulating inflammation markers was identified (Cohen f = 0.051). Specifically, predisaster perceived health risk was associated with postdisaster circulating inflammation markers if predisaster depressive symptoms were greater than 8.10 on the Center for Epidemiologic Studies Depression Scale. CONCLUSIONS: These findings add to our understanding of the complex interactions between stress, depression, and immune responses. Indeed, findings provide a potential mechanism (i.e., inflammation) explaining the association between exposure to major life stressors and negative mental and physical health outcomes.

Attachment and telomere length: more evidence for psychobiological connections between close relationships, health, and aging.

Individuals with a history of poor interpersonal relationships are more likely to demonstrate negative health outcomes than those who have had high quality relationships. We sought to evaluate how attachment orientations, stress-induced respiratory sinus arrhythmia (RSA), and self-reported stress were associated with length of telomeres measured from peripheral blood mononuclear cells. Participants (N = 213) completed self-report measures of attachment and stress. Measurement of RSA was conducted before and after a stressful task and a blood draw was completed for analysis of telomere length. Attachment orientations were not directly associated with telomere length; however, we found that high attachment anxiety was associated with shorter length of telomeres via high self-reported stress. Attachment avoidance was also associated with telomere length via self-reported stress, but only among those with high stress-induced RSA. Exploratory analyses of T cell subsets indicated that stress was most strongly associated with telomeres from CD8CD28+ cells in comparison to CD8CD28- and CD4 cells. Study findings indicate that attachment orientations are associated with telomere length via stress, providing novel insights into the mechanisms through which close relationships can impact health and aging.

Low childhood subjective social status and telomere length in adulthood: The role of attachment orientations.

Low subjective social status (SSS) in childhood places one at greater risk of a number of health problems in adulthood. Theoretical and empirical evidence indicates that exposure to supportive parenting may buffer the negative effects of low childhood SSS on adult health. Given the importance of supportive caregivers and close others for the development of attachment orientations throughout the lifespan, attachment theory may be important for understanding why some individuals are resilient to the negative effects of low childhood SSS on adult health while others are not. We examined if attachment anxiety and attachment avoidance altered the association between childhood subjective social status (SSS) and length of telomeres in white blood cells in adulthood. Shorter telomere length is associated with increased risk of age-related diseases including cancer, type 2 diabetes, and cardiovascular disease. Participants (N = 128) completed self-report measures of childhood SSS and attachment orientations, as well as a blood draw. We found that among those with low childhood SSS, low attachment anxiety was associated with longer telomere length in white blood cells in comparison to high attachment anxiety controlling for participant age, sex, race, body mass index, and adult SSS. Among those with high childhood SSS, low attachment anxiety was associated with a slight decrease in telomere length. Attachment avoidance was unrelated to length of telomeres. Such findings provide further evidence for the role that close relationships may have on buffering SSS related health disparities.

Anxiety sensitivity moderates the painful effects of feeling burdensome to others.

Perceived burdensomeness (PB), the perception of being a burden to others, is associated with pain and physical symptoms. Anxiety sensitivity (AS), the fear of arousal-related sensations, arising from beliefs that the sensations may have adverse personal consequences (physical, cognitive, and social), may increase risk for pain responding, particularly in anxiety-provoking (e.g. socially threatening) contexts. Accordingly, individuals high in AS may have a stronger pain response when experiencing PB than those low in AS. Undergraduate participants (n = 262) completed the Anxiety Sensitivity Index (ASI-3), and then were randomly assigned to re-live an experience when they were either burdensome to others (burdensome condition) or contributed equally to a group (control condition). Both social and physical self-reported pain were assessed post-manipulation. Those high in AS reported significantly higher pain ratings in the burdensome condition than the control condition; for those low in AS, pain did not change across conditions. In particular, being fearful of the physical repercussions of anxiety (AS physical concerns) while also feeling burdensome to others was associated with greater physical pain. AS may exacerbate the already painful effects of feeling burdensome to others, and may have important implications for the development of future suicide- and pain-related interventions.

eHealth and mHealth interventions in the treatment of fatigued cancer survivors: A systematic review and meta-analysis.

OBJECTIVES: To (1) evaluate existing eHealth/mHealth interventions developed to help manage cancer-related fatigue (CRF); and (2) summarize the best available evidence on their effectiveness. METHODS: A comprehensive literature search of PubMed, MEDLINE, EMBASE, and the Cochrane Library up to November 2016 was conducted. Study outcomes were extracted, tabulated, and summarized. Random effects meta-analyses were conducted for the primary outcome (fatigue), and the secondary outcomes quality of life and depression, yielding pooled effect sizes (r), and 95% confidence intervals (CI). RESULTS: For eHealth interventions, our search of published papers identified 9 completed studies and 6 protocols for funded projects underway. No studies were identified for mHealth interventions that met our inclusion criteria. A meta-analysis of the 9 completed eHealth studies revealed a statistically significant beneficial effect of eHealth interventions on CRF (r = .27, 95% CI [.1109 - .4218], P < 0.01). Therapist-guided eHealth interventions were more efficacious then self-guided interventions (r = .58, 95% CI: [.3136 - .5985, P < 0.001). Small to moderate therapeutic effects were also observed for HRQoL (r = .17, 95% CI [.0384 - .3085], P < 0.05) and depression (r = .24, 95% CI [.1431 - .3334], P < 0.001). CONCLUSIONS: eHealth interventions appear to be effective for managing fatigue in cancer survivors with CRF. Continuous development of eHealth interventions for the treatment of CRF in cancer survivors and their testing in long-term, large-scale efficacy outcome studies is encouraged. The degree to which mHealth interventions can change CRF in cancer survivors need to be assessed systematically and empirically.

Attachment Orientations, Respiratory Sinus Arrhythmia, and Stress Are Important for Understanding the Link Between Childhood Socioeconomic Status and Adult Self-Reported Health.

BACKGROUND: Low childhood socioeconomic status (SES) is reliably associated with poor adult health. Social environments early in life and physiological stress responses are theorized to underlie this link; however, the role of attachment orientations is relatively unknown. PURPOSE: In this study, we examined whether attachment orientations (i.e., attachment anxiety and attachment avoidance) and self-reported stress were mediators of the association between childhood SES and self-reported health in adulthood. Furthermore, we examined whether parasympathetic nervous system functioning was a moderator of associations between attachment orientations and self-reported stress. METHODS: Participants (N = 213) provided self-reports of childhood SES, attachment orientations, general stress, and self-rated health. Respiratory sinus arrhythmia (RSA) was measured at rest, as well as during an acute social stressor. RESULTS: Low childhood SES was associated with poor self-reported health via the serial pathway from attachment anxiety to general stress. Moreover, attachment avoidance was associated with self-reported health via general stress, but only among those with high stress-induced RSA. Findings were independent of participant age, sex, race, body mass index, baseline RSA, and adult SES. CONCLUSIONS: Attachment theory is useful for understanding why those from low SES backgrounds are at greater risk of negative health outcomes in adulthood. Findings extend our knowledge of how interpersonal relationships in childhood can shape emotional and physical health outcomes in adulthood.

The utility of patient-reported outcome measures among patients with myalgic encephalomyelitis/chronic fatigue syndrome.

PURPOSE: Debilitating fatigue is a core symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, the utility of patient-reported symptom outcome measures of fatigue for ME/CFS patients is problematic due to ceiling effects and issues with reliability and validity. We sought to evaluate the performance of three patient-reported symptom measures in a sample of ME/CFS patients and matched controls. METHODS: Two hundred and forty ME/CFS patients and 88 age, sex, race, and zip code matched controls participated in the study. Participants completed the Multidimensional Fatigue Inventory-20, DePaul Symptom Questionnaire, and RAND SF-36. RESULTS: The general and physical fatigue subscales on Multidimensional Fatigue Inventory-20, as well as the role of physical health on the RAND SF-36, demonstrated questionable or unacceptable internal consistency and problematic ceiling effects. The DePaul Symptom Questionnaire demonstrated excellent internal reliability, and less than 5 % of participants were at the ceiling on each subscale. The post-exertional malaise subscale on the DePaul Symptom Questionnaire demonstrated excellent clinical utility as it was able to differentiate between ME/CFS patients and controls (OR 1.23, p < .001) and predicted ceiling effects on other patient-reported outcome subscales. A score of 20 on the post-exertional malaise subscale of the DePaul Symptom Questionnaire optimally differentiated between patients and controls. CONCLUSIONS: Significant ceiling effects and concerns with reliability and validity were observed among Multidimensional Fatigue Inventory-20 and RAND SF-36 subscales for ME/CFS patients. The DePaul Symptom Questionnaire addresses a number of concerns typically identified when using patient-reported outcome measures with ME/CFS patients; however, an improved multidimensional patient-reported outcome tool for measuring ME/CFS-related symptoms is warranted.

"One Scar Too Many:" The Associations Between Traumatic Events and Psychological Distress Among Undocumented Mexican Immigrants.

Undocumented immigration often presents with multiple stressors and contextual challenges, which may diminish mental health. This study is the first to provide population-based estimates for the prevalence of traumatic events and its association to clinically significant psychological distress among undocumented Mexican immigrants in the United States. This cross-sectional study used respondent-driven sampling to obtain and analyze data from clinical interviews with 248 undocumented Mexican immigrants residing in high-risk neighborhoods near the California-Mexico border. Overall, 82.7% of participants reported a history of traumatic events, with 47.0% of these meeting the criteria for clinically significant psychological distress. After controlling for relevant covariates, having experienced material deprivation, odds ratio (OR) = 2.26, 95% CI [1.18, 4.31], p = .013, and bodily injury, OR = 2.96, 95% CI [1.50, 5.83], p = .002, and not having a history of deportation, OR = 0.36, 95% CI [0.17, 0.79], p = .011, were associated with clinically significant psychological distress. These results support the need to revisit health and immigration policies and to devise solutions grounded in empirical evidence aimed at preventing the negative effects of trauma and psychological distress in this population.

Exercise, inflammation, and fatigue in cancer survivors.

Cancer-related fatigue significantly disrupts normal functioning and quality of life for a substantial portion of cancer survivors, and may persist for years following cancer treatment. While the causes of persistent fatigue among cancer survivors are not yet fully understood, accumulating evidence suggests that several pathways, including chronic inflammation, autonomic imbalance, HPA-axis dysfunction, and/or mitochondrial damage, could contribute towards the disruption of normal neuronal function and result in the symptom of cancer-related fatigue. Exercise training interventions have been shown to be some of the more successful treatment options to address cancer-related fatigue. In this review, we discuss the literature regarding the causes of persistent fatigue in cancer survivors and the mechanisms by which exercise may relieve this symptom. There is still much work to be done until the prescription of exercise becomes standard practice for cancer survivors. With improvements in the quality of studies, evidenced-based exercise interventions will allow exercise scientists and oncologists to work together to treat cancer-related fatigue.

Mastery matters most: How mastery and positive relations link attachment avoidance and anxiety to negative emotions.

Attachment avoidance and anxiety are associated with negative emotions. However, the mechanisms underlying these associations are not fully understood. We investigated environmental mastery and positive relations with others as two mechanisms behind the attachment-emotion link in a sample of 343 adults. As predicted, attachment avoidance and anxiety were related to greater fear, hostility, envy and depression through lower mastery. Contrary to our hypothesis, positive relations mediated only the attachment-depression link. In addition, by adopting a moderated mediation approach, we were able to show that mastery mattered most for individuals high on avoidance: The indirect effect of avoidance through lack of mastery on fear, hostility and depression (but not on envy) increased with higher avoidance scores. Contrary to our predictions, poor relationships did not matter more as sources of negative emotions as anxiety increased. These findings underscore that the emotional life of avoidantly attached individuals is especially jeopardised by poor mastery.